Additionally, using in vivo microdialysis, we measured the impact of acute and multiple 1BnTIQ administrations on l-DOPA-induced dopamine release in the striatum. These data were compared with results from behavioral tests in which we measured the effect of 1BnTIQ and l-DOPA on locomotor activity. Finally, we determined the effect of the repeated administration of 1BnTIQ on the l-DOPA-induced elevation of caspase-3 activity in the hippocampus. An ex vivo neurochemical study indicated that both acute and chronic 1BnTIQ injections strongly inhibited l-DOPA-induced increases in the concentration of dopamine and all of its metabolites in dopaminergic structures. In contrast, in vivo microdialysis studies suggested that the differences in 1BnTIQ’s effects are dependent on the type of treatment. A single dose of 1BnTIQ intensified the elevation of dopamine release induced by l-DOPA administration , while multiple administrations of 1BnTIQ significantly enhanced the basal dopamine levels while partially diminishing the effects of l-DOPA injection . Additionally, we found that chronic administration of 1BnTIQ completely blocked the l-DOPA-induced increase in caspase-3 activity in the hippocampus. These findings indicate that both acute and chronic administrations of 1BnTIQ disturbs the behavioral and biochemical effects of l-DOPA in the rat. The data presented from ex vivo and in vivo studies clearly suggest that 1BnTIQ’s effects may be connected with the inhibition of DAT and/or COMT activity in the brain. Furthermore, elevated endogenous levels of 1BnTIQ may pose a serious risk in PD patients undergoing l-DOPA therapy.Environmental factors and endogenously produced toxins, such as 1-benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ), are considered to be involved in the pathogenesis of Parkinson’s disease (PD). In this study, we investigated the impact of single and multiple 1BnTIQ (25 and 50 mg/kg i.p.) administration on  Control rats were treated with the appropriate vehicle. Rats were killed by decapitation 2 h after last drug injections and different brain structures were dissected for analysis. The experiments were carried out between 9:00 and 16:00.1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ) was administered at a dose of 25 or 50 mg/kg intraperitoneally (i.p.) once or chronically for 14 consecutive days. In the mixed group, All experimental procedures were carried out in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals and were granted an approval from the Bioethics Commission as compliant with Polish Law. All experimental procedures were approved by the Local Bioethics Commission of the Institute of Pharmacology, Polish Academy of Sciences in Kraków.l-DOPA  was obtained commercially. The compounds were dissolved in a 0.9 % NaCl solution.1-Benzyl-1,2,3,4-tetrahydroisoquinoline (1BnTIQ hydrochloride) was synthesized (according to Cannon and Webster l-DOPA (100 mg/kg i.p.) was given acutely 15 min after 1BnTIQ administration. Each group consisted of five to six animals.Locomotor activity was assessed in actometers  linked on-line to a compatible IBM PC. Each cage (43 × 44 × 25 cm) perimeter was lined with an array of 15 × 15 photocell beams located 3 cm from the floor surface as reported previously  were assayed by high-performance liquid chromatography (HPLC) with electrochemical detection (Hewlett Packard 1049A). The tissue samples were weighed and homogenized in ice-cold 0.1 M perchloroacetic acid containing 0.05 mM ascorbic acid. After centrifugation , the supernatants were filtered through RC 58 0.2-im cellulose membranes . The HP 1050 chromatograph  was equipped with C18 columns. The electrochemical cell potential was 800 mV. The mobile phase consisted of 0.05 M citrate–phosphate buffer (pH 3.5), 0.1 mM EDTA, 1 mM sodium octyl sulfonate, and 3.5 % methanol. The flow rate was maintained at 1 ml/min. DA and its metabolites were quantified by chromatograph peak height in comparison with standards run on the day of analysis. Each group consisted of five to six animals.Two hours after the last 1BnTIQ injection, rats were killed by decapitation, and the substantia nigra and striatum were immediately dissected. The tissue was frozen on dry ice (−70 °C) until use in a biochemical assay. The levels of DA and its metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), 3-methoxytyramine (3-MT), and homovanillic acid (HVA), as well as the l-DOPA (100 mg/kg i.p.) was given once, 15 min after last 1BnTIQ administration. Rats were decapitated 3 h after the last injection. The assessment of caspase-3 activity was performed as previously described , which is preferentially cleaved by caspase-3. The absorbance of Ac-DEVD-pNA was monitored continuously over 60 min with a Multiskan Spectrum Microplate Spectrophotometer . Data were analyzed with Ascent software, normalized to the absorbance in vehicle-treated cells, and expressed as the percent of control ± SEM of three to four independent experiments. The absorbance of blanks, acting as no-enzyme controls, was subtracted from each value.Caspase-3 activity was determined according to Nicholson et al. . 1BnTIQ 2, 1 mM MgCl2, 0.3 mM NaH2PO4, and 1.7 mM Na2HPO4 (pH 7.4) at a flow rate of 1.5 μl/min with a microinfusion pump . Samples were collected from freely moving rats in 20-min intervals after a 3-h wash-out period. 1BnTIQ was injected (acute or chronic: for 14 consecutive days) in a 50 mg/kg i.p. and dialysis samples were collected for 180 min. In the mixed groups, l-DOPA (100 mg/kg i.p.) was administered 40 min after the last 1BnTIQ injection. All dialysates were immediately frozen on dry ice (−70 °C) until use in a biochemical assay.Rats were anesthetized with ketamine (75 mg/kg) and xylazine (10 mg/kg) and secured in a stereotaxic frame . Vertical microdialysis guide cannulas  were implanted into the striatum (STR) according to the following stereotaxic coordinates: A/P +1.0, L/M +2.5, and V/D –3.5 mm from bregma and dura (G. Paxinos and C. H. Watson). 7 days after surgery, microdialysis probes were inserted into the cannulas, and the striatum was perfused with an artificial cerebrospinal fluid (aCSF) consisting of 140 mM NaCl, 2.7 mM KCl, 1.2 mM CaClLevels of DA and its extraneuronal metabolite, 3-MT, were assayed in dialysates (20 μl) using HPLC with electrochemical detection as described above.Chromatographic data were processed using the ChemStation computer program . DA and its metabolites were quantified by chromatograph peak height in comparison with standards run on the day of analysis. At the end of the experiment, frozen brains were examined histologically for correct probe placement. Each group consisted of six animals.A two-way analysis of variance (ANOVA) for repeated measures was used to analyze the results of the behavioral test (locomotor activity). Differences between control and experimental groups were assessed with Duncan’s post hoc test. Data from the microdialysis study (acute 1BnTIQ treatment) were analyzed by a one-way ANOVA for repeated measures. The results from experiments evaluating chronic 1BnTIQ administration were analyzed by a two-way ANOVA for repeated measures, followed by (if significant differences arose) Duncan’s post hoc test.n = 6).The results of the biochemical experiments were analyzed by a two-way ANOVA, followed, when appropriate, by Duncan’s post hoc test. The total catabolism rate of DA was calculated from the ratio of the concentration of the final DA metabolite, HVA, to the concentration of DA and was expressed as a catabolism rate index ([HVA]/[DA] × 100), as previously described in detail  produced a significant increase in the horizontal locomotor activity of rats (P < 0.05) from 40 to 60 min. In the same time frame, 1BnTIQ given alone (25 mg/kg i.p.) did not change locomotor activity  locomotor activity only during the first 10 min of measurement  produced a significant increase in horizontal locomotor activity (P < 0.01) from 30 to 70 min. In the mixed group, 1BnTIQ completely antagonized l-DOPA-induced hyperactivity.The chronic (14-day) administration of 1BnTIQ at a low dose of 25 mg/kg i.p. reduced (l-DOPA administration (100 mg/kg i.p.) was completely antagonized by co-administration of 50 mg/kg 1BnTIQ following chronic treatment  and l-DOPA  on the DA concentration in the substantia nigra . Duncan’s post hoc analysis demonstrated that administration of l-DOPA strongly increased the level of DA . In contrast, both concentrations of 1BnTIQ produced reductions in DA concentration. 1BnTIQ co-administered with l-DOPA completely antagonized l-DOPA-induced increases in DA (the DA level remained just below the control level) , as well as l-DOPA  on the concentration of DOPAC in the substantia nigra . The post hoc analysis indicated that acute administration of l-DOPA produced massive elevation of DOPAC concentration , and this effect was strongly blocked by both concentrations of 1BnTIQ  and l-DOPA  treatment on the levels of 3-MT, as well as an interaction between 1BnTIQ and l-DOPA  ; 1BnTIQ completely antagonized this effect  and l-DOPA  had a significant effect on the HVA concentration in the substantia nigra . The post hoc analysis showed that l-DOPA administration strongly increased the level of HVA , and this effect was weakened by both concentrations of 1BnTIQ  also had a significant effect on the rate of DA metabolism, measured as [HAV]/[DA]  or interaction between 1BnTIQ and l-DOPA . Duncan’s post hoc analysis demonstrated that acute doses of l-DOPA strongly increased the rate of DA metabolism , and a similar effect was observed when 1BnTIQ (50 mg/kg) was given in combination with l-DOPA.F = 26.7, P < 0.01) and l-DOPA  treatments on the DA concentration . Duncan’s post hoc test showed that acute dose of l-DOPA increased the DA concentration . Both concentrations of 1BnTIQ completely antagonized this effect  and l-DOPA  treatments on DOPAC levels, as well as an interaction between 1BnTIQ and l-DOPA  . This l-DOPA-induced effect was completely blocked by 1BnTIQ administration  or l-DOPA  on 3-MT concentration in the striatum . Duncan’s post hoc test showed that an acute dose of l-DOPA or 1BnTIQ (50 mg/kg) reduced the levels of 3-MT (approximately 30 %). A similar effect was observed in the mixed groups.A two-way ANOVA further revealed a significant effect of acute administration of 1BnTIQ  and l-DOPA  treatments on HVA levels, as well as an interaction between 1BnTIQ and l-DOPA . The post hoc analysis showed that treatment with l-DOPA induced a strong elevation in the level of HVA (approximately 900 %). This effect was partially antagonized by 1BnTIQ administration  on the rate of DA metabolism measured as [HAV]/[DA]  or interaction between 1BnTIQ and l-DOPA . Duncan’s post hoc analysis demonstrated that acute administration of l-DOPA increased the rate of DA metabolism ; the strongest effect was observed when 1BnTIQ (50 mg/kg) was administered concomitantly with l-DOPA (approximately 500 %)  on the DA concentration  on the level of DA. There was no significant interaction between the chronic administration of 1BnTIQ and the acute dose of l-DOPA . Duncan’s post hoc test showed that the acute administration of l-DOPA produced an increase in the DA concentration . Additionally, when 1BnTIQ (50 mg/kg) given chronically was coupled with an acute dose of l-DOPA, a significant increase in the level of DA was observed  , as well as acute l-DOPA administration  on the DOPAC concentration in the substantia nigra . The post hoc analysis showed that l-DOPA produced a massive increase in the DOPAC concentration ; this effect was partially blocked by chronic treatment with 1BnTIQ  on the level of 3-MT  significantly affected the 3-MT concentration. There was no interaction between chronic administration of 1BnTIQ and acute administration of l-DOPA . Duncan’s post hoc test showed that acute doses of l-DOPA produced an increase in 3-MT concentration . When 1BnTIQ (50 mg/kg) given chronically was coupled with an acute dose of l-DOPA, a significant elevation in the levels of 3-MT  was also observed , as well as acute l-DOPA administration  on the HVA concentration in the substantia nigra . The post hoc analysis showed that l-DOPA produced a massive increase in the HVA concentration ; this effect was partially blocked by chronic treatment with both concentrations of 1BnTIQ  affected the rate of DA metabolism measured as [HVA]/[DA]  or interaction between 1BnTIQ and l-DOPA . Duncan’s post hoc analysis demonstrated that acute treatment with l-DOPA strongly increased the rate of DA metabolism ; a similar effect was observed in the mixed groups when 1BnTIQ (25 and 50 mg/kg) was coupled with acute l-DOPA  on the DA concentration . The statistical analysis revealed no interaction between chronic administration of 1BnTIQ and l-DOPA administration . The post hoc test indicated that acute doses of l-DOPA increased the level of DA  and that this effect was antagonized only by chronic treatment with a lower (25 mg/kg) concentration of 1BnTIQ  as well as the acute administration of l-DOPA  on the DOPAC concentration in rat striatum . The post hoc analysis showed that l-DOPA produced a massive increase in DOPAC concentration ; this effect was completely blocked by chronic treatment with both concentrations of 1BnTIQ  and acute administration of l-DOPA  both significantly affected the 3-MT concentration in striatum . Duncan’s post hoc test showed that l-DOPA decreased the level of 3-MT  and this effect was reversed by chronic treatment with both concentrations of 1BnTIQ  and acute l-DOPA administration  on the HVA concentration in the striatum . The post hoc analysis demonstrated that l-DOPA strongly increased the HVA concentration ; this effect was partially antagonized only by chronic treatment with a lower (25 mg/kg) concentration of 1BnTIQ  and acute l-DOPA administration  produced significant effects on the rate of DA metabolism measured as [HAV]/[DA] . Duncan’s post hoc analysis demonstrated that chronic treatment with a higher (50 mg/kg) concentration of 1BnTIQ and acute administration of l-DOPA induced an increase the rate of DA metabolism . Only a lower dose (25 mg/kg) of 1BnTIQ given chronically could partially antagonize this effect  or l-DOPA  on the 3-MDOPA concentration in striatum . Duncan’s post hoc test indicated that l-DOPA produced a massive increase the level of 3-MDOPA ; this effect was strongly blocked  by acute treatment with 1BnTIQ (50 mg/kg i.p.). Similarly, a two-way ANOVA revealed a significant effect of chronic administration of 1BnTIQ  and acute administration of l-DOPA  on the concentration of 3-MDOPA in the striatum. Here again, the interaction between 1BnTIQ and l-DOPA was significant . The post hoc analysis demonstrated that l-DOPA strongly increased the 3-MDOPA concentration (P < 0.01); this effect was strongly inhibited by chronic treatment with a lower (25 mg/kg) concentration of 1BnTIQ (Table P < 0.05) (Table A two-way ANOVA demonstrated a significant effect of acute treatment with 1BnTIQ (l-DOPA (100 mg/kg i.p.) induced a significant increase  in the activity of caspase-3 in the hippocampus. This effect was completely inhibited by multiple injections of 1BnTIQ at both concentrations (P < 0.01)  produced only a slight increase in this activity  . However, an effect of time  and an interaction between time and treatment were detected . Duncan’s post hoc analysis showed that acute l-DOPA administration produced a significant (P < 0.01) and long-lasting increase in DA release in the rat striatum (by approximately 500 %)  (P < 0.01) in the striatum  or me  . As for DA, an effect of time  was detected, but the interaction between time and treatment was not significant . Duncan’s test indicated that acute l-DOPA administration produced a significant (P < 0.05) increase in the concentration of 3-MT in the rat striatum (up to 250 %)  or me  on DA release (treatment 1), but the effect of acute dose of l-DOPA (treatment 2) was not significant (100 mg/kg i.p.) . No interaction between treatment 1 and treatment 2 was found  , as well as an interaction between time and treatment 2 . However, there was no interaction between time and treatment 1  or between time, treatment 1, and treatment 2 . Duncan’s post hoc test indicated that acute l-DOPA administration produced a significant (P < 0.01) and long-lasting increase in DA release in the striatum (up to 500 %)  (S.) Fig. a. The stl-DOPA when compared to the group treated with l-DOPA alone  or of treatment 2 after an acute dose of l-DOPA (100 mg/kg i.p.) on the concentration of 3-MT . Furthermore, there was no interaction between treatment 1 and treatment 2  , time versus treatment 1 , or time versus treatment 1 versus treatment 2 . However, there was a significant interaction between time and treatment 2 . Duncan’s post hoc analysis showed that acute l-DOPA administration produced a significant (P < 0.05) elevation in the concentration of 3-MT (up to 250 %); this effect was completely antagonized by chronic administration of 1BnTIQ  , as a precursor of DA, causes a significant increase in DA metabolism, its concentration, and the concentration of all DA metabolites in the extrapyramidal brain structures substantia nigra and striatum. 1BnTIQ, at both investigated concentrations (25 and 50 mg/kg), completely antagonized the effect of l-DOPA in the rat brain. Comparing the results of our behavioral test and our ex vivo and in vivo biochemical experiments, we observed that 1BnTIQ does not always act in the same direction. In the behavioral and ex vivo experiments, 1BnTIQ completely antagonized the l-DOPA-induced biochemical effects, while the in vivo microdialysis studies demonstrated the potentiation by 1BnTIQ of l-DOPA-evoked DA release in the striatum  inhibitors  improves the bioavailability of l-DOPA  the DA reuptake transporter , produces depletion of striatal DA, such that even synthesized DA is not stored in vesicles efficiently  causes an increase in DA and all its metabolites  both in the substantia nigra and in the striatum  does not produce significant changes in DA release  in the brain. Therefore, COMT is responsible both for the metabolic inactivation of extraneuronal DA to 3-MT and for the metabolism of l-DOPA to 3-MDOPA  administration, augmented l-DOPA effect and was produced an additional increase in the extraneuronal DA concentration  in striatum (Fig. l-DOPA effect, likely as a result of the tolerance development (Fig. l-DOPA-produced an increase of the extraneuronal DA concentration in microdialysis study (Figs. 1BnTIQ given acutely 40 min before ent Fig. a. The efdy Figs. a.l-DOPA is the gold standard for the treatment of PD symptoms. l-DOPA can lead to adverse effects, either as a result of oxidative stress because it has the potential to auto-oxidize to a quinine derivative, generating ROS and depleting striatal GSH (Ogawa et al.  ex vivo experiments: acute l-DOPA injection produced a significant increase in caspase-3 activity, an effect that was completely inhibited by chronic administration of 1BnTIQ at both tested concentrations (Fig. l-DOPA neuronal uptake.It is well known that although in vitro study that 1BnTIQ, at micromolar concentrations, has neurotoxic activity in rat hippocampal cultures, in which it increases apoptotic markers (caspase-3 activity and LDH release; Wąsik et al.  ex vivo studies suggested that chronic administration of 1BnTIQ did not have neurotoxic effects on dopaminergic neurons in the substantia nigra, as assessed by tyrosine hydroxylase activity and the level of alpha-synuclein (Wąsik et al. in vitro experiments carried out in human dopaminergic cells showed that 1BnTIQ increased alpha-synuclein expression and caused nuclear damage (Shavali et al. We know from our previous  ex vivo analysis in demonstrating both acute and chronic 1BnTIQ antagonisms of l-DOPA-induced locomotor hyperactivity in rat (Figs. l-DOPA administrations, such as sniffing and sometimes licking were still present.The results obtained from our behavioral studies are in agreement with the results of the biochemicalat Figs. a, b. Howl-DOPA-evoked behavioral and biochemical effects. The data from our ex vivo biochemical analysis and in vivo microdialysis study suggest that the molecular mechanism of action of 1BnTIQ may involve its inhibition of either or both DAT and COMT activities in the brain. Furthermore, elevated endogenous levels of 1BnTIQ may cause serious adverse effects in PD patients undergoing of l-DOPA therapy.In conclusion, our results demonstrate that 1BnTIQ is not only an endogenous neurotoxin that disrupts the activity of dopaminergic neurons but is also an antagonist of


IgG4-related disease is a recently recognized systemic disease characterized by storiform fibrosis with infiltration of IgG4-positive plasma cells. In rare incidences, IgG4-related renal disease can present as a solitary mass lesion at renal pelvis and can pose a diagnostic challenge since these lesions mimic malignancy. Herein, we present a rare case of IgG4-related disease presenting as inflammatory pseudotumor lesion, involving the renal pelvis and also neighboring renal parenchyma.A 75-year-old man with no history of IgG4-related disease underwent computed tomography (CT) scan for evaluation of prostatic cancer. The CT scan incidentally revealed a mass lesion located at the right renal pelvis. Radiologic findings were highly suggestive of malignancy. Therefore, the patient underwent right nephroureterectomy. Microscopically, the mass lesion showed storiform fibrosis with diffuse and intense inflammatory cell infiltration. Infiltrating cells were mainly histiocytes and plasma cells. Tubulointerstitium adjacent to the lesion also showed fibrosis with abundant plasmacytic infiltration. Immunohistochemical staining revealed the presence of IgG4-positive plasma cells in both the mass lesion and tubulointerstitium (mean of 94/HPF per field).Considering these findings, we diagnosed the mass lesion as IgG4-related inflammatory pseudotumor of the renal pelvis. In patients with renal pelvic masses, IgG4-related inflammatory pesudotumor should be considered in the differential diagnosis to avoid unnecessary surgical intervention. IgG4-related disease is a recently recognized systemic disease characterized by advanced scleral fibrosis with extensive infiltration of IgG4-positive plasma cells . IgG4-reA 75-year-old man, with no history of IgG4-related disease or any other autoimmune disease such as, systemic lupus erythematosus or Sjiogrens syndrome, was diagnosed with prostatic adenocarcinoma by needle biopsy. For further evaluation, computed tomography (CT) scan was performed. The CT scan incidentally revealed a 5-cm-wide mass lesion located at the right renal pelvis. The lesion was in the renal pelvis, and as a result, hydronephrosis was also present Fig . MagnetiGross examination of the resected specimen showed a 5.2 cm sized whitish firm mass lesion. The mass lesion was mainly located at the renal pelvis blocking the ureter pathway and renal parenchyma adjacent to the mass lesion also seemed to be involved Fig . MicroscThe first report indicating that serum IgG4 levels were elevated in patients with autoimmune pancreatitis and that pancreatic lesion of such patients showed infiltration of IgG4-positive plasma cells was published in 2001 .In most cases, IgG4-related disease occurs in men 62 to 83%) and in those older than 50 years . The dis3% and inKidneys are not spared in IgG4-related disease. Most of the reported cases of IgG4-related disease involving the kidney have synchronous or metachronous involvement in other organs . HoweverSince most of the IgG4-related renal disease shows radiologic abnormalities, imaging study plays an essential role . IgG4-reIn rare cases, IgG4-related renal disease can affect the renal pelvis and forms a single unilateral mass, as observed in our present case. Such lesions can pose a diagnostic challenge, because they mimic malignant tumors of the renal pelvis, especially if there is no other organ involvement. To the best of our knowledge, this is the third case of isolated renal pelvic IgG4-related disease to be reported in the English literature . The cliIn our present case, the imaging findings strongly suggested that the mass lesion was a malignant tumor. The radiologist mainly suspected the mass to be urothelial carcinoma of the renal pelvis. Moreover, the patient did not present any urologic abnormalities, such as hematuria or proteinuria. Since, IgG4-related disease was not included in the differential diagnosis, neither evaluation of serum IgG4 level nor preoperative biopsy was performed. Therefore, the patient underwent unnecessary radical excision.A renal pelvic mass arising from IgG4-related disease should be differentiated from genitourinary malignancy, metastatic cancer, and lymphomas to avoid unnecessary surgery. However, unfortunately, this differentiation on the basis of radiologic criteria alone is extremely difficult. Several reports have shown that IgG4-related kidney disease has been mistaken for malignant mass and diagnosed only after invasive operations . More thIn conclusion, we have presented a rare case of IgG4-related inflammatory pseudotumor affecting both the renal parenchyma and pelvis. In our case, preoperative biopsy or checking of the serum IgG4 levels was not performed due to lack of evidence for IgG4-related disease. This case emphasizes the importance of considering that IgG4-related diseases can involve the kidney and give rise to mass-like lesions and mimic renal malignancy.Written informed consent was obtained from the patient for publication of this Case Report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.


Observed differences may reflect selection based on favourable physical attributes, or training adaptations. To reduce this discrepancy, some RLC players should reduce fat mass and increase lean mass, which may be of benefit for the 2015 season and beyond.Super League (SL) and Championship (RLC) rugby league players will compete against each other in 2015 and beyond. To identify possible discrepancies, this study compared the anthropometric profile and body composition of current SL  and RLC  players using dual-energy X-ray absorptiometry (DXA). A cross-sectional design involved DXA scans on 67 SL  and 46 RLC  players during preseason. A one-way ANOVA was used to compare age, stature, body mass, soft tissue fat percentage, bone mineral content (BMC), total and regional  fat and lean mass between SL forwards, SL backs, RLC forwards and RLC backs. No significant differences in age, stature or body mass were observed. SL forwards and backs had relatively less soft tissue fat (17.5 ± 3.7 and 14.8 ± 3.6  Domestically, the European Super League (SL) and Australasian National Rugby League (NRL) are regarded as the highest playing standard world-wide . In the Success in RL requires players to have well-developed anthropometric , body composition and physical  characteristics ,3. BM isvs. 1.4 ± 0.3%), with forwards spending a greater proportion of time in collisions than backs (6.5 ± 0.9 vs. 2.7 ± 0.8%) [To date, the majority of research examining the anthropometric and body composition profiles of RL players have used the sum of skinfold assessment to determine body composition ,9,10,11. ± 0.8%) . In comp ± 0.8%) ,16,17,18 ± 0.8%) .Given the re-structuring of the leagues, it is timely to investigate the differences between SL forwards, SL backs, RLC forwards and RLC backs for stature, BM, and DXA-derived three compartment total and regional body composition. In doing so, valuable avenues might be identified for the physical preparation of players for 2015 and beyond. Given that SL players are full-time professional and RLC players are more likely to be part-time semi-professional, it is hypothesized that SL forwards and RLC forwards are taller and heavier, with greater lean and fat mass than SL backs and RLC backs. It is also hypothesized that SL forwards and SL backs would have greater lean mass and lower fat mass in comparison to RLC forwards and RLC backs.A cross-sectional design was used to compare the stature, BM, soft tissue fat percentage, bone mineral content alongside total and combined  regional  fat mass and lean mass of SL forwards, SL backs, RLC forwards and RLC backs. Players were classified based on their primary playing position. Forwards included props, hookers, second rowers, and loose forwards. Backs included half-backs, centres, wingers, and full-backs. Players were tested during the last phase of the pre-season training period (January–February), two to three weeks prior to their first competitive league match, where body composition would be expected to be optimal.n = 29, forwards: n = 38), and forty-six semi-professional players were from two RLC clubs (backs: n = 20 and forwards: n = 26). Ethics approval for the study was granted by the Carnegie Faculty Research Ethics Committee  and complied with the Declaration of Helsinki on human research and international standards. Written informed consent was provided in addition to permission from the respective rugby clubs.One hundred and thirteen RL players participated in the study. Sixty-seven professional players were from two European SL clubs  to the nearest 0.1 cm and BM was measured using calibrated electronic scales  to the nearest 0.1 kg. All participants were scanned in a euhydrated state , on a nOne skilled technologist led and analysed all scans following the manufacturer’s guidelines for patient positioning. The regions of interest were manually placed to enable the appropriate cuts according to the manufacturer’s instructions. The regions of interest are illustrated in p<0.05. Before analysis, normality and equality of variance of the variables were assessed using a Kolmogorov-Smirnov test. One-way ANOVA were used to compare body size and body composition parameters between the SL and RLC backs and forwards. A Bonferroni post-hoc analysis was used to determine where any significant differences occurred. SPSS applies the Bonferroni adjustment by multiplying all p values for post-hoc comparisons by the number of pairwise comparisons (n = 6), to allow the alpha level to remain as p<0.05. Effect sizes, using Cohen’s d were calculated between groups. For Cohen’s d, a modification to the effect size scale of Cohen [All statistical analyses were computed using SPSS version 20 , with all statistical significance set at of Cohen  were useof Cohen . 95% conof Cohen .There were no significant differences between groups for age or stature. BM was significantly greater in forwards than backs within and between leagues. There were no significant differences in BM between SL forwards and RLC forwards, or SL backs and RLC backs. Moderate effects for stature were observed between SL forwards and SL backs, and SL forwards and RLC backs. Body mass differences were moderate between SL forwards and SL backs, SL forwards and RLC backs, SL backs and RLC forwards, and RLC forwards and RLC backs.SL backs had a significantly lower soft tissue fat percentage compared to all other groups, and soft tissue fat percentage was lower in SL forwards than RLC forwards and RLC backs. Total and regional  fat mass were significantly lower in SL backs than all other groups. SL forwards had a significantly lower total and regional trunk fat mass than RLC forwards.Soft tissue fat percentage and total fat mass showed moderate effects between SL forwards and SL backs, SL forwards and RLC forwards, and SL forwards and RLC backs, while large effects were observed between SL backs and RLC forwards, and SL and RLC backs.A moderate difference was observed for arms and legs fat mass between SL forwards and SL backs. Large effects were observed between SL backs and RLC forwards, and SL backs and RLC backs for arms, legs and trunk fat mass. Differences in trunk fat mass were moderate for SL forwards and SL backs, SL forwards and RLC forwards.SL forwards had a significantly greater total and regional arm and leg lean mass than SL backs and RLC backs. SL forwards and SL backs had significantly greater regional trunk lean mass than RLC backs, and SL forwards had significantly greater regional trunk lean mass than RLC forwards.Moderate differences were observed between SL forwards and SL backs, SL forwards and RLC forwards, SL backs and RLC backs, and RLC forwards and RLC backs for total lean mass. Differences between SL forwards and RLC backs were large.Large effects were observed between SL forwards and RLC backs for arms, legs and trunk lean mass, while moderate effects were observed between RLC forwards and RLC backs for arm and trunk lean mass. Moderate effects were observed between SL forwards and SL backs, and SL forwards and RLC forwards for arms lean mass. Moderate effects were also observed between SL forwards and SL backs for legs lean mass, and SL forwards and RLC forwards, and SL backs and RLC backs for trunk lean mass. Small effects were also observed between SL forwards and SL backs for trunk lean mass.Corresponding with their greater BM, total BMC was significantly greater in SL forwards than SL backs and RLC backs. Similarly, RLC forwards had a significantly greater total BMC than RLC backs. A small difference was observed between SL forwards and RLC forwards for total BMC. Differences between SL forwards and SL backs, SL backs and RLC backs, and RLC forwards and RLC backs were moderate, while differences between SL forwards and RLC backs were large for total BMC.This is the first study to compare the anthropometry and three-compartment total and regional body composition parameters of SL and RLC players, using DXA. Our findings suggest that stature and BM are well-matched between SL and RLC forwards and SL and RLC backs. However, there were distinct differences in body composition. Namely these differences are characterised by lower soft tissue fat percentage in SL backs compared to RLC forwards and backs, and greater lean mass in SL forwards than RLC backs, thus we accept our hypothesis. As expected, forwards at both SL and RLC standard were heavier than SL and RLC backs, respectively. The findings of this study identify body composition targets for RLC players competing against SL players in the 2015 league restructure.Our results demonstrate BM was similar between SL and RLC forwards, and between SL and RLC backs. Although, when observations of body composition were made, the higher fat mass and lower lean mass in RLC forwards might be a disadvantage when the two leagues compete against each other. RL forwards are required to produce high amounts of force whilst withstanding multiple collisions ,26, thusThe differences in lean and fat mass between SL and RLC backs is of interest, given that backs are required to perform repeated bouts of high-speed running over greater distances than forwards during a match . As suchThe explanation for the observed differences is likely due to SL players being full-time professional athletes, whereas RLC players are mainly employed part-time. In this respect, SL players are more likely to be able to dedicate a greater amount of time to training, recovery and nutritional habits, which concurrently would affect lean and fat mass. Further, expertise  are more likely to be available within a professional club as opposed to a semi-professional part-time club. The identified differences in body composition between standards might also exist based on identification, selection and recruitment of players. A recent retrospective study of UK Academy RL players showed that a lower sum of four skinfolds (at 13–15 years old) was associated with long-term career progression [The main regional differences observed in this study were greater fat and lower lean mass in the trunk of RLC forwards, and greater fat mass in the arms, trunk and legs of RLC backs, compared to their SL peers by position. These differences may reflect training and recovery practices, and suggest that strength and conditioning programmes for RLC players may benefit from focussing on trunk exercises , which would develop the trunk more favourably. Optimising trunk composition and strength is key for forwards and backs, creating a stable framework for generating and transferring force during contact .vs. RLC backs), because backs need to defend or attack against forwards within a match. The large differences in mean total lean mass between SL forwards and RLC backs  was far greater than the difference observed between SL backs and RLC forwards , which may affect a tackle or successful attack, although the technical elements should also be considered. The discrepancy might also increase injury risk amongst RLC players, which has recently been identified in both SL and RLC players [It is also important to consider differences between playing standards and positions (e.g., SL forwards  players . Bone-re players .In addition to anthropometry and body composition, further considerations for team success in the new league structure should be given to the skill level ,30, physTo conclude, body size was well-matched between SL and RLC forwards, and SL and RLC backs, although distinct differences in body composition exist. Specific to the findings of the current study, RLC forwards and backs might benefit from reducing overall fat mass and increasing lean mass, specifically in the trunk in order to match the body composition of players at a higher standard. RLC backs may benefit from reducing fat mass in the limbs. The effects of body composition discrepancies between teams on injury occurrence represent a valuable avenue for further research. An individualised approach should be adopted to optimise the body composition profiles of players in line with on-field performance indicators. In addition to the skill level and collective experience of a team, a greater lean mass and lower body fat for some players might be of value for consideration by RLC teams if they are to physically match SL teams following the 2015 RL league restructure.


IgG4-related hypophysitis is a recently described entity belonging to the group of IgG4-related diseases. Many other organs can also be affected, and it is more common in older men. To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy and the majority affecting multiple organs. The aim of this report is to present two cases of biopsy-proven IgG4-related hypophysitis occurring in two young female patients with no evidence of involvement of other organs at the time of diagnosis.IgG4-related hypophysitis belongs to the group of IgG4-related diseases, and is a fibro-inflammatory condition characterized by dense lymphoplasmacytic infiltrates rich in IgG4-positive plasma cells and storiform fibrosis.It is more common in older men, but young women may also present this type of hypophysitis.Although involvement of other organs is frequent, isolated pituitary disease is possible.Frequent clinical manifestations include anterior hypopituitarism and/or diabetes insipidus.The diagnosis may be confirmed with any of the following criteria: a pituitary biopsy with lymphoplasmacytic infiltrates, with more than ten IgG4-positive cells; a sellar mass and/or thickened pituitary stalk and a biopsy-proven involvement of another organ; a sellar mass and/or thickened pituitary stalk and IgG4 serum levels >140 mg/dl and sellar mass reduction and symptom improvement after corticosteroid treatment.Glucocorticoids are recommended as first-line therapy. Hypophysitis is a rare entity characterised by chronic inflammation of the pituitary, and is classified as primary and secondary based on its aetiology. Secondary hypophysitis includes cases resulting from other sellar lesions ; from therapeutic use of immunomodulatory drugs  or as a consequence of systemic diseases such as Wegener's granulomatosis, tuberculosis, sarcoidosis or syphilis postpartum period, and frequently associated with other autoimmune disorders et al. The primary forms comprise five histopathological subtypes: lymphocytic or autoimmune, granulomatous, xanthomatous, necrotising, and IgG4-positive plasma cell-rich hypophysitis To date, 32 cases of IgG4-related hypophysitis have been reported in the literature, 11 of which included confirmatory tissue biopsy A 25-year-old woman presented to our clinic with a history of secondary amenorrhoea for the past eight months. Her relevant past history revealed chronic anaemia due to thalassaemia minor, menarche at age 13 years and no prior pregnancies. She was found to present normal vital signs and her physical examination was unremarkable. She was not taking any prescribed medication.Initial laboratory tests revealed hypogonadotrophic hypogonadism without hyperprolactinaemia and possible but not proven secondary adrenal failure . Brain mBased on lesion size and image characteristics, the presumptive diagnosis was a macroadenoma, so glucocorticoid replacement therapy was started and the tumour later resected through a transsphenoidal approach with no complications. After surgery, amenorrhoea persisted and secondary hypothyroidism was detected. Oral contraceptives and thyroxine (50 μg daily) were prescribed.Three months later a new MRI of the pituitary gland showed a persistent suprasellar tumour C and D iAn MRI repeated after four months showed significant reduction in the pituitary mass lesion, demonstrating a good response to the low-dose steroids E and F. A 37-year-old woman came for consultation because of severe headache, secondary amenorrhoea, polydipsia, and polyuria (urine output 10 l/day), weight loss and fatigue. Her past medical history noted a menarche at 12 years of age, no pregnancies and gluten-sensitive enteropathy that had improved shortly after starting a gluten-free diet. She was normotensive, and she had no abnormality detected on physical examination.The brain MRI showed a pituitary lesion extending into the suprasellar region with signs of intratumoural bleeding and compression of the optic chiasm A and B. Replacement treatment was started with hydrocortisone 15 mg/day, oral desmopressin 0.05 mg every 8 h, as well as the oral contraceptive. The patient underwent transsphenoidal surgery (TSS) with the presumptive diagnosis of pituitary macrodenoma with intratumoural haemorrhage.Histopathology results reported IgG4-related hypophysitis A and B aThe patient's general health improved over subsequent follow-up. A repeat MRI performed 30 days after surgery showed a substantial reduction in sellar lesion size C and D aIgG4-related disease is a fibro-inflammatory condition characterised by lesions with dense lymphoplasmacytic infiltrates, rich in IgG4-positive plasma cells, storiform fibrosis and often, though not always, high plasma IgG4 concentrations IgG4-related hypophysitis was first described in 2004 based on clinical data et al. established five criteria for IgG4 hypophysitis diagnosis: i) the presence of mononuclear cell infiltrates within the pituitary gland rich in plasma cells and lymphocytes, with more than ten IgG4-positive cells; ii) a sellar mass and/or thickened pituitary stalk; iii) biopsy-proven involvement of other organs, with IgG4-positive immunostaining; iv) increased IgG4 serum levels (>140 mg/dl); and v) reduction in sellar mass size and symptom improvement after corticosteroid treatment. The authors propose that IgG4-related hypophysitis diagnosis may be confirmed when any of the following criteria combinations are met: criterion i alone, criteria ii+iii or ii+iv+v In 2011, Leporati Although the definitive diagnosis of hypophysitis is histopathological, imaging characteristics such as a symmetrical enlargement of the pituitary gland, rapid intense and uniform gadolinium enhancement, lack of erosion or depression of the sellar floor In our study, none of the patient presented characteristic pituitary changes detected by MRI for hypophysitis; instead, the images were heterogeneous and contrast enhancement was irregular. Moreover, in the first case there was considerable invasion of the sphenoid sinus and, in the second, signs of bleeding were present. Because these images did not initially suggest hypophysitis, both patients were submitted to TSS at which time definitive diagnosis of IgG4-related hypophysitis was established under the first Leporati's criterion, as also occurred in 11 of the 32 cases published to date Of the 32 cases reported in the literature, 29 were men aged between 40 and 81 years, and 28 patients had other IgG4-related diseases, mostly pulmonary lesions, retroperitoneal fibrosis, autoimmune pancreatitis, lymphadenopathies, sialoadenitis, pachymeningitis, and kidney lesions With respect to clinical manifestations, both patients presented hypogonadotrophic hypogonadism and one had diabetes insipidus, in agreement with findings in the literature, where 25 of 32 cases presented varying degrees of hypopituitarism, 21 had diabetes insipidus and 16 patients presented both conditions Concerning treatment, glucocorticoids are recommended as first-line therapy. More than half of the published cases received prednisolone (0.5–1 mg/kg per day), although some patients respond well to hydrocortisone replacement therapy In conclusion, we report two cases of IgG4-related hypophysitis in young nulliparous women, the youngest to date, without typical radiological pituitary images, in whom the diagnosis was histologically confirmed. Notably, the disease was restricted to the pituitary and response to relatively low-dose glucocorticoids has been favourable.Written informed consent was obtained from the two patients.P Fainstein Day is the main Endocrinologist Physician who followed the patients and she reviewed and edited the manuscript. G A Sosa and S Bell conducted the literature review and manuscript construction. A Carrizo and P Ajler performed the surgeries. S B Christiansen was responsible for the histology-related aspect of both cases. M Pietrani was responsible for the imaging-related aspect of both cases. M Glerean, M Loto, and S Lovazzano contributed towards patient care as part of the Department of Endocrinology.


Many disposal concepts currently show that concrete is an effective confinement material used in engineered barrier systems (EBS) at a number of low-level radioactive waste (LLW) disposal sites. Cement-based materials have properties for the encapsulation, isolation, or retardation of a variety of hazardous contaminants. The reactive chemical transport model of HYDROGEOCHEM 5.0 was applied to simulate the effect of hydrogeochemical processes on concrete barrier degradation in an EBS which has been proposed to use in the LLW disposal site in Taiwan. The simulated results indicated that the main processes that are responsible for concrete degradation are the species induced from hydrogen ion, sulfate, and chloride. The EBS with the side ditch drainage system effectively discharges the infiltrated water and lowers the solute concentrations that may induce concrete degradation. The redox processes markedly influence the formations of the degradation materials. The reductive environment in the EBS reduces the formation of ettringite in concrete degradation processes. Moreover, the chemical conditions in the concrete barriers maintain an alkaline condition after 300 years in the proposed LLW repository. This study provides a detailed picture of the long-term evolution of the hydrogeochemical environment in the proposed LLW disposal site in Taiwan. The engineered barriers system (EBS) is an integral part of the radioactive waste disposal facility. The EBS represents the manmade, engineered materials of a repository, including the waste form, waste canisters, concrete barrier, buffer materials, backfill, and seals, and can be used as physical and/or chemical obstructions to prevent or hinder the migration of radionuclides  disposal sites in most countries IAEA , b. OverThe hydrogeochemical environment of an LLW repository is determined by the composition of groundwater and mineral formation, which may influence the chemical compatibility of backfill material, the concrete barrier, and the buffer material in the near field. The durability of cementitious material in service environments has presented a number of concerns, such as whether the EBS may be completely isolated from the groundwater and the accompanying hydrogeochemical reactions and key aqueous species in the groundwater that affect the degradation of the concrete barrier of the repository, and the influence of the redox processes on the formations of degradation materials. To obtain further insights into these interactions and provide a detailed overview of the long-term evolution in the hydrogeochemical environment of the concrete barrier, a reactive chemical transport model of HYDROGEOCHEM 5.0 , aluminate (Ca3Al2O6), and ferrite (4CaO·Al2O3·Fe2O3), abbreviated as C3S, C2S, C3A, and C4AF, respectively. When these constituents are mixed with water, calcium–silicate–hydrate (C–S–H), portlandite (Ca(OH)2(s)), ettringite (Aft), monosulfate (AFm), and hydrogarnet form in the cement hydration process. These hydration products also control the setting and hardening of the concrete. These alterations have direct consequences on the engineering properties of the concrete barrier. Figure Concrete is mainly composed of a mixture of cement, water, and aggregates. The aggregates consist of minerals such as sand, gravel, and stone, which are chemically inert to water and concrete solid. The mineral compounds in cement are calcium silicates , h is the pressure head (L), t is the time (T), z is the potential head (L), q is the source or sink representing the artificial injection or withdrawal of fluid [(L3/L3)/T], ρ0 is the referenced fluid density at zero biogeochemical concentration (M/L3), ρ is the fluid density with dissolved biogeochemical concentrations (M/L3), ρ* is the fluid density of either injection (=ρ*) or withdraw (=ρ) (M/L3), α′ is the modified compressibility of the soil matrix (1/L), β′ is the modified compressibility of the liquid (1/L), ne is the effective porosity (L3/L3), and S is the degree of effective saturation of water.A modified Richard’s equation describes the density-dependent fluid flow in variably-saturated media. It is derived based on the continuity of fluid, continuity of solid, motion of fluid (Darcy’s law), consolidation of the media, and the compressibility of water, as follows:The finite element method was used to solve Eqs. , 2), an, an2), aCi be the concentration of the ith species, the governing equation for Ci was obtained by applying the principle of mass balance in integral form as follows:L is the transport operator denotingCi is the concentration of the i-th species in units of chemical mass per water volume [M/L3]; ri is the production rate of the i-th species because of biogeochemical reactions in chemical mass per water volume per unit time [M/L3/T]; M is the number of biogeochemical species; D is the dispersion coefficient tensor [L2/T]; and Mi is the source/sink  of the i-th species in chemical mass per unit volume of media [M/L3/T].The governing equations for transport were derived based on the continuity of mass and Fick’s flux laws. The main transport and fate processes are advection, dispersion/diffusion, source/sink, and biogeochemical reactions (including radioactive decay). The general transport equation governing the temporal-spatial distribution of any biogeochemical species in a reactive system is described below. Let Four types of boundary conditions  were implemented in HYDROGEOCHEM5.0.ith species; μik is the reaction stoichiometry of the ith species in the kth reaction associated with the reactants; νik is the reaction stoichiometry of the ith species in the kth reaction associated with the products; {N} = {1, 2, …, N} in which N is the number of reactions.The formulation of rate equations for all N reactions is the crucial factor in modeling mixed equilibrium and geochemical kinetic reactions. A rate equation must be specified to quantitatively describe a general geochemical reaction that is written as:NE fast/equilibrium reactions  and NK slow/kinetic reactions, i.e., N = NE + NK.Let us assume that there are Rk is the rate of the kth kinetic reaction, Ai is the activity of the ith species, kth kinetic reaction, respectively, and NK is the number of kinetic reactions. The forward and backward rate constants cannot be determined sequentially with the measurement of concentration-versus-time curves of all species because NK equations in Eq. , and the concentrations of geochemical species may be theoretically derived asy in Eq. , as follαL and αT are the longitudinal and transverse diffusivity, respectively [L]; δ is Kronecker delta tensor; |V| is the magnitude of the Darcy’s velocity [L/T]; Dw is the molecular diffusion coefficient of pure water [L2/T]; τ is tortuosity; m is the cementation exponent  methods were used for temporal discretization of the governing partial differential equations in the flow module and reactive transport module. The Galerkin finite element method was used for spatial discretization of the modified Richards equation that governs the distribution of pressure fields. For scalar reactive transport equations, either the conventional finite element methods or the hybrid Lagrangian–Eulerian finite element methods were used for spatial discretization. The chemical equilibrium equations were solved by the Newton–Raphson method or Picard method.The composition and phase development of hydration products as the chemical reaction of cement with groundwater flow influences the lifetime performance of the concrete barrier. The thermodynamic modeling of Portland cement in the subsurface system of cementitious media was formulated and applied to assess the performance of concrete barriers.2–H2O, CaO–Al2O3–SiO2–H2O, CaO–Al2O3–SO3–CO2–Cl–H2O in the water and cement-based materials. In addition, Galíndez and Molinero  in the proposed site of Arnold et al. (The simulation region with an elevation of 40 m at the bottom was discretized with 3918 elements and 4146 nodes. The grid comprised cells of dimensions Δx, the Δy varied from 1 to 0.1 m, and Δz = 2 m, as illustrated in Fig. d et al. . The est+, K+, Ca2+, Al3+, OH−, HCO3−, Cl−, SO42−, H4SiO4, Fe3+, e−, 37 aqueous species, and 10 minerals of precipitation/dissolution reactions. The model simulation time was 300 years with an initial time-step of 1.0 × 10−5 year, and a maximal allowable time-step of 0.01 year. In addition, the precipitation/dissolution on the change of porosity, hydraulic conductivity, and hydrodynamic dispersion of cementitious media may be a crucial hydrogeochemical mechanism in the concrete degradation. Thus, the effect of precipitation/dissolution reactions on both the flow and the reactive transport were also considered in the simulations. Moreover, pyrite oxidation and sulfate reduction reactions were also incorporated in the simulation scenarios to evaluate the effect of redox processes on the formations of degradation materials. Table The cementitious materials of the concrete of the EBS may interact with the groundwater when the repository begins to operate. It is crucial to avoid the concrete immersion by the inflow of groundwater to mitigate this type of interaction. The Taiwan Power Company proposed a side ditch design to install at the bottom of the disposal tunnel and allow the drainage of inflow water. If the groundwater inflow is drained from the side ditch, the effect of concrete degradation on the performance of EBS may be reduced. Hence, the simulation scenarios considered in this study were the performance assessment of EBS with and without the side ditch. Table Case 1: LLW repository without side ditch and redox processes.Case 2: LLW repository with side ditch and without redox processes.Case 3: LLW repository with side ditch and redox processes.Three cases of reactive transport simulations were considered, as follows:The simulations of Cases 1, 2, and 3 were conducted by using HYDROGEOCHEM 5.0. The simulated results revealed notable differences in the concrete degradation. Figure −2 mol/l at the vertical left, right, and horizontal top edge areas of the concrete barrier within 100 years. After 300 years, as illustrated in Fig. −2 M because of the continuous sulfate intrusion. However, the ettringite was mildly formed in Case 2, with an amount of 1.53 × 10−4 M precipitated at the top right edge of the concrete barrier after 300 years (Fig. In Case 1, the ettringite was formed with a maximal amount of approximately 2.49 × 10ars Fig. b.Fig. 7E−1 mol/l of Friedel’s salt formed at the vertical left, right edge and horizontal top edge areas of the concrete barrier within 100 years. The amount of Friedel’s salt increases as time progress reaching a maximal value of approximately 2.70 × 10−1 M in 300 years, as illustrated in Fig. −1 M at the vertical left edge of the concrete barrier after 300 years, as shown in Fig. −4 M precipitated at top right edge of the concrete barrier after 300 years (Fig. 2S in the groundwater. Figures 2S was formed at the left, top, and right edge of the concrete barrier. Thus, the sulfate reduction can reduce the concentration of sulfate and ettringite formation. Therefore, the redox processes significantly influence on the formation of degradation materials. Reduction environment in the EBS can reduce the ettringite formation in the concrete degradation processes.In Case 1, the maximal amount was approximately 2.94 × 10ars Fig. a. As thears Fig. b. In Casars Fig.  pointed This study considered limited chemical reactions under the chemical equilibrium condition; therefore, the comprehensive reactions of the cementitious phase and the chemical kinetics should be included in future reactive chemical transport simulations. Based on the simulated results, the hydrogen ion can result in the dissolution of portlandite and increases the concentration of calcium in the pore water. The sulfate anion reacts with cement to form ettringite. The chloride from the pore water enters the cementitious materials to form Friedel’s salt. Luna et al.  pointed A proposed site for final disposal of LLW of Daren is on the selected list in Taiwan. To investigate the hydrogeochemical reactions and effect on concrete degradation in the proposed LLW repository site, HYDROGEOCHEM 5.0 model was applied to simulate the complex chemical interactions between the cement minerals of the concrete and groundwater flow and reactive chemical transport resulting from water–rock interaction in the proposed site. Simulation results show the main processes responsible for concrete degradation involve geochemical reactive species induced from hydrogen ion, sulfate, and chloride. The intrusion of hydrogen ion from groundwater results the dissolution of portlandite. However, the portlandite still maintains alkaline condition in proposed LLW repository, the concrete used as a confinement material in EBS may remain in well durable condition. The sulfate-induced concrete degradation may form the ettringite and the chloride-induced concrete degradation form Friedel’s salt. Thaumasite and monocarboaluminate are also formed as carbonate aggregates by sulfate attack, and carbonate intrusion, respectively. The formation of ettringite, Friedel’s salt, thaumasite and monocarboaluminate may result a volume expansion. The EBS with the side ditch efficiently drains the ground water and lowers the concentration of concrete degradation induced species. The degree of concrete degradation on performance of EBS with side ditch is much lower than the disposal tunnel without the side ditch. Moreover, the redox processes significantly influence on the formations of degradation materials. Reductive environment in the EBS can reduce the ettringite formation in the concrete degradation processes. The results of the study provide a detail picture of the long-term evolution of the hydrogeochemical environment of the proposed LLW disposal site in Taiwan. The chemical kinetics effect should be included in future reactive chemical transport simulations. Moreover, the interaction among water and other minerals of cement, bentonite, and backfill materials in the near field, volume-expanded cracks and seismic induced-fractures should also be considered in the future research. The development of advanced numerical models that coupled with thermo-hydraulic–mechanical–chemical processes is especially welcomed.


These findings yield a general quantitative description of the AIDS infection dynamics in Brazil since the beginning. They also provide clues about the effectiveness of treatment and control programs against the infection, that has had a different impact depending on the number of inhabitants of cities. In this framework, our results give insights into the overall dynamics of AIDS epidemic, which may contribute to select empirically accurate models.Brazil holds approximately 1/3 of population living infected with AIDS (acquired immunodeficiency syndrome) in Central and South Americas, and it was also the first developing country to implement a large-scale control and intervention program against AIDS epidemic. In this scenario, we investigate the temporal evolution and current status of the AIDS epidemic in Brazil. Specifically, we analyze records of annual absolute frequency of cases for more than 5000 cities for the first 33 years of the infection in Brazil. We found that  The spreading of epidemics is a threat to the world public health. It has also been arising large scientific attention due to the potential harm to the society The study of the epidemiology of HIV infection using accurate surveillance data has been providing essential information in guiding rational control and intervention programs, as well as in monitoring trends of the epidemic in many countries In the present work, we investigate the evolution and current status of the AIDS epidemic in Brazil by analyzing its annual absolute frequency per city. Our analysis points in the direction of an alternative approach to the usual methods of epidemics analysis, emphasizing how the dynamics of the virus at the level of municipalities behaves collectively. The data on the AIDS cases were obtained from DATASUS, a database of the national public health system freely available online and maintained by the Department of Informatics of the Brazilian Health System i,ty, defined as the number of new AIDS cases diagnosed in the year t at a given city i. It is valid noting that the System Data Registry of DATASUS hosts only mandatory cases of AIDS reported by health professionals to health services. Therefore, the number of HIV positive patients was not available in DATASUS until 2012, but only the number of AIDS cases. Altogether, we analyze data ranging from 1980 up to 2012 of 5138 Brazilian cities with at least one AIDS case in the aforementioned period. Up to the end of 2012, the infection had already reached more than 5000 cities (∼90% of the Brazilian cities). We start with an overview of the spatial spreading of the virus. Next, we focus on the temporal evolution of the infection in Brazilian cities.In this section we report the results that we obtained by analyzing the empirical data which cover the first 33 years of the AIDS infection in Brazil. Specifically, we investigate the annual absolute frequency i,ty and the histograms along the axis detail the annual absolute frequencies as function of the geographic position of the cities. A chronological evolution of the AIDS cases per year among Brazilian cities is available as . In the next few years, new satellite cases came out and the infection started spreading to a larger area. In this mean time, the infection spread to other cities and the whole country was already taken by the end of the 1990s. The current status of the AIDS infection in Brazil is depicted in lable as . As cleatY, the total annual absolute frequency at each year t, obtained by summing i,ty over the total of N Brazilian cities, tY and compares it with the curve t, emphasizing their discreteness nature. The curve of a has the dimension of cases/year, β goes with year−1, while b and First we considered t = 0, a least-squared regression to the data  for fixed years. P of the set of all the i,ty in the year 2012 in comparison with the power law decay As usually happens in a epidemic spreading, the AIDS infection had focus in a specific region and then spread to a larger area . To investigate this possible size dependence, we crossed the AIDS data with data on the population of cities obtained from IBGE. In particular, we found It is clear that an allometric relationship between two variables is usually outlined by the probability distribution of both the variables. Studies in the literature investigate such type of connection. As an example, there is an evident relationship between homicides and population/urban indicators year see  and Figuyear see  and  cami,ty 〉 in years and defined as an arithmetic mean of i,ty: Group I accommodates 4029 cities with 〈i,ty〉<2. Group II encompasses 565 cities with 2≤〈yi,t〉≤10. Group III accommodates 259 cities with 10<〈i,ty〉≤84, and, finally, Group IV covers 48 cities with 〈i,ty〉>84. It is evident from i,ty has a well-defined allometry with the population of cities. For this reason, separate groups of cities accordingly to 〈i,ty〉 is also equivalent to separate i,ty by population-sizes, apart from random fluctuations. In As pointed out before, Brazil is a forefront reference in providing AIDS prevention campaigns and treatment services (i) logistic-type growth of total AIDS cases per year with an exponential regime in the first few years of the AIDS spreading and (ii) power law-type decaying of the actual reproduction number; (iii) power law behavior with a robust exponent in the PDF of the annual absolute frequency among cities; (iv) a robust allometric relationship between the epidemic and the population of the cities; and, finally, (v) different profile for the temporal evolution of the epidemics depending on the average absolute frequency of cases in the cities.In the present work, we showed that the AIDS epidemic in Brazil (1980–2012) exhibits the following growth patterns: The result shown in ca. 1992 occurs because it is the region where the small time scale is already broken (ca. 10 years for AIDS).It is well-known that the number of cases of a new infection in a confined area grows exponentially. For the AIDS epidemics in Brazil, we found that this exponential provides the parameter inset of  which arWe also showed that the distribution of the AIDS epidemics in small spatial scales (over cities) follows a power law behavior for the whole period with an decreasing exponent typically around 1.9 and systematically below the inverse-square law Click here for additional data file.Table S1Data used in our analysis. This comma separated file (CSV) has 5566 lines and 38 columns. The first line is a header specifying the contents of the columns.(CSV)Click here for additional data file.


Antimicrobial resistance is a major contemporary public health threat. Strategies to contain antimicrobial resistance have been comprehensively set forth, however in developing countries where the need for effective antimicrobials is greatest implementation has proved problematic. A better understanding of patterns and determinants of antibiotic use and resistance in emerging economies may permit more appropriately targeted interventions.Viet Nam, with a large population, high burden of infectious disease and relatively unrestricted access to medication, is an excellent case study of the difficulties faced by emerging economies in controlling antimicrobial resistance.Our working group conducted a situation analysis of the current patterns and determinants of antibiotic use and resistance in Viet Nam. International publications and local reports published between 1-1-1990 and 31-8-2012 were reviewed. All stakeholders analyzed the findings at a policy workshop and feasible recommendations were suggested to improve antibiotic use in Viet Nam.Here we report the results of our situation analysis focusing on: the healthcare system, drug regulation and supply; antibiotic resistance and infection control; and agricultural antibiotic use.Market reforms have improved healthcare access in Viet Nam and contributed to better health outcomes. However, increased accessibility has been accompanied by injudicious antibiotic use in hospitals and the community, with predictable escalation in bacterial resistance. Prescribing practices are poor and self-medication is common – often being the most affordable way to access healthcare. Many policies exist to regulate antibiotic use but enforcement is insufficient or lacking.Pneumococcal penicillin-resistance rates are the highest in Asia and carbapenem-resistant bacteria (notably NDM-1) have recently emerged. Hospital acquired infections, predominantly with multi-drug resistant Gram-negative organisms, place additional strain on limited resources. Widespread agricultural antibiotic use further propagates antimicrobial resistance.Future legislation regarding antibiotic access must alter incentives for purchasers and providers and ensure effective enforcement. The Ministry of Health recently initiated a national action plan and approved a multicenter health improvement project to strengthen national capacity for antimicrobial stewardship in Viet Nam. This analysis provided important input to these initiatives. Our methodologies and findings may be of use to others across the world tackling the growing threat of antibiotic resistance. Antimicrobial resistance is a global concern and a particularly pressing issue in resource-limited countries. Respiratory, diarrheal, sexually-transmitted and nosocomial infections are leading causes of death in the developing world  and theiAntibiotic drug pressure is a key driver of resistance. Whilst it is an unavoidable consequence of antibiotic use – both rational and irrational – unnecessary antibiotic pressure can and must be reduced. The World Health Organization (WHO) published comprehensive recommendations designed to restrict the emergence and spread of antimicrobial resistant organisms, promoting prudent use of antimicrobials in humans, food-producing animals and aquaculture .With a population exceeding 91 million, Viet Nam is the world’s 13th most populous country  attended by the Vietnamese Ministry of Health (MoH), WHO, hospital directors, universities, research organizations and local and international experts in public health, agriculture, microbiology, pharmacy, and clinical infectious diseases. During this and subsequent meetings, a framework for the situation analysis was outlined Figure , with thThe analysis focused on bacterial diseases, excluding HIV, malaria and tuberculosis, and is divided into three sections: (1) healthcare system, drug regulation and supply; (2) antibiotic resistance and infection control; and (3) agricultural antibiotic use. All available sources in international and local literature since 1990 were identified, synthesized and discussed at a policy meeting.We identified sources by searching PubMed for published papers from 1-1-1990 to 31-8-2012. The following search criteria were used: ‘antibiotic consumption’, ‘antibiotic resistance’, ‘healthcare access’, ‘drug access’, and ‘Viet Nam’. In addition, we consulted relevant unpublished reports and local Vietnamese papers and expertise. Clarification was sought from study investigators for both international and local documents when methodology or results were unclear. Information on existing policy was obtained from the MoH. Basic health indicators were obtained from the WHO, United Nations and CIA World Factbook ,6.The findings were presented at a policy workshop (June 2011) attended by local stakeholders representing the same areas of expertise as the initial stakeholder meeting. All studies were assessed for possible bias at the policy workshop before stakeholders were asked to recommend feasible policy changes to control antibiotic resistance. These recommendations were presented to the MoH to assist their formulation of a national action plan to strengthen national capacity for antimicrobial stewardship in Viet Nam.Since the 1986 market reforms, several measures have improved healthcare access in Viet Nam, including health insurance schemes, enhanced infrastructure and health facilities and deregulation of drug retail . ApproxiOut-of-pocket health expenditures as a proportion of total health expenditures are estimated at 61% . Self-meIn primary care empiric antimicrobial treatment is the norm as limited resources make diagnostics difficult . At presHalf of all drugs consumed in Viet Nam are made locally and more than 50% of these are antibiotics . Most doThe Pharmaceutical Law (2005) made antibiotics prescription-only drugs. Despite this, antibiotics continue to be dispensed without a doctor’s prescription . In 2007Several MoH departments issue these drug policies and are responsible for regulating private and public healthcare facilities. In 2006, 230 full-time health inspectors were employed to regulate over 39,000 pharmacy outlets . Given tDrug regulation and supply is also problematic at the local level. The MoH instructs all hospitals to appoint a Drug and Therapeutics Committee (DTC). The DTC is responsible for implementing MoH guidelines, establishing lists of commonly used drugs in their hospitals and advising on rational antibiotic therapy. Certain “reserved” antibiotics, should only be dispensed after consultation with the DTC. A recent MoH instruction requires hospitals to implement local guidelines for rational and safe drug use, monitor antibiotic prescribing, strengthen hospital pharmacies and train staff to improve knowledge of drug use. However, these requirements are often not met by hospitals.nd and 3rd generation cephalosporins, followed by oral broad-spectrum penicillins, macrolides/azalides and fluoroquinolones. Importantly, relatively new injectable antibiotics  are sold in hospitals, whilst older antibiotics, (e.g. chloramphenicol) predominate in retail pharmacies.In 2008–09, the most commonly sold antibiotics were oral 2Antibiotics constitute on average 36% of hospital treatment expenditure . InjectaParticularly concerning is perioperative antibiotic prophylaxis . Most suhttp://vsid.vn/en/about-vinares.html)[The importance of antimicrobial stewardship is not routinely addressed in medical or pharmacy training thus knowledge and prescribing habits remain poor. An ongoing initiative led by the Vietnamese Society of Infectious Diseases aims to raise awareness of the need for sensible prescribing and improve hospital antibiotic use (res.html).Streptococcus pneumoniae penicillin-resistance rates increased from 8% to 75% in Ba Vi [Mothers usually treat sick children without consulting a healthcare provider. In 1999, 91% of children in Ba Vi with symptoms of acute respiratory tract infection (ARI) were treated with broad-spectrum penicillins, 78% of them self-medicating. This corresponded to 75% of all children in that community . From 19in Ba Vi . In 2007in Ba Vi .Reasons for irrational antibiotic prescribing are the same as in other countries: perceived patient expectation; time constraints; lack of knowledge; lack of diagnostics; pressure, incentives and advertising from industry; and financial benefits for the prescriber . High ouBelow we summarize data for key bacteria. Most data are derived from site-specific, hospital-based studies, yet the majority of illness occurs where there are few diagnostic facilities.Streptococcus suis is the leading cause of bacterial meningitis in adults in Viet Nam. An increase in tetracycline and chloramphenicol resistance was observed in S. suis over an 11-year period, associated with agricultural antibiotic use [From 1995 to 2000, penicillin-resistance amongst community-acquired invasive pneumococci increased from 8% to over 70%  . Viet Naotic use .Staphylococcus aureus isolates from blood showed 19% were methicillin resistant (n = 80) [A recent study on (n = 80) . Nationa(n = 80) .An enterobacteriaceae study in Ho Chi Minh City reported extended-spectrum beta-lactamase prevalence of 43.8% amongst hospitalized patients (n = 71) with complicated intra-abdominal infections, bloodstream infections, nosocomial pneumonia and ventilator-associated pneumonia. Prevalence has been reported to be as high as 81% amongst ICU enterobacteriaceae .Salmonella Typhi isolated in a southern Viet Nam study from 1994 were multi-drug resistant (MDR) [S. Typhi isolates are resistant to nalidixic acid [Shigella spp. to: trimethoprim-sulfamethoxazole, 81%; tetracycline, 74%; ciprofloxacin, 10%; and ceftriaxone, 5% [Vibrio cholerae in Viet Nam [Escherichia coli is positively correlated with community antibiotic use [Over 70% of nt (MDR) . Nalidixnt (MDR)  Another xic acid  and thisxic acid . High rexone, 5% . Over 75xone, 5% . High raViet Nam  and prevotic use .Helicobacter pylori, the bacteria strongly associated with peptic ulcer disease. A study in children reported clarithromycin, metronidazole, and amoxicillin resistance rates of: 50.9%, 65.3%, and 0.5%, respectively. Importantly, clarithromycin resistance was associated with eradication failure [Of note are the high resistance rates amongst  failure .Pseudomonas aeruginosa and Acinetobacter baumannii HAIs  have been reported from both northern and southern Viet Nam. Furthermore these bacteria have been found in the Hanoi environment and reported in a patient admitted to a Ho Chi Minh City hospital ,42. HighS. aureus is not.In one Hanoi hospital, SSIs were associated with increased post-operative stay (8.2 days) and excess direct costs (110 USD per patient) . HAIs arIn 2007 most district hospitals had infection control committees but could do little to tackle issues due to limited resources. It was noted that guidelines were often outdated . A recenEffective infection control is difficult as most Vietnamese hospitals are old, overcrowded and workloads are high. Bed occupancy can exceed 100%, especially during communicable disease outbreaks. The family is essential to care: bringing food, feeding and cleaning the patient, and this is difficult to monitor. Hospital water and solid waste is often disposed without pretreatment .Viet Nam is part of the WHO clean hands campaign and more than 40% of healthcare workers know the basics of hand hygiene, however lack of facilities are reported to underlie low compliance (13.4%) . SeveralSeventy percent of pharmaceuticals used in animals are antibiotics . Certainβ-lactams, aminoglycosides, macrolides, tetracyclines, (fluoro)quinolones, phenicols, pleuromutilins, lincosamides, sulfonamides, diaminopyrimidine (trimethoprim) [Many antibiotics used to treat human disease are used in agriculture: thoprim) . Farmersthoprim) . One stuthoprim) . AlarminCampylobacter in chickens was highest in Viet Nam [Salmonellae in retail chicken and pork meat is MDR, with 78.4% of isolates resistant to at least one antibiotic [In a study performed across 4 continents, prevalence of MDR Viet Nam . Sixty-stibiotic . An intetibiotic . Recentltibiotic .In June 2011 a policy workshop attended by local stakeholders representing the same areas of expertise as the initial stakeholder meeting was convened and the evidence gained from this situation analysis was discussed. Coordinated and concerted action was recognized as key to tackling antimicrobial resistance in Viet Nam and other emerging economies. This action must be carefully considered to minimize possible adverse health impacts.A better understanding of appropriate antimicrobial use must be fostered amongst clinicians. The development of a national antibiotic stewardship program is central to this. Surveillance programs that specifically monitor antimicrobial use in hospitals, the community and agriculture need to be established. Public educational initiatives should be considered and have potential for great impact given the high adult literacy rate of 93.4%. It was agreed that adequate legislation already exists to control antimicrobial resistance in Viet Nam but there is an urgent need to prioritize effective enforcement and imposition of appropriate penalties Table . Better 1. Enforcement of existing regulations involving antibiotic use in hospitals, the community and agriculture with stronger regulatory capacity and monitoring. The imposition of penalties in a more effective way should be considered.2. Develop an antibiotic stewardship program (ASP) with an ASP steering committee that includes standard treatment guideline (STG) development, implementation, regular updates, and audits. STGs need to be evidence based and use local epidemiology and resistance rates.3. Create three national surveillance programs and create the required national reference laboratories to ensure the availability and quality of testing for the surveillance program. The three national surveillance programs are:• Hospital antibiotic use and resistance (conducted by MoH)• Community antibiotic use and resistance (conducted by NIHE)• Antibiotic use, resistance and residue in animals (conducted by MARD).4. Improve access to non-medicated animal feed for farmers . It is r5. Improve education regarding antibiotic use and resistance for those working in the healthcare system and agriculture.6. The MoH and MARD are recommended to develop a joint action plan. During its development, stakeholders  should be consulted.NIHE = National Institute for Hygiene and Epidemiology.MARD = Ministry of Agriculture and Rural Development.FAO = Food and Agriculture Organization of the United Nations.Policy priorities proposed by local stakeholders during a policy workshop in June 2011 which has assisted the MoH with formulation of a national action plan to improve national capacity for antimicrobial stewardship in Viet Nam. Many of these priorities may be applicable to other emerging economies tackling the growing threat of antimicrobial resistance.Formulating policy to tackle antimicrobial resistance requires a broad analysis of a country and its health system to better understand the patterns and determinants that drive antibiotic use and resistance. To do this it is essential to consult local data, however this can be of poor quality, inadequate or absent. For example whilst substandard or counterfeit antibiotics  are not recognized as a particular problem in Viet Nam, there is insufficient data to draw reliable conclusions with respect to drug quality.We found that it was necessary to carefully examine the data and investigate the reliability of the sources before drawing conclusions upon which we could make credible policy recommendations. Identifying areas of sub-optimal data is important as it can motivate improvement. High quality local data is essential to allow effective interventions to be designed and appropriately targeted.Effective recommendations to alter antibiotic use must consider the incentives for manufacturers, providers and purchasers. Mapping and addressing of the incentive structures is difficult and requires long-term cooperation between local stakeholders and policy makers. Regular review of any intervention is necessary to assess whether it has been successful in modifying these incentives and changing behavior.Increased access to antibiotics has contributed to improved health outcomes in Viet Nam. However antibiotic overuse in hospitals, the community and agriculture has promoted rapid development of bacterial resistance, eroding the health asset antimicrobials constitute. As a result Viet Nam, like many emerging economies, faces a considerable challenge in attempting to control antimicrobial resistance.Antimicrobial resistance may represent the greatest global threat by an Emerging Infectious Disease issue. Its insidious nature may not have the cache of SARS, pandemic influenza or Ebola but its impact on public health is likely to be far greater. Like other Emerging Infectious Diseases, drug resistance can quickly spread from one country to another and hence the need for concerted national and international action.There is consensus amongst the political and medical leadership of Viet Nam that antibiotic resistance is a serious and growing problem. The emergence and spread of carbapenem-resistant Gram-negative bacteria, a phenomenon not unique to Viet Nam, illustrates this. High resistance rates mean that many antibiotic regimens in current treatment guidelines are already ineffective across a broad range of clinical syndromes and pathogens. There are many examples of legislation and initiatives designed to limit unnecessary antibiotic use Table . HoweverHigh individual out-of-pocket expenditure may have increased consumer control and weakened the influence of the State on the healthcare market. Policies to reduce out-of pocket expenditure through health insurance may reduce the ability of individuals to shape the healthcare market and be important in revitalizing the influence of the State . Point-oThere are many barriers preventing effective enforcement of regulations designed to improve antimicrobial stewardship in developing countries: insufficient funding and lack of expertise, human resources and financial incentives. It is important to foresee possible negative consequences of enforcement: financial losses and reduced healthcare access. Accounting for this will improve policy implementation in these settings. Furthermore, it is important to know where to focus regulatory efforts: a focal point too far downstream may create targets too numerous or dispersed for enforcement to be feasible.Patients, physicians, veterinarians, clinics and hospitals, and retailers – from large pharmacies to local drug sellers – have little motivation to weigh the negative impact of their antibiotic use on others, especially those in the future. Policy solutions must alter incentives for patients, physicians and others in the healthcare system to act in society’s best interests. Better quantification and mapping of the incentive structure for antibiotic prescribing in emerging economies would support the design of more effective interventions.Antibiotic resistance does not yet top any list of national healthcare problems for Viet Nam or other emerging economies. Antibiotic stewardship should not drain resources from more pressing concerns. Done correctly, controlling antibiotic resistance should either be cost neutral or one of the few health interventions that saves money.Recently the MoH in Viet Nam has approved a national action plan to control antibiotic resistance, which includes development of systematic surveillance structures to monitor antibiotic use and resistance, and laboratory participation in quality assurance schemes. However, it is not yet known what budget will be made available to implement this national action plan. Part of this analysis has provided important input to this initiative, illustrating that with relatively little effort and funds, a lot can be achieved on a national scale. We believe it can be a useful framework for similar initiatives in other countries, and emerging economies in particular.The authors’ declare that they have no competing interests.Conception and design: All authors, Data collection and analysis: All authors, Drafting of manuscript: KVN, NTTD, AC, HFLW, Final editing and approval: All authors.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2458/13/1158/prepub


An immunoglobulin G4 (IgG4)-related disease is important disease in differential diagnosis of tumors in kidney, pancreas, lung and other organs. The imaging findings of IgG4-related kidney diseases are usually expressed as defect contrast region, while cystic formation in kidney is extremely rare. Here, we report a case of IgG4-related tubulointerstitial nephritis with renal cystic change caused by the narrowing or obstruction of collecting duct in renal medulla.18 F-fluorodeoxyglucose (FDG)-PET/CT scan showed moderate FDG accumulation of cystic tumor in marginal lesion. In addition, FDG-PET/CT scan also showed moderate FDG accumulation in the pancreatic body. Laparoscopic right nephrectomy was performed. Histological examination was revealed lymphoplasmacytic infiltrate with focal fibrosis and severe narrowing or obstruction of lumen of collecting duct in renal medulla. Furthermore, the IgG4 positive plasma cells infiltrated exceeding 10 cells per one high-power field in renal medulla. The ratio of IgG4-plasma cells to IgG-positive plasma cells was about 50%. The serum level of IgG4 was also elevated (218 mg/dl). Based on these findings, we finally diagnosed IgG4-related tubulointerstitial nephritis with renal cystic change.Abdominal contrasted CT scan showed a 31 × 24 mm cystic tumor at the upper pole of the right kidney and multiple low-attenuation areas in the left kidney. IgG4-related kidney disease might cause cystic formation by severe narrowing and obstruction of collecting duct. An immunoglobulin G4 (IgG4)-related disease is a newly-proposed clinical disease entity characterized by elevated serum IgG4 and IgG4 positive plasma cell infiltration in various organs. IgG4-related disease was first described as autoimmune pancreatitis (AIP) and has subsequently been described in other organs -3. The aA 63-year-old woman was referred to Kochi University Hospital with a renal tumor discovered by medical examination, incidentally discovered on a computed tomography (CT) scan. There was no previous medical history and family history of kidney disease. Her vital signs were normal value. Blood electrolytes, proteinogram, renal function and hepatic enzymes showed all normal value. Soluble IL-2 receptor was slightly elevated ). The other tumor markers were all within the normal range. Abdominal contrasted CT scan showed a 31 × 24 mm cystic tumor at the upper pole of the right kidney and multiple low-attenuation areas in the left kidney . 18 F-fluorodeoxyglucose (FDG)-Positron Emission Tomography/Computed Tomography (PET/CT) scan showed moderate FDG accumulation of cystic tumor in marginal lesion (Figure n Figure a and b. n Figure c and d.In Figure e. The ran Figure f. In conn Figure g and h. n Figure a and b. n Figure c and d. To our knowledge, renal cystic formation of IgG4-related disease in our case is the first reported case in English literatures. The imaging findings of IgG4-related kidney diseases are usually expressed as defect contrast region based mainly on interstitial lesion. While, the mass formation is also found in some cases ,7. TheseOne might point that IgG4-related kidney disease occurred with simple renal cyst in this case. However, simple renal cyst generally arises from proximal origin  and she If this cystic tumor had been diagnosed as an IgG4-related kidney disease by needle biopsy before surgery, we could avoid unnecessary operation and provide steroid therapy. Therefore, it is important to consider a differential diagnosis with IgG4-related disease from malignant cystic disease similar to imaging in this case. Further case investigations on relationship between imaging findings and pathological results should be examined in IgG4-related kidney disease.IgG4-related kidney disease might cause cystic formation by severe narrowing and obstruction of collecting duct.Written informed consent was obtained from the patient for publication of this case report and the accompanying images. A copy of written consent is available for review by the Editor-in-Chief of this journal.IgG4: Immunoglobulin G4; AIP: Autoimmune pancreatitis; PAX: Paired box; EMA: Epithelial membrane antigen; RCC-Ma: Renal cell carcinoma marker antigen.The authors declare that they have no competing interests.HF drafted the report. YT, SF, KI, SF, YT and TS cared for patient and approved the final version of the manuscript. MM and NK performed histopathological examinations. All authors reviewed the report and approved final version of the manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2490/14/54/prepub