[The implementation and management of disease risk reduction claims in the European Union and the United States].

The improvement of food labeling can improve consumers' health awareness, reduce the burden of chronic diseases on the health and economy, and promote the development of the healthy food industry. Disease Risk Reduction Claim has been developed in European Union and the U.S. for over 20 years, with mature management methods and experience, but it is still lacking in China. Learning and drawing on the international management experience of food disease risk reduction claims can assist China to establish food disease risk reduction claims and improve the food health claims and labeling system.

Forkhead box M1 (FOXM1) transcription factor is a key oncogenic driver of aggressive human meningioma progression.

AIMS: Aggressive meningioma remains incurable with neither chemo- nor targeted therapies proven effective, largely due to unidentified genetic alterations and/or aberrant oncogenic pathways driving the disease progression. In this study, we examined the expression and function of Forkhead box M1 (FOXM1) transcription factor during meningioma progression. METHODS: Human meningioma samples (n = 101) were collected, followed by Western blotting, quantitative PCR, immunohistochemical and progression-free survival (PFS) analyses. For in vitro assays, FOXM1 was overexpressed or knocked-down in benign (SF4433 and SF4068) or malignant (SF3061 and IOMM-Lee) human meningioma cell lines respectively. For in vivo studies, siomycin A (a FOXM1 inhibitor)-pretreated or control IOMM-Lee cells were implanted subcutaneously in nude mice. RESULTS: FOXM1 expression was increased in higher grades of meningioma and correlated with the mitotic index in the tumour tissue. Moreover, FOXM1 was increased in recurrent meningioma compared with the matched primary lesions. The patients who had higher FOXM1 expression had shorter PFS. In the subsequent in vitro assays, knockdown of FOXM1 in malignant meningioma cell lines resulted in decreased tumour cell proliferation, angiogenesis and invasion, potentially via regulation of ß-catenin, cyclin D1, p21, interleukin-8, vascular endothelial growth factor-A, PLAU, and epithelial-to-mesenchymal transition-related genes, whereas overexpression of FOXM1 in benign meningioma cell lines had the opposite effects. Last, suppression of FOXM1 using a pharmacological inhibitor, siomycin A, decreased tumour growth in an in vivo mouse model. CONCLUSIONS: Our data demonstrate that FOXM1 is a key transcription factor regulating oncogenic signalling pathways in meningioma progression, and a promising therapeutic target for aggressive meningioma.

Association of exposure to secondhand smoke at home with early age at menarche in South Korea.

OBJECTIVES: The secular trend in age at menarche (AAM) has declined both worldwide and in Korea. Early AAM is associated with the risk of several diseases, reproductive capacity, and psychological problems. We aimed to investigate the relationship between secondhand smoke (SHS) exposure at home and early puberty onset using AAM in Korean adolescents. STUDY DESIGN: This is a retrospective cross-sectional study. METHODS: This study used data from the Korea Youth Risk Behavior Web-based Survey 2014-2015. We used the mean AAM (12.2 years) as a determinant of early AAM. After the exclusion of girls without menarche or who did not respond, the total population comprised 63,618 participants. We categorized AAM as 'early' and 'average or late.' Adolescents with SHS exposure were assigned to the 'never exposed,' 'light exposure,' and 'heavy exposure' groups. Multiple logistic regression analyses were performed. RESULTS: We observed a positive association, approximately 1.12 times, between early AAM and high SHS exposure (odds ratio [OR], 1.12; 95% confidence interval [CI], 1.05-1.19). Girls who started smoking before the age of 12 years (OR, 1.68; 95% CI, 1.41-1.99) showed a stronger association with early AAM than non-smokers. Active smoking showed a stronger association with early AAM. Never smokers with high SHS exposure at home were 1.13 times likelier to have an early AAM (OR, 1.13; 95% CI, 1.05-1.22) than those without SHS exposure. CONCLUSIONS: In addition to active smoking, SHS may also be a risk factor for early AAM. Education aimed at active and secondhand smoking prevention is needed to protect children against early AAM.

Delayed viral suppression during antiviral therapy is associated with increased hepatocellular carcinoma rates in HBeAg-positive high viral load chronic hepatitis B.

The treatment option in chronic hepatitis B (CHB) patients with persistent low-level viremia despite entecavir or tenofovir monotherapy is unclear. This study investigated the development of hepatocellular carcinoma (HCC) or cirrhosis in hepatitis B e antigen (HBeAg)-positive high viral load CHB patients, according to the time needed to achieve complete viral suppression. A total of 325 HBeAg-positive CHB patients with high viral load who were recently started on antiviral therapy with entecavir or tenofovir were included. The enrolled patients were divided into 2 groups with 4 separate criteria based on the time needed to achieve complete viral suppression: within 1, 2, 3 or 4 years of therapy initiation. The outcomes were development of HCC and cirrhosis. The cumulative incidence of HCC was significantly higher in patients failing complete viral suppression within 1 year (hazard ratio (HR), 4.54; 95% confidence interval (CI), 1.03-19.93; P = .045) or 2 years (HR, 3.38; 95% CI, 1.24-9.23; P = .018), than patients who achieved complete viral suppression within 1 or 2 years, respectively. Cumulative incidence of cirrhosis was also significantly higher in patients failing suppression within 1 year (HR, 1.95; 95% CI, 1.04-3.66; P = .037) or 2 years (HR, 2.44; 95% CI, 1.41-4.22; P = .001). When the time for achieving viral suppression exceeded 2 years, the cumulative incidence of HCC or cirrhosis was not different regardless of viral suppression. Complete hepatitis B virus suppression within 2 years of antiviral therapy initiation is associated with risk reduction in HCC or cirrhosis development.

The gamma-glutamyl transferase to platelet ratio and the FIB-4 score are noninvasive markers to determine the severity of liver fibrosis in chronic hepatitis B infection.

Objective Noninvasive liver fibrosis evaluation is an important issue in chronic hepatitis B infection, and may be assessed using transient elastography (Fibroscan) or with blood markers. We compared the value of Fibroscan with that of a panel of routine serum markers. Materials and methods We recruited 278 chronic hepatitis B patients who underwent Fibroscan and HBV DNA testing. Fibroscan assessments were made, and blood taken for the measurement of the gamma-glutamyl transferase (GGT) to platelet ratio (GPR), platelet count, aspartate aminotransaminase (AST), alanine aminotransaminase (ALT), international normalised ratio (INR), total cholesterol, trigylcerides, bilirubin, mean platelet volume (MPV), AST to platelet ratio index (APRI) and neutrophil to lymphocyte ratio. Results A fibrosis index based on four factors (FIB-4) and GPR were higher and platelets were lower in mild liver fibrosis than in non-liver fibrosis. GGT, AST, ALT, INR, MPV, APRI, FIB-4, GPR, and NLR were higher, and platelet and cholesterol were lower in severe liver fibrosis than in mild liver fibrosis. Elevated GPR (Odds ratio 95% CI 9.1 [1.66-50.0] p = 0.011) and FIB-4 (2.3 [1.2-4.2], p = 0.01) were associated with greater risk of liver fibrosis. The areas under the curve (AUC) were for GPR 0.84 at a cut-off of 0.299 and for FIB-4 0.82 at cut-off 1.571. Conclusions FIB-4 and GPR may be useful blood markers for evaluating the severity of liver fibrosis in chronic hepatitis B patients. Further prospective study is required to validate these noninvasive blood markers in a clinical practice.

[Magnetic resonance imaging findings and differential diagnosis of renal epithelioid angiomyolipoma comparing with renal no-epithelioid angiomyolipoma].

Objective: To investigate whether MRI findings can differentiate renal epithelioid angiomyolipoma (EAML) from renal no-epithelioid (typical) angiomyolipoma. Methods: A total of 44 patients were collected from General Hospital of PLA.These cases were obtained from January 2009 to June 2015.To retrospectively analyze these mainly MRI findings among 12 cases of EAML (age from 27 to 61 years, male 2 cases, female 10 cases, mean age was 46.7 years); 32 cases of renal no-epithelioid AML (age from 34 to 70 years old, male 9 cases, female 23 cases, mean age was 53.4 years old) as case control study. MRI findings included gender, T(2)WI, the signal on gross fat, pseudocapsle, necrosis or cystic degeneration, DWI, hemorrhage and the peak in three phases of dynamic enhancement.All data were analyzed statistically using SPSS version 19.0 (IBM, Armonk, NY, USA). χ(2) test and a single order chart were used to analyze the enumeration data. Results: Comparing with renal no-epithelioid angiomyolipoma, minimal fat, necrosis or cystic degeneration and hemorrhage were statistical significance. P values were 0.002, 0.007, 0.025, respectively.Gender, solid components of tumors on T(2)WI, the signal of DWI, pesudocapsule and the peak of enhancement had no statistical significance. P values were 0.863, 0.053, 0.479, 0.460, respectively. Conclusion: Comparing with renal no-epithelioid AML, necrosis or cystic degeneration and hemorrhage with minimal fat are characteristic MRI findings of EAML.

[Atypical MRI appearance of hepatic focal nodular hyperplasia].

OBJECTIVE: To explore the atypical MRI findings of focal nodular hyperplasia (FNH) of the liver. METHODS: Retrospective analyses were conducted for 13 cases (10 males and 3 females) confirmed pathologically as FNH after surgery or biopsy with liver MRI examination from January 2012 to June 2015 in PLA General Hospital. RESULTS: There were 22 focal lesions in 12 cases, and diffuse pattern in 1 case. In the 22 focal lesions, there were 3 lesions with fatty change, 1 lesion with hemorrhage, 7 lesions with pseudo-capsule, regarding to dynamic contrast-enhanced pattern: 12/22 lesions with gradually increasing enhancement, 3/22 lesions with rapid wash-in and wash-out, and 7/22 lesions with rapid wash-in and slow wash-out. The hepatocyte-specific agent examinations were performed in 20/22 lesions, and 20/20 lesions showed iso- to hyper-intensity to the liver parenchyma in the hepatocyte phase.There was 1 case (female) showing diffuse lesions with obvious fatty change, and all the lesions took up the hepatocyte-specific agent in hepatocyte phase. CONCLUSION: The atypical focal nodular hyperplasia often occurs in middle age males and could demonstrate fatty change, hemorrhage, pseudo-capsule, various enhancement patterns. And when the FNH showed atypical routine MRI findings, the use of the hepatocyte-specific agent could facilitate the diagnosis.

Comparison of the efficacies of oral iron and pramipexole for the treatment of restless legs syndrome patients with low serum ferritin.

BACKGROUND AND PURPOSE: It is not clear which is preferred between iron supplement and a dopamine agonist in the treatment of restless legs syndrome (RLS) with iron deficiency. The efficacies of oral iron supplementation and pramipexole for treatment of RLS with low-normal serum ferritin (15-50 ng/ml) were compared. METHODS: Thirty RLS patients who took either oral iron or pramipexole for 12 weeks and were followed at 2, 4, 8 and 12 weeks after treatment commencement were enrolled. Severities of RLS symptoms were assessed using the international RLS study group rating scale for severity (IRLS) at every visit. Treatment response was defined as a decrease in IRLS score of at least 50% from baseline. RESULTS: The 30 subjects were assigned equally to an iron or pramipexole group. At baseline, IRLS scores and serum ferritin levels were similar between these two groups. After 12 weeks, IRLS scores were lower than those at baseline in both groups (iron -9.1 ± 7.07, P < 0.001; pramipexole -8.7 ± 8.31, P = 0.001) and similar between the two groups. Changes in IRLS scores from baseline were similar between the two groups at each visit. The response rates of the groups were identical at 46.7%. CONCLUSIONS: Pramipexole was not different from oral iron in terms of efficacy and improvement speed in RLS patients with a low-normal serum ferritin, but response rate of either oral iron or pramipexole alone was moderate. Some proportion of RLS patients with iron deficiency might benefit from combined use of oral iron and dopamine agonists.

Efficacy of palonosetron for the prevention of postoperative nausea and vomiting: a randomized, double-blinded, placebo-controlled trial.

BACKGROUND: The aim of this study was to evaluate the efficacy of palonosetron, the latest 5-HT3 receptor antagonist, for the prevention of postoperative nausea and vomiting (PONV) during the first 72 h after operation. METHODS: In this randomized, double-blinded, placebo-controlled study, 204 healthy inpatients who were undergoing elective surgery with general anaesthesia were enrolled. Patients were divided into two groups: the palonosetron group (palonosetron 0.075 mg i.v.; n=102) and the placebo group (normal saline i.v.; n=102). The treatments were given after the induction of anaesthesia. The incidence of nausea, vomiting, severity of nausea, and the use of rescue anti-emetics during the first 72 h after surgery were evaluated. RESULTS: The incidence of PONV was lower in the palonosetron group compared with the placebo group during the 0-24 h (33% vs 47%) and 0-72 h period (33% vs 52%) (P<0.05), but not during the 24-72 h postoperative period (6% vs 11%). The incidence of nausea was also significantly lower in the palonosetron group than in the placebo group during the 0-24 and 0-72 h period (P<0.05), but not during the 24-72 h postoperative period. However, there were no significant differences in the incidence of vomiting, and the use of rescue anti-emetics between the groups. CONCLUSIONS: Palonosetron 0.075 mg i.v. effectively reduced the incidence of PONV during the first 72 h after operation, with most of the reduction occurring in the first 24 h.

First report: Robotic pelvic exenteration for locally advanced rectal cancer.

AIM: The aim of this study was to present the feasibility and surgical outcome of robotic en bloc resection of the rectum and with prostate and seminal vesicle invaded by rectal cancer. METHOD: The details of three consecutive cases involving male patients in their forties, with locally invasive low rectal cancers are presented. The da Vinci robotic system was used by experienced colorectal and urological surgeons to perform en bloc resection of the rectum, prostate and seminal vesicles. RESULTS: In the first case, coloanal and vesico-urethral anastomoses were performed, and the second included an end colostomy and vesico-urethral anastomosis. The bladder and bulbar urethra were also removed en bloc in the third case, with robotic intracorporeal ileal conduit formation and end colostomy. There was no major complication postoperatively. In the second patient there was a minor leakage at the vesico-urethral anastomosis. The third was readmitted the following week with a urinary infection which settled with intravenous antibiotics. In the first case, the circumferential resection margin was microscopically positive but the patient is currently free of recurrence after 14 months. In the second and third cases, all margins were clear. CONCLUSION: This the first report of the use of the da Vinci robotic system for pelvic exenteration in patients with locally advanced rectal cancer invading the prostate and seminal vesicles. The robot may have a potential role in selected patients requiring exenterative pelvic surgery particularly in men.

Geographic information system-coupling sediment delivery distributed modeling based on observed data.

Spatially distributed sediment delivery (SEDD) models are of great interest in estimating the expected effect of changes on soil erosion and sediment yield. However, they can only be applied if the model can be calibrated using observed data. This paper presents a geographic information system (GIS)-based method to calculate the sediment discharge from basins to coastal areas. For this, an SEDD model, with a sediment rating curve method based on observed data, is proposed and validated. The model proposed here has been developed using the combined application of the revised universal soil loss equation (RUSLE) and a spatially distributed sediment delivery ratio, within Model Builder of ArcGIS's software. The model focuses on spatial variability and is useful for estimating the spatial patterns of soil loss and sediment discharge. The model consists of two modules, a soil erosion prediction component and a sediment delivery model. The integrated approach allows for relatively practical and cost-effective estimation of spatially distributed soil erosion and sediment delivery, for gauged or ungauged basins. This paper provides the first attempt at estimating sediment delivery ratio based on observed data in the monsoon region of Korea.

Identification of metabolically active proteobacterial and archaeal communities in the rumen by DNA- and RNA-derived 16S rRNA gene.

AIMS: To gain new insights into the metabolic contribution of bacterial group in the rumen. METHODS AND RESULTS: Both DNA- and RNA-derived bacterial 16S ribosomal materials from bovine rumen contents were used as the template for bacterial community and analyse microbiota by three methods namely custom phylogenetic microarray, quantitative real-time PCR and denaturing gradient gel electrophoresis techniques. Bacterial analysis showed that genera affiliating with the Proteobacteria apparently made a greater metabolic contribution to rumen function than their population sizes indicated. Analysis of another rumen microbial group, the methanogens, using clone libraries for the expressed methyl coenzyme reductase subunit A (mcrA) revealed that an uncultivated methanogen clade contributes one-third of RNA-derived mcrA sequences based on a limited number of clones analysed. These uncultivated methanogen species were not observed in the mcrA gene library based on the DNA-derived sequences. CONCLUSIONS: The comparison of results obtained from DNA- and RNA-derived materials suggests that some of the Proteobacteria and novel methanogen species appeared to be low in abundance in the rumen maintained on grain-based diets might play a greater role in rumen metabolism. SIGNIFICANCE AND IMPACT OF THE STUDY: These studies provide the first report to compare high-throughput analysis of bacterial 16S rRNA genes from DNA- and RNA-derived materials to indicate differences that species make to community structure and metabolic activity.

Effects of dexmedetomidine on inflammatory responses in patients undergoing laparoscopic cholecystectomy.

BACKGROUND: Dexmedetomidine has been shown to reduce pro-inflammatory cytokine levels in rats with sepsis and in severely ill patients. The aim of this study was to document the effects of dexmedetomidine on inflammatory responses during and after surgery. MATERIALS AND METHODS: Patients undergoing laparoscopic cholecystectomy were enrolled. After induction of anaesthesia, patients in the dexmedetomidine group (n = 24, group D) received a loading dose of dexmedetomidine (1.0 µg/kg), followed by infusion of dexmedetomidine at 0.5 µg/kg/h. A saline-treated group (n = 23, group S) served as a control. Intraoperative mean arterial pressure (MAP), heart rate (HR), and amount of rescue analgesic administered as post-anaesthetic care were compared between the groups. The pro-inflammatory cytokines tumour necrosis factor (TNF)-α, interleukin (IL)-1ß, and IL-6, and anti-inflammatory cytokines IL-4 and IL-10 were quantified by sandwich enzyme-linked immunoassay at three times: after anaesthesia induction (T0), at the end of peritoneal closure (T1), and 60 min after surgery (T2). The C-reactive protein (CRP) level and leukocyte count were measured on post-operative day 1. RESULTS: At time points T1 and T2, the IL-1ß, TNF-α, and IL-10 levels were lower in group D than in group S (P < 0.05). The CRP level and leukocyte count on post-operative day 1 were also lower in group D (P < 0.05), as were intraoperative MAP, HR, and amount of rescue analgesic administered after surgery. CONCLUSIONS: Dexmedetomidine administration during surgery reduced intraoperative and post-operative secretion of cytokines, as well as post-operative leukocyte count and CRP level.

The immunomodulatory role of esmolol in patients undergoing laparoscopic gastrectomy due to gastric cancer.

Esmolol has a beneficial effect on the T helper 1/T helper 2 balance in patients with heart failure. The aim of this study was to investigate the immunomodulatory role of esmolol during and after surgery. Patients undergoing laparoscopic gastrectomy due to gastric cancer were enrolled. Patients in the esmolol group (n = 15) received esmolol during surgery, and a saline-treated group (n = 14) served as a control. Cytokines were quantified by sandwich enzyme-linked immunoassays before, during and after surgery. The esmolol group was associated with higher ratios of interferon-γ/interleukin-4 (T helper 1/T helper 2 signature cytokines) than the saline group during (2.36 vs 0.57, respectively, p = 0.041) and after (5.79 vs 0.69, respectively, p = 0.033) surgery. The postoperative increase in interleukin-6 was attenuated in the esmolol group, and the C-reactive protein level on postoperative day 1 was significantly lower in the esmolol group than in the saline group (mean (SD) 26.2 (18.3) mmol.l(-1) vs 56.8 (44.3) mmol.l(-1), p = 0.021). Our findings suggest that esmolol played an immunomodulatory role and mitigated the postoperative inflammatory response in patients under surgical and anaesthetic stress.

Estimating the GIS-based soil loss and sediment delivery ratio to the sea for four major basins in South Korea.

This paper describes a sediment delivery ratio (SDR) using the Geographic Information System (GIS)-based Revised Universal Soil Loss Equation (RUSLE), to calculate the soil loss and sediment rating curve (SRC) basis of measured data in the six basins of Four Rivers, South Korea. The data set for calculating SDR was prepared during 3 years from 2008 to 2010. Mean soil loss in the six basins of Four Rivers was 515-869 t km(-2) yr(-1) and mean specific sediment yield (SSY) was 20-208 t km(-2) yr(-1) with basin size. The SDR ranged from 0.03 to 0.33 in the six rivers. Most sediment flows in the monsoon period from June to September (mean Max.: >97%; mean Min.: >84%), but SDR is lower than those of similar continental river basins. This is due to environmental factors, for example rainfall characteristics and associated run-off, soil characteristics and cultivated patterns with increasing basin size. This research provides the first application of SDR based on the observed field data in South Korea.

The relaxant effect of ginseng saponin on the bladder and prostatic urethra: an in vitro and in vivo study.

AIM: To assess the effects of ginseng saponin on relaxation of the bladder and prostatic urethra and to determine its mechanism of action. MATERIALS AND METHODS: For the in vitro study, prostatic urethra muscle strips were harvested from 18 male New Zealand rabbits. The strips were mounted in organ baths and connected to force displacement transducers. After stabilization, maximal tissue contractions were obtained by the application of phenylepinephrine to the urethra strips, and a dose-response curve for ginseng saponin was constructed (10(-6)-10(-2)M). After pretreatment of urethra strips with N-nitro-L-arginine methyl ester (L-NAME), another dose-response curve for ginseng saponin was constructed. For the in vivo study, we used adult male Sprague-Dawley rats divided into three groups [control, partial bladder outlet obstruction (PBOO) and saponin-fed groups], and we monitored the vesical pressure (P(ves)) and urethral perfusion pressure (UPP). RESULTS: The ginseng saponin induced a significant dose-dependent relaxant effect on the prostatic urethra strips. A significant relaxant effect of ginseng saponin was observed from 10(-3)M, and ginseng saponin significantly relaxed urethra strips by 50.2 ± 20.26% at 10(-2)M. The relaxant effect was partially inhibited with L-NAME pretreatment. In the in vivo study, the change in UPP between baseline and relaxation was significantly higher in the saponin group than in the control or PBOO group (p < 0.001). The saponin group showed a significantly lower baseline P(ves) than the PBOO group. CONCLUSIONS: We observed a significant relaxation effect of ginseng saponin on the bladder and prostatic urethra in both in vitro and in vivo studies. The mechanism by which ginseng saponin induces relaxation appears to involve the nitric oxide/nitric oxide synthase pathway.

Elevated levels of macrophage migration inhibitory factor in women with metabolic syndrome.

Metabolic syndrome is a complex clinical disorder characterized by obesity, a disturbance of glucose metabolism, dyslipidemia, and hypertension, leading to increased cardiovascular risk. Macrophage migration inhibitory factor (MIF) is a proinflammatory cytokine produced both by innate immune cells and by adipocytes, and it plays an important role in inflammatory and cardiovascular diseases. The goal of this study was to evaluate the expression of circulating MIF in patients with metabolic syndrome. A study was conducted involving 172 persons who attended the Jeju National University Hospital Health Promotion Center. Among the 172 subjects, 88 patients with metabolic syndrome and 84 healthy control subjects were included. Serum MIF levels were considerably higher in patients with metabolic syndrome than in healthy subjects (mean±SEM, 1413.0-pg/ml±102.6 vs. 1077.0-pg/ml±-91.3, p=0.016). Among the metabolic syndrome patients, MIF levels were significantly increased in women (1403.0-pg/ml±114.2 vs. 921.3 pg/ml±117.3, p=0.005), but not in men. Even after further linear regression adjustment for age and body mass index, the expression of MIF for women with metabolic syndrome was still clearly elevated when compared to healthy subjects (p=0.011). Circulating MIF concentrations showed a gender disparity between healthy and metabolic syndrome subjects. An elevation of systemic MIF in women with metabolic syndrome may contribute to pathogenesis of metabolic syndrome or to the development of metabolic syndrome-related diseases, such as atherosclerosis and type 2 diabetes mellitus.

Comparative clinical manifestations of IgG4- related and IgG4-negative primary tubulointerstitial nephritis.

AIMS: To evaluate the prevalence of IgG4-related tubulointerstitial nephritis (TIN) and compare the clinical manifestations of IgG4-related and IgG4-negative primary TIN. METHODS: Of 5,174 renal biopsies obtained between January 1996 and February 2010, 46 were positive for primary TIN without other kidney disease. Biopsy tissues were lost for 2 patients. The remaining 44 samples were assayed by immunoperoxidase staining with monoclonal mouse antibody to human IgG4. RESULTS: Of the 44 patients with primary TIN, 12 (27%) were identified as IgG4+ plasma cells/HPF ≥ 10 and 32 (73%) as < 10. Estimated glomerular filtration rate (eGFR) was lower and proteinuria was higher in patients with IgG4+ plasma cells/ HPF ≥ 10 (p < 0.05). No other parameter such as age; gender distribution; incidence of hypertension, diabetes mellitus, drug history, pyuria; concentrations of hemoglobin and alkaline phosphatase; or kidney size differed significantly. Of the 44 patients with primary TIN, 25 (57%) were identified as IgG4-positive (IgG4+ plasma cells/HPF ≥ 1) and 19 (43%) as IgG4-negative. The two groups did not differ in age; gender distribution; incidence of hypertension, diabetes mellitus, drug history, pyuria, or proteinuria; concentrations of hemoglobin and alkaline phosphatase; eGFR; or kidney size. The improvement rate, however, was significantly higher in IgG4-positive than in IgG4-negative patients (p = 0.045). Of the 25 IgG4- positive and 19 IgG4-negative patients, 18 and 13, respectively, were treated, and 18 and 7, respectively, improved (p = 0.002). The median number of IgG4-positive plasma cells/HPF in the former group was 8 (range 1 - 90). The number of IgG4-positive plasma cells was significantly associated with the degree of proteinuria (r = 0.471, p = 0.018) and age (r = 0.529, p = 0.007). CONCLUSION: Routine IgG4 staining is necessary in patients with primary TIN. Early treatment is also important in patients with IgG4-related primary TIN.

Early-onset Charcot-Marie-Tooth patients with mitofusin 2 mutations and brain involvement.

Mutations of the mitofusin 2 (MFN2) gene have been reported to be the most common cause of the axonal form of Charcot-Marie-Tooth disease (CMT). A prospective brain MRI study was performed on 18 early-onset CMT patients with MFN2 mutations, and a high frequency (39%) of brain abnormalities was found. Early-onset patients showed multiple scattered or confluent brain lesions that involved gray matter as well as white matter. Patterns of brain involvement in early-onset patients differed from those of late-onset patients and other hereditary peripheral neuropathies. In addition, one CMT patient demonstrated a brain lesion before the development of peripheral neuropathy.