An overview of the reclassification of COVID-19 of the Infectious Diseases Control Law in Japan.

Japan's responses to COVID-19 have been conducted based on the Act on the Prevention of Infectious Diseases and Medical Care for Patients with Infectious Diseases (the Infectious Diseases Control Law) and the Act on Special Measures against Novel Influenza, etc. (the Act on Special Measures), as COVID-19 is classified as the category of "the Novel Influenza etc." under the Infectious Diseases Control Law. The government's Novel Coronavirus Response Headquarters decided to reclassify COVID-19 as a Category V infectious disease under the Infectious Diseases Control Law in May 2023 since the disease has become less lethal. Accordingly, the countermeasures such as surveillance and medical care are going to be reviewed, and COVID-19 prevention actions will depend on personal choices (Prior to the review in May, mask usage will be changed from 13 March). However, this does not mean that infection control measures are no longer necessary; it is recommended that such measures be taken in certain settings in order to prevent the elderly and those who at a high risk of severe illness from being infected, even after the disease is classified as Category V.

Real-Time Survey of Vaccine Safety of the mRNA-1273 SARS-CoV-2 Vaccine in Workplace Vaccination at Keio University.

The mRNA-1273 Moderna COVID-19 vaccine was introduced to combat the COVID-19 global pandemic in 2020. Although the safety of the vaccine has been investigated worldwide, real-world safety data is scarce in Japan. An online, real-time survey of adverse events following immunization (AEFIs) with mRNA-1273 was conducted in the setting of a workplace vaccination program at the School of Pharmacy, Keio University from 26 June 2021, to 11 June 2022. Participants were requested to take four surveys during a seven-day follow-up period after each of the first, second, and third booster doses. The maximum number of responses, from 301 respondents, was obtained on day 0 (vaccination date) for the first dose. 98% of respondents reported local and systemic AEFIs for the second dose on day 1. No noticeable difference in local reactions was seen among the three doses. Females reported more AEFIs than males, and the young group (18-29 years) reported a higher rate than the middle age group (≥30 years) after the first dose. Age and gender differences in rates decreased at the second and third doses. This survey confirmed that the safety profile of mRNA-1273 in a real-world setting was similar to that derived from the clinical trials, and that the agent was well-tolerated.

SARS-CoV-2 Infection among Medical Institution Faculty and Healthcare Workers in Tokyo, Japan.

Objective To consider effective measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in medical institutions, this study estimated the SARS-CoV-2 infection rate among healthcare workers (HCWs) in Tokyo, Japan, and determined the specific findings for mild coronavirus disease 2019 (COVID-19) cases. Methods This study analyzed the results of serologic tests to detect immunoglobulin G antibodies against SARS-CoV-2 and evaluated the demographic and clinical characteristics of the faculty and HCWs at a Tokyo medical institution in August 2020. The demographic and clinical characteristics of participants with antibody-positive results were compared to those of participants with antibody-negative results. Materials This study recruited 2,341 faculty and HCWs at a Tokyo medical institution, 21 of whom had a COVID-19 history. Results Of the 2,320 participants without a COVID-19 history, 20 (0.862%) had positive serologic test results. A fever and dysgeusia or dysosmia occurred with greater frequency among the participants with positive test results than in those with negative results [odds ratio (OR), 5.475; 95% confidence interval (CI), 1.960-15.293 and OR, 24.158; 95% CI, 2.693-216.720, respectively]. No significant difference was observed in the positivity rate between HCWs providing medical care for COVID-19 patients using adequate protection and other HCWs (OR, 2.514; 95% CI, 0.959-6.588). Conclusion To reduce the risk of COVID-19 spread in medical institutions, faculty and HCWs should follow standard and necessary transmission-based precautions, and those with a fever and dysgeusia or dysosmia should excuse themselves from work as soon as possible.

Control of a Nosocomial Outbreak of COVID-19 in a University Hospital.

BACKGROUND: Nosocomial spread of coronavirus disease 2019 (COVID-19) causes clusters of infection among high-risk individuals. Controlling this spread is critical to reducing COVID-19 morbidity and mortality. We describe an outbreak of COVID-19 in Keio University Hospital, Japan, and its control and propose effective control measures. METHODS: When an outbreak was suspected, immediate isolation and thorough polymerase chain reaction (PCR) testing of patients and health care workers (HCWs) using an in-house system, together with extensive contact tracing and social distancing measures, were conducted. Nosocomial infections (NIs) were defined as having an onset or positive test after the fifth day of admission for patients and having high-risk contacts in our hospital for HCWs. We performed descriptive analyses for this outbreak. RESULTS: Between March 24 and April 24, 2020, 27 of 562 tested patients were confirmed positive, of whom 5 (18.5%) were suspected as NIs. For HCWs, 52 of 697 tested positive, and 40 (76.9%) were considered NIs. Among transmissions, 95.5% were suspected of having occurred during the asymptomatic period. Large-scale isolation and testing at the first sign of outbreak terminated NIs. The number of secondary cases directly generated by a single primary case found before March 31 was 1.74, compared with 0 after April 1. Only 4 of 28 primary cases generated definite secondary infection; these were all asymptomatic. CONCLUSIONS: Viral shedding from asymptomatic cases played a major role in NIs. PCR screening of asymptomatic individuals helped clarify the pattern of spread. Immediate large-scale isolation, contact tracing, and social distancing measures were essential to containing outbreaks.

Inhibitory effect of edaravone on systemic inflammation and local damage in skeletal muscles following long-term ischemia to murine hind limb.

PURPOSE: The purpose of this study was to evaluate local and systemic pathology in a murine model of ischemia-reperfusion (I/R) injury induced by long-term application of a tourniquet on the hind limbs and to assess the protective effects of edaravone, a potent systemic scavenger of free radicals, using this model. METHODS: Sixty C57BL6 mice were divided in two groups, with one group receiving a 3 mg/kg intraperitoneal injection of edaravone and the other group receiving an identical amount of saline 30 min before ischemia under deep anesthesia. The left thigh of each animal was constricted for 4 h with a 4.5-oz. orthodontic rubber band to induce ischemia; 4 h was the critical duration for skeletal muscles. After ischemia, specimens of skeletal muscles, both kidneys, and plasma were collected at 0, 2, 12, 24, 48, and 72 h. Injury to the skeletal muscles and vacuolar degeneration of the kidneys were histologically assessed. Additionally, apoptosis of skeletal muscle cells was assessed by analysis of caspase 3/7 activity and TUNEL staining. Plasma tumor necrosis factor (TNF)-α levels were measured using an enzyme-linked immunosorbent assay kit. RESULTS: Skeletal muscles exhibited prominent injury of myofibers at 12 h after I/R injury, with clear upregulation of plasma TNF-α expression and histologic evidence of tubular dysfunction of the kidneys. Plasma TNF-α levels declined and histologic renal damage was ameliorated in edaravone-treated mice, but treatment did not protect skeletal muscle following ischemia for 4 h. Nonetheless, compared with group S, expression of the apoptosis marker caspase 3/7 was significantly inhibited in the skeletal hind limb muscles of Ed-group mice affected by reperfusion injury following ischemia for 4 h. CONCLUSION: The present study demonstrated that edaravone is a potentially useful drug for systemic or local treatment of reperfusion injury resulting from long-term ischemia.

Effect of Dialkyl Ammonium Cationic Surfactants on the Microfluidity of Membranes Containing Raft Domains.

It has been reported that a lot of receptors localize in lipid raft domains and that the microfluidity of these domains regulates the activation of these receptors. In this study, we focused on the lipid raft and in order to evaluate the physicochemical effects of surfactants on microfluidity of lipid membranes, we used liposomes comprising of egg-yolk L-α-phosphatidylcholine, egg-yolk sphingomyelin, and cholesterol as a model of cell membranes containing raft domains. The microfluidity of the domains was characterized by fluorescence spectrometry using 1,6-diphenyl-1,3,5-hexatriene and 2-dimethylamino-6-lauroylnaphthalene. Among several surfactants, dialkylammonium-type cationic surfactants most efficiently increased the microfluidity. It is therefore concluded that (1) the electrostatic interaction between the cationic surfactant and eggPC/eggSM/cholesterol liposome could be important, (2) surfactants with alkyl chains more effectively inserted into membranes than those with acyl chains, and (3) cationic surfactants with lower Tm values have a greater ability to increase the fluidity.

Pregnant woman with non-comatose autoimmune acute liver failure in the second trimester rescued using medical therapy: A case report.

We present the case of a 25-year-old woman at 16 weeks of gestation who presented with non-comatose autoimmune acute liver failure and was at high risk of developing fulminant hepatitis. Predictive formulas indicated a high probability of developing fulminant hepatitis. Unenhanced computed tomography showed marked hepatic atrophy and broadly heterogeneous hypoattenuating areas. The course of her illness was subacute, and the etiology of liver injury was unclear. Considering all of the above, we predicted a poor prognosis. Plasma exchange (PE) and continuous hemodiafiltration (CHDF) therapy were initiated just after admission. A few days after admission, a high titer (×80) of antinuclear antibody was noted. Because autoimmune hepatitis (AIH) was considered a cause of liver failure, treatment with moderate prednisolone (30 mg/day) doses was administrated, with careful consideration of her pregnancy. Thereafter, her laboratory findings and clinical course gradually improved without the need for liver transplantation. A liver biopsy at 18 days after admission indicated a diagnosis of AIH. She continued the pregnancy and delivered a healthy baby without any complications. Eventually, prednisolone doses were decreased to 10 mg, after which her liver function worsened. The second liver biopsy also indicated a diagnosis of AIH. Accordingly, low-dose prednisolone and azathioprine doses (50 mg/day) were administrated to recover her liver function, after which her liver function regained normalcy. This case illustrates that a pregnant woman with non-comatose autoimmune acute liver failure in the first or second trimester of pregnancy and her fetus can be rescued by PE/CHDF therapy and safe moderate doses of prednisolone.

Prevalence and characteristics of headaches in a socially active population working in the Tokyo metropolitan area -surveillance by an industrial health consortium.

OBJECTIVE: The goal of this study was to determine the prevalence and clinical characteristics of headaches among socially active people working in the Tokyo metropolitan area. METHODS: We cross-sectionally surveyed 7,917 individuals. The survey assessed demographic characteristics, the prevalence and characteristics of headaches and physician attendance. RESULTS: The lifetime prevalence of migraines was 8.9%, while that of tension-type headaches was 14.7%. Women exhibited a higher prevalence of migraines than men (15% vs. 3.7%; p<0.001). The prevalence of migraines and tension-type headaches differed among occupations. Susceptibility to migraines and tension-type headaches related to working overtime was observed. With respect to the influence of migraines on social activities, 22.4% of the migraineurs had been obliged to miss work due to headaches several times a year. As many as 59.4% of the sufferers had never consulted a physician about their headaches. Moreover, 24.6% of the migraineurs were not in touch with any physician at the time of the survey. The most common reason why they had stopped visiting their physician was that they had been told their headaches were not fatal. CONCLUSION: Migraines adversely affect social activities. These data provide important information for understanding the features of migraines and tension-type headaches in socially active people working in the Tokyo metropolitan area.

Acyl-CoA:cholesterol acyltransferase 1 mediates liver fibrosis by regulating free cholesterol accumulation in hepatic stellate cells.

BACKGROUND & AIMS: Acyl-coenzyme A: cholesterol acyltransferase (ACAT) catalyzes the conversion of free cholesterol (FC) to cholesterol ester, which prevents excess accumulation of FC. We recently found that FC accumulation in hepatic stellate cells (HSCs) plays a role in progression of liver fibrosis, but the effect of ACAT1 on liver fibrosis has not been clarified. In this study, we aimed to define the role of ACAT1 in the pathogenesis of liver fibrosis. METHODS: ACAT1-deficient and wild-type mice, or Toll-like receptor 4 (TLR4)(-/-)ACAT1(+/+) and TLR4(-/-)ACAT1(-/-) mice were subjected to bile duct ligation (BDL) for 3 weeks or were given carbon tetrachloride (CCl4) for 4 weeks to induce liver fibrosis. RESULTS: ACAT1 was the major isozyme in mice and human primary HSCs, and ACAT2 was the major isozyme in mouse primary hepatocytes and Kupffer cells. ACAT1 deficiency significantly exaggerated liver fibrosis in the mouse models of liver fibrosis, without affecting the degree of hepatocellular injury or liver inflammation, including hepatocyte apoptosis or Kupffer cell activation. ACAT1 deficiency significantly increased FC levels in HSCs, augmenting TLR4 protein and downregulating expression of transforming growth factor-ß (TGFß) pseudoreceptor Bambi (bone morphogenetic protein and activin membrane-bound inhibitor), leading to sensitization of HSCs to TGFß activation. Exacerbation of liver fibrosis by ACAT1 deficiency was dependent on FC accumulation-induced enhancement of TLR4 signaling. CONCLUSIONS: ACAT1 deficiency exaggerates liver fibrosis mainly through enhanced FC accumulation in HSCs. Regulation of ACAT1 activities in HSCs could be a target for treatment of liver fibrosis.

Free cholesterol accumulation in hepatic stellate cells: mechanism of liver fibrosis aggravation in nonalcoholic steatohepatitis in mice.

UNLABELLED: Although nonalcoholic steatohepatitis (NASH) is associated with hypercholesterolemia, the underlying mechanisms of this association have not been clarified. We aimed to elucidate the precise role of cholesterol in the pathophysiology of NASH. C57BL/6 mice were fed a control, high-cholesterol (HC), methionine-choline-deficient (MCD), or MCD+HC diet for 12 weeks or a control, HC, high-fat (HF), or HF+HC diet for 24 weeks. Increased cholesterol intake accelerated liver fibrosis in both the mouse models without affecting the degree of hepatocellular injury or Kupffer cell activation. The major causes of the accelerated liver fibrosis involved free cholesterol (FC) accumulation in hepatic stellate cells (HSCs), which increased Toll-like receptor 4 protein (TLR4) levels through suppression of the endosomal-lysosomal degradation pathway of TLR4, and thereby sensitized the cells to transforming growth factor (TGF)ß-induced activation by down-regulating the expression of bone morphogenetic protein and activin membrane-bound inhibitor. Mammalian-cell cholesterol levels are regulated by way of a feedback mechanism mediated by sterol regulatory element-binding protein 2 (SREBP2), maintaining cellular cholesterol homeostasis. Nevertheless, HSCs were sensitive to FC accumulation because the high intracellular expression ratio of SREBP cleavage-activating protein (Scap) to insulin-induced gene (Insig) disrupted the SREBP2-mediated feedback regulation of cholesterol homeostasis in these cells. HSC activation subsequently enhanced the disruption of the feedback system by Insig-1 down-regulation. In addition, the suppression of peroxisome proliferator-activated receptor γ signaling accompanying HSC activation enhanced both SREBP2 and microRNA-33a signaling. Consequently, FC accumulation in HSCs increased and further sensitized these cells to TGFß-induced activation in a vicious cycle, leading to exaggerated liver fibrosis in NASH. CONCLUSION: These characteristic mechanisms of FC accumulation in HSCs are potential targets to treat liver fibrosis in liver diseases including NASH.

Effect of Telmisartan or Losartan for Treatment of Nonalcoholic Fatty Liver Disease: Fatty Liver Protection Trial by Telmisartan or Losartan Study (FANTASY).

AIM: This study compared the effects of telmisartan and losartan on nonalcoholic fatty liver disease (NAFLD) and biochemical markers of insulin resistance in hypertensive NAFLD patients with type 2 diabetes mellitus. METHODS: This was a randomized, open-label, parallel-group comparison of therapy with telmisartan or losartan. Nineteen hypertensive NAFLD patients with type 2 diabetes were randomly assigned to receive telmisartan at a dose of 40 mg once a day (n = 12) [DOSAGE ERROR CORRECTED] or losartan at a dose of 50 mg once a day (n = 7) for 12 months. RESULTS: The telmisartan group showed a significant decline in serum free fatty acid (FFA) level (from 0.87 ± 0.26 to 0.59 ± 0.22 mEq/L (mean ± SD), P = 0.005) and a significant increase in L/S ratio (P = 0.049) evaluated by CT scan, while these parameters were not changed in the losartan group. CONCLUSION: Although there was no significant difference in improvement in liver enzymes with telmisartan and losartan treatment in hypertensive NAFLD patients with type 2 diabetes after 12 months, it is suggested that telmisartan may exert beneficial effects by improving fatty liver.

Effects of lipid membrane curvature on lipid packing state evaluated by isothermal titration calorimetry.

In this report, we present a novel approach for the elucidation of the physicochemical properties of lipid membranes by isothermal titration calorimetry (ITC) to quantify the heat absorbed during the solubilization of vesicles into TritonX-100 micelles. By using large and small unilamellar vesicles for comparison, this method provides calorimetric data on the gel-to-liquid-crystalline phase transition and its curvature effects and, in particular, the enthalpy change upon membrane deformation from a planar to a curved shape, which cannot be obtained by the conventional approach using differential scanning calorimetry. The results showed quantitatively that the increase in membrane curvature increases the enthalpy of 1,2-dimyristoyl-sn-glycero-3-phosphocholine membranes both below and above the phase-transition temperature, and that the effect is more significant for the former condition. The calorimetric data obtained are further discussed in relation to the elastic bending energy of the membranes and membrane-peptide interaction.

p53/p66Shc-mediated signaling contributes to the progression of non-alcoholic steatohepatitis in humans and mice.

BACKGROUND & AIMS: The tumor suppressor p53 is a primary sensor of stressful stimuli, controlling a number of biologic processes. The aim of our study was to examine the roles of p53 in non-alcoholic steatohepatitis (NASH). METHODS: Male wild type and p53-deficient mice were fed a methionine- and choline-deficient diet for 8 weeks to induce nutritional steatohepatitis. mRNA expression profiles in normal liver samples and liver samples from patients with non-alcoholic liver disease (NAFLD) were also evaluated. RESULTS: Hepatic p53 and p66Shc signaling was enhanced in the mouse NASH model. p53 deficiency suppressed the enhanced p66Shc signaling, decreased hepatic lipid peroxidation and the number of apoptotic hepatocytes, and ameliorated progression of nutritional steatohepatitis. In primary cultured hepatocytes, transforming growth factor (TGF)-ß treatment increased p53 and p66Shc signaling, leading to exaggerated reactive oxygen species (ROS) accumulation and apoptosis. Deficient p53 signaling inhibited TGF-ß-induced p66Shc signaling, ROS accumulation, and hepatocyte apoptosis. Furthermore, expression levels of p53, p21, and p66Shc were significantly elevated in human NAFLD liver samples, compared with results obtained with normal liver samples. Among NAFLD patients, those with NASH had significantly higher hepatic expression levels of p53, p21, and p66Shc compared with the group with simple steatosis. A significant correlation between expression levels of p53 and p66Shc was observed. CONCLUSIONS: p53 in hepatocytes regulates steatohepatitis progression by controlling p66Shc signaling, ROS levels, and apoptosis, all of which may be regulated by TGF-ß. Moreover, p53/p66Shc signaling in the liver appears to be a promising target for the treatment of NASH.

A high-cholesterol diet exacerbates liver fibrosis in mice via accumulation of free cholesterol in hepatic stellate cells.

BACKGROUND & AIMS: Some studies have indicated that dietary cholesterol has a role in the progression of liver fibrosis. We investigated the mechanisms by which dietary cholesterol might contribute to hepatic fibrogenesis. METHODS: C57BL/6 mice were fed a high-cholesterol diet or a control diet for 4 weeks; liver fibrosis then was induced by bile-duct ligation or carbon tetrachloride administration. Hepatic stellate cells (HSCs) were isolated from mice fed high-cholesterol diets or from Niemann-Pick type C1-deficient mice, which accumulate intracellular free cholesterol. RESULTS: After bile-duct ligation or carbon tetrachloride administration, mice fed high-cholesterol diets had significant increases in liver fibrosis and activation of HSCs compared with mice fed control diets. There were no significant differences in the degree of hepatocellular injury or liver inflammation, including hepatocyte apoptosis or Kupffer cell activation, between mice fed high-cholesterol or control diets. Levels of free cholesterol were much higher in HSCs from mice fed high-cholesterol diets than those fed control diets. In cultured HSCs, accumulation of free cholesterol in HSCs increased levels of Toll-like receptor 4 (TLR4), leading to down-regulation of bone morphogenetic protein and activin membrane-bound inhibitor (a pseudoreceptor for transforming growth factor [TGF]ß); the HSCs became sensitized to TGFß-induced activation. Liver fibrosis was not aggravated by the high-cholesterol diet in C3H/HeJ mice, which express a mutant form of TLR4; HSCs that express mutant TLR4 were not activated by accumulation of free cholesterol. CONCLUSIONS: Dietary cholesterol aggravates liver fibrosis because free cholesterol accumulates in HSCs, leading to increased TLR4 signaling, down-regulation of bone morphogenetic protein and activin membrane-bound inhibitor, and sensitization of HSC to TGFß. This pathway might be targeted by antifibrotic therapies.

Beneficial effects of ethanol consumption on insulin resistance are only applicable to subjects without obesity or insulin resistance; drinking is not necessarily a remedy for metabolic syndrome.

Although moderate drinking has been shown to lower insulin resistance levels, it is still unclear whether alcoholic beverages could be remedies for insulin resistance. To elucidate this, the correlation between levels of ethanol consumption and insulin resistance were cross-sectionally examined in 371 non-diabetic male Japanese workers. Multiple regression analysis demonstrated that the ethanol consumption level was inversely correlated with the insulin resistance level assessed by homeostatic model assessment (HOMA-IR, p = 0.0014), the serum insulin level (p = 0.0007), and pancreatic ß-cell function, also assessed by HOMA (HOMA-ß, p = 0.0002), independently from age, body mass index (BMI), and blood pressure, liver function tests, and lipid profiles status, as well as serum adiponectin. The correlations were true in subjects with normal BMIs (up to 25.0 kg/m(2), n = 301) or normal HOMA-IR (up to 2.0 µIU·mg/µL·dL n = 337), whereas all of them were non-significant in those with excessive BMIs (n = 70) or in those with HOMA-IR of more than 2.0 (n = 34). Although it is still unclear whether the reductions of these parameters by ethanol consumption are truly due to the improvement of insulin resistance, at least, these effects are not applicable to subjects with obesity and/or insulin resistance. Thus, alcoholic beverages could not be remedies for insulin resistance or metabolic syndrome.

Relationship between waist circumferences measured at the umbilical level and midway between the ribs and iliac crest - a solution to the debate on optimal waist circumference standards in the diagnostic criteria of metabolic syndrome in Japan.

AIM: The waist circumference (WC) cut-off values in the diagnostic criteria of metabolic syndrome (MetS) established in Japan (Japanese criteria) differ from those established by the International Diabetes Federation (IDF) for Asians (IDF criteria). METHODS: To settle this contradiction, a cross-sectional study of Japanese aged 20-65 years was performed. After excluding subjects suffering from significant diseases other than those constituting MetS, excessive drinkers, and regular smokers, 835 males and 1,304 females were examined. WC was measured at the umbilical level (UWC) and midway between the ribs and iliac crest (MWC) according to both criteria in each subject. RESULTS: Upper limits of reference intervals of MWC estimated in subjects free from MetS were 84.6 and 84.3 cm in older (40-65 years) and younger (20-39) males, and 78.4 and 70.5 cm in older and younger females, respectively; those of UWC were 86.4, 86.2, 87.9 and 78.9 cm, respectively. Receiver operating characteristic (ROC) curves for MWC to predict UWC reproduced the relationships of the two types of cut-off values in each population. CONCLUSION: WC cut-off values in the Japanese and IDF criteria have the potential to be valid as cut-off values of UWC and MWC in Japanese, respectively. Their difference can be explained by the variation in the WC definition, and they can stand together without inconsistency. Acceptance of the recently prevailing view that the WC standard in IDF for Asian males should be 85 cm and the introduction of new criteria for younger females in consideration of their generation differences in both criteria could facilitate their higher compatibility.

Serum immunoglobulin a concentration is an independent predictor of liver fibrosis in nonalcoholic steatohepatitis before the cirrhotic stage.

BACKGROUND AND AIMS: The similarity of alcoholic liver disease and nonalcoholic steatohepatitis (NASH) in terms of pathogenic mechanisms suggests that immunoglobulin A (IgA) may play an important role in the pathogenesis of NASH. We aimed to determine whether serum IgA concentrations allow a diagnosis of liver fibrosis in NASH. METHODS: We compared serum IgA concentrations between 108 patients with stages 0-2 NASH and 19 patients with stage 3 NASH. RESULTS: In a univariate analysis, age (P < 0.0001), gender (P = 0.0039), serum albumin level (P = 0.0192), AST (P < 0.0001), AST/ALT ratio (P < 0.0001), platelet count (P = 0.0027), hyaluronic acid level (P < 0.0001), fasting blood sugar (FBS) (P = 0.0013), IRI (P = 0.0001), prothrombin time (%) (P = 0.0287), IgA (P < 0.0001), total sum of IgG, IgA, and IgM (P = 0.0049), and IgA/(IgG + IgA + IgM) (P = 0.0105) were significantly elevated in severe-stage NASH patients compared with the early-stage NASH group. Multiple logistic regression analysis showed that in severe-stage NASH patients, only serum IgA concentrations were significantly elevated (P = 0.0225) relative to early-stage NASH patients. The area under the curve (AUC) of serum IgA concentrations was 0.758 for detecting severe-stage NASH compared with early-stage NASH. CONCLUSIONS: Serum IgA concentration could be a useful independent predictor for assessing the pre-cirrhotic progression of NASH.

Plasma free myristic acid proportion is a predictor of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Serum free fatty acid (FFA) composition and abnormal fatty acid metabolism have been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, we determined if the serum FFA composition can provide accurate diagnosis of NASH. METHODS: We compared fasting serum FFA compositions in 20 patients with simple steatosis to those in 77 patients with NASH, including 65 patients with early-stage NASH. RESULTS: By univariate analysis, the proportions of serum free myristic acid (P = 0.002) and palmitoleic acid (P = 0.033) and the stearoyl CoA desaturase (SCD)-1 index (P = 0.047) were significantly elevated in NASH patients in comparison to patients with simple steatosis. Only the serum free myristic acid proportion was significantly elevated in the early-stage NASH group in comparison to the simple steatosis group (P = 0.003). Multiple logistic regression analysis demonstrated that the serum free myristic acid proportion was significantly elevated in all patients with NASH (P = 0.011) and the subset of patients with early-stage NASH (P = 0.012) in comparison to those with simple steatosis. The area under the curve (AUC) for the serum free myristic acid proportion was 0.734 to detect NASH and 0.719 to detect early-stage NASH in comparison to simple steatosis. CONCLUSIONS: Serum free myristic acid proportion could be a useful independent predictor to differentiate NASH from simple steatosis.

Extraskeletal subcutaneous osteosarcoma of the upper arm: A case report.

Extraskeletal osteosarcoma (ESOS) occurs in approximately 1% of soft tissue sarcomas and 2-4% of all osteosarcomas. In particular, subcutaneous osteosarcoma is extremely rare, occurring in less than 10% of ESOS cases. This report presents a case of a subcutaneous tumor in the upper arm of a 79-year-old male. Imaging and pathological findings led to the conclusion that the soft tissue tumor should be diagnosed as subcutaneous osteosarcoma. Additionally, this case report documented the clinicopathological findings of the extraskeletal subcutaneous osteosarcoma in this case and discussed its clinical features by reviewing cases previously described in the literature.

Lemon grass (Cymbopogon citratus) ameliorates murine spontaneous ileitis by decreasing lymphocyte recruitment to the inflamed intestine.

OBJECTIVE: Aberrant leukocyte migration has been implicated in the pathogenesis of inflammatory bowel disease (IBD). Lemon grass is a natural herb that contains citral, which suppresses lymphocyte expression of gut homing molecules by inhibiting retinoic acid formation. We therefore hypothesized that lemon grass intake could ameliorate excess migration of leukocytes to the inflamed intestine in chronic ileitis. METHODS: Migration of fluorescence-labeled T cells to microvessels in the ileal mucosa of SAMP1/Yit mice was monitored using intravital microscopy. In some mice, lemon grass solution was administered for two weeks. For evaluation of the effects on chronic ileitis, mice were treated with lemon grass for 26 weeks. RESULTS: Surface expression of beta7 and CCR9 on T lymphocytes was stronger in SAMP1/Yit mice than in AKR/J mice. Lemon grass treatment attenuated the surface expression of beta7-integrin and CCR9. The number of adherent lymphocytes to microvessels in chronic inflamed ileum was significantly few when lymphocytes were isolated from lemon grass treated mice. Long-term lemon grass treatment improved ileitis in SAMP1/Yit mice, which was assessed by body weight, histological changes and the infiltration of beta7-positive cells. CONCLUSION: Lemon grass ameliorated ileitis through decreasing lymphocyte migration by inhibiting beta7-expression, suggesting its therapeutic usefulness for IBD.