Adrenocortical Adenoma With Protrusion Into the Inferior Vena Cava Initially Suspected to Be Adrenocortical Carcinoma.

Adrenal tumors with invasion into the inferior vena cava (IVC) are typically malignant. Here, we present a case of adrenocortical adenoma with protrusion into the IVC. A 70-year-old man was referred to our hospital after his magnetic resonance imaging scan of the abdomen coincidently revealed a right adrenal tumor invading the IVC. We suspected an aggressive adrenal carcinoma and tumor resection was performed. However, all 3 existing pathological criteria (Weiss, modified Weiss, and Helsinki) suggested the tumor was benign. Immunohistochemistry for CD31 showed the tumor inside the central adrenal vein (CAV), right adrenal vein (RAV), and IVC was entirely covered with CD31-positive vascular endothelial cells. The CAV is known to sometimes lack smooth muscle in its walls and normal adrenocortical cells covered by endothelial cells sometimes protrude into the CAV from this gap. These findings suggest that this tumor likely protruded into the IVC by pushing against the CAV wall, rather than by invasion into the vascular wall. In the case with adrenal tumors protruding into the IVC, the fact that the tumor surface was covered by vascular endothelial cells was considered supportive of its benign nature.

Optically Electroactive Polymer Synthesized in a Liquid Crystal with Cyclosporin A─Circularly Polarized Electron Spin Resonance.

Cyclosporine A (CsA), a naturally derived biomaterial and physiologically active substance, is commonly used as an immunosuppressant. In this study, CsA was revealed to function as a chiral inducer of cholesteric liquid crystals (CLCs) with a high helical twisting power. CsA induced helical structures in 4-cyano-4'-pentylbiphenyl, a synthetic liquid crystal (LC) used for general purposes. Electrochemical polymerization in CLC with CsA was also performed. The polymer prepared in CLC showed electro-optical activity via chiral induction by CsA. Synchrotron X-ray diffraction measurements indicated that the polymer film prepared in the CLC formed in the manner of LC molecular arrangement through molecular form imprinting from the LC order, although the polymer exhibited no liquid crystallinity. The polymer showed structural color and laser light oscillation diffraction derived from its periodic structure. The anisotropy of the circularly polarized electron spin resonance signals for the resulting polymer with respect to the magnetic field was observed.

Protocol of a Prospective Observational Study on Lifestyle and Quality of Life in Adults with Type 1 Diabetes in Japan.

INTRODUCTION: Recent studies have shown that the quality of life (QOL) of people living with type 1 diabetes (T1D) is poor and must be improved. However, the living situation and QOL of adults living with T1D in Japan have not been fully clarified. This study will examine their lifestyle, QOL, and clinical situation, as well as the relationships between them. METHODS: This is a prospective, 5-year follow-up observational study. Between December 2019 and September 2021, we enrolled adults in Japan who were living with T1D and receiving insulin therapy, and are acquiring longitudinal clinical data and the responses to seven questionnaires regarding lifestyle and QOL. The primary study outcomes are (1) the relationship between Problem Areas in Diabetes (PAID) scores and various factors including demographic data, clinical characteristics, medical history, lifestyle habits, treatment history, biochemical data, and the scores of questionnaires; and (2) the relationship between Beck Depression Inventory (BDI)-II scores and various factors aforementioned. The secondary outcomes are the relationships between various factors aforementioned and each of the following: (1) blood glucose control, (2) blood lipid control, (3) dietary patterns, (4) fear of hypoglycemia, (5) sleep patterns, and (6) physical activity. PLANNED OUTCOME: We registered 352 participants. The median age was 49 (41-63) years, and the median duration of T1D was 13 (8-20) years. All the results will be available in 2026. We expect to clarify the factors associated with decreased QOL, and that this knowledge will contribute to improving QOL in adults in Japan who are living with T1D and receiving insulin therapy. TRIAL REGISTRATION: Clinical Trials.gov identifier, UMIN000044088.

Diabetic ketoacidosis due to a sensor defect of FreeStyle Libre: A case report.

The FreeStyle Libre Flash Glucose Monitoring System allows users to obtain sensor glucose values by scanning with the reader or their mobile phone. We report a case of a 59-year-old man with type 1 diabetes mellitus who developed diabetic ketoacidosis due to a sensor defect. After replacing the sensor with a new one, the glucose value shown in the device was much lower than usual, which made him consider that he was hypoglycemic. Accordingly, he reduced his insulin dose and eventually developed diabetic ketoacidosis. He was unaware of the discrepancy due to the lack of self-monitoring of his blood glucose, although he was educated to do. In sum, glucose monitoring with the FreeStyle Libre is helpful; however, it is necessary to remind the patient that a sensor defect leading to a severe complication frequently happens.

Clinical characteristics of adrenal insufficiency induced by pembrolizumab in non-small-cell lung cancer.

BACKGROUND AND AIM: Immune checkpoint inhibitors have significantly improved the clinical outcomes of many cancer types, but they induce a range of immune-related adverse events (irAEs). Although adrenal insufficiency (AI) is a rare irAE, it can lead to serious consequences. This study aimed to determine the clinical features of patients with advanced non-small-cell lung cancer (NSCLC) who developed AI following pembrolizumab treatment. METHODS: We retrospectively reviewed and analyzed the clinical data of all patients with NSCLC treated with pembrolizumab at Juntendo University Hospital from February 2017 to December 2020. The diagnosis of AI was established based on the Endocrine Emergency Guidance for the acute management of endocrine complications of checkpoint inhibitor therapy in the UK and the clinical practice guidelines of the Japan Endocrine Society. RESULT: AI was clinically suspected in 59 out of 186 patients treated with pembrolizumab, and 10 (5.4%) cases were confirmed. The symptoms included hyponatremia (n = 9), fatigue (n = 8), and loss of appetite (n = 6). All patients had low adrenocorticotropic hormone (ACTH) levels, and five patients were diagnosed with isolated ACTH deficiency. All patients completely recovered with corticosteroid replacement. The median time to onset of AI was 8.0 (range 3.8-15.2) months. The median progression-free survival in these patients was 22.4 (95% confidence interval 11.2-not reached) months. CONCLUSION: The incidence of AI among patients treated with pembrolizumab is more frequent than previously reported. In addition, secondary AI, especially isolated ACTH deficiency, is a major form of AI induced by pembrolizumab.

Ultrasonic helical coil electrochemical reactor for simultaneous electrolysis-sonification-electrochemical polymerization, and applications for pollen cleaning.

Electrochemical polymerization of aniline by a combination of ultrasonic waves and electrolysis of water was performed. This method involves three processes: 1) creation of O2 micro bubbles produced by electrolysis of water on the anode side, 2) depolarization of the bubbles at the electrode surface via mechanical vibration using ultrasonic waves to diffuse ions in the electrolyte solution, and 3) progression of direct current (DC) electrochemical polymerization to yield a conductive polymer with fine pores on the surface. The diameter of the pores is on the micrometer scale and is similar in size to pollens. The combination of the electronic function of the conductive polymer and porous polymer surface can be applied as a method to collect allergens such as dust and flower pollens. Electrical adsorption and desorption of pollen was conducted with the porous polyaniline synthesized using a micro-bubble sonic-electrochemical preparation.

Defective autophagy in vascular smooth muscle cells enhances the healing of abdominal aortic aneurysm.

Autophagy is an evolutionarily conserved cellular catabolic process essential for cell homeostasis, and thus its failure is associated with several diseases. While autophagy has been reported to play a role in vascular smooth muscle cells (SMCs) in vascular disorders, its precise role in the pathogenesis of abdominal aortic aneurysm (AAA) has not yet been elucidated. In this study, we investigated the role of SMC autophagy in AAA formation. As a mouse model of AAA, we used control apolipoprotein E-deficient (apoeKO) mice and Atg7cKO (SMC-specific Atg7-deficient mice):apoeKO mice administered angiotensin II for 4 weeks. Intriguingly, Kaplan-Meier curves showed that the survival rates of Atg7cKO:apoeKO mice were significantly higher than those of apoeKO mice. The hematoma area in AAA of Atg7cKO:apoeKO mice was smaller than in apoeKO mice despite the lack of a significant difference in AAA incidence between the two groups. Furthermore, the amount of granulomatous tissues was significantly larger and the collagen-positive area within AAA was significantly larger in Atg7cKO:apoeKO mice than in apoeKO mice. In accordance with these findings, SMCs cultured from Atg7cKO mice showed increased expression of collagens, independent of angiotensin II action. Taken together, our data suggest that defective autophagy in SMCs elicits AAA healing that may underlie the better survival rate under dyslipidemia and angiotensin II infusion.

Sequential micro-Maltese cross array in the ground beetle Carabus insulicola.

The exoskeleton of the ground beetle Carabus insulicola was observed using polarizing optical microscopy (POM) with simultaneous transmitted and reflected light. The surface showed iridescence owing to the periodic microstructure. A Maltese cross array of the inner layer of the elytra was observed. The matrix of the middle layer of the elytra is composed of protein with the arrangement of a cholesteric liquid crystal (CLC)-like helical structure. The scanning electron microscopy observations revealed the layers structure of the exoskeleton of the ground beetle. Synchrotron X-ray diffraction measurement evaluated crystallinity of the exoskeleton.　Morphology of the Maltese cross array of the beetle has similarity with synthetic chiral-CLC.

Conjugated Polymer Films Having a Uniaxial Molecular Orientation and Network Structure Prepared by Electrochemical Polymerization in Liquid Crystals.

A new method for fabricating conjugated polymer films was developed using electrochemical polymerization in liquid crystals and magnetic orientation. A uniaxial main chain orientation and a crosslinked network structure were achieved with this method. By employing eight types of monomers, the influence of the crosslinking for the film was investigated. The crosslinking was found to improve the solvent resistance of the conjugated polymer films. This new method is expected to be useful in various applications, such as high-powered organic electronic devices with durability.

Effects of Synbiotic Supplementation on Chronic Inflammation and the Gut Microbiota in Obese Patients with Type 2 Diabetes Mellitus: A Randomized Controlled Study.

The aim of this study was to investigate the effects of 24-week synbiotic supplementation on chronic inflammation and the gut microbiota in obese patients with type 2 diabetes. We randomized 88 obese patients with type 2 diabetes to one of two groups for 24 weeks: control or synbiotic (Lacticaseibacillus paracasei strain Shirota (previously Lactobacillus casei strain Shirota) and Bifidobacterium breve strain Yakult, and galactooligosaccharides). The primary endpoint was the change in interleukin-6 from baseline to 24 weeks. Secondary endpoints were evaluation of the gut microbiota in feces and blood, fecal organic acids, high-sensitivity C-reactive protein, lipopolysaccharide-binding protein, and glycemic control. Synbiotic administration for 24 weeks did not significantly affect changes in interleukin-6 from baseline to 24 weeks (0.35 ± 1.99 vs. -0.24 ± 1.75 pg/mL, respectively). Relative to baseline, however, at 24 weeks after synbiotic administration there were positive changes in the counts of Bifidobacterium and total lactobacilli, the relative abundances of Bifidobacterium species such as Bifidobacterium adolescentis and Bifidobacterium pseudocatenulatum, and the concentrations of acetic and butyric acids in feces. No significant changes in inflammatory markers were found in the synbiotic group compared to the control group. However, synbiotic administration at least partially improved the gut environment in obese patients with type 2 diabetes.

Effect of thyroxine treatment on pregnancy outcomes in infertile Japanese women with TSH levels between 2.5 µIU/mL and the upper reference limit: a retrospective study.

Recent randomized controlled studies have revealed that levothyroxine (LT4) treatment improves pregnancy outcomes only in infertile women with subclinical hypothyroidism who have thyroid autoantibodies (TAs), but not for those with high TSH levels within the normal range who have TAs. Here, we retrospectively investigated pregnancy outcomes in infertile Japanese women with 2.5 µIU/mL ≤ TSH < upper reference limit (URL). Between 2012 and 2018, 286 patients diagnosed with infertility were followed for more than 1 year at our institution. Among them, we included 106 patients with 2.5 µIU/mL ≤ TSH < URL. We divided these patients into four groups based on the combination of TA positivity and LT4 treatment status to assess the effects of LT4 treatment considering TA positivity on the incidence of pregnancy or miscarriage. In this study, we did not find any significant differences in the rates of pregnancy or miscarriage among the four groups (p = 0.81 and 0.52, respectively). In addition, logistic regression analysis showed that age and history of miscarriage were associated with the incidence of pregnancy, but presence of TAs and LT4 treatment status were not and that no variables examined were associated with the incidence of miscarriage. In summary, we were not able to demonstrate the benefit of LT4 treatment for pregnancy outcomes in Japanese euthyroid infertile women with 2.5 µIU/mL ≤ TSH < URL regardless of TA status in this study.

Influence of Short-Term Dietary and Therapeutic Iodine Restriction on the Therapeutic Effects of Radioactive Iodine Therapy in Patients with Graves' Disease.

Background: Several studies have investigated the factors affecting the effects of radioactive iodine (131I) treatment (RAIT) in patients with Graves' disease. However, the influence of dietary or therapeutic iodine on the effect of RAIT has not been fully elucidated yet. The aim of this study was to investigate whether dietary or therapeutic iodine before RAIT influences the therapeutic effects of RAIT with a fixed-dose regimen and a short-term restriction of iodine intake in an iodine-sufficient area. Materials and Methods: We retrospectively analyzed 81 Japanese patients with Graves' disease treated with the following RAIT regimen: dietary iodine restriction for 7 days as well as discontinuation of antithyroid drugs (ATDs), potassium iodine (KI), or both for 5 days before RAIT. On the day of RAIT, we measured urinary iodine content to estimate daily iodine intake. After RAIT, we adjusted the dose of ATDs, KI, or both according to serum thyroid hormone levels every 1-2 months. Using the data from these patients, we investigated the effect of dietary and therapeutic iodine on the therapeutic effects of RAIT. The therapeutic effects at 1 year after RAIT were evaluated based on the necessity of ATDs, KI, or both. Results: Dietary iodine intake was weakly correlated with 131I uptake (RAIU), but the dose of therapeutic iodine was not correlated with RAIU. The therapeutic effects of RAIT were strongly negatively associated with estimated thyroid volume before RAIT. Neither dietary iodine intake nor therapeutic iodine before RAIT affected this association. Conclusion: This study did not find an association between short-term dietary or therapeutic iodine restriction before RAIT and the therapeutic effects of RAIT in an iodine-sufficient area.

Induction of Polyacetylene to a Chiral Smectic Liquid Crystal-Chiral Direct Conversion.

The synthesis of polyacetylene-bearing pyrimidine-type three-ringed mesogenic core exhibiting smectic C (SmC) characteristics was conducted. Gas-phase iodine doping of the polymer provided evidence of chemical interaction between the polyene and iodine, which acted as an electron acceptor. The side-chain fluorine atom tilted the mesogen moiety to form SmC as a tilted liquid crystal. The addition of a small amount of chiral inducer yielded SmC* of the polymer as the chiral version of SmC. The liquid crystallinity and electronic properties of the π-conjugated chiral liquid crystal polymer with a helical structure were evaluated.

Effect of Plasma Exchange in Thyroid Storm With Consideration of Its Distribution Into the Extravascular Space.

Plasma exchange (PE), which directly removes some plasma thyroid hormones, is a treatment option for thyroid storm. However, the effect of PE has not been accurately assessed yet. Here we assessed the effect of PE in a patient with thyroid storm while taking into consideration the distribution of thyroid hormones in the extravascular space. A 51-year-old woman with thyroid storm underwent 2 PE procedures at our hospital. By measuring changes in thyroid hormone levels in plasma, fresh frozen plasma (FFP) used, and waste fluid during each 2.5-hour PE procedure, we calculated the efficiency of thyroid hormone removal based on the hypothesis that total thyroid hormone content before and after PE is the same. During the patient's first PE procedure, the estimated thyroxine (T4) balance in the extravascular space (ΔX) was -70 µg, which corresponds to approximately 19% of T4 in the waste fluid. During the second PE procedure, ΔX was -131 µg, which corresponds to approximately 52% of T4 in the waste fluid. These data indicated that the source of removed T4 during PE varies. The amount of T4 removed from the extravascular space should be taken into account during assessment of the effect of PE in thyroid storm.

Synthesis of Polyaniline/Scarlet 3R as a Conductive Polymer.

Polyaniline (PANI) was prepared in the presence of the acidic dye scarlet 3R. Color tuning was performed on PANI through doping-dedoping processes and by changing the solvent used during the optical absorption spectroscopic measurements. The chemical structure of the resulting polymer-dye composite was analyzed using infrared absorption spectroscopy, and it showed the occurrence of secondary doping in m-cresol. The shape of the UV-Vis optical absorption spectra for the composite solution is dependent on the types of organic solvents used during the analysis, which was influenced by the conformation of PANI and the ionic interactions between PANI and scarlet 3R.

Synthesis of Polyaniline in Seawater.

To date, polyaniline (PANI) has been synthesized in pure water. Aside from this, the application of PANI as a conducting polymer could be extended if it can be effectively synthesized in seawater, which constitutes 70% of the surface of the Earth. The production of functional plastics using natural resources without any additional purification would improve industrial production and enhance the comfort associated with our daily life. However, no examples of the effective application of seawater to PANI synthesis have been reported. Herein, PANI with an electrical conductivity of ~10-2 S/cm was synthesized in seawater as the reaction solvent. The electron spin resonance measurements confirmed the role of the polarons of PANI as charge carriers. In addition, a PANI/silk composite was prepared in seawater to produce a conducting cloth for further applications. The performance of the PANI prepared in seawater as the solvent was comparable to that of the PANI prepared in pure water. Thus, the proposed method allowed for the production of the conducting polymer via a convenient and low-cost method. This is the first study to report the usage of seawater as an abundant natural resource for synthesizing conducting polymers, promoting their wide application.

Cellular Autophagy in α Cells Plays a Role in the Maintenance of Islet Architecture.

Autophagy is known to play a pivotal role in intracellular quality control through the degradation of subcellular damaged organelles and components. Whereas autophagy is essential for maintaining ß-cell function in pancreatic islets, it remains unclear as to how the cellular autophagy affects the homeostasis and function of glucagon-secreting α cells. To investigate the role of autophagy in α cells, we generated a mutant mouse model lacking Atg7, a key molecule for autophagosome formation, specifically in α cells. Histological analysis demonstrated more glucagon-positive cells, with a multilayered structure, in the islets under Atg7 deficiency, although metabolic profiles, such as body weight, blood glucose, and plasma glucagon levels were comparable between Atg7-deficient mice and control littermates. Consistent with our previous findings that Atg7 deficiency suppressed ß-cell proliferation, cellular proliferation was suppressed in Atg7-deficient α cells. These findings suggest that α-cell autophagy plays a role in maintaining α-cell area and normal islet architecture but appears to be dispensable for metabolic homeostasis.

Mixed gangliocytoma-pituitary adenoma containing GH and GHRH co-secreting adenoma cells.

SUMMARY: A 67-year-old woman with a past history of type 2 diabetes mellitus presented with worsening glycemic control. She had some acromegaly symptoms and magnetic resonance imaging demonstrated a pituitary tumor. Endocrinological examination found the resting growth hormone (GH) level within the normal range, but elevated insulin-like growth factor 1 level. A 75 g oral glucose tolerance test showed inadequate suppression of nadir GH levels. Acromegaly due to GH-secreting pituitary tumor was diagnosed. The patient underwent endoscopic transsphenoidal surgery resulting in gross total removal of the tumor and recovered well postoperatively. Histological examination of the tumor showed coexistence of relatively large gangliocytoma cells and pituitary adenoma cells, suggesting mixed gangliocytoma-pituitary adenoma. In addition, colocalization of GH and GH-releasing hormone (GHRH) in pituitary adenoma cells was revealed, so the adenomatous components were more likely to produce GHRH in our mixed gangliocytoma-pituitary adenoma case. Mixed gangliocytoma-pituitary adenoma is very rare, and the present unique case demonstrated only the adenomatous components associated with GHRH production. LEARNING POINTS: Sellar gangliocytoma coexisting with pituitary adenoma is recognized as a mixed gangliocytoma-pituitary adenoma and is very rare. A proposed developmental mechanism of growth hormone (GH)-secreting mixed gangliocytoma-pituitary adenoma involves GH-releasing hormone (GHRH) produced by the gangliocytic components promoting the growth of tumor including GH-secreting adenomatous components. Since our present case indicated that the adenomatous components of mixed gangliocytoma-pituitary adenoma could secrete both GH and GHRH simultaneously, progression of GH-secreting mixed gangliocytoma and pituitary adenoma may involve exposure to spontaneously produced GHRH due to the adenomatous components.

Electrochemical Synthesis of Poly(3,4-ethylenedioxythiophene) Film Having Dot Structures for Diffraction Grating.

Poly(3,4-ethylenedioxythiophene) (PEDOT) dot micro/nanostructures are synthesized by electrochemical polymerization in a concentrated hydroxypropyl cellulose (HPC) liquid crystal electrolyte solution. Surface observations by scanning electron microscopy and atomic force microscopy reveal micro/nanostructures having hemisphere-like dots on the surface of the PEDOT film, which causes light diffraction at ultraviolet and visible light wavelengths. The size of the dots depends on the concentration of the HPC electrolyte solution, decreasing with increasing the HPC concentration. Electrochemical oxidation and reduction causes changes in the color of the PEDOT film and the diffracted light. Moreover, Au coating on the surface of the PEDOT film enhances the diffracted light reflection intensity by more than tenfold compared to the noncoated PEDOT film.

Synthesis of Polyazobenzenes Exhibiting Photoisomerization and Liquid Crystallinity.

While only a few studies have investigated the synthesis of main chain-type polyazobenzenes, they continue to draw an increasing amount of attention owing to their industrial applications in holography, dyes, and functional adhesives. In this study, dibromoazobenzene was prepared as a monomer for constructing azo-based π-conjugated polymers. Miyaura⁻Suzuki cross-coupling polymerization was conducted to develop copolymers containing an azobenzene unit as a photoisomerization block and a pyrimidine-based liquid crystal generator block. The prepared polymers exhibited thermotropic liquid crystallinity and underwent cis and trans photoisomerization upon irradiation with ultraviolet and visible light. Furthermore, the photoisomerization behavior was examined using optical absorption spectroscopy and synchrotron X-ray diffraction spectrometry.