The present study examined factors in subjects diagnosed with hyperglycemia during periodic medical checkups. In total, 9,324 subjects (males: 4532, females: 4792) visited the Takagi Hospital for medical checkups in 2019. Eighty-two subjects (59 males) whose fasting blood glucose exceeded 126 mg/dL for the first time during the annual or biannual follow-up were included. Sex- and age-matched controls were selected from subjects without hyperglycemia. Data from cases with hyperglycemia were compared to data from themselves one or two years before hyperglycemia. BMI, waist circumference, echo and/or CT-detected fatty liver, and blood pressure were higher in cases than in controls. Fasting blood glucose and hemoglobin Alc were higher in cases. Blood test results indicated that triglyceride, LDL cholesterol, AST, ALT, and y-GTP were significantly enhanced in cases. Multiple logistic regression analysis revealed that BMI, waist circumference, blood pressure, triglyceride, ALT, and y-GTP were significant independent risk factors for cases with hyperglycemia. These risk factors were already enhanced in the cases of themselves in one or two years before hyperglycemia. In conclusion, BMI, waist circumference, blood pressure, and fatty liver indicated by ALT and y-GTP were exacerbated concomitant with hyperglycemia, and increases in these factors preceded hyperglycemia.

We conducted a retrospective case-control study to assess the efficacy of personalized health guidance interventions provided by public health nurses on individuals with type 2 diabetes mellitus and obesity who sought medical checkups. A selection was made of individuals who had made regular visits (two or more times) to the Takagi Hospital for medical checkups between January 1, 2017, and October 31, 2021. Two hundred eight subjects (cases) who received health guidance intervention were divided into two groups: one group without pharmacotherapy for diabetes mellitus in medical institutions (n = 92) and another group with pharmacotherapy (n = 116). Cases were provided with individual health guidance interventions by public health nurses for a duration of 30 minutes, in accordance with the Japanese clinical guidelines for the prevention of lifestyle-related diseases. Sex-and age matched controls were chosen from individuals with diabetes mellitus who did not receive any health guidance. The health guidance intervention for cases without pharmacotherapy resulted in improvements in various health indicators, including body weight, body mass index, waist circumference, diastolic blood pressure, serum triglyceride levels, and yglutamyl trans-peptidase. Conversely, these positive effects were not observed in the control group who did not receive any health guidance. The therapeutic effects of health guidance were observed in cases where pharmacotherapy was administered. In conclusion, the implementation of individual health guidance interventions may prove to be effective for individuals with type 2 diabetes mellitus and obesity who regularly attend medical checkups.

CASE:84-year-old woman had been diagnosed hypothyroidism before, but she did not take tablets of thyroid hormone prescribed. Anorexia and decreased consciousness level were discovered by workers of the facility. Her family doctor found thyroid function abnormality as a cause, and she was introduced to our hospital to treat because the whole body condition was bad. Her physical examination was observed that JCS was 3-10. Laboratory examination showed that TSH 562.81 μIU/mL, fT4 0.40 ng/mL, pH 7.33, and Na 124 mEq/L. It was not a contradictory finding with the diagnostic criteria of mucus edema coma. Blood and peritoneal dialysis is denied, although her data indicated eGFR 8-10 ml/min/1.73 m2. Her hospitalization was long-term, but exhibited finally good clinical course. After three months of hospitalization, she was discharged from the hospital. The problems were as follows. The clear guideline of myxedema coma with end-stage renal failure state and many complications was not found. She and her family did not hope dialysis under this condition.We treated a case of myxedema coma in a case of an elderly person with terminal renal failure who did not hope dialysis. In addition to myxedema coma as a rare disease, there are many basic diseases in the elderly. Although it was a difficult case, it is important to repeatedly confirm the explanation and the intention of the person and the family with regard to the selection of the treatment policy.

BACKGROUND Psoriasis is known as the most frequent disease treated by long-term topical steroids. It is also known that patients with thick, chronic plaques require the highest potency topical steroids. However, the treatment is limited to up to four weeks due to risk of systemic absorption. CASE REPORT An 80-year-old man was diagnosed with type 2 diabetes 16 years before, and was being administered insulin combined with alpha glucosidase inhibitor. He was diagnosed with plaque psoriasis and his oral steroid treatment was switched to topical steroid treatment due to lack of improvement and poorly controlled blood glucose level. The hypoglycemic events improved after the psoriatic lesions improved. CONCLUSIONS Control of blood glucose level is difficult at the very beginning of topical steroid treatment for psoriasis especially if a patient is receiving insulin treatment. Intense monitoring of blood glucose level during initiation of topical steroid treatment is necessary to prevent unfavorable complications.

Background: Recently, natural mutation of Tyrosine kinase 2 (Tyk2) gene has been shown to determine susceptibility to murine virus-induced diabetes. In addition, a previous human genome-wide study suggested the type 1 diabetes (T1D) susceptibility region to be 19p13, where the human TYK2 gene is located (19p13.2).Methods: Polymorphisms of TYK2 gene at the promoter region and exons were studied among 331 healthy controls, and 302 patients with T1D and 314 with type 2 diabetes (T2D) in the Japanese.Findings: A TYK2 promoter haplotype with multiple genetic polymorphisms, which are in complete linkage disequilibrium, named TYK2 promoter variant, presenting decreased promoter activity, is associated with an increased risk of not only T1D (odds ratio (OR), 2.4; 95% confidence interval (CI), 1.2 to 4.6; P= 0.01), but also T2D (OR, 2.1; 95% CI, 1.1 to 4.1; P= 0.03). The risk is high in patients with T1D associated with flu-like syndrome at diabetes onset and also those without anti-glutamic acid decarboxylase autoantibody.Interpretation: The TYK2 promoter variant is associated with an overall risk for diabetes, serving a good candidate as a virus-induced diabetes susceptibility gene in humans.Funding: Ministry of Education, Culture, Sports, Science and Technology and of Health, Labor and Welfare of Japan. (C) 2015 The Authors. Published by Elsevier B. V.

Accumulating evidence suggests that viruses play an important role in the development of diabetes. Although the diabetogenic encephalomyocarditis strain D virus induces diabetes in restricted lines of inbred mice, the susceptibility genes to virus-induced diabetes have not been identified. We report here that novel Tyrosine kinase 2 (Tyk2) gene mutations are present in virus-induced diabetes-sensitive SJL and SWR mice. Mice carrying the mutant Tyk2 gene on the virus-resistant C57BL/6 background are highly sensitive to virus-induced diabetes. Tyk2 gene expression is strongly reduced in Tyk2 -mutant mice, associated with low Tyk2 promoter activity, and leads to decreased expression of interferon-inducible genes, resulting in significantly compromised antiviral response. Tyk2- mutant pancreatic β-cells are unresponsive even to high dose of Type I interferon. Reversal of virus-induced diabetes could be achieved by β-cell-specific Tyk2 gene expression. Thus, reduced Tyk2 gene expression in pancreatic β-cells due to natural mutation is responsible for susceptibility to virus-induced diabetes.

We investigate energy barriers and minimum energy paths (MEPs) for transitions from dislocation-pair defects to perfect lamellae in self-assembly of AB-diblock copolymer plus A-or B-homopolymer blends using self-consistent field theory (SCFT) and the numerical string method. For neutral substrates, all minimum energy paths discovered by the string method show two successive energy barriers. The two-barrier qualitative nature of the MEPs appears not to depend on the presence or absence of small amounts of homopolymer. For the first energy barrier, the barrier height shows pronounced increase with addition of A-homopolymer due to localization of A-homopolymer on the T-junction core of the dislocation. For chemo-epitaxially patterned substrates (stripes of A-attractive substrate alternating with neutral substrate), the presence of A-attractive stripes helps draw the system towards a perfect lamellar configuration, and energy barriers along the MEP are reduced, in some cases disappearing entirely. Our findings provide guidance on how the presence of homopolymer and chemo-epitaxial prepatterns affect the stability of defective morphologies.

We use self-consistent field theory to investigate the self-assembly of AB diblock copolymers on chemically patterned substrates. The striped substrates consist of attractive domains alternating with neutral ones. Using our simulations, we observe the formation of different self-assembled morphologies in the polymer film and compute their formation free energy for various pattern widths and wetting conditions. We found that perpendicular lamellae are best formed when the A-attractive stripes have a width near half the natural lamellar period in bulk, but lamellar structures with wide bases are also formed in wide stripes. We also computed the formation energy of isolated dislocations and found that the energy cost is ≈ 50-110kT for ±15nm deviations from optimal commensurability conditions.

We have done SCFT simulations to investigate the directed self-assembly on CH pitch division. The structural change by the thickness Lz of oval prepattern reveals that perpendicular cylinders are favored when Lz is not commensurate with the distance between cylinders L0. In this case linear rows of cylinders are along major radius for narrow ovals, and wider ovals tend to pack additional rows of cylinders in a staggered hexagonal arrangement. Sweeping from neutral to PMMA attractive substrates causes a transition from cylinders that penetrate completely through the film, to cylinders that terminate in nearly spherical caps. Thus a neutral substrate would be favorable in order to get cylinders that penetrate completely through the film.

The Directed Self-Assembly (DSA) method is becoming a key complementary technology for enabling lithographic pattern feature shrinkage. Recent DSA technology has developed remarkable improvements in many aspects of materials and process. Polystyrene-b-polymethylmethacrylate (PS-b-PMMA) block copolymer (BCP) is a typical material used in DSA, but more advanced materials are required for achieving patterning less than 10 nm in size. High-chi, block copolymers are being researched as next generation PS-b-PMMA material successors. Polymers with high-chi produce smaller pattern sizes than PS-b-PMMA. However, doing DSA with these high-chi materials requires a special method to separate one phase of BCP - such as phase separation in solvent. We have done further research to improve high-chi materials to enable better DSA technology. Here we report 8.4 nm half-pitch line patterns were formed with our high-chi block co-polymer, annealing under air. DSA is a candidate for next generation lithography. However, DSA materials are not used alone. DSA materials are always used with guide pattern to "direct" self assembly materials. Currently ArF resist is well studied as guide pattern. ArF resist is extended to use further generation, but the required resolution level is already severe for 193nm patterning. Employment of blend DSA could improve the ArF pattern profile.

A 73-year-old Japanese man with Hashimoto's disease and diabetes mellitus received regular medical checkups for type 2 diabetes care. Blood tests indicated macrocytic anemia (red blood cell count, 279×104 /μL; hemoglobin, 12.2 g/dL; hematocrit, 34.0%; mean corpuscular volume, 121.9 fL). The laboratory data demonstrated a normal folic acid level with a low vitamin B12 level. An endoscopic examination indicated no signs of gastric or intestinal bleeding. Positive results for anti-intrinsic factor antibodies were strongly suggestive of pernicious anemia. The patient refused cobalamin injections to treat the anemia. However, the oral administration of mecobalamin for the treatment of diabetic neuropathy was simultaneously initiated. Subsequently, the anemia gradually improved. Oral mecobalamin was presumably effective for pernicious anemia management. Anemia is frequently observed in elderly patients, and the incidence of pernicious anemia increases with age. Anemia is conventionally treated with cobalamin injections. Currently, the oral administration of mecobalamin is not the typical treatment for anemia. However, as in our case, a few reports have documented positive results following oral mecobalamin treatment. Moreover, oral mecobalamin is a fairly recent, novel, noninvasive mode of treatment, making it ideal for elderly patients, who are generally frail. This case suggests the efficacy of mecobalamin for the treatment of pernicious anemia.

Type 1 diabetes mellitus results form progressive loss of pancreatic β cells. The virus, as one of environmental factors, has been long considered to play a role in the development of type 1 diabetes. The D variant of encephalomyocarditis (EMC-D) virus induced susceptible strain of mice to become type 1 diabetes. We have already reported that innate immunity may play an important role in protection against EMC-D virus-induced diabetes (Arch Virol, 2008). In the present study, we analyzed the role of Tyk2 gene in the pathogenic mechanism of EMC-D virus-induced diabetes by using Tyk2 gene knockout (KO) mice. Tyk2 gene KO C57BL/6J mice, mouse strain resistant to EMC-D virus-induced diabetes, developed diabetes. In order to examine whether Tyk2 gene expression was important in parenchymal or immune cells to protect against EMC-D virus-induced diabetes, we developed splenic chimera mice. Tyk2 gene expression was important in parenchymal cells, but not in spleen cells, to resist against EMC-D virus-induced diabetes. Consistently, mice specifically expressed Tyk2 gene only in pancreatic β cells prevented EMC-D virus-induced diabetes. These observations suggest that Tyk2 gene expressed in pancreatic β cells plays a significant role in preventing EMC-D virus-induced diabetes in mice.

Introduction Continuous subcutaneous insulin injection (CSII) is an effective method for controlling blood glucose. However, complications include cutaneous complications (e.g., inflammation and infection) and uncontrollable blood glucose due to insulin leaks, obstruction, and technical problems, which may lead to hyperglycemia such as diabetic ketoacidosis (DKA) or hypoglycemia. However, other than islet or pancreas transplantation, CSII is the best method for controlling blood glucose.History A patient with DKA using an old-type CSII instrument was referred to our hospital.Investigation At first, we could not understand why DKA had occurred because the skin at the infusion site appeared to be in good condition. However, the syringe was found to be broken when the instrument was unlocked and the pump was removed.Conclusion To exchange older CSII instruments for newer models may be the safer alternative to prevent syringe accidents.

BACKGROUND:Several epidemiological studies have reported that diabetes mellitus is a risk factor for hepatocellular carcinoma (HCC) in hepatitis C virus (HCV)-positive patients. However, it is unclear whether or not post-challenge hyperglycemia is a risk factor. The purpose of this study was to determine the association between post-challenge hyperglycemia and hepatocarcinogenesis in HCV-positive patients.METHODS:A total of 203 HCV-RNA-positive subjects (108 males, mean age 54.3 ± 10.8 years; 95 females, mean age 56.6 ± 10.3 years; genotype 1b/2a/2b/3a: 152/38/12/1) who underwent liver biopsy and a 75-g oral glucose tolerance test, and who were treated with interferon (IFN) were enrolled in this study. None of the subjects had been treated with antidiabetic drugs. The subjects underwent ultrasonography and/or computed tomography every 6 months after the end of the IFN therapy.RESULTS:Thirteen patients, including one patient who achieved a sustained viral response (SVR) with IFN, developed HCC. On multivariate analysis, male sex, age >65 years, excessive alcohol consumption, non-SVR, liver steatosis area >5% in liver specimens, and 120-min post-challenge hyperglycemia were risk factors for the development of HCC. After matching subjects for sex, age, alcohol intake, and response to the IFN therapy, advanced fibrosis stages [hazard ratio (HR) 2.8], liver steatosis (HR 5.4), and 120-min post-challenge hyperglycemia (HR 4.9) were significant risk factors for the development of HCC. Furthermore, after matching for the fibrosis stage, liver steatosis (HR 5.7) and 120-min post-challenge hyperglycemia (HR 6.9) remained as significant factors for HCC development.CONCLUSION:Post-challenge hyperglycemia is an independent risk factor for HCC in HCV-positive patients.

我々は，ABO血液型不適合造血幹細胞移植後の患者のドナー型赤血球の検出が，全自動輸血検査システム（AutoVue）では試験管法に比べ一定の期間遅れることを経験してきた．この遅れの原因を検討するため，A型のHLA完全一致，非血縁ドナーから骨髄移植を受けたO型の1症例を対象とし，比重差で分離した赤血球の最上層，上層，中層，および下層についてA型赤血球産生回復の推移を検討した．A型赤血球はday32に，AutoVueでは最上層のみに検出された．試験管法では被凝集価は，全体で32倍であった．また，分離検体では，最上層は64倍と上層，下層の8倍に比べ有意に高かった．day35にはAutoVueでA型赤血球は下層にも検出され，上下層の差は移植2カ月後に消失した．ドナー型赤血球は移植後早期には，網赤血球を含め比重の小さい若い赤血球の割合が多いため，赤血球の上層部に多く検出されると考えられた．AutoVueにおけるドナー型赤血球の検出の遅れは，AutoVueが遠心分離後の赤血球の最下層を吸引するためと判明した． ABO血液型不適合造血幹細胞移植後の患者のドナー型赤血球の早期確認のためには，遠心分離後の赤血球の最上層を用い，そのモニタリングは赤血球層全体をよく混和したものを用いることが，効果的かつ正確である．

今回我々は，松山赤十字病院における2006年1月～12月の輸血開始基準値（トリガー値），すなわち赤血球濃厚液，新鮮凍結血漿，血小板濃厚液輸血前のそれぞれヘモグロビン値，プロトロンビン時間，血小板数を後方視的に調査し，輸血用血液の適正使用を2005年の厚生労働省の指針と比較して評価した．輸血当日の検査実施率は，赤血球濃厚液では78.1％，新鮮凍結血漿では54.8％，血小板濃厚液では77.5％であった．疾患別にみた赤血球濃厚液の適正使用率（輸血トリガー値遵守率）は，血液疾患では76.7％と高かったが，周術期は41.0％，慢性出血は33.3％と低かった．新鮮凍結血漿の適正使用率は，すべての疾患において低かった（7.7～22.7％）．血小板濃厚液の適正使用率は，出血・播種性血管内凝固症候群（DIC）では92.6％，周術期は67.4％，急性白血病・悪性リンパ腫は85.0％と高く，再生不良性貧血・骨髄異形成症候群（MDS）では37.6％，固形腫瘍・他は18.5％と低かった．調査期間の半ばより血小板濃厚液注文の予約制が導入され，血液疾患では血小板濃厚液の適正使用率が高くなった．これには各担当医師がトリガー値を再認識し，検査技師も出庫前の検査値確認をより徹底したことが関係していた． 当院において，適正使用の推進には，輸血部門の出庫前検査値確認と，医師による輸血トリガー値の再認識が極めて有用であった．