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Aim: We sought to investigate the release of neutrophil extracellular traps (NETs) in neutrophils from individuals with rheumatoid arthritis (RA) and controls and compare the presence of NETs in gingival tissues according to periodontal status. Also, the association between single nucleotide polymorphisms (SNPs) of the peptidyl arginine deaminase type 4 (PADI4) gene and the GTG haplotype with RA, periodontitis and NETs was evaluated in vitro. Materials and Methods: Peripheral neutrophils were isolated by density gradient, and NET concentration was determined by the PicoGreen method. Immunofluorescence was studied to identify NETs by co‐localization of myeloperoxidase (MPO)‐citrullinated histone H3 (H3Cit). Genotyping for SNPs (PADI4_89; PADI4_90; PADI4_92; and PADI4_104) was performed in 87 individuals with RA and 111 controls. Results: The release of NETs in vitro was significantly higher in individuals with RA and periodontitis and when stimulated with Porphyromonas gingivalis. Gingival tissues from subjects with RA and periodontitis revealed increased numbers of MPO‐H3Cit‐positive cells. Individuals with the GTG haplotype showed a higher release of NETs in vitro and worse periodontal parameters. Conclusions: The release of NETs by circulating neutrophils is associated with RA and periodontitis and is influenced by the presence of the GTG haplotype. [ABSTRACT FROM AUTHOR]

Aims: The differential diagnosis of small hepatocellular nodules in cirrhosis between dysplastic nodules and hepatocellular carcinoma (HCC) remains challenging on biopsy. As TERT promoter (pTERT) mutations may indicate the nodules already engaged in the malignant process, the aim of this study was to identify histological criteria associated with pTERT mutations by detecting these mutations by ddPCR in small formalin‐fixed paraffin‐embedded (FFPE) hepatocellular nodules arising in cirrhosis. Methods and results: We built a bicentric cohort data set of 339 hepatocellular nodules < 2 cm from cirrhotic samples, divided into a test cohort of 299 resected samples and a validation cohort of 40 biopsies. Pathological review, based on the evaluation of 14 histological criteria, classified all nodules. pTERT mutations were identified by ddPCR in FFPE samples. Among the 339 nodules, ddPCR revealed pTERT mutations in 105 cases (31%), including 90 and 15 cases in the test and validation cohorts, respectively. On multivariate analysis, three histological criteria were associated with pTERT mutations in the test cohort: increased cell density (P = 0.003), stromal invasion (P = 0.036) and plate‐thickening anomalies (P < 0.001). With the combination of at least two of these major criteria, the AUC for predicting pTERT mutations was 0.84 in the test cohort (sensitivity: 86%, specificity: 83%) and 0.81 in the validation cohort (sensitivity: 87%, specificity: 76%). Conclusions: We identified three histological criteria as surrogate markers of pTERT mutations that may be used in routine biopsy to more clearly classify small hepatocellular nodules arising in cirrhosis. [ABSTRACT FROM AUTHOR]

The properties of nanocomposites are directly affected by the filler–matrix interaction and therefore surface filler modification is often necessary to improve the mechanical properties of nanocomposites. Our study evaluated surface modification of sepiolite (SEP) on properties of poly(butylene adipate‐co‐terephthalate) (PBAT)‐based nanocomposites. The nanofillers were modified using two organic modifiers, octadecyl isocyanate (OI), and 3‐aminopropyltriethoxysilane (APTES). OI showed higher treatment efficiency than APTES and better results in alkyl groups on the surface of the nanofiller, with crystalline profile, which remained in the nanocomposites. The effect of organo‐sepiolites on the properties of PBAT nanocomposites was investigated by DSC, XRD, TGA, FTIR, scanning electron microscopy (SEM), and mechanical tensile tests. TGA analysis showed that the addition of O‐SEP on PBAT decreases its thermal stability. SEM analysis showed cavities and fiber tips in the matrix associated with clay agglomerates and some untreated clay faces, which impair filler‐matrix interfacial adhesion. Both treatments increased the elastic modulus and preserved the elongation and tensile strength of PBAT and the treatment with OI results in a higher modulus. Although some studies to improve the clay dispersion are necessary, the promising results reveal the potential of using OI and APTES as SEP modifiers to reinforce PBAT or other polyesters. [ABSTRACT FROM AUTHOR]

Consistent with other eukaryotes, the Trypanosoma brucei mitochondrial genome encodes mainly hydrophobic core subunits of the oxidative phosphorylation system. These proteins must be co‐translationally inserted into the inner mitochondrial membrane and are synthesized by the highly unique trypanosomal mitoribosomes, which have a much higher protein to RNA ratio than any other ribosome. Here, we show that the trypanosomal orthologue of the mitoribosome receptor Mba1 (TbMba1) is essential for normal growth of procyclic trypanosomes but redundant in the bloodstream form, which lacks an oxidative phosphorylation system. Proteomic analyses of TbMba1‐depleted mitochondria from procyclic cells revealed reduced levels of many components of the oxidative phosphorylation system, most of which belong to the cytochrome c oxidase (Cox) complex, three subunits of which are mitochondrially encoded. However, the integrity of the mitoribosome and its interaction with the inner membrane were not affected. Pull‐down experiments showed that TbMba1 forms a dynamic interaction network that includes the trypanosomal Mdm38/Letm1 orthologue and a trypanosome‐specific factor that stabilizes the CoxI and CoxII mRNAs. In summary, our study suggests that the function of Mba1 in the biogenesis of membrane subunits of OXPHOS complexes is conserved among yeast, mammals and trypanosomes, which belong to two eukaryotic supergroups. [ABSTRACT FROM AUTHOR]

Robust implementation of quantum key distribution requires precise state generation and measurements, as well as the choice of an optimal encoding to minimize channel disturbance. Time‐bin encoding represent a good candidate for fiber links as birefingence does not perturb this kind of states whereas stable and low‐error encoders and decoders are available for polarization encoding. Here a cross‐encoded scheme where high accuracy quantum states are prepared through a self‐compensating, calibration‐free polarization modulator and transmitted using a polarization‐to‐time‐bin converter is presented. The receiver performs time‐of‐arrival measurements in the key‐generation basis and converts qubits back to polarization encoding for measurements in the control basis. Temporal synchronization between the transmitter and receiver is performed with a qubit‐based method that does not require additional hardware to share a clock reference. The system is tested in a 12‐h run and demonstrates good and stable performance in terms of key and quantum bit error rates. The flexibility of this approach represents an important step toward the development of hybrid networks with both fiber‐optic and free‐space links. [ABSTRACT FROM AUTHOR]

Objective: To assess the burden and consequences of migraine in Brazil in terms of health‐related quality of life (HRQoL), work productivity and daily activities, and healthcare resource utilization (HRU). Background: Despite existing data on how migraine affects populations worldwide, there are limited data on the burden of migraine in Latin America. Methods: This cross‐sectional study used patient‐reported data from the 2018 Brazil National Health and Wellness Survey. HRQoL scores (EuroQol 5‐dimension 5‐level [EQ‐5D‐5L]; 36‐item Short Form Health Survey, version 2 [SF‐36v2]; and Short Form 6‐dimension [SF‐6D]), impairments to work productivity and daily activities (Work Productivity and Activity Impairment questionnaire), and all‐cause HRU were compared between migraine respondents and matched non‐migraine controls. Results: Of the 12,000 total respondents in the survey database, 1643 self‐reported a physician diagnosis of migraine and were propensity score matched 1:1 with controls without migraine. HRQoL was lower in patients with migraine versus non‐migraine controls, with significantly lower SF‐36v2 physical (mean [± SD] 50.3 [7.5] vs. 52.0 [7.6]) and mental component (mean [± SD] 42.9 [10.2] vs. 46.0 [9.9]) summary scores and SF‐6D (mean [± SD] 0.7 [0.1] vs. 0.7 [0.1]) and EQ‐5D‐5L (mean [± SD] 0.7 [0.2] vs. 0.8 [0.2]) utility scores (all p < 0.001). Patients with migraine reported higher levels of work productivity loss (mean [± SD], 40.6% [31.4%] vs. 28.6% [30.9%], including absenteeism 12.8% [19.1%] vs. 8.4% [17.1%] and presenteeism 35.0% [28.7%] vs. 24.8% [28.0%]; all p < 0.001); activity impairment (mean [± SD] 36.0% [28.8%] vs. 25.5% [28.1%]; p < 0.001); and significantly higher HRU in the past 6 months (healthcare provider and emergency department visits [mean [± SD] 7.2 [9.5] vs. 4.5 [6.3] and 1.7 [3.8] vs. 0.9 [2.2]; both p < 0.001] and hospitalizations [mean [± SD] 0.4 [2.7] vs. 0.2 [1.1]; p = 0.002]) than controls. Conclusion: Migraine is associated with poorer HRQoL, higher all‐cause HRU, and greater activity impairment and work productivity loss versus non‐migraine controls in Brazil. [ABSTRACT FROM AUTHOR]

Exonucleasic domain POLE (edPOLE) mutations, which are responsible for a hypermutated tumor phenotype, occur in 1–2% of colorectal cancer (CRC) cases. These alterations represent an emerging biomarker for response to immune checkpoint blockade. This study aimed to assess the molecular characteristics of edPOLE-mutated tumors to facilitate patient screening. Based on opensource data analysis, we compared the prevalence of edPOLE mutations in a control group of unselected CRC patients (n = 222) vs a group enriched for unusual BRAF/RAS mutations (n = 198). Tumor mutational burden (TMB) and immune infiltrate of tumors harboring edPOLE mutations were then analyzed. In total, 420 CRC patients were analyzed: 11 edPOLE-mutated tumors were identified, most frequently in microsatellite (MMR)-proficient young (< 70 years) male patients, with left-sided tumors harboring noncodon 12 KRAS mutation. The prevalence of edPOLE-mutated tumors in the control vs the experimental screening group was, respectively, 0.45% (n = 1) vs 5.0% (n = 10). Among the 11 edPOLE-mutated cases, two had a low TMB, three were hypermutated, and six were ultramutated. EdPOLE-mutated cases had a high CD8+ tumor-infiltrating lymphocyte (TIL) infiltration. These clinicopathological and molecular criteria may help to identify edPOLE mutations associated with a high TMB in CRC, and improve the selection of patients who could benefit from immunotherapy. [ABSTRACT FROM AUTHOR]

The article investigates the prognostic value of psoas muscle area (PMA) in patients undergoing vascular surgery. Topics discussed include link between sarcopenia and poor surgical outcomes in high-risk surgeries, mortality after aortic aneurysm repair and lower limb revascularization, and how PMA can help clinicians identify patients who might benefit from interventions prior to surgery.

Background: IgG4‐related disease is a fibroinflammatory and immune‐mediated condition, which has extremely variable clinical manifestations. In this study, we aim to investigate the clinicopathological features of IgG4‐related disease involving the oral and maxillofacial region. Methods: Cases of IgG4‐related disease manifesting in the oral and maxillofacial region were retrieved from three Brazilian institutions. Clinical and serological data were obtained from the patients' medical charts, while microscopic and immunohistochemical findings were revised by oral pathologists. Diagnosis followed the American College of Rheumatology/European League against Rheumatism criteria. Results: Seven patients diagnosed with IgG4‐related disease were included in this study. Women were affected in all analysed cases, with a mean age of 55.4 years. Two patients presented with the clinical involvement of more than one oral and maxillofacial anatomic site. Therefore, our sample comprised nine oral and maxillofacial anatomic sites affected by IgG4‐related disease. The submandibular gland was affected in four cases, the tongue and the parotid gland in two cases each, and the palate in one case. In a few cases, exploratory lower lip biopsy was used as a diagnostic approach. A moderate‐to‐severe lymphoid infiltrate containing plasma cells and lymphocytes, with an increased IgG4/IgG ratio, was common. Treatment varied and steroids were the most frequently used (57.4%). Six patients remained alive, while one died from unknown causes. Conclusion: Although major salivary glands are commonly affected by IgG4‐related disease, the oral cavity can also be involved, and lower lip biopsy may be an auxiliary diagnostic tool. [ABSTRACT FROM AUTHOR]

Tumour diagnosis relies on the visual examination of histological slides by pathologists through a microscope eyepiece. Digital pathology, the digitalization of histological slides at high magnification with slides scanners, has raised the opportunity to extract quantitative information due to image analysis. In the last decade, medical image analysis has made exceptional progress due to the development of artificial intelligence (AI) algorithms. AI has been successfully used in the field of medical imaging and more recently in digital pathology. The feasibility and usefulness of AI assisted pathology tasks have been demonstrated in the very last years and we can expect those developments to be applied to routine histopathology in the future. In this review, we will describe and illustrate this technique and present the most recent applications in the field of tumour histopathology. LINKED ARTICLES: This article is part of a themed issue on Molecular imaging - visual themed issue. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v178.21/issuetoc. [ABSTRACT FROM AUTHOR]

This article is a response to a letter regarding a study on the role of microvascular invasion (mVI) in predicting the recurrence of hepatocellular carcinoma (HCC) after resection. The authors clarify that mVI is defined as the presence of vascular invasion of small vessels, and this definition is widely accepted among pathologists. They also state that all surgical specimens in their study were analyzed by trained pathologists, and the calibration between predicted and observed recurrence rates was excellent. The prevalence of mVI in their study falls within the range reported in other recent publications. The authors conclude that their study provides a robust framework for stratifying the risk of HCC recurrence after resection. [Extracted from the article]

This work is an investigation of the effect of different nanofillers: organically modified montmorillonite (MMT), sepiolite (SEP) and nano titanium dioxide (nTiO2) and combination of them in poly(butylene adipate‐co‐terephthalate) (PBAT) films. Thermal morphological and rheological analyses were conducted to explain the behavior of this nanoparticles on O2 and water vapor permeability coefficients, light transmission, and mechanical properties presented in previous study. Thermal stability of the nanocomposites was slightly decreased by the nanofillers presence. Differential scanning calorimetry and X‐ray analyses were carried out to investigate the crystallization behavior of nanocomposites. Transmission electron microscopic analysis showed regular and homogeneous dispersion of the nanoparticles, but scanning electron microscopy showed lack of adhesion in the sepiolite‐PBAT interface. Rheological measurements showed significant increase in both complex viscosity and storage modulus due to interactions between clays and PBAT and the effect of sepiolite and nTiO2 on improving the exfoliation of montmorillonite as synergism between the nanofillers. [ABSTRACT FROM AUTHOR]

This work evaluated the effect of the combination of nanofillers: organically modified montmorillonite (MMT), sepiolite (SEP) and nano titanium dioxide (TiO2) on the oxygen and water vapor permeability coefficients, light transmission and mechanical properties of poly(butylene adipate‐co‐terephthalate) (PBAT) aiming at packaging application. The clays concentrations were chosen considering percolation threshold from the clays aspect ratio by TEM analyses. Comparing to neat PBAT, oxygen and vapor permeability coefficients showed reduction with the increase of MMT while SEP and nano‐TiO2 did not show significant influence. However, nano‐TiO2 was the only filler able to reduce UV and visible light transmission. Nanofillers and their combinations showed to be statistically significant for the increase in Young's modulus, although the tensile strength and elongation showed no influence. The results were discussed in terms of the fillers' morphology and dispersion. Nielsen's model was applied to estimate the aspect ratio of the MMT in nanocomposites. [ABSTRACT FROM AUTHOR]

Currently, several small-molecule inhibitors are investigated in clinical trials for cholangiocarcinoma patients such as ERK1/2 oral inhibitors (NCT04566393), BRAF inhibitor (NCT04190628), or IDH1 inhibitor (NCT02989857). According to their anatomical origin along the biliary tree, CCAs are classified into three distinct entities: intrahepatic CCAs (iCCA), hilar or peri-hepatic tumors, and distal CCAs developed from the extrahepatic bile ducts. ICCA is the second most common liver cancer after hepatocellular carcinoma, and shows a poor overall prognosis with a 5-year survival less than 10% for patients with advanced disease. [Extracted from the article]

Background & aims: The recent approval of direct acting anti‐virals (DAA) has dramatically changed the landscape of hepatitis C virus (HCV) therapy. Whether viral clearance could promote liver carcinogenesis is debated. It has been hypothesized that changes in intrahepatic immune surveillance following viral cure could favour tumour growth. This study aimed at characterizing the intrahepatic immune changes induced by HCV cure following DAA therapy. Methods: Patients with compensated cirrhosis who underwent surgical resection for hepatocellular carcinoma (HCC) after sustained virological response (SVR) to DAA therapy were included. A control group of untreated HCV‐infected patients with compensated cirrhosis was selected. RNA was extracted from tumoral and non‐tumoral tissues and analysed using the Nanostring Immuno‐Oncology‐360 panel. Immune cells were quantified by immunohistochemistry. Results: Twenty patients were included: 10 patients with a DAA‐induced SVR and 10 untreated controls. All of them had a de novo BCLC 0/A HCC. Non‐tumoral tissue profiling showed down‐regulation of interferon‐related genes (including MX1, ISG15 and IFIT1) after DAA therapy. No other differences in immune profiles/immune cell densities were identified between the two groups. The intra‐tumoral immune profiles of HCCs that occurred after DAA therapy were not qualitatively or quantitatively different from those of tumours occurring in untreated patients. Conclusion: In conclusion, removal of HCV infection after DAA‐based therapy results only in a down‐regulation of interferon‐stimulated genes in non‐tumoral tissues from patients with cirrhosis who develop HCC. These minor changes in the liver immune microenvironment are unlikely to favour HCC occurrence or recurrence after DAA‐induced SVR. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between oral piercings and periodontal health or inflammation in patients seeking treatment at the University of Basel, Switzerland. Material and methods: Records of patients from the pool of patients at the Department of Periodontology, Endodontology and Cariology were consecutively screened between November 2016 and January 2017. Eighteen patients with a tongue and/or a lip piercing were included. Three out of 18 patients wore both piercings, that is 14 tongue piercings and seven lip piercings were assessed. Epidemiologic, socio‐economic, piercing characteristics and clinical parameters were recorded. Periodontal findings in teeth close to the piercing were compared to the parameters of the total dentition. Results: In patients with a tongue piercing (n = 14), percentages of sites with bleeding on probing, probing pocket depths ≥6 mm, clinical attachment loss ≥6 mm and gingival recessions ≥2 mm were more frequently increased in teeth close to the piercing compared to teeth not affected by the piercing. In patients with a lip piercing (n = 7), periodontal findings did not differ markedly in teeth close to the piercing compared to teeth not affected by the piercing. Conclusions: Tongue piercings may negatively affect periodontal conditions of teeth with close proximity to the piercing. [ABSTRACT FROM AUTHOR]

Few single nucleotide polymorphisms (SNPs) have been reproducibly associated with hepatocellular carcinoma (HCC). Our aim was to test the association between nine SNPs and HCC occurrence. SNPs in genes linked to HCC (DEPDC5, GRIK1, KIF1B, STAT4, MICA, DLC1, DDX18) or to liver damage (PNPLA3‐rs738409, TM6SF2‐rs58542926) in GWAS were genotyped in discovery cohorts including 1,020 HCC, 2,021 controls with chronic liver disease and 2,484 healthy individuals and replication was performed in prospective cohorts of cirrhotic patients with alcoholic liver disease (ALD, n = 249) and hepatitis C (n = 268). In the discovery cohort, PNPLA3 and TM6SF2 SNPs were associated with HCC (OR = 1.67 [CI95%:1.16–2.40], p = 0.005; OR = 1.45 [CI95%:1.08–1.94], p = 0.01) after adjustment for fibrosis, age, gender and etiology. In contrast, STAT4‐rs7574865 was associated with HCC only in HBV infected patients (p = 0.03) and the other tested SNP were not linked with HCC risk. PNPLA3 and TM6SF2 variants were independently associated with HCC in patients with ALD (OR = 3.91 [CI95%:2.52–6.06], p = 1.14E‐09; OR = 1.79 [CI95%:1.25–2.56], p = 0.001) but not with other etiologies. PNPLA3 SNP was also significantly associated with HCC developed on a nonfibrotic liver (OR = 2.19 [CI95%:1.22–3.92], p = 0.007). The association of PNPLA3 and TM6SF2 with HCC risk was confirmed in the prospective cohort with ALD. A genetic score including PNPLA3 and TM6SF2 minor alleles showed a progressive significant increased risk of HCC in ALD patients. In conclusion, PNPLA3‐rs738409 and TM6SF2‐rs58542926 are inherited risk variants of HCC development in patients with ALD in a dose dependent manner. The link between PNPLA3 and HCC on nonfibrotic liver suggests a direct role in liver carcinogenesis. What's new? Multiple single nucleotide polymorphisms (SNPs) have been associated with hepatocellular carcinoma (HCC) through genome‐wide association studies (GWAS). Few of these variants, however, have been cross‐validated, raising questions about their relation to HCC. Here, nine SNPs previously linked to HCC or liver damage were selected for investigation in European patients. Two of the variants, PNPLA3 rs738409 and TM6SF2 rs58542926, were found to be associated with HCC risk specifically in patients with alcoholic liver disease. PNPLA3 rs738409 was also associated with HCC in patients with nonfibrotic livers, where it potentially influences liver carcinogenesis via modification of protein function without altering gene expression. [ABSTRACT FROM AUTHOR]

Background: In 2012, the Liver Transplant French Study Group built the alpha-fetoprotein-score (AFP-score), which improved significantly the prediction of tumor recurrence in case of liver transplantation for HCC when compared to Milan criteria. The aim of the study was to test the AFP score in case of liver resection (LR) for HCC.Methods: From 1990 to 2012, 347 patients underwent a liver resection for HCC developed on chronic liver disease (CLD). All patients with solitary HCC <60 mm were included. The primary end point was to investigate if the AFP-score at the first LR was predictive of recurrence and if recurrence occurred within the AFP-score. The secondary end points were overall survival (OS) and disease-free survival.Results: One hundred and eight patients fulfilled the inclusions criteria. After a median follow-up of 65.4IQR [13-114] months, recurrence occurred in 64.8% (70/108) patients. Among the study population, 96 were "in AFP-score" (i.e., ≤2) of whom 60.4% (58/96) developed a recurrence that was cured in curative intent. In contrast, all patients "out AFP-score" experienced recurrence, and 25% were eligible for curative treatment. At the end of the follow-up, 26 patients were listed for liver transplantation (LT). Among them, 21 were finally transplanted. The 5-year OS after salvage LT was 68.5%95%CI [50.2-93.0].Conclusion: AFP-score is a useful tool for patients selection after LR for solitary HCC developed on CLD. For patients "in AFP-score," up-front LR provides good survival and allows to avoid up-front LT in case of recurrence. [ABSTRACT FROM AUTHOR]

Abstract: Glycogen storage disease type I (GSDI) is a rare genetic pathology characterized by glucose‐6 phosphatase (G6Pase) deficiency, translating in hypoglycemia during short fasts. Besides metabolic perturbations, GSDI patients develop long‐term complications, especially chronic kidney disease (CKD). In GSDI patients, CKD is characterized by an accumulation of glycogen and lipids in kidneys, leading to a gradual decline in renal function. At a molecular level, the activation of the renin‐angiotensin system is responsible for the development of renal fibrosis, eventually leading to renal failure. The same CKD phenotype was observed in a mouse model with a kidney‐specific G6Pase deficiency (K.G6pc−/− mice). Furthermore, GSDI patients and mice develop frequently renal cysts at late stages of the nephropathy, classifying GSDI as a potential polycystic kidney disease (PKD). PKDs are genetic disorders characterized by multiple renal cyst formation, frequently caused by the loss of expression of polycystic kidney genes, such as PKD1/2 and PKHD1. Interestingly, these genes are deregulated in K.G6pc−/− kidneys, suggesting their possible role in GSDI cystogenesis. Finally, renal cysts are known to predispose to renal malignancy development. In addition, HNF1B loss is a malignancy prediction factor. Interestingly, Hnf1b expression was decreased in K.G6pc−/− kidneys. While a single case of renal cancer has been reported in a GSDI patient, a clear cell renal carcinoma was recently observed in one K.G6pc−/− mouse (out of 36 studied mice) at a later stage of the disease. This finding highlights the need to further analyze renal cyst development in GSDI patients in order to evaluate the possible associated risk of carcinogenesis, even if the risk might be limited. [ABSTRACT FROM AUTHOR]

Hereditary hemochromatosis (HH) is a genetic disease associated with progressive iron overload, eventually leading in some cases to damage of parenchymal organs, such as the liver, pancreas, and heart. Although the gene had been identified (HFE), HH pathogenesis remains to be fully elucidated. We report here, for the first time, a case of inadvertent transplantation of a liver from a donor with C282Y/H63D compound heterozygosity into a nonhemochromatotic 19-year-old Caucasian male recipient with primary sclerosing cholangitis. Progressive iron overload occurred over 1.5 years, as observed in liver biopsies and iron studies, after ruling out secondary causes of iron overload. This case strengthens the hypothesis that the liver, rather than the small intestine, plays a primary role in the maintenance of iron homeostasis. [ABSTRACT FROM AUTHOR]

Background & Aim Sorafenib is the standard of care for patients with hepatocellular carcinoma ( HCC) and macrovascular invasion ( MVI), with limited survival. Retrospective surgical studies have reported prolonged survival in this situation. This study aimed to compare the overall survival of patients with HCC and MVI treated with surgical resection or sorafenib. Methods A total of 143 patients with HCC and MVI but no extra-hepatic spread, treated with surgical resection ( SR-patients; n=75) or sorafenib ( SOR-patients; n=68) in four French centres between 1990 and 2013 were reviewed retrospectively. A propensity score analysis was performed to reduce bias. Results SR-patients were significantly younger and had a lower tumour burden than SOR-patients. Median overall survival ( OS) rates were 10.1 months [95% CI: 4.1-16.1] in SR-patients and 12.9 months [95% CI: 7.9-17.9] in SOR-patients ( P=.959). The 90-day mortality rate was 16% (n=12) in SR-patients and 7.5% (n=5) in SOR-patients ( P=.196). SR-patients had a median disease-free survival of 4.60 months [95% CI: 3.3-5.9]. Under the propensity analysis, median OS was 12.0 months [95% CI: 5.5-18.5] in SR-patients vs 9.7 months [95% CI: 6.1-13.3] in SOR-patients ( P=.682). Under multivariate analysis, extensive MVI ( HR=1.956, P=.024) and bilirubin >17 μmol/L ( HR=1.738, P=.011) were the two factors significantly associated with mortality. Conclusion Under a propensity score analysis, the overall survival of patients with HCC and MVI undergoing surgical resection was similar to that achieved with sorafenib. We were not able to identify a patient subgroup experiencing a surgery-related improvement in survival, and quality of life was not evaluable. [ABSTRACT FROM AUTHOR]

Citrus fruit and juices represent one of the main sources of compounds with a high potential for health promoting properties. Among these compounds, flavanones (such as hesperetin, naringenin, eriodictyol, isosakuranetin, and their respective glycosides), which occur in quantities ranging from ∼180 to 740 mg/L (depending on the Citrus species and cultivar) are responsible for many biological activities. These compounds support and enhance the body's defenses against oxidative stress and help the organism in the prevention of cardiovascular diseases, atherosclerosis, and cancer. Moreover, among other properties, they also show anti-inflammatory, antiviral, and antimicrobial activities. This review analyzes the biochemistry, pharmacology, and biology of Citrus flavanones, emphasizing the occurrence in Citrus fruits and juices and their bioavailability, structure-function correlations and ability to modulate signal cascades both in vitro and in vivo. © 2017 BioFactors, 43(4):495-506, 2017 [ABSTRACT FROM AUTHOR]

The dysplasia epiphysealis hemimelica (DEH) is a rare disease of unknown etiology consisting in an abnormal osteocartilaginous growth at the epiphysis, usually hemimelic with histological findings similar to benign osteochondroma. In this case series, we described the results of the arthroscopic treatment of 2 consecutive cases of intra-articular ankle localization of DEH in 2 patients aged 9 and 10 years. The good result obtained, persistent at the 5-year follow-up, leads us to consider the arthroscopic approach as a reliable treatment in patient affected by intra-articular ankle DEH. [ABSTRACT FROM AUTHOR]

Aim Discordance between pre- LT imaging and explanted liver findings have been reported after liver transplantation ( LT) for hepatocellular carcinoma ( HCC), suggesting the need of reassessing the risk of HCC recurrence post- LT. Our aims were to compare pre- LT imaging and explants features and to test the performances of four explant-based predictive models of recurrence in an external cohort. Methods Staging according to pre- LT imaging and explant features were compared. Four explants-based models were retrospectively tested in a cohort of 372 patients transplanted for HCC in 19 French centres between 2003 and 2005. Accuracies of the scores were compared. Results Pre- LT imaging underestimated tumour burden in 83 (22.7%) patients according to Milan criteria. The highest AUCs for prediction of 5-years recurrence were observed in the 'Up to seven' (0.7915 [95% CI: 0.7339-0.849]) and Decaens models (0.747 [95% CI: 0.6877-0.806]), with two levels of risk: low (10%) and high (>50%). Chan and Iwatsuki models identified 3 and 4 levels of risk, but had lower AUCs (0.68 and 0.70) respectively. Accuracy of the 'Up to seven' model was superior to the Decaens model ( P=.034), which was superior to the Chan model ( P=.0041) but not to the Iwatsuki model ( P=.17). Conclusion Pre- LT imaging underestimates tumour burden, and prediction of recurrence should be reassessed after LT. The explant-based 'Up to seven' and Decaens models provided the best accuracy for prediction of 5-year recurrence, identifying only two levels of risk. New models are needed to further refine the prediction of recurrence after LT. [ABSTRACT FROM AUTHOR]

Introduction. The vascularized corticoperiosteal flap is harvested from the medial femoral condyle and it is nourished by the articular branch of the descending genicular artery and the superomedial genicular artery. This flap is usually harvested as a free flap for the reconstruction of bone defects at forearm, distal radius, carpus, hand, and recently at lower limb too. Case Report. A 50-year-old Caucasian man referred to our department for hypertrophic nonunion of the distal femur, refractory to the conservative treatments. The first surgical choice was the revision of the nail and the bone reconstruction with a corticoperiosteal pedicled flap from the medial femoral condyle. We considered union to have occurred 3.5 months after surgery when radiographs showed bridging of at least three of the four bony cortices and clinically the patient was able to walk with full weight bearing without any pain. At the last follow-up (25 months), the patient was completely satisfied with the procedure. Discussion. The corticoperiosteal flap allows a faster healing of fractures with a minimal morbidity at the donor site. We suggest that the corticoperiosteal pedicled flap graft is a reliable and effective treatment for distal femur nonunion. [ABSTRACT FROM AUTHOR]

Purpose: To determine the value of quantitative analysis of the hepatobiliary phase (HBP) in gadobenate dimeglumine (Gd-BOPTA)-enhanced magnetic resonance imaging (MRI) to differentiate focal nodular hyperplasia (FNH) from hepatocellular adenoma (HCA).Materials and Methods: Thirty-eight patients bearing 67 lesions (40 FNH; 27 HCA) were retrospectively included in this Institutional Review Board-approved study. The same volumetric interpolated breath-hold examination (VIBE) T1 -weighted sequences were performed before and after contrast injection on a 1.5T MRI, with HBP images acquired with a mean delay of 80 minutes (range 60-120 min). After a visual assessment of lesions enhancement (qualitative HBP analysis), the HBP signal intensity ratio (SIR) and the lesion-to-liver contrast enhancement ratio (LLCER) were calculated for each lesion by two observers (Mann-Whitney test). The sensitivities, specificities (receiver operating characteristic [ROC] curve analysis) and interobserver correlation (intraclass coefficient, ICC) of quantitative HBP analysis were determined.Results: All FNH and 44.4% of HCA appeared hyper- or isointense relative to the adjacent liver on qualitative HBP analysis. The mean SIR (P < 0.01) and LLCER (P < 0.0001) of FNH were significantly higher than that of HCA. The area under the ROC curve for the differentiation of FNH from HCA with LLCER was 0.98 for both observers. With a cutoff value of -0.3%-observer 1 with highest experience- LLCER assessment provided respective sensitivity and specificity values of 100% and 96.2% for the differentiation of FNH from HCA. The ICC was 0.7 for SIR measurements and 0.8 for LLCER measurements.Conclusion: Quantitative LLCER assessment allows an accurate differentiation of FNH from HCA, even in hyper- or isointense HCA on HBP images. [ABSTRACT FROM AUTHOR]

BACKGROUND: Medulloblastoma (MB) is the most common malignant pediatric brain tumor and is currently treated with combined therapies. Recent advances in genetics and protein expression in this entity have led to the elaboration of a new molecular classification, and novel targeted therapies are currently under trial. This objective of this study was to describe the cytomorphologic features of MB in cerebrospinal fluid (CSF). METHODS: The authors conducted a retrospective study of 194 CSF samples from 70 pediatric patients who had a history of primary MB. The samples consisted of CSF cytospins that were stained according to the May-Grunwald Giemsa and/or Papanicolaou methods. RESULTS: In 32 patients, it was possible to establish a confident diagnosis of metastatic MB. Common morphologic features included cell clustering, nuclear irregularity, molding and enlargement, and prominent nucleoli. Multinucleation as well as mitotic and apoptotic figures were less frequently observed. Fifteen samples that presented neither cell clustering nor nuclear molding were classified as suspicious. CONCLUSIONS: Cell clustering with nuclear molding is a key feature for the diagnosis of leptomeningeal metastasis of MB. [ABSTRACT FROM AUTHOR]

Aims Bile duct adenomas ( BDA) and bile duct hamartomas ( BDH) are benign bile duct lesions considered neoplastic or secondary to ductal plate malformation, respectively. We have reported previously a high prevalence of BRAF V600E mutations detected by allele-specific polymerase chain reaction assay in BDA, and suggested that BDA may be precursors to a subset of intrahepatic cholangiocarcinomas harbouring V600E mutations. The aim of the present study was to assess the existence of BRAF V600E mutations, using immunohistochemical methods, in additional BDA as well as in BDH. Methods and results Fifteen BDA and 35 BDH were retrieved from the archives of the pathology departments of two French university hospitals. All cases were reviewed by two pathologists specialized in liver diseases. BRAF V600E mutational status was investigated by immunohistochemistry. Mutated BRAF mutant protein was detected in 53% of the BDA and in none of the cases of BDH. Conclusion Our findings suggest that BDA and BDH are different processes, and that BDA represent true benign neoplasms. They also support the hypothesis that mutated BDA might precede the development of the subset of intrahepatic cholangiocarcinomas harbouring BRAF V600E mutations. [ABSTRACT FROM AUTHOR]

The PI3K/AKT pathway is considered to play a major role in bladder carcinogenesis, but its relationships with other molecular alterations observed in bladder cancer remain unknown. We investigated PI3K/AKT pathway activation in a series of human bladder urothelial carcinomas (UC) according to PTEN expression, PTEN deletions and FGFR3, PIK3CA, KRAS, HRAS, NRAS and TP53 gene mutations. The series included 6 normal bladder urothelial samples and 129 UC (Ta n = 25, T1 n = 34, T2-T3-T4 n = 70). Expression of phospho-AKT (pAKT), phospho-S6-Ribosomal Protein (pS6) (one downstream effector of PI3K/AKT pathway) and PTEN was evaluated by reverse phase protein Array. Expression of miR-21, miR-19a and miR-222, known to regulate PTEN expression, was also evaluated. pAKT expression levels were higher in tumors than in normal urothelium ( p < 0.01), regardless of stage and showed a weak and positive correlation with pS6 (Spearman coefficient RS = 0.26; p = 0.002). No association was observed between pAKT or pS6 expression and the gene mutations studied. PTEN expression was decreased in PTEN-deleted tumors, and in T1 ( p = 0.0089) and T2-T3-T4 ( p < 0.001) tumors compared to Ta tumors; it was also negatively correlated with miR-19a ( RS = −0.50; p = 0.0088) and miR-222 ( RS = −0.48; p = 0.0132), but not miR-21 ( RS = −0.27; p = 0.18) expression. pAKT and PTEN expressions were not negatively correlated, and, on the opposite, a positive and moderate correlation was observed in Ta ( RS = 0.54; p = 0.0056) and T1 ( RS = 0.56; p = 0.0006) tumors. Our study suggests that PI3K/AKT pathway activation occurs in the entire spectrum of bladder UC regardless of stage or known most frequent molecular alterations, and independently of low PTEN expression. [ABSTRACT FROM AUTHOR]

This further allows the uptake of tumour antigens from dying tumour cells and an optimal antigen presentation to T cells. Indeed, several reported HCC subtypes are known to be linked to distinct biological features, and tumours mutated for CTNNB1 have the ability to exclude T cells from their microenvironment and may thus be less sensitive to these approaches.11-14 There are also, however, several unanswered questions: what is the optimal sequencing/timing for both therapies? The landscape of therapeutic agents for hepatocellular carcinoma (HCC) is rapidly evolving, with the standard of care for patients with advanced disease now being the association of atezolizumab, an immunomodulator, and bevacizumab, an anti-angiogenic agent.1 Durable responses have been also observed with the immune checkpoint inhibitor nivolumab, and they may be preferentially observed for tumours with particular gene expression inflammatory signatures.2 The overall prognosis of patients, however, remains poor, and one of the next challenges to enhance the efficacy of immunotherapy will be to assess the benefits of its association with locoregional treatments (LRT), such as percutaneous ablation or transarterial chemo-embolisation (TACE). [Extracted from the article]

An introduction is presented in which the editor discusses various reports within the issue on topics including cyberactivism as a tool of collective action and an object of policy, how the regulation of copyright issues opens up new spaces of contentious politics and climate change campaign.

Improper use of electronic media is considered a major contributing factor to childhood obesity. However, exergames, a new generation of active games, have made it possible to combine electronic entertainment with physical exercise. The purpose of this systematic review was to analyze the use of exergaming as a strategic tool in the fight against childhood obesity. Information was retrieved from the databases SciELO, LILACS, Pubmed, Ebsco, and Science Direct, using the search words “egames,” “exergames,” “exergaming,” “new generation of video games,” “active video games,” “energy expenditure,” “body composition,” and “physical activity” in English and Portuguese, covering the period January 2008 to April 2012. Nine articles met the inclusion criteria. Exergaming was found to increase physical activity levels, energy expenditure, maximal oxygen uptake, heart rate, and percentage of physical activity engaged in and to reduce waist circumference and sedentary screen time. Thus, exergaming may be considered a highly relevant strategic tool for the adoption of an active and healthy lifestyle and may be useful in the fight against childhood obesity. [ABSTRACT FROM AUTHOR]

Calderaro J, Moroch J, Pierron G, Pedeutour F, Grison C, Maillé P, Soyeux P, de la Taille A, Couturier J, Vieillefond A, Rousselet M C, Delattre O & Allory Y (2012) Histopathology 61, 428-435 SMARCB1/INI1 inactivation in renal medullary carcinoma Aims: Renal medullary carcinoma (RMC), a rare and highly aggressive tumour which occurs in patients with sickle-cell disease, shares many clinicopathological features with collecting duct carcinoma (CDC). The molecular mechanisms underlying RMC and CDC are mainly unknown, and there is ongoing debate about their status as distinct entities. Loss of expression of SMARCB1/INI1, a chromatin remodelling regulator and repressor of cyclin D1 transcription, has been reported recently in RMC. The aim of our study was to investigate if such loss of expression is specific for RMC. SMARCB1/INI1 genetic alterations and cyclin D1 expression were also studied. Methods and results: Using immunochemistry, neoplastic cells showed complete loss of SMARCB1/INI1 expression in all six cases of RMC but in only one of 22 cases of CDC. In two RMC cases investigated, comparative genomic hybridization demonstrated complete loss of one SMARCB1/INI1 allele, with no other genomic imbalances, and no mutations were found on the remaining allele. Cyclin D1 was expressed in all RMCs, suggesting that SMARCB1/INI1 inactivation may result in increased cyclin D1 transcription. Conclusions: The specific SMARCB1/INI1 inactivation observed in RMCs suggests that RMC and CDC are different entities. [ABSTRACT FROM AUTHOR]

Although a number of enteric viruses have been identified in children with acute gastroenteritis, the majority of cases of gastroenteritis remain undiagnosed. In order to provide more insights into the epidemiology of enteric viruses that are not included usually in routine diagnostic tests, cases of childhood sporadic gastroenteritis of unknown etiology requiring hospital admission in Parma, Italy, during 2008-2009, were screened for astrovirus (AstV), sapovirus (SaV), and bocavirus (BoV). The stools of 712 children, negative for rotavirus, norovirus, adenovirus, enterovirus, and reovirus, were examined by PCR or RT-PCR for AstV, BoV, and SaV. The prevalence of AstV, BoV, and SaV in the patients examined was 2.1%, 3.2%, 2.4%, respectively, with the viruses being detected mostly in children <3 years of age. AstV strains were characterized by sequencing as types 1, 2, and 4, with a AstV-1 peak occurring in the 2008 fall-winter season. BoV strains were characterized as types 1, 2, and 3, with BoV-3 circulating more frequently in the 2008 autumn and winter season and BoV-2 during March-April 2009. The most common SaVs were GI.2 and GII.1 while GIV and GV SaVs were detected sporadically. Overall, AstV, BoV, and SaV infections accounted for 7.7% of the sporadic cases of acute gastroenteritis with unknown etiology selected for the study. Different virus types and lineages were found to circulate and temporal peaks of virus activity were also demonstrated, suggesting either small clusters of infections or small outbreaks or epidemics in local population. J. Med. Virol. 84:643-650, 2012. © 2011 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

A fuzzy controller for improving Fault Ride-Through (FRT) capability of Variable Speed Wind Turbines (WTs) equipped with Doubly Fed Induction Generator (DFIG) is presented. The controller is designed in order to compensate the voltage at the Point of Common Coupling (PCC) by regulating the reactive and active power generated by WTs. The performances of the controller are evaluated in some case studies considering a different number of wind farms in different locations. Simulations, carried out on a real 37-bus Italian weak distribution system, confirmed that the proposed controller can enhance the FRT capability inmany cases. [ABSTRACT FROM AUTHOR]

Intracystic papillary carcinoma (IPC), a breast tumor mainly occuring in the elderly, has long been considered as a variant of ductal carcinoma in situ (DCIS). This is now debated since metastatic cases have been reported. In this study, surgical pieces of 20 IPCs were reassessed, and markers of myopepithelial layer (p63, CD10 and Smooth Muscle Actin) as well as estrogen receptors (ER) and progesterone receptors (PgR) and C-erb-B2 oncoprotein expression were systematically performed and quantified. In 10 cases, an associated unequivocal invasive component was found. In all 20 cases, no myoepithelial layer was found. Eighteen tumors were ER positive, 14 were PgR positive. Moreover, none of the tumors over-expressed C-erb-B2 oncoprotein. Therefore this study showed that in all cases of IPC there were microscopic features of invasive carcinoma despite good clinical prognostic indicators, and that precise characterization of tumors requires extensive paraffin embedding of surgical pieces. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate an occupational therapy nutrition education programme for children who are obese with the use of two interactive games. A quasi-experimental study was carried out at a municipal school in Fortaleza, Brazil. A convenient sample of 200 children ages 8–10 years old participated in the study. Data collection comprised a semi-structured interview, direct and structured observation, and focus group, comparing two interactive games based on the food pyramid (video game and board game) used individually and then combined. Both play activities were efficient in the mediation of nutritional concepts, with a preference for the board game. In the learning strategies, intrinsic motivation and metacognition were analysed. The attention strategy was most applied at the video game. We concluded that both games promoted the learning of nutritional concepts. We confirmed the effectiveness of the simultaneous application of interactive games in an interdisciplinary health environment. It is recommended that a larger sample should be used in evaluating the effectiveness of play and video games in teaching healthy nutrition to children in a school setting. Copyright © 2008 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Aim: Our study reports the detection and identification of intestinal spirochetosis in patients with colonic diseases in a tertiary-care hospital over a 12-year period, and includes a description of all cases we diagnosed. Methods: Our patients (8323) underwent colonoscopy and histopathological examinations including transmission electron microscopy (TEM) and light microscopy. Specimens from patients suspected of intestinal spirochetosis at histopathology (17 patients) underwent microbiological investigation performed by culture and molecular methods (16S restriction fragment length polymorphism-polymerase chain reaction [RFLP-PCR], nox RFLP-PCR assays). Results: Seventeen cases were diagnosed: seven patients were infected by B. aalborgi, one by B. pilosicoli, two by both species and four by Brachyspira spp. diagnosed both histopathology and microbiology (culture and molecular methods: 16S RFLP-PCR and nox RFLP-PCR assays). Three cases were referred to as Brachyspira spp. infections using only histopathology, including TEM. Conclusions: Our results demonstrated that intestinal spirochetosis, although rarely occurring, might play a role in chronic diarrhea and suggested a pathogenetic mechanism of intestinal spirochetosis based on the destruction of colonic microvilli and colitis histologically documented, providing additional clinical and pathological information on this entity. This study suggests that metronidazole seems to be the drug of choice for the eradication of intestinal spirochetosis. [ABSTRACT FROM AUTHOR]

This study examined the cellular origin and concentration of nuclear DNA in human urine. Ten subjects provided two entire, first-morning voids: one as a single specimen and one as a consecutive series of samples. The serial samples were centrifuged, organically extracted, and quantified by slot-blot analysis. Total DNA concentrations ranged from 0.02 to 21.3 ng/mL for the males and 25.0 to 96.9 ng/mL for the females. The female samples were found to contain numerous vaginal epithelial cells. DNA was detected in all of the serial samples of nine subjects; however, the DNA concentrations varied considerably. With six subjects, the DNA concentration of the first serial sample was at least three times greater than that of the entire void. DNA was only detected in the first 21% of the void from one male subject. The results of this study have implications for the collection of urine samples. [ABSTRACT FROM AUTHOR]

Background: The present study reports on a prompt diagnosis of colonic amoebiasis with colonic spirochetosis by Brachyspira aalborgi and B. pilosicoli; such diagnosis allowed exclusion of other diseases and resolution of the case after specific treatment. Methods and Results: A 37-year-old Italian man with a history of several months’ mucosal diarrhea travelled to Greece, Romania and Tunisia. After his last trip he presented with an increase of up to 3–5 discharges daily, associated with bloody diarrhea, supporting the clinical suspect of inflammatory bowel disease. Colonoscopy revealed erosions from the cecum to the rectum, and ulcers both in the descending and sigmoid colon. Structures resembling amoebic trophozoites and sinusoidal microorganisms were observed in the colonic biopsies at histopathology and electron microscopy. Entamoeba histolytica DNA was detected by small-subunit rDNA polymerase chain reaction (PCR) from feces, rectal biopsies and isolated trophozoites. Spirochetes were identified from feces, colonic biopsies and cultures using a 16S rDNA restriction fragment length polymorphism-PCR specific for the detection of B. aalborgi and B. pilosicoli. After therapy, the patient was restored to health. Conclusions: The rapid identification of E. histolytica, B. aalborgi and B. pilosicoli using traditional and specific and sensitive molecular methods permitted an accurate diagnosis and a specific therapy. It is suggested that mixed infection by parasites and spirochetes might occur more frequently than expected: it would be of extreme interest and importance to intensify clinical findings, and one infection should not prompt the pathologist/clinician to stop looking. [ABSTRACT FROM AUTHOR]

I Sir: i Bile duct adenomas (BDAs) are benign intrahepatic biliary proliferations consisting of bile ducts arranged in small and tortuous tubules and embedded in a dense fibrous stroma.[1] Microscopically, tubules are lined by a single layer of cuboidal to columnar cells with nuclei showing neither atypia nor mitoses. Background liver and lesions were devoid of hyaline globules, suggesting the absence of 1-antitrypsin deficiency.[[7]] GLO:EW1/01jul20:his14125-fig-0001.jpg PHOTO (COLOR): 1 Typical appearance of bile duct adenoma with small and tortuous tubes arranged in a fibrous stroma (A). Further studies including patients with multiple BDAs are warranted to identify the potential risk factors leading to this particular phenotype, which may be designated "BRAF-associated bile duct adenomatosis". [Extracted from the article]

Background: Nonverbal communication is a crucial aspect of interpersonal relationships, and defective emotion recognition can lead to altered social interactions. The aim of our study was to investigate the relationship between emotion processing and resting‐state functional connectivity (RS‐FC) in frontotemporal lobar degeneration (FTLD). Method: 80 FTLD patients and 65 age‐matched healthy controls underwent brain 3.0 Tesla MRI [3DT1‐weighted and RS‐functional MRI (RS‐fMRI)] and neuropsychological assessment, including the Comprehensive Affect Testing System (CATS). FLAME models in FSL were performed between each emotion construct and RS‐FC changes within crucial networks. Result: FTLD patients performed worse than controls in all CATS‐subtests. In controls, a high performance at the emotion naming and emotion matching constructs was related with increased RS‐FC within the cerebellar network, and a high performance at the emotion discrimination construct was related with increased RS‐FC of the right occipital face area (OFA) within the visuo‐associative network. In FTLD patients, high performances at the emotion naming construct were related with increased RS‐FC of the bilateral OFA within the visuo‐associative network and the bilateral frontal pole within the default‐mode‐network, whereas high performances at the emotion matching construct were related with increased RS‐FC of the left OFA within the visuo‐associative network. Finally, in FTLD patients, high performances at each emotional construct were related with decreased RS‐FC within the basal ganglia network. Conclusion: In healthy controls and FTLD patients, the RS‐FC within crucial networks is related to different constructs of emotion processing. In FTLD, the RS‐FC associated with emotional performances involved a large number of brain regions, likely due to brain functional specificity loss and compensatory attempts. These findings offer potential markers for detecting functional vulnerability linked to social interactions. Disclosures. Supported by the Italian Ministry of Health (GR‐2013‐02357415); European Research Council (StG‐2016_714388_NeuroTRACK). [ABSTRACT FROM AUTHOR]

Background: Ageing is the main risk factor for most neurodegenerative diseases and results in complex transformations of the human brain function. The aim of this study was to investigate how topological organization of the brain connectome changes with age using resting‐state functional MRI and stepwise functional connectivity (SFC) analyses. Method: 138 controls were recruited and divided into two groups according to age: 55 young (20‐30 years [YC]) and 83 old (41‐84 years [OC]). SFC analysis aims to characterize regions that connect to specific seed brain areas at different levels of link‐step distances. Eight well‐known hubs of the human connectome were selected as seeds: middle frontal gyrus, rostral anterior and posterior cingulate cortex, precuneus, inferior parietal, middle temporal and lingual gyri and pericalcarine cortex. Whole‐brain two‐sample t‐test comparisons between groups were performed. Result: At one‐link step distance, in OC, all the seed regions displayed decreased regional–local functional connectivity with superior frontal and medial orbital frontal gyri, rostral anterior and isthmus cingulate cortex, precuneus and middle and inferior temporal gyri relative to YC; across intermediate link‐steps, a reduced connectivity was observed between all seed regions and frontal‐parietal lobes. By contrast, at the first link‐step distance, YC showed lower connectivity only between few seed regions and precentral, paracentral and lateral occipital gyri compared to OC. At intermediate link‐step distances, increased connectivity with sensorimotor regions was found in OC relative to YC. Conclusion: SFC approach might have important implication providing a starting point for evaluating network disruptions in age‐related neurodegenerative disorders. European Research Council (StG‐2016_714388_NeuroTRACK). [ABSTRACT FROM AUTHOR]