Dose-dependent incidence of agranulocytosis in patients treated with methimazole and propylthiouracil.

Agranulocytosis is a serious adverse effect of methimazole (MMI) and propylthiouracil (PTU), and although there have been reports suggesting a dose-dependent incidence in relation to both drugs, the evidence has not been conclusive. The objective of our study was to determine whether the incidences of agranulocytosis induced by MMI and PTU exhibit dose-dependency. The subjects were 27,784 patients with untreated Graves' disease, 22,993 of whom were on an antithyroid drug treatment regimen for more than 90 days. Within this subset, 18,259 patients had been treated with MMI, and 4,734 had been treated with PTU. The incidence of agranulocytosis according to dose in the MMI group was 0.13% at 10 mg/day, 0.20% at 15 mg/day, 0.32% at 20 mg/day, and 0.47% at 30 mg/day, revealing a significant dose-dependent increase. In the PTU group, there were 0 cases of agranulocytosis at doses of 125 mg/day and below, 0.33% at 150 mg/day, 0.31% at 200 mg/day, and 0.81% at 300 mg/day, also revealing a significant dose-dependent increase. The incidence of agranulocytosis at MMI 15 mg and PTU 300 mg, i.e., at the same potency in terms of hormone synthesis inhibition, was 0.20% and 0.81%, respectively, and significantly higher in the PTU group. Our findings confirm a dose-dependent increase in the incidence of agranulocytosis with both drugs, but that at comparable thyroid hormone synthesis inhibitory doses PTU has a considerably higher propensity to induce agranulocytosis than MMI does.

Body Roundness Index Is Better Correlated with Insulin Sensitivity than Body Shape Index in Young and Middle-Aged Japanese Persons.

Aims: The present study aimed to clarify the relationships between novel and traditional anthropometric indices and insulin sensitivity (SI) in young and middle-aged Japanese persons with normal glucose tolerance (NGT), and middle-aged Japanese persons with NGT and glucose intolerance. Methods: Plasma glucose and insulin levels were measured in 1270 young (age <40 years) and 2153 middle-aged persons with NGT (n = 1531) and glucose intolerance (n = 622) during a 75-g oral glucose tolerance test. Height (Ht), weight, and waist circumference (WC) were measured. The body mass index (BMI), WC, and the WC/Ht ratio were used as traditional anthropometric indices. A body shape index (ABSI) and the body roundness index (BRI) were calculated as novel indices. Indices of SI (Matsuda index and 1/homeostasis model assessment of insulin resistance) were calculated and compared with anthropometric indices. Results: The ABSI showed a weak correlation with SI indices in all groups. The BRI showed almost the same correlation with SI indices as the BMI, WC, and WC/Ht in all groups. The inverse correlation between each of the anthropometric indices other than ABSI and SI indices was weak in young persons, at 0.16-0.27 (Spearman's ρ values), but strong in middle-aged persons, at 0.38-1.00. On receiver-operating characteristic (ROC) curve analysis for detection of insulin resistance, the ABSI had a lower area under the ROC curve (AUC) than the other anthropometric indices, and the BRI and the WC/Ht ratio showed similar AUCs. The AUCs for the BRI and WC/Ht ratio were the highest in middle-aged men with NGT and glucose intolerance. Conclusions: The BRI, not the ABSI, was better correlated with SI in young and middle-aged Japanese persons. The BRI and WC/Ht ratio were comparable in their correlations with SI and the detection of insulin resistance in the participants of the present study.

An Evaluation of the Efficacy of Machine Learning in Predicting Thyrotoxicosis and Hypothyroidism: A Comparative Assessment of Biochemical Test Parameters Used in Different Health Checkups.

Objective This study assessed the efficacy of machine learning in predicting thyrotoxicosis and hypothyroidism [thyroid-stimulating hormone (TSH) >10.0 mIU/L] by leveraging age and sex as variables and integrating biochemical test parameters used by the Japan Society of Health Evaluation and Promotion (JHEP) and the Japan Society of Ningen Dock (JND). Subjects and Methods Our study included 20,653 untreated patients with Graves' disease, 3,435 untreated patients with painless thyroiditis, 4,266 healthy individuals, and 18,937 untreated patients with Hashimoto's thyroiditis. Machine learning was conducted using Prediction One on three distinct datasets: the Ito dataset (age, sex, and 30 blood tests and biochemical test data), the JHEP dataset (age, sex, and TP, T-Bil, AST, ALT, γGTP, ALP, CRE, UA, and T-Cho test data), and the JND dataset (age, sex, and AST, ALT, γGTP, CRE, and UA test data). Results The results for distinguishing thyrotoxicosis patients from the healthy control group showed that the JHEP dataset yielded substantial discriminative capacity with an area under the curve (AUC) of 0.966, sensitivity of 92.2%, specificity of 89.1%, and accuracy of 91.7%. The JND dataset displayed similar robustness, with an AUC of 0.948, sensitivity of 92.0%, specificity of 81.3%, and accuracy of 90.4%. Differentiating hypothyroid patients from the healthy control group yielded similarly robust performances, with the JHEP dataset yielding AUC, sensitivity, specificity, and accuracy values of 0.864, 84.2%, 72.1%, and 77.4%, respectively, and the JND dataset yielding values of 0.840, 83.2%, 67.2%, and 74.3%, respectively. Conclusions Machine learning is a potent screening tool for thyrotoxicosis and hypothyroidism.

Incidence and risk factors for Graves' orbitopathy in patients who underwent anti-inflammatory and immunosuppressive treatment during medical treatment for Graves' disease: investigation of 1,553 cases with newly diagnosed Graves' disease and proposal of a predictive score.

Appropriate administration of anti-inflammatory and immunosuppressive treatment (AIIST) is important for patients with Graves' orbitopathy (GO). This study aimed to clarify the incidence and risk factors for GO treated with AIIST and propose a predictive score, among newly diagnosed Graves' disease (GD) patients in Japan. A total of 1,553 GD patients who were newly diagnosed during the year 2011 were investigated. AIIST included local and/or systemic glucocorticoid administration and retrobulbar irradiation. A multivariable Cox proportional hazards model was used to investigate the risk factors for GO underwent AIIST during medical treatment, including at diagnosis, of GD. Then, a GO score was created by summing each point assigned to risk factors based on their coefficient obtained in the Cox model. AIIST was administered to 107 patients (6.9%). The risk factors and hazard ratios for GO underwent AIIST were: age (per 10 years), 1.32 (95% confidence interval: 1.16-1.50), p < 0.0001; TSH binding inhibitory immunoglobulin (TBII) (per 10 IU/L), 1.33 (1.15-1.54), p = 0.0001; and thyroglobulin antibody (TgAb) negativity, 2.98 (1.96-4.59), p < 0.0001. The GO score, ranging from 0 to 8 points, showed moderate performance (area under the curve: 0.71, cut-off value: 5 points, sensitivity: 0.76, specificity: 0.59, positive predictive value: 0.12, negative predictive value: 0.97). AIIST was performed for patients with active manifestations of GO in 6.9% of newly diagnosed GD patients. The risk factors for GO underwent AIIST were higher age, higher TBII, and TgAb negativity. The GO score based on these factors may be useful in managing GO.

Pleiotropic Functions of Nitric Oxide Produced by Ascorbate for the Prevention and Mitigation of COVID-19: A Revaluation of Pauling's Vitamin C Therapy.

Linus Pauling, who was awarded the Nobel Prize in Chemistry, suggested that a high dose of vitamin C (l-ascorbic acid) might work as a prevention or treatment for the common cold. Vitamin C therapy was tested in clinical trials, but clear evidence was not found at that time. Although Pauling's proposal has been strongly criticized for a long time, vitamin C therapy has continued to be tested as a treatment for a variety of diseases, including coronavirus infectious disease 2019 (COVID-19). The pathogen of COVID-19, SARS-CoV-2, belongs to the ß-coronavirus lineage, which includes human coronavirus, severe acute respiratory syndrome (SARS), and Middle East respiratory syndrome (MERS). This review intends to shed new light on vitamin C antiviral activity that may prevent SARS-CoV-2 infection through the chemical production of nitric oxide (NO). NO is a gaseous free radical that is largely produced by the enzyme NO synthase (NOS) in cells. NO produced by upper epidermal cells contributes to the inactivation of viruses and bacteria contained in air or aerosols. In addition to enzymatic production, NO can be generated by the chemical reduction of inorganic nitrite (NO2-), an alternative mechanism for NO production in living organisms. Dietary vitamin C, largely contained in fruits and vegetables, can reduce the nitrite in saliva to produce NO in the oral cavity when chewing foods. In the stomach, salivary nitrite can also be reduced to NO by vitamin C secreted from the epidermal cells of the stomach. The strong acidic pH of gastric juice facilitates the chemical reduction of salivary nitrite to produce NO. Vitamin C contributes in multiple ways to the host innate immune system as a first-line defense mechanism against pathogens. Highlighting chemical NO production by vitamin C, we suggest that controversies on the therapeutic effects of vitamin C in previous clinical trials may partly be due to less appreciation of the pleiotropic functions of vitamin C as a universal bioreductant.

Incidence of and Risk Factors for Neonatal Hypothyroidism Among Women with Graves' Disease Treated with Antithyroid Drugs Until Delivery.

Background: The incidence of neonatal hypothyroidism among newborns born to mothers with Graves' disease (GD) who continued antithyroid drug (ATD) treatment until delivery has never been reported. Objective: Our primary objective was to investigate the incidence of neonatal hypothyroidism among newborns born to mothers with GD who were treated with ATD until delivery. Our secondary objective was to identify the cutoff ATD daily doses for neonatal hypothyroidism risk, based on maternal thyrotropin (TSH) receptor antibody (TRAb) levels. Methods: We conducted a retrospective cohort study. We included 305 pregnant women with GD who were treated with an ATD until delivery (63 treated with methimazole [MMI] and 242 treated with propylthiouracil [PTU]). Umbilical cord TSH, free thyroxine (fT4), and TRAb levels were measured at delivery, and we investigated the respective relationships between neonatal hypothyroidism at delivery and maternal fT4 levels, TRAb levels, and daily ATD doses during pregnancy. Neonatal hypothyroidism was diagnosed when the umbilical cord fT4 level was below the lower limit of the reference range. Results: The incidence of neonatal hypothyroidism at delivery was 19.0% ([confidence interval, CI, 11.2-30.4]; 12/63) in the MMI group and 12.8% ([CI, 9.2-17.6]; 31/242) in the PTU group. Neonatal goiter was observed in one neonate in the PTU group, and two infants in the PTU group required levothyroxine treatment. The daily ATD dose in the third trimester was the strongest predictor of neonatal hypothyroidism at delivery; the cutoff MMI dose was 10 mg/day, and the cutoff PTU dose was 150 mg/day. When the maternal TRAb level in the third trimester was above three times the upper limit of the normal range, the cutoff MMI dose was 20 mg/day, and the cutoff PTU dose was 150 mg/day. Conclusions: Maternal fT4 and TRAb levels were higher in the neonatal hypothyroid group, which suggested prolonged GD activity. Careful follow-up is necessary when maternal GD remains active and the ATD dose to control maternal thyrotoxicosis cannot be reduced.

Clinical characteristics and efficacy of pioglitazone in a Japanese patient with familial partial lipodystrophy due to peroxisome proliferator-activated receptor γ gene mutation.

Familial partial lipodystrophy (FPLD) 3 is a rare genetic disorder caused by peroxisome proliferator-activated receptor γ gene (PPARG) mutations. Most cases have been reported in Western patients. Here, we describe a first pedigree of FPLD 3 in Japanese. The proband was a 51-year-old woman. She was diagnosed with fatty liver at age 32 years, dyslipidemia at age 37 years, and diabetes mellitus at age 41 years. Her body mass index was 18.5 kg/m2, and body fat percentage was 19.2%. On physical examination, she had less subcutaneous fat in the upper limbs than in other sites. On magnetic resonance imaging, atrophy of subcutaneous adipose tissue was seen in the upper limbs and lower legs. Fasting serum C-peptide immunoreactivity was high (3.4 ng/mL), and the plasma glucose disappearance rate was low (2.07%/min) on an insulin tolerance test, both suggesting apparent insulin resistance. The serum total adiponectin level was low (2.3 µg/mL). Mild fatty liver was seen on abdominal computed tomography. On genetic analysis, a P495L mutation in PPARG was identified. The same mutation was also seen in her father, who had non-obese diabetes mellitus, and FPLD 3 was diagnosed. Modest increases in body fat and serum total adiponectin were seen with pioglitazone treatment. Attention should be paid to avoid overlooking lipodystrophy syndromes even in non-obese diabetic patients if they show features of insulin resistance.

Education and licensure of dental technicians.

The Japanese Health, Labour, and Welfare Ministry in 2020 identified the following issues for training and recruitment of dental technicians: early involvement of students in dental practice and dental laboratory work, a curriculum in line with the times, and an extension of the years of training. This paper investigates the education and qualifications of dental technicians in other countries to discuss these issues. The survey method was to use the database PubMed to search the literature since 2001 using the keywords "dental technician," "education," and license" to collect literature related to the pre-graduate education of dental technicians. Information on educational institutions was also included in the survey. The results showed that the countries that introduced joint education between dental technicians and dentists into their educational programs, and the examinations and years of training required for each certification varied from country to country. The curriculum for dental technicians in Japan changed from a time-based to a credit-based system on April 1, 2018. The credit system is characterized by the possibility of each training institution actively engaging in flexible curriculum organization. Dental technician education programs in other countries can provide a valuable reference for each training institute to demonstrate its uniqueness.

Diabetic family history in young Japanese persons with normal glucose tolerance associates with k-means clustering of glucose response to oral glucose load, insulinogenic index and Matsuda index.

Aims: The present study aimed to clarify the relationships between diabetic family history (FH), and dysglycemic response to the oral glucose tolerance test (OGTT), insulin secretion, and insulin sensitivity in young Japanese persons with normal glucose tolerance (NGT). Methods: We measured plasma glucose (PG) and immunoreactive insulin levels in 1,309 young Japanese persons (age <40 years) with NGT before and at 30, 60, and 120 min during a 75-g OGTT. Dysglycemia during OGTT was analyzed by k-means clustering analysis. Body mass index (BMI), blood pressure (BP), and lipids were measured. Insulin secretion and sensitivity indices were calculated. Results: PG levels during OGTT were classified by k-means clustering analysis into three groups with stepwise decreases in glucose tolerance even among individuals with NGT. In these clusters, proportion of males, BMI, BP and frequency of FH were higher, and lipid levels were worse, together with decreasing glucose tolerance. Subjects with a diabetic FH showed increases in PG after glucose loading and decreases in insulinogenic index and Matsuda index. Conclusions: Dysglycemic response to OGTT by k-means clustering analysis was associated with FH in young Japanese persons with NGT. FH was also associated with post-loading glucose, insulinogenic index, and Matsuda index.

Analysis of human clinical and environmental Leptospira to elucidate the eco-epidemiology of leptospirosis in Yaeyama, subtropical Japan.

BACKGROUND: Leptospirosis, a zoonosis caused by species in the spirochete genus Leptospira, is endemic to the Yaeyama region in Okinawa, subtropical Japan. Species of the P1 subclade "virulent" group, within the genus Leptospira, are the main etiological agents of leptospirosis in Okinawa. However, their environmental persistence is poorly understood. This study used a combination of bacterial isolation and environmental DNA (eDNA) metabarcoding methods to understand the eco-epidemiology of leptospirosis in this endemic region. FINDINGS: Polymerase chain reaction (PCR) characterized twelve human clinical L. interrogans isolates belonging to the P1 subclade "virulent" subgroup and 11 environmental soil isolates of the P1subclade "low virulent" subgroup (genetically related to L. kmetyi, n = 1; L. alstonii, n = 4; L. barantonii, n = 6) from the Yaeyama region targeting four virulence-related genes (lipL32, ligA, ligB and lpxD1). Clinical isolates were PCR positive for at least three targeted genes, while all environmental isolates were positive only for lipL32. Analysis of infected renal epithelial cells with selected clinical and environmental strains, revealed the disassembly of cell-cell junctions for the Hebdomadis clinical strain serogroup. Comparison of leptospiral eDNA during winter and summer identified operational taxonomic units corresponding to the species isolated from soil samples (L. kmetyi and L. barantonii) and additional P2 subclade species (L. licerasiae, L. wolffii-related, among others) that were not detected by soil cultivation. Total Leptospira read counts were higher in summer than in winter and the analysis of leptospiral/animal eDNA relationship suggested Rattus spp. as a potential reservoir animal. CONCLUSION: Our study demonstrated high environmental Leptospira diversity in the Yaeyama region, particularly during summer, when most of the leptospirosis cases are reported. In addition, several Leptospira species with pathogenic potential were identified that have not yet been reported in Yaeyama; however, the environmental persistence of P1 subclade species previously isolated from human clinical cases in this region was absent, suggesting the need of further methodology development and surveillance.

Association between sarcopenia and the severity of diabetic polyneuropathy assessed by nerve conduction studies in Japanese patients with type 2 diabetes mellitus.

AIMS/INTRODUCTION: This study examined the association between the severity of diabetic polyneuropathy (DPN) based on the Baba classification, and sarcopenia and its related factors. MATERIALS AND METHODS: The participants were 261 patients with type 2 diabetes mellitus. DPN was classified as stages 0-4 according to the Baba classification. Sarcopenia was diagnosed based on measurements of the skeletal mass index, grip strength and walking speed, using the Asia Working Group for Sarcopenia 2019 diagnostic criteria. RESULTS: The median age of the participants was 67 years, the proportion of men was 58.6%, the median estimated duration of diabetes was 10 years and the median values for glycated hemoglobin were 10.3%. With regard to DPN, the prevalence of Baba classification stages 0-2 was 90.8% (n = 237), and that of stage 3 or 4 was 9.2% (n = 24). The prevalence of sarcopenia was 19.9%. A trend toward an increase in the frequency of slow walking speed was seen as the stage of DPN progressed. The frequencies of sarcopenia and slow walking speed were higher in the group with the Baba classification stages 3 and 4 than in the group with stages 0-2. On multiple logistic regression analyses, however, DPN was not significantly related to sarcopenia and walking speed. CONCLUSIONS: Although severe DPN might be related to sarcopenia, the frequency of severe DPN is low in the clinical setting, indicating that its contribution to sarcopenia is modest.

Secondary Hypogonadism due to Excessive Ingestion of Isoflavone in a Man.

A 54-year-old man had been drinking approximately 1.2 L of soy milk (equivalent to approximately 310 mg of isoflavones) per day for the previous 3 years. He then developed erectile dysfunction and gynecomastia. On an examination in our department in May, blood tests showed low gonadotropin and testosterone levels, indicative of secondary hypogonadism. He stopped drinking soy milk on his own in June of that year. When he was admitted in August, blood tests showed an improved gonadal function. Secondary hypogonadism caused by the excessive intake of isoflavones in soy milk was diagnosed. In men, an excessive intake of isoflavones may cause feminization and secondary hypogonadism.

Comparison of dimension reduction methods on fatty acids food source study.

Serum fatty acids (FAs) exist in the four lipid fractions of triglycerides (TGs), phospholipids (PLs), cholesteryl esters (CEs) and free fatty acids (FFAs). Total fatty acids (TFAs) indicate the sum of FAs in them. In this study, four statistical analysis methods, which are independent component analysis (ICA), factor analysis, common principal component analysis (CPCA) and principal component analysis (PCA), were conducted to uncover food sources of FAs among the four lipid fractions (CE, FFA, and TG + PL). Among the methods, ICA provided the most suggestive results. To distinguish the animal fat intake from endogenous fatty acids, FFA variables in ICA and factor analysis were studied. ICA provided more distinct suggestions of FA food sources (endogenous, plant oil intake, animal fat intake, and fish oil intake) than factor analysis. Moreover, ICA was discovered as a new approach to distinguish animal FAs from endogenous FAs, which will have an impact on epidemiological studies. In addition, the correlation coefficients between a published dataset of food FA compositions and the loading values obtained in the present ICA study suggested specific foods as serum FA sources. In conclusion, we found that ICA is a useful tool to uncover food sources of serum FAs.

Postloading insulinemia is independently associated with arterial stiffness in young Japanese persons.

Associations of arterial stiffness with glucose, insulin, and proinsulin dynamics during the oral glucose tolerance test (OGTT) remain under debate. The aim of this study was to investigate whether plasma glucose (PG), insulin, and proinsulin (Pro) contribute to arterial stiffness, measured by pulse wave velocity (PWV), in young Japanese persons. PG, immunoreactive insulin (IRI), and Pro levels were determined in 1193 young Japanese subjects (<40 years of age) with normal glucose tolerance or nondiabetic hyperglycemia before and at 30, 60, and 120 min during a 75-g OGTT. Participants were divided into two groups according to the median PWV. Background factors, PG, IRI, and Pro levels during the OGTT, and insulin sensitivity (SI) indices in each group were compared. Several multiple regression analysis models were used to evaluate factors contributing to PWV. All IRI and Pro levels before and after glucose loading and the area under the curve (AUC) values for IRI and Pro increased with higher PWV. 1/HOMA-IR and ISI-Matsuda as measures of SI decreased with higher PWV. The IRI AUC and Pro level before glucose loading (Pro0) were independently associated with PWV, in addition to male sex, heart rate, and mean blood pressure. The IRI AUC had a stronger relationship with PWV than Pro0. The IRI AUC had an independent relationship with PWV, whereas both SI indices did not. Postloading insulinemia, but not reduced SI, was independently associated with arterial stiffness in young Japanese persons.

Glucose Effectiveness Decreases in Relationship to a Subtle Worsening of Metabolic Parameters in Young Japanese with Normal Glucose Tolerance.

Background: The aim of the study was to investigate the relationship between glucose effectiveness (Sg) and some metabolic parameters in male and female young Japanese. Methods: We measured plasma glucose and immunoreactive insulin levels in 1309 young Japanese persons (age <40 years) with normal glucose tolerance (NGT) before and at 30, 60, and 120 min during a 75 gram oral glucose tolerance test. We also measured serum adiponectin and high-sensitivity C-reactive protein (hsCRP) levels and oral glucose effectiveness (SgIO), and investigated factors related to SgIO. Results: The results of Spearman correlation analysis revealed that high-density lipoprotein cholesterol (HDL) and adiponectin were positively correlated with SgIO, whereas the proportion of males, body mass index, waist circumference (WC), systolic blood pressure (SBP), diastolic blood pressure, triglycerides (TG), and hsCRP were inversely correlated with SgIO. The results of multiple regression analysis indicated negative correlations between SgIO and the proportion of males, WC, and SBP and a positive correlation with HDL. The results of multiple regression analysis excluding WC indicated negative correlations between SgIO and the proportion of males, SBP, and TG and positive correlations with HDL and adiponectin. Conclusions: Sg decreased with a subtle worsening of metabolic parameters, even in young persons with NGT. Decreased Sg may be involved in the development of glucose intolerance in individuals with worse metabolic parameters.

Fabrication of titanium restoration by means of calcium aluminate-bonded magnesia investment material and one-chamber arc casting apparatus.

Cast titanium restoration for molars has high biocompatibility and is covered by the Japanese national health insurance. Titanium casting requires specific investment material and casting apparatus. A cast restoration for the mandibular left second molar was fabricated using titanium in this study. A wax pattern fabricated on a definitive cast was invested in calcium aluminate-bonded magnesia investment material. Titanium was cast using an argon gas pressure one-chamber casting apparatus. No defects were observed on the surface and the hole was clearly reproduced. A smooth surface on the restoration was obtained by polishing at low speed. Reproductivity and polishing properties of the titanium restoration fabricated in this study were comparable to those of conventional dental metal restorations.

Insulin and Proinsulin Dynamics Progressively Deteriorate From Within the Normal Range Toward Impaired Glucose Tolerance.

CONTEXT: Slight elevations in plasma glucose (PG) manifest in advance of diabetes onset, but abnormalities in immunoreactive insulin (IRI), proinsulin (Pro), and adiponectin dynamics during this stage remain poorly understood. OBJECTIVE: The objective of this work is to investigate whether IRI and Pro dynamics become abnormal as glucose tolerance deteriorates from within the normal range toward impaired glucose tolerance (IGT), as well as the relationship between PG, and these dynamics and serum adiponectin levels. DESIGN: A cross-sectional study was designed. SETTING: This study took place at Jichi Medical University in Japan. PARTICIPANTS AND MEASUREMENTS: PG, IRI, and Pro levels were determined in 1311 young Japanese individuals (age < 40 years) with normal or IGT before and at 30, 60, and 120 minutes during a 75-g oral glucose tolerance test. Participants were assigned to 4 groups according to glucose tolerance, and then background factors, adiponectin levels, insulin sensitivity (SI), and insulin secretion (ß) indexes were determined. RESULTS: PG levels as well as IRI and Pro levels 60 and 120 minutes after glucose-loading increased incrementally with deteriorating glucose tolerance. All measures of ß and the SI measure index of insulin sensitivity (ISI)-Matsuda decreased incrementally. Serum adiponectin levels were not significantly different among the glucose tolerance groups, but were independently and negatively correlated with fasting glucose. CONCLUSIONS: Early ß decreased and postloading Pro levels became excessive in a progressive manner as glucose tolerance deteriorated from within the normal range toward IGT.

Factors involved in body weight loss and its maintenance in morbidly obese inpatients.

BACKGROUND: Body weight loss in patients with obesity improves abnormal glucose tolerance, dyslipidemia and hypertension; however, it is difficult to maintain this loss of body weight. The objective of this study was to examine factors involved in body weight loss and its maintenance in morbidly obese inpatients. METHOD: The subjects were 31 patients (11 males and 20 females) who were admitted to hospital for obesity management. Factors involved in body weight changes during hospitalization and after discharge were examined retrospectively. The mean age was 58.1 ± 13.6 years and body mass index (BMI) was 40.2 ± 10.2 kg/m2. Twenty-four patients were complicated with type 2 diabetes mellitus. Diet therapy was 23.8 ± 3.9 kcal/kg ideal body weight/day. RESULTS: Excess weight loss (EWL) during hospitalization varied from 4.2 to 61.7%. Since EWL was affected by duration of hospital stay, the subjects were divided by the median of EWL per day. The subjects with greater EWL per day had lower body weight, BMI and fat mass on admission in the entire (n = 31), diabetic (n = 24), and non-diabetic subjects (n = 7), respectively. EWL per day was not different between diabetic and non-diabetic subjects. Follow-up data revealed that BMI remained unchanged 3 months after discharge but modestly increased 1 year after discharge, irrespective of EWL per day during hospitalization. In diabetic subjects followed up 1 year after discharge (n = 15), the increase in body weight was smaller than that in non-diabetic subjects (n = 3). CONCLUSION: These results suggest that EWL in morbidly obese inpatients is greater than those with lower baseline BMI and fat mass. The presence of diabetes had no effects on EWL during hospitalization. EWL during hospitalization was not correlated with its maintenance after discharge. Diabetic patients displayed lesser degree of body weight gain after discharge, possibly due to the effects of anti-diabetic medications.

Fabrication systems for restorations and fixed dental prostheses made of titanium and titanium alloys.

PURPOSE: In recent years, the application of restorations and fixed dental prostheses to molars by computer-aided design-computer-aided manufacturing (CAD/CAM) with composite resin has been increasing. Titanium and titanium alloy having a high tissue affinity and good biocompatibility are suitable for cases where CAD/CAM fabrications are inadequate, such as allergic reaction to metal. Many studies have reported methods of production with titanium and titanium alloys. The purpose of this review is to survey the clinical application of titanium and titanium alloy restorations and fixed dental prostheses with various fabrication systems. STUDY SELECTION: A literature search in PubMed was performed for various fabrication systems of titanium and titanium alloy from 2010 through 2019. The search keywords were "titanium", "titanium alloy", "CAD/CAM", "cast", "fabrication system", "marginal gap", "internal gap", and "clinical performance". Only relevant studies are summarized and discussed in this review. RESULTS: With any fabrication system, titanium and titanium alloy restorations and fixed dental prostheses fabricated with various systems were within the clinically acceptable ranges of marginal gap and internal fit. Additionally, these restorations were considered to have less effect on the periodontal issues. Although metal-ceramic restoration has clinical performance problems, such as ceramic fracture, fabrications with only titanium and titanium alloy were reported to have good clinical performance. CONCLUSIONS: Regardless of the fabrication system, titanium and titanium alloy restorations and fixed dental prostheses can be applied clinically. Titanium and titanium alloys are thought to be a promising alternative to the dental metals currently used.