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Background: Lower gastrointestinal perforation (LGP) is an acute abdominal condition associated with a high mortality rate. Timely and accurate diagnosis is crucial. Nevertheless, a diagnostic delay has been estimated to occur in approximately one-third of the cases, and the factors contributing to this delay are yet to be clearly understood. This study aimed to evaluate the diagnostic process for appropriate clinical reasoning and availability of image interpretation in cases of delayed diagnosis of LGP. Methods: A secondary data analysis of a large multicenter retrospective study was conducted. This descriptive study analyzed data from a multicenter, observational study conducted across nine hospitals in Japan from January 2015 to December 2019. Out of 439 LGP cases, we included 138 cases of delayed diagnosis, excluding patients with traumatic or iatrogenic perforations, or those secondary to mesenteric ischemia, appendicitis, or diverticulitis. Clinical history and computed tomography (CT) imaging information were collected for 138 cases. Additionally, information on the clinical course of 50 cases, which were incorrectly diagnosed as gastroenteritis, constipation, or small bowel obstruction, was also collected. Results: In 42 (30.4%) cases of delayed diagnosis of LGP, CT imaging was performed before diagnosis, indicating a missed opportunity for timely diagnosis. Moreover, 33 of the 50 patients initially diagnosed with gastroenteritis, constipation, or small bowel obstruction at the time of initial examination had atypical findings that were not consistent with the initial diagnosis. Of the 138 cases with delayed diagnosis in our study, 67 cases (48.6%) showed problems with either the interpretation of CT scans or with the process of clinical reasoning. Conclusion: Our retrospective study results indicate that approximately half of the cases with delayed diagnosis of LGP were due to problems in interpreting CT images or in clinical reasoning. This finding suggests that clinical reasoning and image interpretation by radiologists are important in improving the diagnostic process for LGP. [ABSTRACT FROM AUTHOR]

Background: While drugs are sometimes taken during deliberate self‐harm (DSH), no study has attempted to analyze drugs in the blood of DSH patients and compare them with prescribed medications or other drugs. In this study, drugs were analyzed from the blood of DSH patients, and the detected, prescribed, and suspected drugs were documented. Methods: Patients who practiced DSH and were transferred to the emergency sites of Fukuoka University Hospital between April 2021 and September 2022 participated in the study. Psychiatrists assessed information such as the history of psychiatric treatment and recent methods of DSH, as well as prescribed drugs within 1 month of presenting to the hospital. Blood samples were analyzed using LC–MS/MS. Participants were divided into groups according to whether or not they were prescribed psychotropics within 1 month. Results: Fifty‐five patients were enrolled in the study. Forty had been prescribed psychotropics within 1 month of hospital admission. However, non‐prescribed drugs (NPD) were detected in 42 of the 55 participants (76%). The detection of NPD was significantly high among patients with overdose of medications and OTC drugs (p = 0.036), but NPD were also detected in patients who engaged in other methods (n = 14), and in patients without prescribed medication (n = 10). Discussion: This is the first study focused on the drug analysis of blood from patients engaging in DSH. Approximately 80% of the DSH patients in this study had taken NPD, revealing a large discrepancy between prescribed medications and those detected in the blood. [ABSTRACT FROM AUTHOR]

Background: Kidney transplant patients have lower antibody acquisition after SARS-CoV-2 vaccination. The efficacy of vaccines in Japanese kidney transplant patients with specific characteristics, such as predominant living-donor, ABO-incompatible kidney transplant, and low-dose immunosuppression, requires verification. Methods: We conducted a prospective study to estimate anti-SARS-CoV-2 antibody levels in 105 kidney transplant patients and 57 controls. Blood samples were obtained before vaccination, 1, 3, and 6 months after second vaccination, and 1 month after third vaccination. We investigated antibody acquisition rates, antibody levels, and factors associated with antibody acquisition. Results: One month after second vaccination, antibody acquisition was 100% in the controls but only 36.7% in the kidney transplant group (P < 0.001). Antibody levels in positive kidney transplant patients were also lower than in the controls (median, 4.9 arbitrary units vs 106.4 arbitrary units, respectively, P < 0.001). Years after kidney transplant (odds ratio 1.107, 95% confidence interval 1.012–1.211), ABO-incompatible kidney transplant (odds ratio 0.316, 95% confidence interval 0.101–0.991) and mycophenolate mofetil use (odds ratio 0.177, 95% confidence interval 0.054–0.570) were significant predictors for antibody acquisition after second vaccination. After third vaccination, antibody positivity in the kidney transplant group increased to 75.3%, and antibody levels in positive patients were 71.7 arbitrary units. No factors were associated with de novo antibody acquisition. Conclusions: In Japanese kidney transplant patients, years after kidney transplant, ABO-incompatible kidney transplant and mycophenolate mofetil use were predictors for antibody acquisition after second vaccination. Third vaccination improves antibody status even in patients who were seronegative after the second vaccination. [ABSTRACT FROM AUTHOR]

To investigate the relationship between white blood cell (WBC) count and incidence of hyper-low-density lipoprotein (LDL) cholesterolemia in a population-based longitudinal study. This is a retrospective study using data of annual health check-ups for residents of Iki City, Japan. A total of 3312 residents (≥ 30 years) without hyper-LDL cholesterolemia at baseline were included in this analysis. Primary outcome was incidence of hyper-LDL cholesterolemia (LDL cholesterol levels ≥ 3.62 mmol/L and/or use of lipid lowering drugs). During follow-up (average 4.6 years), 698 participants development of hyper-LDL cholesterolemia (incidence 46.8 per 1000 person-years). Higher incidence of hyper-LDL cholesterolemia was observed among participants with higher leukocyte count (1st quartile group: 38.5, 2nd quartile group: 47.7, 3rd quartile group: 47.3, and 4th quartile group: 52.4 per 1,000 person-years, P = 0.012 for trend). Statistically significant relation was observed even after adjustment for age, gender, smoking, alcohol intake, leisure-time exercise, obesity, hypertension and diabetes: hazard ratio 1.24 (95% confidence interval 0.99 to 1.54) for 2nd quartile group, 1.29 (1.03–1.62) for 3rd quartile group and 1.39 (1.10–1.75) for 4th quartile group, compared with 1st quartile group (P for trend = 0.006). Increased WBC count was related to incidence of hyper-LDL cholesterolemia in general Japanese population. [ABSTRACT FROM AUTHOR]

Background: Vibrio vulnificus is typically present in seawater, fish, and shellfish, and is known to cause severe sepsis, particularly in patients with liver diseases such as cirrhosis. V. vulnificus is one of the most dangerous waterborne pathogens, and infection mainly occurs in western Japan during the summer, with an increased fatality rate. Herein, we report the case of a patient with primary biliary cholangitis and sepsis caused by V. vulnificus infection sustained through shrimp shelling. Case presentation: An 82-year-old Japanese Asian woman with no medical history or underlying disease developed redness, swelling, and pain, which extended from the right fingers to the upper arm. A diagnosis of sepsis due to cellulitis was made. Blood culture detected V. vulnificus; thus, minocycline was administered in addition to meropenem. The disease course was uneventful, and the patient was discharged on day 28 of hospitalization. Symptoms in the right upper arm developed 1 day after the patient shelled a large number of shrimp; therefore, the infection route was assumed to be through wounds sustained during shrimp shelling. We suspected liver disease and measured serum anti-mitochondrial M2 antibody levels, leading to the diagnosis of primary biliary cholangitis. Conclusions: As in this case, small wounds caused by handling fish and shrimp are a potential source of infection. Patients with severe V. vulnificus infection should be thoroughly assessed for the presence of liver diseases such as primary biliary cholangitis. [ABSTRACT FROM AUTHOR]

Analysis of longitudinal dynamics of humoral immune responses to the BNT162b2 COVID-19 vaccine might provide useful information to predict the effectiveness of BNT162b2 in preventing SARS-CoV-2 infection. Herein, we measure anti-RBD IgG at 1, 3 and 6 months (M) after the second dose of BNT162b2, and at 1 M after a third dose of BNT162b2 vaccination in 431 COVID-19-naïve healthcare workers (HCWs) in Japan. All HCWs mounted high-anti-RBD IgG responses after the two-dose regimen of BNT162b2 vaccinations. Older persons and males presented lower anti-RBD IgG responses than younger adults and females, respectively. The decay in anti-RBD IgG started from 1 M after the second dose of BNT162b2 and anti-RBD IgG titers dropped to nearly one-tenth at 6 M after the second vaccination. Subsequently, the participants received a third dose of BNT162b2 at 8 M after the second dose of BNT162b2 vaccine. Anti-RBD antibody titers 1 M after the third dose of BNT162b2 increased seventeen times that of 6 M after the second dose, and was twice higher than the peak antibody titers at 1 M after the second dose of vaccination. The negative effect of age for the male gender on anti-RBD IgG antibody titers was not observed at 1 M after the third dose of BNT162b2 vaccine. There were no notable adverse events reported, which required hospitalization in these participants. These results suggest that the third dose of BNT162b2 safely improves humoral immunity against SARS-CoV-2 with no major adverse events. [ABSTRACT FROM AUTHOR]

Although respiratory syncytial virus (RSV) is a major cause of respiratory tract infection in children, no effective therapies are available. Recently, RSV G, the attachment glycoprotein, has become a major focus in the development of therapeutic strategies against RSV infection. Treatment of RSV-infected cultured cells with maoto, a traditional herbal medicine for acute febrile diseases, significantly reduced the viral RNA and titers. RSV attachment to the cell surface was inhibited both in the presence of maoto and when RSV particles were pre-treated with maoto. We demonstrated that maoto components, Ephedrae Herba (EH) and Cinnamomi Cortex (CC), specifically interacted with the central conserved domain (CCD) of G protein, and also found that this interaction blocked viral attachment to the cellular receptor CX3CR1. Genetic mutation of CX3C motif on the CCD, the epitope for CX3CR1, decreased the binding capacity to EH and CC, suggesting that CX3C motif was the target for EH and CC. Finally, oral administration of maoto for five days to RSV-infected mice significantly reduced the lung viral titers. These experiments clearly showed the anti-RSV activity of EH and CC mixed in maoto. Taken together, this study provides insights for the rational design of therapies against RSV infection. Two components within the traditional herbal medicine maoto can bind to the G protein of the respiratory syncytial virus, blocking the virus from entering mammalian cells. [ABSTRACT FROM AUTHOR]

Lower gastrointestinal perforation is rare and challenging to diagnose in patients presenting with an acute abdomen. However, no study has examined the frequency and associated factors of diagnostic errors related to lower gastrointestinal perforation. This large-scale multicenter retrospective study investigated the frequency of diagnostic errors and identified the associated factors. Factors at the level of the patient, symptoms, situation, and physician were included in the analysis. Data were collected from nine institutions, between January 1, 2015 and December 31, 2019. Timely diagnosis was defined as diagnosis at the first visit in computed tomography (CT)-capable facilities or referral to an appropriate medical institution immediately following the first visit to a non-CT-capable facility. Cases not meeting this definition were defined as diagnostic errors that resulted in delayed diagnosis. Of the 439 cases of lower gastrointestinal perforation identified, delayed diagnosis occurred in 138 cases (31.4%). Multivariate logistic regression analysis revealed a significant association between examination by a non-generalist and delayed diagnosis. Other factors showing a tendency with delayed diagnosis included presence of fever, absence of abdominal tenderness, and unavailability of urgent radiology reports. Initial misdiagnoses were mainly gastroenteritis, constipation, and small bowel obstruction. In conclusion, diagnostic errors occurred in about one-third of patients with a lower gastrointestinal perforation. [ABSTRACT FROM AUTHOR]

We aimed to investigate the association between serum uric acid (SUA) level and development of hypertension as well as the interaction effect of chronic kidney disease (CKD) on this relationship in the general Japanese population. We included 7895 participants aged ≥30 years from the ISSA‐CKD study, a population‐based retrospective cohort study that used annual health check‐up data of residents from Iki Island, Japan. After the exclusion of 1881 with l < 1‐year follow‐up, 2812 with hypertension at baseline, and 165 with missing information on SUA, a total of 3037 participants were enrolled in this analysis. Participants were divided into four groups according to the quartiles of SUA level at baseline, and multivariable‐adjusted hazard ratios for new‐onset hypertension were calculated. Stratified analyses were performed for each subgroup (defined by sex, age, alcohol intake, and CKD) to assess the interaction effects. During a mean follow‐up period of 4.4 years, 943 participants developed hypertension. The first quartile group was set as the reference group, and the multivariable‐adjusted hazard ratios (95% confidence interval) for new‐onset hypertension were 1.11 (0.90–1.36) in the second quartile, 1.25 (1.02–1.54) in the third quartile, and 1.35 (1.07–1.70) in the fourth quartile compared with those in the reference group (p =.007 for trend). The stratified analyses showed that the association between SUA and hypertension was significantly stronger in participants with CKD than in those without CKD (p =.035 for interaction). SUA level is an independent risk factor for new‐onset hypertension. This tendency was significantly stronger in participants with CKD. [ABSTRACT FROM AUTHOR]

Background: When using rapid antigen test kits for the diagnosis of influenza, false‐negative results may occur if done too soon after the onset of symptoms. The purpose of this study was done to determine clinical laboratory items other than rapid antigen testing are useful for diagnosing influenza. Methods: The subjects were 915 patients who visited the outpatient clinic of hospital between April 2010 and March 2017 during the influenza epidemic seasons, from December to April, and had both fever of 37.0 degrees or more and cold symptoms. Results: Of the 214 patients who met the inclusion criteria, 176 had influenza. Multivariate analysis extracted patient consultation within four days of onset, fever of 37 degrees or higher, posterior pharyngeal lymphoid follicles, CRP of 0.77 mg/dL or less, and a lymphocyte count of 900/μL less as independent variables. Conclusion: In previous study, lymphoid follicles on the posterior pharyngeal wall and decreased lymphocyte count were reported as influenza‐specific findings. Both were confirmed with high specificity in our study, indicating that both would be useful when patients with influenza‐like symptoms were false‐negative for the rapid antigen test. [ABSTRACT FROM AUTHOR]

Maoto, a traditional kampo medicine, has been clinically prescribed for influenza infection and is reported to relieve symptoms and tissue damage. In this study, we evaluated the effects of maoto as an herbal multi-compound medicine on host responses in a mouse model of influenza infection. On the fifth day of oral administration to mice intranasally infected with influenza virus [A/PR/8/34 (H1N1)], maoto significantly improved survival rate, decreased viral titer, and ameliorated the infection-induced phenotype as compared with control mice. Analysis of the lung and plasma transcriptome and lipid mediator metabolite profile showed that maoto altered the profile of lipid mediators derived from ω-6 and ω-3 fatty acids to restore a normal state, and significantly up-regulated the expression of macrophage- and T-cell-related genes. Collectively, these results suggest that maoto regulates the host's inflammatory response by altering the lipid mediator profile and thereby ameliorating the symptoms of influenza. [ABSTRACT FROM AUTHOR]

Both GIM doctors in Japan and family medicine physicians in the US offer medical services in the clinic and hospital settings; however, family medicine doctors see patient of all ages. Application of Kampo therapies can have a positive effect on these conditions and offer additional treatment options for these complex patients (2). In conclusion, providing medical care having a viewpoint of Kampo medicine or integrative medicine is to be effective in various fields of GIM promoting overall patient well-being and offering an adjunct to current conventional medical therapies. [Extracted from the article]

The herbal medicine, maoto, has been traditionally prescribed to patients with influenza in Japan. To better understand the efficacy of maoto for the treatment of influenza, a randomized trial was conducted for comparison with oseltamivir or zanamivir. Adult patients with influenza symptoms, including fever, positive for quick diagnostic kit for influenza within 48 h of fever onset were assessed for enrollment. The data of 28 patients randomly assigned to maoto ( n = 10), oseltamivir ( n = 8), or zanamivir ( n = 10) were analyzed for the duration of fever (>37.5°C) and total symptom score from symptom cards recorded by the patient. Viral isolation and serum cytokine measurements were also done on days 1, 3, and 5. Maoto granules, a commercial medical dosage form, are made from four plants: Ephedra Herb, Apricot Kernel, Cinnamon Bark, and Glycyrrhiza Root. Median durations of fever of patients assigned maoto, oseltamivir, or zanamivir were 29, 46, or 27 h, respectively, significantly different for maoto and oseltamivir. No significant between-group differences were found in total symptom score among three groups. Viral persistent rates and serum cytokine levels (IFN-α, IL-6, IL-8, IL-10, and TNF-α) during the study period showed no differences among three groups. The administration of oral maoto granules to healthy adults with seasonal influenza was well tolerated and associated with equivalent clinical and virological efficacy to neuraminidase inhibitors. [ABSTRACT FROM AUTHOR]

Falling is a complex phenomenon that involves interaction of multiple risk factors. The authors analyzed factors related to falls in a geriatric hospital to elucidate interaction of multiple risk factors for falls in elderly inpatients. Subjects were 364 patients (mean age, 81.7; women 76.7%) who were aged 60 years and over and had been hospitalized for more than 6 months between April 2000 and March 2001. A signal detection model was used to identify baseline variables that best divided the sample into subgroups using incidence of falling as an outcome variable. During a follow-up period, 91 patients (25%) had at least one incident of fall. Out of 14 independent variables, a higher-order interaction consisting of six significant variables was identified. Consequently, the subjects were categorized into seven subgroups whose fall rate varied 5.7–80.9%. We found that the combination of non-bedridden state, dementia, and medication of tranquilizers or sleeping drugs was the highest fall rate (80.9%). Signal detection analysis is useful to identify the combination of multiple risk factors of falling, and applicable to develop prevention programs for each subgroups. [ABSTRACT FROM AUTHOR]

Type I interferon (IFN) possesses antiviral and antitumor activities and also having an immune regulatory effect, activating cellular immune response and upregulating several cytokines. Recent study has shown that type I IFN upregurates the dendritic cell production of IL-15 capable of activating natural killer cells and CD8+ memory T lymphocytes. However, it is still unknown if type I IFN induces IL-15 production in non-immune cells and if type I IFN affects IL-15 production in vivo. The present study investigated the effect of type I IFNs on IL-15 expression in hepatocellular carcinoma (HCC) cell lines in vitro and in patients with chronic hepatitis C in vivo. When three HCC cell lines, Huh7, HepG2, and JHH4 were cultured in vitro, IFN upregulation of IL-15 expression was observed at both the mRNA and protein levels. In experiments using Huh7 cells, upregulation of IL-15 expression occurred within 24 h of the start of IFN stimulation, and both IFN-α and -β dose-dependently increased IL-15 production in the range from 100 U/ml to 10,000 U/ml of concentration. IFN-β showed stronger activity in IL-15 production induction in vitro than IFN-α. For in vivo examination, sera were obtained from 21 chronic hepatitis C patients treated with IFN and 29 healthy individuals, and the serum IL-15 level was quantified by ELISA. The serum IL-15 level of chronic hepatitis C patients before IFN treatment was similar to that of the healthy controls and significantly increased only during the IFN administration period. These results confirm that IFN-α/β induce IL-15 production and also suggest that IL-15 may be associated with type I IFN-induced immune response. [ABSTRACT FROM AUTHOR]

Although bacille Calmette–Guérin (BCG) has been used worldwide as the only vaccine for tuberculosis, its protective efficacy in human adults is controversial. To investigate human immunological responses to Mycobacterium tuberculosis after BCG vaccination, we analyzed IFN-γ and IL-10 production by peripheral blood mononuclear cells (PBMC) from health-care workers five times throughout the year after BCG vaccination. Of 449 health-care workers, 36 (8.0%) were negative by the tuberculin skin test, and of these, 20 were vaccinated with BCG. Because all the subjects had received BCG vaccination as infants, the present vaccination was considered to be a revaccination. The cytokine responses of the vaccinated and control tuberculin skin-test-positive subjects ( n = 6) were followed at 0, 2, 4, and 8 weeks and at 12 months. The mean IFN-γ production by PBMC when cultured with purified protein derivative (PPD) gradually increased, reached a peak at week 8, and then declined until 12 months, with four exceptions who showed no IFN-γ elevation. The IFN-γ level of the vaccinated group at week 0 was significantly lower than that of the controls. The mean IL-10 production in response to PPD reached a peak at week 2, and then declined to its lowest point at week 8. These results indicate that the BCG vaccine can induce a type I cytokine response to M. tuberculosis in most tuberculin skin-test-negative adults at week 8, suggesting the immunological efficacy of vaccination. [ABSTRACT FROM AUTHOR]

We report the case of a 25-year-old male Japanese homosexual with primary human immunodeficiency virus (HIV)-1 infection and early stage syphilis. Approximately 60 days after HIV exposure by sex with another man, the patient abruptly had high fever, after which he experienced a variety of severe, prolonged symptoms such as painful oral mucosa ulcerations, rash, lymphadenopathy, splenomegaly, and a 5.5-kg weight loss. Serum lactate dehydrogenase and liver biochemical test values were elevated. Antibodies to HIV by both enzyme-linked immunosorbent assay (ELISA) and Western blot (WB) test were negative at the time of symptom onset, but serum HIV-1 RNA level was 1 585 000 copies/ml. Antibody seroconversions were found on day 9 after the onset of symptoms by ELISA and on day 16 by WB test, suggesting primary HIV infection. Within 2 weeks of starting highly active antiretroviral therapy (HAART), all symptoms except lymphadenopathy were resolved, and the serum HIV-1 RNA level dramatically decreased to 5011 copies/ml, eventually becoming undetectable by the standard method. The patient has remained asymptomatic for the 18 months since symptom resolution after HAART, and HIV-1 RNA remains undetectable. [ABSTRACT FROM AUTHOR]

Using first- and second-generation branched-DNA probe assays (1st- and 2nd-bDNA), we investigated the predictors of favorable clinical response to interferon (IFN) treatment in patients with chronic HCV viremia. A total of 122 patients (85 genotype 1b and 37 genotype 2a) with chronic HCV viremia received 24-week IFN-α treatment. Patients with sustained clearance of serum HCV RNA by polymerase chain reaction at six months after IFN treatment were defined as having a sustained response (SR). HCV RNA level was determined by 1st- and 2nd-bDNA assays prior to treatment. Mean HCV RNA level by 1st-bDNA was significantly higher in genotype 1b patients [5.4 × 106 HCV genome equivalent (Meq)/ml] than in genotype 2a patients (0.9 Meq/ml) ( P < 0.05). There was no significant difference between patients with these genotypes in the level by 2nd-bDNA (1b: 5.2 Meq/ml and 2a: 3.1 Meq/ml). SR was achieved by 43 (35.2%) of 122 patients. Mean HCV RNA levels by both the 1st- and 2nd-bDNA of SR patients (1.0 and 1.9 Meq/ml) were significantly lower than those of non-SR patients (5.3 and 6.0 Meq/ml) (both P < 0.05). The SR rate in genotype 2a patients (59.5%) was significant higher than in genotype 1b patients (24.7%) ( P < 0.05). Stepwise logistic regression analysis showed that HCV RNA level ≦1.0 Meq/ml by 2nd-bDNA (odds ratio = 7.6, compared to level > 1.0 Meq/ml, P < 0.05) was a significant predictive cutoff for SR. Using 2nd-bDNA, a significantly higher rate of SR was found in genotype 1b patients with level ≤1.0 Meq/ml (57.6%) than in those with level >1.0 Meq/ml (3.8%) ( P < 0.05). The SR rate of genotype 2a patients with level >1.0 Meq/ml (68.6%) was somewhat higher than for those with level ≤1.0 Meq/ml (52.4%). These findings suggested that, using 2nd-bDNA, a low HCV RNA level of ≦1.0 Meq/ml was the most favorable marker of successful IFN treatment and that patients with genotype 2a, even those with level >1.0 Meq/ml, had a high rate of SR to IFN treatment. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To determine the profile of cytokine secretion by CD4+ T helper (Th) cells in chronic hepatitis C virus (HCV) infection, we used flow cytometry to determine the percentage of interferon (IFN)-γ and interleukin (IL)-4 producing cells from CD4+ T lymphocytes in peripheral blood obtained from patients chronically infected with HCV. METHODS: Peripheral blood mononuclear cells isolated from 89 HCV infected subjects (22 asymptomatic carriers, 56 patients with chronic hepatitis, and 11 patients with liver cirrhosis) and 24 healthy controls were stained with surface CD4 and intracellular IFN-γ and IL-4. Serum soluble IL-2 receptor (sIL-2R) levels were analyzed by ELISA. RESULTS: The frequency of IFN-γ producing CD4+ cells in asymptomatic HCV carriers, patients with chronic hepatitis, and patients with liver cirrhosis were significantly higher than those of healthy controls (p < 0.01, respectively). In contrast, the percentages of IL-4-producing CD4+ cells were very low, and there were no significant correlations with disease progression. A significant elevation in serum sIL-2R levels was found in chronic HCV infection compared to healthy controls, and serum sIL-2R levels significantly correlated with the frequency of IFN-γ-producing cells. CONCLUSIONS: In HCV infected subjects, both serum sIL-2R and IFN-γ are increased in chronic HCV infection no matter the stage of disease, meaning they are no different in asymptomatic carriers, patients with chronic hepatitis, and patients with liver cirrhosis, and that Th1 cytokine or Th1 cells may participate in the pathogenesis of liver damage in chronic HCV infection. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the effects of long-term weight gain from the age of 20 on incidence of hyper-low-density-lipoprotein (LDL) cholesterolemia in the general population of Japanese people. Methods: We conducted a population-based retrospective cohort study using annual health checkup data for residents of Iki City, Nagasaki Prefecture, Japan. A total of 3179 adult (≥30 years old) men and women without hyper-LDL cholesterolemia at baseline, who underwent two or more health checkups were included in the analysis. Information on weight gain (≥10 kg) after 20 years of age was obtained using questionnaire. The outcome of this study was development of hyper-LDL cholesterolemia defined as LDL-cholesterol level ≥3.62 mmol/L and/or initiation of lipid-lowering medications. Results: During a mean follow-up period of 4.53 years, 665 of the 3179 participants developed hyper-LDL cholesterolemia (46.5/1000 person-years). The incidence of hyper-LDL cholesterolemia was higher in participants with a weight gain of ≥10 kg (55.3/1000 person-years) than among those with a weight gain of <10 kg (41.8/1000 person-years). This association remained statistically significant even after adjustment for age, sex, smoking, daily drinking, exercise, obesity, hypertension, and diabetes (multivariable hazard ratio 1.31, 95% confidence interval 1.08–1.58, p = 0.006). Conclusion: A weight gain of ≥10 after 20 years of age affected the development of hyper-LDL cholesterol regardless of age, sex, and obesity in a general population of Japanese. [ABSTRACT FROM AUTHOR]

Background: We investigated whether eating speed was associated with the incidence of diabetes in a Japanese general population. Methods: A total of 4853 Japanese individuals without diabetes at baseline were analyzed. Self-reported eating speed was categorized as slow, medium, and fast on the basis of questionnaire responses. The study outcome was the incidence of diabetes. Results: After an average follow-up period of 5.1 years, 234 individuals developed diabetes. The incidence of diabetes per 1000 person-years was 4.9 in the slow eating speed group, 8.8 in the medium eating speed group, and 12.5 in the fast eating speed group, respectively (*** p < 0.001 for trend). The HRs were 1.69 (95%CI 0.94–3.06) for the medium eating speed and 2.08 (95%CI 1.13–3.84) for the fast eating speed, compared to the slow eating speed (* p = 0.014 for trend) after adjustment for age, gender, smoking status, drinking, exercise, obesity, hypertension, and dyslipidemia. Conclusion: Faster eating speed increased a risk for the incidence of diabetes in a general Japanese population. [ABSTRACT FROM AUTHOR]

Pharmacological activities of the traditional Japanese herbal medicine (Kampo) are putatively mediated by complex interactions between multiple herbal compounds and host factors, which are difficult to characterize via the reductive approach of purifying major bioactive compounds and elucidating their mechanisms by conventional pharmacology. Here, we performed comprehensive compound, pharmacological and metabolomic analyses of maoto, a pharmaceutical-grade Kampo prescribed for flu-like symptoms, in normal and polyI:C-injected rats, the latter suffering from acute inflammation via Toll-like receptor 3 activation. In total, 352 chemical composition-determined compounds (CCDs) were detected in maoto extract by mass spectrometric analysis. After maoto treatment, 113 CCDs were newly detected in rat plasma. Of these CCDs, 19 were present in maoto extract, while 94 were presumed to be metabolites generated from maoto compounds or endogenous substances such as phospholipids. At the phenotypic level, maoto ameliorated the polyI:C-induced decrease in locomotor activity and body weight; however, body weight was not affected by individual maoto components in isolation. In accordance with symptom relief, maoto suppressed TNF-α and IL-1β, increased IL-10, and altered endogenous metabolites related to sympathetic activation and energy expenditure. Furthermore, maoto decreased inflammatory prostaglandins and leukotrienes, and increased anti-inflammatory eicosapentaenoic acid and hydroxyl-eicosapentaenoic acids, suggesting that it has differential effects on eicosanoid metabolic pathways involving cyclooxygenases, lipoxygenases and cytochrome P450s. Collectively, these data indicate that extensive profiling of compounds, metabolites and pharmacological phenotypes is essential for elucidating the mechanisms of herbal medicines, whose vast array of constituents induce a wide range of changes in xenobiotic and endogenous metabolism. Systems biology of traditional medicine: comprehensive analysis of a traditional Japanese medicine, maoto Pharmacological activities of Kampo, or traditional Japanese herbal medicine, are putatively mediated by complex interactions between the plant-derived compounds and endogenous molecules. To elucidate these properties, we performed comprehensive phytochemical profiling, and pharmacological and metabolomic analyses of maoto, an herbal remedy for flu-like symptoms. In the plasma of maoto-treated rats, we detected maoto-derived compounds, metabolites produced from the chemical transformation of maoto compounds by host metabolism and gut microbes, and endogenous metabolites that were appeared following maoto administration. In an acute inflammatory rat model, maoto ameliorated symptoms of sickness behavior, suppressed inflammatory cytokines, and extensively affected common metabolites and lipid mediators. These data suggest that the diverse chemical composition of Kampo broadly affects the host's endogenous metabolism and exerts specific pharmacological effects. [ABSTRACT FROM AUTHOR]