Search

Objective There is no consensus on whether platinum doublet chemotherapy or lenvatinib and pembrolizumab (LEN/PEM) is superior for advanced or recurrent endometrial cancer. Thus, this study aimed to compare the prognosis and adverse events in patients with advanced or recurrent endometrial cancer treated with platinum doublet chemotherapy or LEN/PEM. Methods We retrospectively reviewed the medical records of patients who received platinum doublet chemotherapy or LEN/PEM at our institution for advanced or recurrent endometrial cancer and had a history of platinum-based chemotherapy between January 2013 and August 2023. Results During the study period, 11 regimens were identified in the platinum doublet chemotherapy group, and 11 regimens were identified in the LEN/PEM group. The objective response rates of the platinum doublet chemotherapy and LEN/ PEM groups were 36.4% and 54.5% (P=0.67), respectively. The 6-month progression-free survival (PFS) rates of the platinum doublet chemotherapy and LEN/PEM groups were 27.3% (95% confidence interval [CI], 13.8%–40.7%) and 70.0% (95% CI, 55.5%–84.5%), respectively. The differences were significant between the two groups. Multivariate analyses of histology, prior lines of chemotherapy, platinum-free intervals, and regimens revealed that the LEN/PEM group had significantly better PFS rates. Conclusion Treatment with LEN/PEM resulted in significantly longer PFS than that of treatment with platinum doublet chemotherapy in patients with advanced and recurrent endometrial cancer. However, further large-scale studies are required to validate these findings.

Objective: We present an unusual case of a small para-aortic lymphocele causing duodenal stenosis after lymphadenectomy and discuss its treatment. Case report: Our case involved a 57-year-old woman with endometrial cancer who underwent surgery, including para-aortic lymphadenectomy. On postoperative day 7, projectile vomiting occurred. Computed tomography (CT) revealed a small lymphocele in the dorsal duodenum, causing duodenal stenosis. Transpercutaneous and transduodenal puncture or surgical procedures were difficult because the cyst was too small. Per endoscopic and gastrointestinal series findings on the postoperative day 22, a liquid diet was presumed to be able to pass through the narrow portion. Hence, concentrated liquid food was administered orally; no vomiting occurred. At 2 months postoperatively, CT showed no lymphocele. Conclusion: Conservative treatment involving waiting for spontaneous lymphocele reduction with a concentrated fluid diet may be considered in such cases if fluid passage is confirmed with endoscopy and gastrointestinal series.

Introduction: The retinal pigment epithelium (RPE) plays essential roles in maintaining retinal functions as well as choroidal capillaries and can lead to visual disorders if dysfunctional. Transplantation of human-induced pluripotent stem cell-derived RPE (hiPSC-RPE) is a promising therapy for such RPE impaired conditions including age-related macular degeneration. The challenge with cell suspension transplantation is targeted delivery of graft cells and undesired cell reflux. Gelatin hydrolysate, a soluble variant with specific molecular weight distribution, is examined in this study for its potential use in hiPSC-RPE suspension transplantation, particularly in reducing cell reflux and enhancing RPE engraftment. Methods: A retinal bleb model was created using polydimethylsiloxane (PDMS) soft lithography to quantify cellular reflux. We examined the effects of gelatin hydrolysate on the hiPSC-RPE of various aspects of cell behavior and performance such as cell viability, hypoxia reaction, morphology, induction of inflammation and immune responses. Results: Gelatin hydrolysate at 5 % concentration effectively mitigated cell reflux in vitro mimic, improved cell viability, reduced cell aggregation, and had an inhibitory effect on hypoxic reactions due to cell deposition with hiPSC-RPE. Additionally, gelatin hydrolysate did not affect cell adhesion and morphology, and decreased the expression of major histocompatibility complex class II molecules, which suggests reduced immunogenicity of hiPSC-RPE. Conclusion: Gelatin hydrolysate is considered a valuable and useful candidate for future regenerative therapies in hiPSC-RPE suspension transplantation.

The plasmasphere within Earth’s magnetosphere plays a crucial role in space physics, with its electron density distribution being pivotal and strongly influenced by solar activity. Very Low Frequency (VLF) waves, including whistlers, provide valuable insights into this distribution, making the study of their propagation through the plasmasphere essential for predicting space weather impacts on various technologies. In this study, we evaluate the performance of different deep learning model sizes for lightning whistler detection using the YOLO (You Only Look Once) architecture. To achieve this, we transformed the entirety of raw data from the Arase (ERG) Satellite for August 2017 into 2736 images, which were then used to train the models. Our approach involves exposing the models to spectrogram diagrams—visual representations of the frequency content of signals—derived from the Arase Satellite’s WFC (WaveForm Capture) subsystem, with a focus on analyzing whistler-mode plasma waves. We experimented with various model sizes, adjusting epochs, and conducted performance analysis using a partial set of labeled data. The testing phase confirmed the effectiveness of the models, with YOLOv5n emerging as the optimal choice due to its compact size (3.7 MB) and impressive detection speed, making it suitable for resource-constrained applications. Despite challenges such as image quality and the detection of smaller whistlers, YOLOv5n demonstrated commendable accuracy in identifying scenarios with simple shapes, thereby contributing to a deeper understanding of whistlers’ impact on Earth’s magnetosphere and fulfilling the core objectives of this study.

Key Clinical Message In a patient with anti‐aminoacyl tRNA synthetase antibody and anti‐OJ antibody syndrome, interventions likes warming, prostaglandins, and antiplatelets failed. However, prednisolone pulse treatment rapidly halted disease progression. Patients with mild interstitial pneumonia, myositis, and extremity necrosis should be promptly considered for anti‐synthetase syndrome and receive immunosuppression after ruling out other causes. Abstract Anti‐aminoacyl tRNA synthetase (ARS) autoantibodies are myositis‐specific, and patients who test positive for ARS and have common clinical features are usually diagnosed with antisynthetase antibody syndrome (antisynthetase syndrome). Anti‐ARS antibodies include histidyl‐tRNA synthetase‐1 (Jo‐1), anti‐threonyl (PL‐7), anti‐alanyl (PL‐12), anti‐glycyl (EJ), anti‐asparaginyl (KS), anti‐tyrosyl (Ha), and anti‐phenylalanyl (Zo) tRNA synthetases. Among these, anti–isoleucyl tRNA synthetase (OJ) autoantibodies are extremely rare, and patients with these are frequently complicated by interstitial pneumonia. We report the case of an older man with ARS antibody syndrome who tested positive for anti‐OJ and anti‐Sjögren's‐syndrome‐related antigen A (Ro‐52) antibodies. He had muscle weakness due to myositis and unparalleled rapid and severe finger necrosis. Pulsed prednisolone effectively treated the myositis symptoms and terminated the progression of finger necrosis.

Retinal pigment epithelium (RPE) cells show heterogeneous levels of pigmentation when cultured in vitro. To know whether their color in appearance is correlated with the function of the RPE, we analyzed the color intensities of human-induced pluripotent stem cell-derived RPE cells (iPSC-RPE) together with the gene expression profile at the single-cell level. For this purpose, we utilized our recent invention, Automated Live imaging and cell Picking System (ALPS), which enabled photographing each cell before RNA-sequencing analysis to profile the gene expression of each cell. While our iPSC-RPE were categorized into four clusters by gene expression, the color intensity of iPSC-RPE did not project any specific gene expression profiles. We reasoned this by less correlation between the actual color and the gene expressions that directly define the level of pigmentation, from which we hypothesized the color of RPE cells may be a temporal condition not strongly indicating the functional characteristics of the RPE.

Obesity and ageing are the most important risk factors for sleep apnoea syndrome (SAS); however, the role of body mass index (BMI) on sleep status in healthy older adults is unclear. To explore sleep parameters according to BMI among active older adults, we cross-sectionally examined the relationship between sleep-related parameters and BMI in 32 Japanese adults aged from 83 to 95 years without long-term care who were unaware of having SAS. Correlation and linear regression analyses were performed. Moderate or severe SAS prevalence was high in both those with low (68.8%) and high (68.8%) BMI. A higher increase in apnoea-hypopnoea index (AHI) was negatively correlated with sleep depth in the high-BMI group. In the low-BMI group, the number of awakenings and age were positively correlated with AHI. Older adults may have SAS regardless of their BMI, and the sleep status of patients with SAS may vary by BMI.

The prognosis for cancer of unknown primary site (CUP) is poor, and squamous cell carcinoma of the unknown primary site (SCCUP) is a rare histological type. CUP is often treated with aggressive multimodal treatments, while the treatment of single-area localized CUP remains controversial. We retrospectively reviewed the medical records of patients with CUP. SCCUP in women was classified according to several definitions. Based on the histologic type and site, they were classified into favorable and unfavorable subsets. We further divided SCCUP into two types (single and multiple areas) and reviewed treatment and efficacy. Among the 227 female CUP patients, 36 (15%) had SCCUP. The median age was 59.9 years (range, 31–90 years). Most patients (61.1%) had a good performance status. Of the SCCUP patients, 22 had cancer in a single area, and 14 in multiple areas. Single-area SCCUP was further divided into favorable (16 cases) and unfavorable subsets (6 cases). In the favorable subset, local treatment was predominant, and almost all cases had a good prognosis. Even in the unfavorable subset, local therapy was combined with systemic chemotherapy in only two cases, and four cases showed no recurrences. Local treatment may be effective for single-area SCCUP, even in the unfavorable subset.

ABSTRACTThe effect of the heating rate on crystallization and densification of sol–gel-derived TiO2 films has been investigated. The TiO2 gel films were prepared from Ti(OC3H7i)4 solutions containing alcohols (2-butanol and 2-methoxyethanol), glycols (propylene glycol, diethylene glycol and dipropylene glycol) and chelating agents (acetylacetone and benzoylacetone) as organic additives, followed by heat treatment to 800°C at various heating rates. In the cases without organic additives and with alcohols, anatase films were obtained irrespective of the heating rate, where the refractive indexes of the films were higher for slower heating rate. Conversely, for the films prepared with glycols and chelating agents, rapid heating activated crystallization and densification. In particular, addition of chelating agents led to the formation of rutile films with much higher refractive indexes than those of the anatase films.

Chemotherapy and radiation therapy can cause gonadal dysfunction in women of reproductive age. Ovarian tissue cryopreservation is performed to restore fertility by allowing transplantation of the patient’s frozen-thawed ovarian tissue or through future in vitro maturation and in vitro fertilization of frozen-thawed oocytes. Herein, we describe our initial experience with vaginal natural orifice transluminal endoscopic surgery for ovarian tissue preservation in a young woman with malignant tumor. A 23-year-old woman with anaplastic lymphoma kinase-positive malignant lymphoma was scheduled for hematopoietic stem cell transplantation after experiencing relapse following R-cyclophosphamide, doxorubicin, vincristine, and prednisolone therapy. Ovarian tissue cryopreservation was selected as only MII2 oocytes were collected. Vaginal natural orifice transluminal endoscopic surgery was performed to excise the left ovary. Ovarian tissues were frozen using the vitrification method. The operative time was 37 min, and blood loss was minimal. Pathological examination revealed no metastatic findings of malignant lymphoma and no thermal damage to the ovarian tissue due to bipolar disorder. The patient was discharged on the first day postoperatively, and her postoperative course was uneventful. The vaginal natural orifice transluminal endoscopic surgery technique can provide a safe and effective alternative to laparoscopy or laparotomy for the cryopreservation of ovarian tissue in young patients with cancer. We believe this method has potential application in sexually mature female cancer survivors.

Coronavirus disease 2019 (COVID-19) has affected medical practice. More than 7,000,000 patients died worldwide after being infected with COVID-19; however, no specific laboratory markers have yet been established to predict death related to this disease. In contrast, electrocardiographic changes due to COVID-19 include QT prolongation and ST-T changes; however, there have not been studies on the ambulatory electrocardiographic markers of COVID-19. We encountered three patients diagnosed as having COVID-19 who did not have a prior history of significant structural heart diseases. All patients had abnormalities in ambulatory echocardiogram parameters detected by high-resolution 24 h electrocardiogram monitoring: positive late potentials (LPs) and T-wave alternans (TWA), abnormal heart rate variability (HRV), and heart rate turbulence (HRT). Case 1 involved a 78-year-old woman with a history of chronic kidney disease, Case 2 involved a 76-year-old man with hypertension and diabetes, and Case 3 involved a 67-year-old man with renal cancer, lung cancer, and diabetes. None of them had a prior history of significant structural heart disease. Although no significant consistent increases in clinical markers were observed, all three patients died, mainly because of respiratory failure with mild heart failure. The LP, TWA, HRV, and HRT were positive in all three cases with no significant structural cardiac disease at the initial phase of admission. The further accumulation of data regarding ambulatory electrocardiographic markers in patients with COVID-19 is needed. Depending on the accumulation of data, the LP, TWA, HRV, and HRT could be identified as potential risk factors for COVID-19 pneumonia in the early phase of admission.

Key Clinical Message We report an extremely rare occurrence of adult‐onset Still's disease (AOSD) in a patient with ulcerative colitis. The possibility of autoinflammatory conditions such as AOSD should be considered when evaluating or treating symptoms suspected as side effects of the severe acute respiratory syndrome coronavirus 2 vaccination, regardless of the associated comorbidities. Summary A woman in her 50s with a history of stable ulcerative colitis (UC) for 20 years, managed using salazosulfapyridine, presented with migratory rashes, spiking fever, edema, and joint pain that started 1 week after receiving the BNT162B2 mRNA vaccine against severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2). Laboratory tests revealed extremely high serum ferritin levels. The patient was diagnosed with adult‐onset Still's disease (AOSD) based on the relevant classification criteria after ruling out other diseases. Detection of high levels of interleukin‐18, an inflammatory cytokine related to AOSD, supported the diagnosis. Nonsteroidal anti‐inflammatory drug monotherapy alone resulted in significant improvements in both the abovementioned symptoms and the elevated inflammatory marker levels. AOSD in a patient with UC is extremely rare. Only one case of AOSD with UC was reported before the coronavirus disease 2019 era. This case indicates that SARS‐CoV‐2 vaccination can trigger a hyperinflammatory response, classified as AOSD, in a patient with UC, which is extremely rare.

Background: Sample size re-estimation (SSR) is a method used to recalculate sample size during clinical trial conduct to address a lack of adequate information and can have a significant impact on study size, duration, resources, and cost. Few studies to date have summarized the conditions and circumstances under which SSR is applied. We therefore performed a systematic review of the literature related to SSR to better understand its application in clinical trial settings. Methods: PubMed was used as the primary search source, supplemented with information from ClinicalTrials.gov where necessary details were lacking from PubMed. A systematic review was performed according to a pre-specified search strategy to identify clinical trials using SSR. Features of SSR, such as study phase and study start year, were summarized. Results: In total, 253 publications met the pre-specified search criteria and 27 clinical trials were subsequently determined as relevant in SSR usage. Among trials where the study phase was provided, 2 (7.4%) trials were Phase I, 5 (18.5%) trials were Phase II, 11 (40.7%) trials were Phase III, and 2 (7.4%) trials were Phase IV. Conclusion: Our results showed that SSR is also used in Phase I and II, which involve earlier decision making. We expect that SSR will continue to be used in early-phase trials where sufficient prior information may not be available. Furthermore, no major trends were observed in relation to therapy area or type of SSR, meaning that SSR may become a feasible and widely applied method in the future.

Abstract Background The prevalence of Holter‐based late potentials (H‐LPs) in cases of fatal cardiac events has increased. Although the noise level of H‐LP is higher than that of conventional real‐time late potential (LP) recording, a procedure to reduce the noise severity in H‐LP by increasing the averaging beats has not been investigated. Methods We enrolled 104 patients with post‐myocardial infarction (MI) and 86 control participants. Among the patients, 30 reported sustained ventricular tachycardia (VT), and the remaining 74 had unrecorded VT. H‐LPs were measured twice in all groups to evaluate the efficacy of increasing the averaging beats for H‐LPs. Thereafter, the average of LP was calculated at 250 (default setting), 300, 400, 500, 600, 700, and 800 beats. Results Across all three groups (MI‐VT group, MI non‐VT group, and control group), the noise levels significantly decreased in consonance with the increase in averaging beats. In the MI‐VT group, the H‐LP positive rate considerably increased with the increase in the averaging beats from 250 to 800 both at night and daytime. In the MI‐VT group, the LP parameters significantly deteriorated, which led to a positive judgment corresponding to the increment of the averaged night and day beats. The H‐LP positive rates were unchanged in the MI non‐VT and control groups, while the LP parameters remained consistent, despite the increased averaging beats in the MI non‐VT and control groups. Conclusion Increasing the calculated averaging beats in H‐LPs can improve the sensitivity of predicting fatal cardiac events in patients with MI.

We report a case of a 70-year-old female patient with locally advanced endometrial cancer with primary empty sella who developed multiple immune-related adverse events (irAEs), including hypopituitarism coinciding with the complete response to radiotherapy after receiving immune checkpoint inhibitors. A computed tomography scan acquired after a traffic accident led to the discovery of endometrial cancer that had invaded the vulva and primary empty sella. Following adriamycin and cisplatin, pembrolizumab was administered for three cycles. No irAEs were observed during treatment, but the tumor was progressive. The patient underwent radiotherapy for the residual tumor. Four months after the last dose of pembrolizumab, hypopituitarism caused secondary adrenal insufficiency, primary hypothyroidism, and pseudogout at the end of radiotherapy. The tumor later achieved a complete response. In conclusion, radiotherapy after immune checkpoint inhibitor (ICI) therapy is expected to have an antitumor effect by stimulating tumor-specific immunity. However, proper management of irAEs is necessary. Patients with primary empty sella may be prone to pituitary insufficiency induced by ICIs.

The morphology of larvae is a key factor influencing their behaviour, performance and ultimately their survival. There is evidence indicating a significant morphological variability among broods, and that this may be related to the size or conditions of the mother. However, this maternal influence is not consistent across decapod crustaceans. Using 35 broods from different mothers of the crab Hemigrapsus takanoi collected in the same locality of inner Tokyo Bay and at the same time, we tested the hypothesis that there is a positive relationship between the size of the mother and the progeny’s morphology. Our results indicate that different patterns in the length of the lateral, rostral and dorsal spines differentiated two distinct morphogroups of larvae. These morphogroups were linked to the size of the mother, showing that larger mothers produced bigger larvae with longer carapace spines. It is possible that larger size and longer spines can influence swimming performance and predator avoidance, respectively. These relationships should be tested in future experimental studies.

IntroductionMaintaining high cognitive functions is desirable for “wellbeing” in old age and is particularly relevant to a super-aging society. According to their individual cognitive functions, optimal intervention for older individuals facilitates the maintenance of cognitive functions. Cognitive function is a result of whole-brain interactions. These interactions are reflected in several measures in graph theory analysis for the topological characteristics of functional connectivity. Betweenness centrality (BC), which can identify the “hub” node, i.e., the most important node affecting whole-brain network activity, may be appropriate for capturing whole-brain interactions. During the past decade, BC has been applied to capture changes in brain networks related to cognitive deficits arising from pathological conditions. In this study, we hypothesized that the hub structure of functional networks would reflect cognitive function, even in healthy elderly individuals.MethodTo test this hypothesis, based on the BC value of the functional connectivity obtained using the phase lag index from the electroencephalogram under the eyes closed resting state, we examined the relationship between the BC value and cognitive function measured using the Five Cognitive Functions test total score.ResultsWe found a significant positive correlation of BC with cognitive functioning and a significant enhancement in the BC value of individuals with high cognitive functioning, particularly in the frontal theta network.DiscussionThe hub structure may reflect the sophisticated integration and transmission of information in whole-brain networks to support high-level cognitive function. Our findings may contribute to the development of biomarkers for assessing cognitive function, enabling optimal interventions for maintaining cognitive function in older individuals.

Abstract This study evaluated the influence of positive peritoneal cytology (PPC) on the prognosis of patients with stage IA endometrial cancer, and the usefulness of adjuvant chemotherapy in their treatment. We retrospectively analyzed the data of patients with stage IA endometrial cancer admitted in our hospital between 2005 and 2015. Among 989 patients who underwent peritoneal cytology, 135 (13.7%) had PPC. Multivariate analysis extracted several independent risk factors for recurrence in stage IA patients, including those with PPC. Adjuvant chemotherapy did not cause a significant difference in the 5-year relapse-free survival rate in patients with PPC (p = 0.78). Similarly, the 5-year recurrence-free survival rate with or without chemotherapy was not different among type II cancer patients (p = 0.11). However, the baseline risk of 5-year relapse-free survival without chemotherapy in patients with PPC and type II was very low (66.7%). While PPC was an independent risk factor for recurrence in stage IA endometrial cancer, adjuvant chemotherapy did not influence the survival rate in patients with PPC. While it is controversial whether adjuvant chemotherapy should be administered in stage IA uterine cancer with only PPC as a prognostic factor, it should be considered for early-stage patients who have multiple risk factors for recurrence.

BackgroundThe advent of novel monitoring technologies has dramatically increased the use of ambulatory electrocardiography (AECG) devices. However, few studies have conducted detailed large-scale investigations on the incidence of arrhythmias over 24 h, especially ectopy, in healthy individuals over a wide age range.ObjectivesThis study aimed to investigate the incidence of arrhythmias detected using AECG and associated factors, in healthy individuals, over a wide age range.MethodsIn this cross-sectional study, we performed AECG on 365 healthy volunteers (median [interquartile range]: 48 [36, 67], 20–89 years, 165 men) under free-running conditions for 24 h. Ultrasonic echocardiography and heart rate variability analysis were performed to explore the factors associated with the incidence of arrhythmias.ResultsThe 97.5th percentile of single ventricular ectopy (VE) was 149/day, 254/day, and 1,682/day in the 20–39-, 40–59- and 60–89-year age groups, respectively; that of single supraventricular ectopy (SVE) was 131/day, 232/day, and 1,063/day, respectively. Multivariate analysis revealed that aging was the only independent significant factor influencing the frequency of VE (β = 0.207, P = 0.001). Age (β = 0.642, P

Abstract Several clinical studies have been conducted into the practicality and safety of regenerative therapy using hESC/iPSC-retinal pigment epithelium (RPE) as a treatment for the diseases including age-related macular degeneration. These studies used either suspensions of RPE cells or an RPE cell sheet. The cells can be injected using a minimally invasive procedure but the delivery of an intended number of cells at an exact target location is difficult; cell sheets take a longer time to prepare, and the surgical procedure is invasive but can be placed at the target area. In the research reported here, we combined the advantages of the two approaches by producing a quickly formed hiPSC-RPE strip in as short as 2 days. The strip readily expanded into a monolayer sheet on the plate, and after transplantation in nude rats, it showed a potency to partly expand with the correct apical/basal polarity in vivo, although limited in expansion area in the presence of healthy host RPE. The strip could be injected into a target area in animal eyes using a 24G canula tip.

ABSTRACT BACKGROUND: Dysbiosis of the gut microbiota is frequently found in cases of obesity and related metabolic diseases, such as type 2 diabetes mellitus. The composition of the microbiota in diabetics is similar to that of obese people, thereby causing increased energy uptake efficiency in the large intestine of obese people, maintenance of a systemic inflammatory state, and increased insulin resistance. Bariatric surgery seems to entail an improvement in gut dysbiosis, leading to an increased diversity of the gut microbiota. AIMS: This study aimed to present a literature review on obesity-associated gut dysbiosis and its status post-bariatric surgery. METHODS: A systematic review of primary studies was conducted in PubMed, SciELO, BIREME, LILACS, Embase, ScienceDirect, and Scopus databases using DeCS (Health Science Descriptors) with the terms “obesity,” “intestinal dysbiosis,” “bariatric surgery,” and “microbiota.” RESULTS: We analyzed 28 articles that had clinical studies or literature reviews as their main characteristics, of which 82% (n=23) corresponded to retrospective studies. The sample size of the studies ranged from 9 to 257 participants and/or fecal samples. The epidemiological profile showed a higher prevalence of obesity in females, ranging from 24.4 to 35.1%, with a mean age of around 25–40 years. There was a variation regarding the type of bariatric surgery, migrating between the Roux-en-Y bypass, adjustable gastric banding, and vertical gastrectomy. Of the 28 studies, 6 of them evaluated the gut microbiota of obese patients undergoing bariatric surgery and their relationship with type 2 diabetes mellitus/glucose metabolism/insulin resistance. CONCLUSIONS: The intestinal microbiota is an important influencer in the regulation of the digestive tract, and obese individuals with comorbidities (diabetes mellitus, hypercholesterolemia, and metabolic syndrome) present important alterations, with an unbalance normal state, generating dysbiosis and the proliferation of bacterial species that favor the appearance of new diseases. Patients who undergo bariatric surgery present an improvement in the intestinal microbiota imbalance as well as reversibility of their comorbidities, increasing their life expectancy.

Vasomotricity, defined by measurements of contraction or relaxation, is important to support correct blood supply and needs to be finely regulated during hemodynamic changes. Disruptions in either contraction or relaxation, mainly endothelium-mediated, are closely related to cardiovascular diseases and are found during early events of vascular structural alterations, including vessel remodeling. Both acute vasomotor changes and chronic vascular remodeling are regulated by redox processes, such as the production of nitric oxide (NO), which is the major vasoactive endothelium-derived paracrine molecule. However, it is still unclear if vasomotricity can be regulated by direct redox reactions or thiol posttranslational modifications induced by secondary mediators. Here, we have reviewed the literature concerning the control of vascular function based on redox processes and merged evidence with mechanisms supporting structural alterations. Such knowledge is important to summarize the resulting vascular effects that occur upon inhibition of specific redox regulators. This may provide a landscape to better understand the complex redox regulation of vasomotricity and determine a hierarchical map of events involving NO biology, calcium transient regulation, actin cytoskeleton and extracellular matrix organization. In addition, we have proposed that the thiol oxidoreductase protein disulfide isomerase A1 (PDI) has the potential to act as a central hub connecting these processes with local oxidant generation, which may globally impact vascular function in physiologic and pathologic processes. Altogether, the understanding of these redox processes may lead to potential therapeutic redox targets able to prevent or treat functional or structural vascular alterations.

Study Objectives: Aging is a risk factor for sleep apnoea syndrome (SAS), which is associated with lower quality of life and sudden mortality. However, SAS is often overlooked in older adults without suspicions. Therefore, this study aimed to evaluate SAS incidence and 48 other general factors in older adults.Methods: This cross-sectional study included all non-caregiver-certified, healthy individuals (N = 32) who survived during the long-term cohort study and agreed to participate in apnoea-hypopnoea index (AHI) measurement (aged 83–95 years). AHI and 48 other general factors were evaluated, and simple linear regression analysis was used to identify potential AHI-related factors. Stepwise evaluation was further performed using multiple linear regression analyses.Results: Although no individuals were previously diagnosed with SAS, 30 (93.75%) participants had some degree of SAS (AHI > 5/h), and 22 (68.75%) had severe or moderate SAS (AHI > 15/h). Compared with typical single risk factors represented by body mass index, combining daily steps and other factors improved the fit to the multiple linear regression. Combining daily steps and body mass index improved the fit for males and combining daily steps and red blood cell count improved the fit for females.Conclusion: SAS was highly prevalent in unaware healthy Japanese older adults; combinations of daily steps and body mass index, and daily steps and red blood cell count may predict AHI in such individuals without the need for a specific AHI test.

Background and Objectives: Holter-based late potentials (LPs) are useful for predicting lethal arrhythmias in organic cardiac diseases. Although Holter-based LPs exhibit diurnal variation, no studies have evaluated the optimal timing of LP measurement over 24 h for predicting lethal arrhythmia that leads to sudden cardiac death. Thus, this study aimed to validate the most effective timing for Holter-based LP testing and to explore factors influencing the diurnal variability in LP parameters. Materials and Methods: We retrospectively analyzed 126 patients with post-myocardial infarction (MI) status and 60 control participants who underwent high-resolution Holter electrocardiography. Among the 126 post-MI patients, 23 developed sustained ventricular tachycardia (VT) (the MI-VT group), while 103 did not (the MI-non-VT group) during the observation period. Holter-based LPs were measured at 0:00, 4:00, 8:00, 12:00, 16:00, and 20:00, and heart rate variability analysis was simultaneously performed to investigate factors influencing the diurnal variability in LP parameters. Results: Holter-based LP parameters showed diurnal variation with significant deterioration at night and improvement during the day. Assessment at the time with the longest duration of low-amplitude signals < 40 μV in the filtered QRS complex terminus (LAS40) gave the highest receiver operating characteristics curve (area under the curve, 0.659) and the highest odds ratio (3.75; 95% confidence interval, 1.45–9.71; p = 0.006) for predicting VT. In the multiple regression analysis, heart rate and noise were significant factors affecting the LP parameters in the MI-VT and control groups. In the non-VT group, the LP parameters were significantly influenced by noise and parasympathetic heart rate variability parameters, such as logpNN50. Conclusions: For Holter-based LP measurements, the test accuracy was higher when the LP was measured at the time of the highest or worst value of LAS40. Changes in autonomic nervous system activity, including heart rate, were factors influencing diurnal variability. Increased parasympathetic activity or bradycardia may exacerbate Holter-based LP parameters.

Recent studies suggest that the maintenance of cognitive function in the later life of older people is an essential factor contributing to mental wellbeing and physical health. Particularly, the risk of depression, sleep disorders, and Alzheimer's disease significantly increases in patients with mild cognitive impairment. To develop early treatment and prevention strategies for cognitive decline, it is necessary to individually identify the current state of cognitive function since the progression of cognitive decline varies among individuals. Therefore, the development of biomarkers that allow easier measurement of cognitive function in older individuals is relevant for hyperaged societies. One of the methods used to estimate cognitive function focuses on the temporal complexity of electroencephalography (EEG) signals. The characteristics of temporal complexity depend on the time scale, which reflects the range of neuron functional interactions. To capture the dynamics, composed of multiple time scales, multiscale entropy (MSE) analysis is effective for comprehensively assessing the neural activity underlying cognitive function in the brain. Thus, we hypothesized that EEG complexity analysis could serve to assess a wide range of cognitive functions in older adults. To validate our hypothesis, we divided older participants into two groups based on their cognitive function test scores: a high cognitive function group and a low cognitive function group, and applied MSE analysis to the measured EEG data of all participants. The results of the repeated-measures analysis of covariance using age and sex as a covariate in the MSE profile showed a significant difference between the high and low cognitive function groups (F = 10.18, p = 0.003) and the interaction of the group × electrodes (F = 3.93, p = 0.002). Subsequently, the results of the post-hoct-test showed high complexity on a slower time scale in the frontal, parietal, and temporal lobes in the high cognitive function group. This high complexity on a slow time scale reflects the activation of long-distance neural interactions among various brain regions to achieve high cognitive functions. This finding could facilitate the development of a tool for diagnosis of cognitive decline in older individuals.

B-cell lymphomas are neoplastic diseases occasionally associated with chronic inflammation. mRNA vaccines for coronavirus disease 2019 (COVID-19) induce inflammatory responses, which often lead to fever and lymphadenopathies indistinguishable from lymphomas. Although both lymphadenopathies and lymphomas can be influential, the correlation between them is unclear. Herein, we present the first case of marginal zone B-cell lymphoma following mRNA COVID-19 vaccination. An 80-year-old Japanese woman presented with a right temporal mass that appeared the morning after she was administered her first mRNA COVID-19 vaccination (BNT162b2). The mass gradually decreased in size but persisted over 6 weeks after her first vaccination (3 weeks after her second vaccination). At her first visit to our hospital, ultrasound revealed the size of the mass to be 28.5 × 5.7 mm, and computed tomography revealed multiple lymphadenopathies in the right parotid, submandibular, jugular, and supraclavicular regions. Initially, we suspected head-and-neck benign lymphadenopathy as a side effect of vaccination. Nine weeks later, the number of swollen submandibular and parotid glands increased, and the lymph nodes further enlarged. Finally, the right temporal mass was diagnosed as marginal zone B-cell lymphoma based on immunohistochemical and flow cytometry findings of biopsy specimens. Our findings suggest that although 4–6 weeks of observation for lymph node inflammation after the second vaccination is recommended, malignancy should also be considered in the differential diagnosis of lymphadenopathy following vaccination.

Abstract Inguinal hernia may contain the bladder as one of its contents, while bilateral inguinal bladder herniation is rare. Urinary obstruction and obesity are associated with increased abdominal pressure and are risk factors of bladder herniation. Clinicians should be aware of the bladder hernia in elderly with chronic dysuria and obesity.

Abstract After pelvic lymphadenectomy (PLA), pelvic vessels, nerve, and ureter are skeletonized. Internal hernias beneath the skeletonized pelvic structure following pelvic lymphadenectomy (IBSPP) are a rare complication following PLA. To the best of our knowledge, only 12 IBSPP cases have been reported and clinical details on such hernias remain unknown. The aim of the study was to investigate the incident and etiology of IBSPP. 1313 patients who underwent open or laparoscopic pelvic lymphadenectomy were identified from our database. A retrospective review was performed. Mean follow-up period was 33.9 months. A total of 12 patients had IBSPP. Multivariate analysis of laparoscopic surgeries group as compared to open surgeries group, para-aortic lymphadenectomy rate, number of dissected lymph nodes by PLA, antiadhesive material use rate, and blood loss were lower in laparoscopic surgeries group: odd ratio (OR) = 0.13 [95% confidence interval (CI) 0.08–0.19], and OR = 0.70 [95% CI 0.50–0.99], OR = 0.17 [95% CI 0.10–0.28], OR = 0.93 [95% CI 0.92–0.94]. However, no significant difference was observed in the incidence of IBSPP between laparoscopic surgery (1.0%) and open surgery (0.8%). All IBSPP occurred in the right pelvic space. These findings may contribute to the development of prevention methods for this disease.

Abstract Background Uterine adenosarcoma, a rare uterine tumor subtype, is a biphasic tumor consisting of epithelial and mesenchymal elements. To date, there is no research comparing the histopathological features and immunohistochemistry of primary and recurrent tumors; furthermore, the relationship between pathology and the clinical course remains unclear. We reviewed the pathology and immunohistochemical features of patients with adenosarcoma and investigated the relevance of the histomorphological features to the clinical course. We also compared the immunohistochemical features of the primary and recurrent tumors. Methods The data of seven patients with adenosarcoma who underwent surgery in our hospital were evaluated. We performed immunohistochemical staining for the progesterone receptor, estrogen receptor, p53, and two Switch/Sucrose Non-Fermentable chromatin remodeling proteins (SMARCA4, BCOR), which were recently developed for the undifferentiated sarcoma diagnosis in addition to conventional staining methods. Results All patients had International Federation of Gynecology and Obstetrics stage IB–IC diseases. All tumors were polypoid and every patient presented with abnormal uterine bleeding. Six patients aged over 50 years and were menopausal; one patient aged under 50 years and was non-menopausal (average age: 59.1 years). Histologically, the sarcomatous components were homologous and heterogenous in six and one patient, respectively. Four and three cases were recurrent and non-recurrent, respectively. The recurrent patients showed high-grade morphology with sarcomatous overgrowth and were negative for ER and PR. Three recurrences could be evaluated by imaging, showing recurrence only in a distant area; biopsy specimens from these tissues revealed the identical mesenchymal component found in the primary tumor without a benign epithelial component. Immunohistochemical staining results were also similar to the corresponding of the original tumor, except for the p53 expression in one patient. At the primary site, p53 was overexpressed in two recurrent patients and had a wild-type level in one recurrent patient; however, all three recurrent tissues showed p53 overexpression. None of our patients showed SMARCA4 loss, and BCOR expression was positive in one case. Conclusions Initial pathological adenosarcoma analysis with appropriate immunohistochemical staining is vital for prognostic assessment. p53 expression might increase at recurrence. SMARCA4 and BCOR might not be an index of malignancy.

Abstract Background We examined risk factors for development of ventricular tachycardia (VT) in pediatric patients with ventricular premature contractions (VPCs) and a structurally normal heart. Methods The subjects were 81 844 first graders and 88 244 seventh graders of Kagoshima City School‐based cardiovascular screening (SCV‐screening) between 2001 and 2015. We retrospectively reviewed the clinical data of students who were diagnosed as having VPC. Results Ventricular premature contractions were observed in 134 first graders (0.16%) and 270 seventh graders (0.31%). On the screening electrocardiograms (ECGs), 43 patients (11%) showed bi‐/trigemini, three patients (0.7%) showed a couplet, and one patient showed VT. We obtained 166 patients' follow‐up information and evaluated 59 patients (36%) as improved, 97 patients (58%) as no change, and 10 patients (6%) as worsened (couplets, five; triplets, two; VT, three). We assumed that these worsened patients have risk factors for development of VT. Comparing the findings of SCV‐screening ECGs of risk patients with the others, a significant difference was observed only in the number of VPCs (per 10 seconds) (mean ± SD; 4.3 ± 2.6 vs 1.8 ± 1.4, P

Background: Nucleic acid amplification testing is the gold standard for SARS-CoV-2 diagnostics, although it may produce a certain number of false positive results. There has not been much published about the characteristics of false positive results. In this study, based on retesting, specimens that initially tested positive for SARS-CoV-2 were classified as true or false positive groups to characterize the distribution of cycle threshold (CT) values for N1 and N2 targets and number of targets detected for each group. Methods: Specimens that were positive for N-gene on retesting and accompanied with S-gene were identified as true positives (true positive based on retesting, rTP), while specimens that retested negative were classified as false positives (false positive based on retesting, rFP). Results: Of the specimens retested, 85/127 (66.9%) were rFP, 16/47 (34.0%) specimens with both N1 and N2 targets initially detected were rFP, and the CT values for each target was higher in rFP than in rTP. ROC curve analysis showed that optimal cutoff values of CT to differentiate between rTP and rFP were 34.8 for N1 and 33.0 for N2. With the optimal cutoff values of CT for each target, out of the 24 specimens that were positive for both N1 and N2 targets and classified as rTP, 23 (95.8%) were correctly identified as true positives. rFP specimens had a single N1 target in 52/61 (85.2%) and a single N2 target in 17/19 (89.5%). Notably, no true positive results were obtained from any specimens with only N2 target detected. Conclusions: These results suggest that retesting should be performed for positive results with a CT value greater than optimal cutoff value for each target or with a single N1 target amplified, considering the possibility of a false positive. This may provide guidance on indications to perform retesting to minimize the number of false positives. [ABSTRACT FROM AUTHOR]

Abstract Background The purpose of this study to compare glenohumeral joint motion during active shoulder axial rotation between subacromial impingement syndrome (SIS) shoulders and asymptomatic shoulders using cine-magnetic resonance imaging (cine-MRI). Measurement of glenohumeral joint motion via manual intervention does not assess the usual glenohumeral joint motion, and the glenoid surface cannot be confirmed manually. However, cine-MRI can produce clear images of glenohumeral joint rotation. Therefore, we sought to measure the active ROM of the glenohumeral rotation using cine-MRI. Methods Seventy-three shoulders in 42 asymptomatic volunteers and 110 SIS shoulders in 103 consecutive patients were included in this study. We evaluated 36 matched pairs (72 shoulders in total) adjusting for baseline characteristics with propensity score matching method. The patients underwent cine-MRI during axial rotation of the adducted arm. During imaging, participants rotated their shoulder from the maximum internal rotation to the maximum external rotation over the first 10 s and then back to the maximum internal rotation over the subsequent 10 s. We assessed internal/external rotation, and compared the asymptomatic and SIS shoulders in this regard. Evaluation of rotation angles was performed on a series of axial images through the humeral head center. Results The mean internal rotation angles of the asymptomatic and patient groups were 55° ± 10° and 41° ± 23°, respectively, (P = .002; 95% Confidence Interval [CI], 51–58 vs 33–49); the mean external rotation angles were 47° ± 15° and 21° ± 25°, respectively, (P

Abstract Background Global demand for energy is on the rise at a time when limited natural resources are fast depleting. To address this issue, microalgal biofuels are being recommended as a renewable and eco-friendly substitute for fossil fuels. Euglena gracilis is one such candidate that has received special interest due to their ability to synthesize wax esters that serve as precursors for production of drop-in jet fuel. However, to realize economic viability and achieve industrial-scale production, development of novel methods to characterize algal cells, evaluate its culture conditions, and construct appropriate genetically modified strains is necessary. Here, we report a Raman microspectroscopy-based method to visualize important metabolites such as paramylon and ester during wax ester fermentation in single Euglena gracilis cells in a label-free manner. Results We measured Raman spectra to obtain intracellular biomolecular information in Euglena under anaerobic condition. First, by univariate approach, we identified Raman markers corresponding to paramylon/esters and constructed their time-lapse chemical images. However, univariate analysis is severely limited in its ability to obtain detailed information as several molecules can contribute to a Raman band. Therefore, we further employed multivariate curve resolution analysis to obtain chain length-specific information and their abundance images of the produced esters. Accumulated esters in Euglena were particularly identified to be myristyl myristate (C28), a wax ester candidate suitable to prepare drop-in jet fuel. Interestingly, we found accumulation of two different forms of myristyl myristate for the first time in Euglena through our exploratory multivariate analysis. Conclusions We succeeded in visualizing molecular-specific information in Euglena during wax ester fermentation by Raman microspectroscopy. It is obvious from our results that simple univariate approach is insufficient and that multivariate curve resolution analysis is crucial to extract hidden information from Raman spectra. Even though we have not measured any mutants in this study, our approach is directly applicable to other systems and is expected to deepen the knowledge on lipid metabolism in microalgae, which eventually leads to new strategies that will help to enhance biofuel production efficiency in the future.

In 2003, Höckel described the laterally extended endopelvic resection (LEER), which may be an effective surgical technique for patients with laterally recurrent cervical cancer (Höckel, 2003). Super-radical hysterectomy, which was introduced by Ryukichi Mibayashi in 1941, is the traditional surgical approach for cervical cancer patients (Kim et al., 2017). These two procedures are similar and belong to the same group (type D) in the Querleu-Morrow classification (Querleu et al., 2017). Until now, no surgical video clearly demonstrated their differences, because technical complexities and concern for procedural safety are still being debated.The present video demonstrated total pelvic exenteration (TPE) for laterally recurrent, previously irradiated cervical cancer that involved both the bladder and rectum. In this case, the recurrent tumor infiltrated the parametrium, reached the left pelvic sidewall, and invaded the left piriform muscle, sacrospinous ligament, and spine segment S2. To completely clear the tumor, we used TPE with super-radical hysterectomy on the right side and LEER on the left. We performed this procedure laparoscopically because improved visualization allows for meticulous dissection and a higher possibility of achieving R0.Surgery time was 9 h 45 min including the time for creation of the ileal conduit and colostomy, and blood loss was 230 ml with no blood transfusion needed. Pathological R0 resection was achieved without any intraoperative and postoperative complications. Compared to super-radical hysterectomy, LEER ensured additional surgical margins.Without any adjuvant treatment, there has been no sign of recurrence during the 12 months that have passed since the surgery.Laparoscopic TPE with super-radical hysterectomy and LEER for laterally recurrent, previously irradiated cervical cancer is a technically feasible and safe surgical option. LEER can ensure more surgical margins than super-radical hysterectomy, and it may be a treatment of choice for more advanced lateral recurrence.

Retinal pigment epithelium (RPE) cells is the outermost layer of the retina and RPE dysfunction is a key factor in the disease pathogenesis of age-related macular degeneration (AMD). Transplantation therapy using induced pluripotent stem cell (iPSC)-derived RPEs has recently received much attention as a treatment for AMD. Preserving these cells under the best possible conditions is important, and preservation methods using Y-27632 have been reported. Rho-associated coiled-coil containing kinase (ROCK) inhibitors are known to inhibit cell death, emerging as important drug candidates for stem cell differentiation and regenerative medicine. However, it has recently been shown that ROCK inhibitors may have a vasodilatory effect on human retinal arterioles, a side effect that should ideally be avoided in RPE transplantation. Although ROCK inhibitors hold great potential, optimizing efficacy while minimizing adverse reactions is critical for translation into a clinical treatment. We examined the effect of transient exposure of RPE cells to ROCK inhibitor Y-27632 to determine whether the extracellular presence of the drug is necessary for ongoing Rho/ROCK downregulation. Human RPE cells were subcultured as a suspension for 4 h in drug-free medium following exposure to Y-27632 for 2 h. A Y-27632 concentration of >10 μM improved cell survival beyond 4 h and cell proliferation in recovery culture medium. ROCK2 expression levels were specifically downregulated by Y-27632 in the Rho/ROCK signaling pathway. In conclusion, we demonstrated that the effect of Y-27632 is not dependent on its extracellular availability and can last beyond the 2 h of exposure. The lasting Rho/ROCK signaling pathway downregulation by Y-27632 suggests that RPE cell transplantation with ROCK inhibitor-free media is possible, which can minimize side effects to host tissue and have wider implications for transplantation methods requiring ROCK inhibition.

Uterine tumors detected after pelvic radiation therapy are rare. We report a case in which an endometrial tumor developed after pelvic radiation therapy for cervical cancer. The patient was a 70-year-old female with a history of pelvic radiotherapy for locally advanced cervical cancer. After 12 months of radiation therapy, magnetic resonance imaging showed tumors in the uterine cavity, and positron emission tomography-computed tomography showed no tumors, except uterine tumors. Since radiation therapy-induced cervical stenosis was conducted, endometrial examination could not be performed without anesthesia. As these tumors were detected after radiation therapy for uterine cancer, malignancy was considered. A laparoscopic-assisted transcervical hysteroscopic resection was performed for the diagnosis and treatment of uterine tumors after radiation therapy. This operative method was useful and enabled us to perform complete resection, observe the abdominal cavity, prepare for the possibility of secondary hysterectomy, and improve safety.

Abstract We present two cases of biopsy‐proven hypertrophic cardiomyopathy (HCM). Both cases showed abnormal electrocardiographic (ECG) findings more than 8 years before diagnosis. A 16‐year‐old healthy male experienced a rescued cardiac arrest. Another male adolescent showed abnormal Q wave and thickened ventricular wall at 15 years old. Retrospective analyses of ECGs performed at 6 years old indicated abnormal ECG findings. However, the diagnosis was normal because no ventricular wall thickening was present in echocardiography. For early diagnosis of HCM to prevent sudden cardiac arrest or death, it is essential to establish ECG and echocardiographic criteria to screen HCM in the young.

Background: The use of coronary computed tomography angiography (CCTA) for noninvasive anatomic detection of coronary artery disease is increasing. Recently, fractional flow reserve (FFR) assessment using routinely acquired CCTA datasets (FFRCT) has been developed. However, there are no reports about changes in coronary atherosclerosis, composition, and FFRCT in patients with type 2 diabetes. Methods: This prospective, multicenter, observational trial evaluated changes in coronary atherosclerosis after alogliptin therapy in patients with type 2 diabetes. Fifty-one patients with type 2 diabetes who underwent CCTA examination and having intermediate coronary artery stenosis were treated with 25 mg of alogliptin. After 48 weeks, CCTA examination was repeated. The primary endpoint was changes in FFRCT, and the secondary endpoint was changes in total atheroma volume (TAV) from the baseline to the 48-week follow-up. Results: The FFRCT decreased from the baseline to follow-up, but not significantly. A significant increase in TAV (from 658.5 mm3 to 668.9 mm3, p = 0.048) was observed. Vessel volume tended to increase, whereas percentage atheroma volume and lumen volume did not change. A significant negative correlation was observed between percentage change in TAV and change in FFRCT (r = −0.185, p = 0.048). A significant increase in calcified plaques (p = 0.01) and a decrease in intermediate-attenuation plaques (p = 0.006) was observed. Conclusions: In Japanese patients with diabetes and intermediate coronary artery stenosis, alogliptin could not improve FFRCT or reduce atheroma volume, whereas the plaque composition changed. A progression of atheroma volume was associated with a reduction in FFRCT. Keywords: Alogliptin, Coronary atherosclerosis, Coronary computed tomography angiography (CCTA), Diabetes mellitus, Fractional flow reserve (FFR)

We previously reported that lysine-demethylase 2A (KDM2A), a Jumonji-C histone demethylase, is activated by gallic acid to reduce H3K36me2 levels in the rRNA gene promoter and consequently inhibit rRNA transcription and cell proliferation in the breast cancer cell line MCF-7. Gallic acid activates AMP-activated protein kinase (AMPK) and increases reactive oxygen species (ROS) production to activate KDM2A. Esters of gallic acid, propyl gallate (PG) and epigallocatechin gallate (EGCG), and other chemicals, reduce cancer cell proliferation. However, whether these compounds activate KDM2A has yet to be tested. In this study, we found that PG and EGCG decreased rRNA transcription and cell proliferation through KDM2A in MCF-7 cells. The activation of both AMPK and ROS production by PG or EGCG was required to activate KDM2A. Of note, while the elevation of ROS production by PG or EGCG was limited in time, it was sufficient to activate KDM2A. Importantly, the inhibition of rRNA transcription and cell proliferation by gallic acid, PG, or EGCG was specifically observed in MCF-7 cells, whereas it was not observed in non-tumorigenic MCF10A cells. Altogether, these results suggest that the derivatization of gallic acid may be used to obtain new compounds with anti-cancer activity.

Under anaerobic conditions, Euglena gracilis produces a large amount of wax ester through mitochondrial fatty acid synthesis from storage polysaccharides termed paramylon, to generate ATP. Trans-2-enoyl-CoA reductases (TERs) in mitochondria have been considered to play a key role in this process, because the enzymes catalyze the reduction of short chain length CoA-substrates (such as crotonyl-CoA). A TER enzyme (EgTER1) has been previously identified and enzymologically characterized; however, its physiological significance remained to be evaluated by genetic analysis. We herein generated EgTER1-knockdown Euglena cells, in which total crotonyl-CoA reductase activity was decreased to 10% of control value. Notably, the knockdown cells showed a severe bleaching phenotype with deficiencies in chlorophylls and glycolipids, but grew normally under heterotrophic conditions (with glucose supplementation). Moreover, the knockdown cells accumulated much greater quantities of wax ester than control cells before and after transfer to anaerobic conditions, which was accompanied by a large metabolomic change. Furthermore, we failed to find any contribution of other potential TER genes in wax ester production. Our findings propose a novel role of EgTER1 in the greening process and demonstrate that this enzyme is dispensable for wax ester production under anaerobic conditions.

Refractory hypothyroidism is caused by decreased gut absorption, increased metabolism, and poor compliance. Previous studies suggested that the weekly oral, suppository, or intramuscular administration of levothyroxine (LT4) is an effective treatment for refractory hypothyroidism. However, limited information is currently available on treatment involving the weekly intravenous administration of LT4. We managed a case of refractory hypothyroidism due to poor compliance, for which, by weekly intravenous LT4 administration, LT4 was intravenously administered weekly at a dose of 300 μg without any adverse effects such as acute ischemic heart diseases or liver dysfunction and effectively maintained the euthyroid status for 14 months. The weekly oral administration of LT4 (700 μg) was also safely performed and was as effective as its intravenous administration. We herein present precise clinical course of the present case including pharmacokinetic data during the weekly intravenous and oral administration of LT4 and discuss the safety and efficacy of the treatments.