Neuroanatomical Predictors of Transcranial Direct Current Stimulation (tDCS)-Induced Modifications in Neurocognitive Task Performance in Typically Developing Individuals.

Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique gaining more attention in neurodevelopmental disorders (NDDs). Due to the phenotypic heterogeneity of NDDs, tDCS is unlikely to be equally effective in all individuals. The present study aimed to establish neuroanatomical markers in typically developing (TD) individuals that may be used for the prediction of individual responses to tDCS. Fifty-seven male and female children received 2 mA anodal and sham tDCS, targeting the left dorsolateral prefrontal cortex (DLPFCleft), right inferior frontal gyrus, and bilateral temporoparietal junction. Response to tDCS was assessed based on task performance differences between anodal and sham tDCS in different neurocognitive tasks (N-back, flanker, Mooney faces detection, attentional emotional recognition task). Measures of cortical thickness (CT) and surface area (SA) were derived from 3 Tesla structural MRI scans. Associations between neuroanatomy and task performance were assessed using general linear models (GLM). Machine learning (ML) algorithms were employed to predict responses to tDCS. Vertex-wise estimates of SA were more closely linked to differences in task performance than measures of CT. Across ML algorithms, highest accuracies were observed for the prediction of N-back task performance differences following stimulation of the DLPFCleft, where 65% of behavioral variance was explained by variability in SA. Lower accuracies were observed for all other tasks and stimulated regions. This suggests that it may be possible to predict individual responses to tDCS for some behavioral measures and target regions. In the future, these models might be extended to predict treatment outcome in individuals with NDDs.

Zirconia Dental Implants Surface Electric Stimulation Impact on Staphylococcus aureus.

Tooth loss during the lifetime of an individual is common. A strategy to treat partial or complete edentulous patients is the placement of dental implants. However, dental implants are subject to bacterial colonization and biofilm formation, which cause an infection named peri-implantitis. The existing long-term treatments for peri-implantitis are generally inefficient. Thus, an electrical circuit was produced with zirconia (Zr) samples using a hot-pressing technique to impregnate silver (Ag) through channels and holes to create a path by LASER texturing. The obtained specimens were characterized according to vitro cytotoxicity, to ensure ZrAg non-toxicity. Furthermore, samples were inoculated with Staphylococcus aureus using 6.5 mA of alternating current (AC). The current was delivered using a potentiostat and the influence on the bacterial concentration was assessed. Using AC, the specimens displayed no bacterial adhesion (Log 7 reduction). The in vitro results presented in this study suggest that this kind of treatment can be an alternative and promising strategy to treat and overcome bacterial adhesion around dental implants that can evolve to biofilm.

Hospital admissions for urticaria in a pediatric emergency department of a tertiary care hospital.

BACKGROUND: Urticaria is a common disorder, estimated to affect 2.1 to 6.7% of children and adolescents, and is a frequent cause of emergency department (ED) admissions. METHODS: The aim of this study was to retrospectively characterize the clinical features of children and adolescents with a diagnosis of urticaria, evaluated in a tertiary care pediatric ED between 2015 and 2019. Statistical analysis was performed using IBM SPSS Statistics®, version 27.0. RESULTS: A total of 2254 episodes of urticaria were counted with 98.1% corresponding to acute urticaria (AU). A suspected trigger factor was identified in 51.6% of the episodes, namely infections (27.8%), drugs (9.9%) and food (7.6%). From these episodes, excluding infections, only 59.2% were referred to an Allergy Consultation for further study, with only 18.8% (drug) and 28.3% (food) confirmed as the AU trigger. Of the 43 episodes of chronic urticaria (CU), 79% were referred to consultation, with 23 being diagnosed with chronic spontaneous urticaria, 8 with inducible urticaria and 3 with both entities. Older age (p < 0.001), personal history of atopy (p = 0.019) and angioedema (p = 0.003) were factors associated with CU, while the presence of other accompanying symptoms (p = 0.007) was associated with AU. Older age (OR = 1.2; p < 0.001) and the presence of angioedema (OR = 2.7; p = 0.007) were identified as independent factors for CU. CONCLUSION: The majority of episodes corresponded to AU. Infections were the main suspected trigger, followed by drugs and food, with an overall confirmation rate ranging from 18 to 30%, highlighting the importance of an allergologic follow-up evaluation.

Cuticular Waxes and Cutin in Terminalia catappa Leaves from the Equatorial São Tomé and Príncipe Islands.

This study presents for the first time an analysis of the content and chemical composition of the cuticular waxes and cutin in the leaves of the widespread and important tropical species Terminalia catappa. The leaves were collected in the equatorial Atlantic islands of São Tomé and Príncipe, in the Gulf of Guinea. The epicuticular and intracuticular waxes were determined via dichloromethane extraction and their chemical composition via GC-MS analysis, and the content and monomeric composition of cutin were determined after depolymerization via methanolysis. The leaves contained an epidermal cuticular coverage of 52.8 µg cm-2 of the cuticular waxes (1.4% of mass) and 63.3 µg cm-2 (1.5% of mass) of cutin. Cuticular waxes include mainly n-alkanols and fatty acids, with a substantial proportion of terpenes in the more easily solubilized fraction, and sterols in the more embedded waxes. Cutin is mostly constituted by C16 fatty acids and dihydroxyacids, also including aromatic monomers, suggesting a largely linear macromolecular arrangement. The high proportion of triacontanol, α-amyrin, ß-amyrin, germanicol, and lupeol in the easily solubilized cuticular fraction may explain the bioactive properties attributed to the T. catappa leaves via the popular medicine, which allows us to consider them as a potential source for the extraction of these compounds.

Incidence and risk factors for moderate/severe COVID-19 in rheumatic diseases patients on hydroxychloroquine: a 24-week prospective cohort.

OBJECTIVES: To evaluate the incidence of COVID-19 and its main outcomes in rheumatic disease (RD) patients on hydroxychloroquine (HCQ) compared to household cohabitants (HC). METHODS: This is a 24-week nationwide prospective multi-centre cohort with a control group without RD and not using HCQ. All participants were monitored through scheduled phone interviews performed by health professionals. Details regarding COVID-19 symptoms, and epidemiological, clinical, and demographic data were recorded on a specific web-based platform. COVID-19 was defined according to the Brazilian Ministry of Health criteria and classified as mild, moderate or severe. RESULTS: A total of 9,585 participants, 5,164 (53.9%) RD patients on HCQ and 4,421 (46.1%) HC were enrolled from March 29th, 2020 to September 30th, 2020, according to the eligibility criteria. COVID-19 confirmed cases were higher in RD patients than in cohabitants [728 (14.1%) vs. 427 (9.7%), p<0.001] in a 24-week follow-up. However, there was no significant difference regarding outcomes related to moderate/ severe COVID-19 (7.1% and 7.3%, respectively, p=0.896). After multiple adjustments, risk factors associated with hospitalisation were age over 65 (HR=4.5; 95%CI 1.35-15.04, p=0.014) and cardiopathy (HR=2.57; 95%CI 1.12-5.91, p=0.026). The final survival analysis demonstrated the probability of dying in 180 days after a COVID-19 diagnosis was significantly higher in patients over 65 years (HR=20.8; 95%CI 4.5-96.1) and with 2 or more comorbidities (HR=10.8; 95%CI 1.1-107.9 and HR=24.8; 95%CI 2.5-249.3, p=0.006, respectively). CONCLUSIONS: Although RD patients have had a higher COVID-19 incidence than individuals from the same epidemiological background, the COVID-19 severity was related to traditional risk factors, particularly multiple comorbidities and age, and not to underlying RD and HCQ.

Predictors of anaphylaxis to peanut and tree nuts in a Mediterranean population.

Background: Peanuts (PN) and tree nuts (TN) are major causes of anaphylaxis worldwide. We aimed to determine the clinical and demographic characteristics associated with anaphylaxis in patients sensitized to PN and/or TN in a Mediterranean population. Methods: We conducted a retrospective study, which included 198 patients allergic to PN and/or TN (allergy symptoms plus specific immunoglobulin E [sIgE] sensitization), evaluated in consultations from January 2015 to December 2020. Univariate analysis and multivariate logistic regression models were developed, including demographic, clinical, and laboratory data as independent variables, and anaphylaxis to each PN and/or TN as a dependent variables. Results: Anaphylaxis was associated with an earlier age of onset of allergy to PN, cashew and/or pistachio, and pine nut allergy but not to other TN allergies. Gender, atopic comorbidities, and cofactors were not associated with PN and/or TN anaphylaxis. Anaphylaxis to PN, cashew and/or pistachio, and pine nut were associated with reactivity to a fewer number of PN and/or TN foods. Although sIgE sensitization to lipid transfer proteins (LTP) was highly prevalent in our population, only seed storage protein (SSP) positivity was associated with anaphylaxis in PN allergy. The absence of pathogenesis-related protein family 10 sensitization correlated with PN and hazelnut anaphylaxis. A higher level of sIgE to almond extract predicted anaphylaxis but the level of sIgE to other PN and/or TN extracts did not predict it. Conclusion: The high prevalence of sensitization to the pan-allergen LTP did not seem to have a significant impact in PN and/or TN allergy severity in our study. Instead, other factors, such as early age of onset and positivity for SSPs, seem to strongly associate with anaphylaxis to specific PN and/or TN. These findings may contribute to individual risk assessment in these populations.

Cutin extraction and composition determined under differing depolymerisation conditions in cork oak leaves.

INTRODUCTION: Cutin is a biopolyester involved in waterproofing aerial plant organs, including leaves. Cutin quantification and compositional profiling require depolymerisation, namely by methanolysis, but specific protocols are not available. OBJECTIVES: Investigate how different methanolysis conditions regarding catalyst concentration effect cutin depolymerisation and monomer release, to better define protocols for cutin content determination and composition profiling. MATERIAL AND METHODS: Cork oak (Quercus suber) dewaxed leaves were reacted with five sodium methoxide (NaOMe) concentrations. Extracts were analysed: glycerol by high-performance liquid chromatography (HPLC) and long-chain lipids by gas chromatography-mass spectrometry (GC-MS). RESULTS: Cutin was completely removed by 3% NaOMe (8.4% of dewaxed leaves), while mild 0.1% and 0.01% NaOMe methanolysis only depolymerised 14% of total cutin. Reactivity of cutin ester bonds is not homogeneous and glyceridic ester bonds are more easily cleaved, releasing the existing glycerol already under the mildest conditions (0.53% with 0.01% NaOMe and 0.41% with 3% NaOMe). The composition of cutin extracts varies with depolymerisation extent, with easier release of alkanoic acids and alkanols, respectively, 34.9% and 8.8% of total monomers at 0.1% NaOMe, while ω-hydroxyacids (49.3% of total monomers) and α,ω-diacids (9.0% of the monomers) are solubilised under more intensive reactive conditions. CONCLUSION: Cutin of Quercus suber leaves is confirmed as a glyceridic polyester of ω-hydroxyacids and alkanoic acids, with minor content of α,ω-diacids, and including coumarate moieties. The protocol for the determination of cutin content and compositional profiling was established regarding catalyst concentration. The molar composition of cutin suggests a macromolecular assembly based on glycerol linked to lipid oligomeric chains with moderate cross-linking.

Performance of DNA methylation-based biomarkers in the cervical cancer screening program of northern Portugal: A feasibility study.

Cervical cancer remains a health concern. Effective screening programs are critical to reduce the incidence and mortality. High-risk HPV (hr-HPV) testing as primary screening tool discloses high sensitivity but suboptimal specificity. Adequate triage tests to reduce unnecessary colposcopy referrals and overdiagnosis/overtreatment are crucial. Hence, we aimed to validate a panel of DNA methylation-based markers as triage test for women hr-HPV+ in the population-based Regional Cervical Cancer Screening Program of Northern Portugal. Firstly, CADM1, MAL, FAM19A4 and hsa-miR124-2 promoter methylation levels were assessed by multiplex QMSP in a testing set of 402 FFPE tissue samples (159 normal samples and 243 cervical lesions, including 39 low-grade intraepithelial squamous lesions [LSIL], 59 high-grade intraepithelial squamous lesions [HSIL] and 145 cancerous lesions). Then, preliminary validation was performed in 125 hr-HPV+ cervical scrapes (including 59 normal samples, 30 LSIL, 34 HSIL and 2 cancerous lesions). Higher MALme , FAM19A4me and hsa-miR124-2me methylation levels were disclosed in histological HSIL or worse (HSIL+) in testing set. Individually, markers depicted over 86% specificity for HSIL+ detection. In validation set, all these genes significantly differed between histological HSIL+ and low-grade squamous intraepithelial lesions or less. In combination, these markers reached 74% specificity and 61% sensitivity for identification of histological HSIL+. We concluded that host gene methylation might constitute a useful referral triage tool of hr-HPV+ women enrolled in the Cervical Cancer Screening Program of Northern Portugal.

Relationship of Tumor Radiation-absorbed Dose to Survival and Response in Hepatocellular Carcinoma Treated with Transarterial Radioembolization with 90Y in the SARAH Study.

Background Little is known about factors that influence the efficacy of transarterial radioembolization (TARE). Purpose To determine the relationship between tumor radiation-absorbed dose and survival and tumor response in locally advanced inoperable hepatocellular carcinoma treated with TARE. Materials and Methods This was a secondary analysis of prospectively acquired data (between December 2011 and March 2015) from participants who received TARE in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma (SARAH) trial (ClinicalTrials.gov identifier: NCT01482442). Tumor-absorbed dose was computed using technetium 99m (99mTc) macroaggregated human albumin (MAA) SPECT/CT. Visual agreement among CT, 99mTc-MAA SPECT/CT, and yttrium 90 (90Y) SPECT/CT or PET/CT was scored as optimal, suboptimal, or not optimal. Overall survival (OS) and tumor response at 6-month follow-up CT (Response Evaluation Criteria in Solid Tumors, version 1.1) were assessed. OS was evaluated using Kaplan-Meier tests. A propensity score comparing participants receiving a tumor dose greater than or equal to 100 Gy (best cut-off according to the receiver operating characteristic curve and median tumor radiation-absorbed dose values in the study groups) with those receiving sorafenib was calculated. Results One hundred twenty-one participants (median age, 67 years; interquartile range [IQR]: 61-73 years; 110 men) were evaluated in the dose-survival group, and 109 (median age, 66 years; IQR: 61-71 years; 100 men) were evaluated in the dose-tumor response group. In the dose-survival group, median OS was 9.3 months (95% confidence interval [CI]: 6.7 months, 10.7 months), and median tumor radiation-absorbed dose was 112 Gy (IQR: 68-220 Gy). Participants who received at least 100 Gy (n = 67) had longer survival than those who received less than 100 Gy (median, 14.1 months [95% CI: 9.6 months, 18.6 months] vs 6.1 months [95% CI: 4.9 months, 6.8 months], respectively; P < .001), and those with optimal agreement (n = 24) had the longest median OS (24.9 months; 95% CI: 9.6 months, 33.9 months). In the dose-tumor response group, tumor radiation-absorbed dose was higher in participants with disease control versus those with progressive disease (median, 121 Gy [IQR: 86-190 Gy] vs 85 Gy [IQR: 58-164 Gy]; P = .02). The highest disease control rate was observed in 31 of 40 participants (78%) with a tumor radiation-absorbed dose greater than or equal to 100 Gy and optimal agreement. Conclusion Higher tumor radiation-absorbed dose computed at technetium 99m macroaggregated human albumin SPECT/CT was associated with better overall survival and disease control in hepatocellular carcinoma treated with transarterial radioembolization with yttrium 90 in the Sorafenib versus Radioembolization in Advanced Hepatocellular Carcinoma trial. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Sofocleous and Kamarinos in this issue.

Hydroxystilbene Glucosides Are Incorporated into Norway Spruce Bark Lignin.

Recent investigations have revealed that, in addition to monolignols, some phenolic compounds derived from the flavonoid and hydroxystilbene biosynthetic pathways can also function as true lignin monomers in some plants. In this study, we found that the hydroxystilbene glucosides isorhapontin (isorhapontigenin-O-glucoside) and, at lower levels, astringin (piceatannol-O-glucoside) and piceid (resveratrol-O-glucoside) are incorporated into the lignin polymer in Norway spruce (Picea abies) bark. The corresponding aglycones isorhapontigenin, piceatannol, and resveratrol, along with glucose, were released by derivatization followed by reductive cleavage, a chemical degradative method that cleaves ß-ether bonds in lignin, indicating that the hydroxystilbene glucosides are (partially) incorporated into the lignin structure through ß-ether bonds. Two-dimensional NMR analysis confirmed the occurrence of hydroxystilbene glucosides in this lignin, and provided additional information regarding their modes of incorporation into the polymer. The hydroxystilbene glucosides, particularly isorhapontin and astringin, can therefore be considered genuine lignin monomers that participate in coupling and cross-coupling reactions during lignification in Norway spruce bark.

Four-Year Impact of Voiding and Storage Symptoms in Patients with Benign Prostatic Hyperplasia Treated with Prostatic Artery Embolization.

PURPOSE: To study the subscore improvement in International Prostate Symptom Scores (IPSS) after prostatic artery embolization (PAE). MATERIALS AND METHODS: A single-center retrospective study was carried out with follow-up from December 2013 to July 2019 in 37 consecutive patients (66.0 ± 8.8 years old) who underwent PAE, comparing resultant scores before and after PAE. IPSS were divided into storage (IPSS-s) subscores and voiding (IPSS-v) subscores. The changes between IPSS-s and IPSS-v at 1, 3, 6, and 12 months' follow-up as well as the last follow-up were compared with baseline scores. The changes in percentages of IPSS-s and IPSS-v and the changes in average IPSS-s-to-total IPSS ratios (IPSS-s/IPSS-t) and IPSS-v-to-IPSS-t ratios (IPSS-v/IPSS-t) were also analyzed. RESULTS: In the study population, consisting of 37 patients, IPSS-t significantly decreased from 16.5 ± 7.2 at baseline to 8.3 ± 5.7 at the last follow-up (4 years later) (P < .0001). Additionally, the changes in IPSS-v symptoms were greater than the changes in IPSS-s symptoms at 1, 3, 6, and 12 months' follow-up, reaching a statistical significance at 6 months with a decrease of 72.9% ± 42.4% for IPSS-v and a decrease of 50.1% ± 52.2% for IPSS-s (P = .009). CONCLUSIONS: PAE can successfully reduce both IPSS-s and IPSS-v with predominant IPSS-v reduction. The improvements in both subscores were sustained for up to 4 years of follow-up.

Tumor burden and liver function in HCC patient selection for selective internal radiation therapy: SARAH post-hoc study.

Aim: To determine whether a liver tumor burden ≤25% and well-preserved liver function (albumin-bilirubin grade 1) are appropriate criteria for identifying patients with unresectable hepatocellular carcinoma who may benefit from selective internal radiation therapy (SIRT) using 90yttrium resin microspheres versus sorafenib. Patients & methods: Post-hoc analysis of patients in the intention-to-treat population of the SARAH trial (SIRT vs sorafenib) with ≤25% tumor burden and albumin-bilirubin grade 1. Primary end point: overall survival. Results: Median overall survival was 21.9 months (95% CI: 15.2-32.5, n = 37) with SIRT and 17.0 months (11.6-20.8, n = 48) with sorafenib (hazard ratios: 0.73; 95% CI: 0.44-1.21; p = 0.22). Conclusion: A combination of good liver function and low tumor burden may be relevant for selection of hepatocellular carcinoma patients for SIRT.

Scaffolds and coatings for bone regeneration.

Bone tissue has an astonishing self-healing capacity yet only for non-critical size defects (<6 mm) and clinical intervention is needed for critical-size defects and beyond that along with non-union bone fractures and bone defects larger than critical size represent a major healthcare problem. Autografts are, still, being used as preferred to treat large bone defects. Mostly, due to the presence of living differentiated and progenitor cells, its osteogenic, osteoinductive and osteoconductive properties that allow osteogenesis, vascularization, and provide structural support. Bone tissue engineering strategies have been proposed to overcome the limited supply of grafts. Complete and successful bone regeneration can be influenced by several factors namely: the age of the patient, health, gender and is expected that the ideal scaffold for bone regeneration combines factors such as bioactivity and osteoinductivity. The commercially available products have as their main function the replacement of bone. Moreover, scaffolds still present limitations including poor osteointegration and limited vascularization. The introduction of pores in scaffolds are being used to promote the osteointegration as it allows cell and vessel infiltration. Moreover, combinations with growth factors or coatings have been explored as they can improve the osteoconductive and osteoinductive properties of the scaffold. This review focuses on the bone defects treatments and on the research of scaffolds for bone regeneration. Moreover, it summarizes the latest progress in the development of coatings used in bone tissue engineering. Despite the interesting advances which include the development of hybrid scaffolds, there are still important challenges that need to be addressed in order to fasten translation of scaffolds into the clinical scenario. Finally, we must reflect on the main challenges for bone tissue regeneration. There is a need to achieve a proper mechanical properties to bear the load of movements; have a scaffolds with a structure that fit the bone anatomy.

Back-to-Back Comparison of Colonoscopy With Virtual Chromoendoscopy Using a Third-Generation Narrow-Band Imaging System to Chromoendoscopy With Indigo Carmine in Patients With Lynch Syndrome.

INTRODUCTION: Colonoscopic screening with indigo carmine chromoendoscopy (ICC) in patients with Lynch syndrome (LS) improves the adenoma detection rate but is time consuming and poorly used in clinical practice. Narrow-band imaging (NBI), a virtual chromoendoscopy technique, highlights superficial mucosal vessels and improves adenoma characterization. We conducted a prospective multicenter trial in a back-to-back fashion to compare the third-generation NBI with ICC for detecting colonic adenomas in patients with LS. METHODS: In a multicenter, prospective, noninferiority trial, 138 patients underwent a double colonoscopy, first with NBI, followed by ICC, in a back-to-back design. The primary noninferiority outcome measure was the number of patients with at least one adenoma after NBI compared with the number of patients with at least one adenoma after NBI and ICC. RESULTS: The 138 analyzable patients were all proven mismatch repair mutation carriers for LS (MLH1 = 33%, MSH2 = 47%, MSH6 = 15%, PMS2 = 4%, and EPCAM = 1%). The mean age (SD) was 40.5 (14.7) years, and 64 (46.4%) were men. The median withdrawal time for an NBI procedure was 8 minutes (interquartile range 6-11) compared with 13 minutes (interquartile range 8-17) for ICC. At least one adenoma was detected during the initial NBI pass in 28 patients (20.3%), and 42 patients (30.4%) had at least one adenoma detected after both NBI and ICC (difference, 10.1%; 95% confidence interval, -0.1%-20.3%); this represents an increase of 50.0% of the adenoma detection rate. ICC detected additional adenomas in 25 patients (18.1%). DISCUSSION: Colonoscopy combining NBI and ICC detects more adenomas than third-generation NBI alone in patients with LS, respectively, 30.4% vs 20.3% (difference, 10.1%; 95% confidence interval, -0.1 to 20.3), thus failing the noninferiority assumption of NBI compared with combined NBI and ICC. Although less time consuming, colonoscopy using the third-generation NBI cannot be recommended to replace ICC in patients with LS.

Overexpression of circulating MiR-30b-5p identifies advanced breast cancer.

BACKGROUND: Breast cancer (BrC) remains the leading cause of cancer-related death in women, mainly due to recurrent and/or metastatic events, entailing the need for biomarkers predictive of progression to advanced disease. MicroRNAs hold promise as noninvasive cancer biomarkers due to their inherent stability and resilience in tissues and bodily fluids. There is increasing evidence that specific microRNAs play a functional role at different steps of the metastatic cascade, behaving as signaling mediators to enable the colonization of a specific organ. Herein, we aimed to evaluate the biomarker performance of microRNAs previously reported as associated with prognosis for predicting BrC progression in liquid biopsies. METHODS: Selected microRNAs were assessed using a quantitative reverse transcription-polymerase chain reaction in a testing cohort of formalin-fixed paraffin-embedded primary (n = 16) and metastatic BrC tissues (n = 22). Then, miR-30b-5p and miR-200b-3p were assessed in a validation cohort #1 of formalin-fixed paraffin-embedded primary (n = 82) and metastatic BrC tissues (n = 93), whereas only miR-30b-5p was validated on a validation cohort #2 of liquid biopsies from BrC patients with localized (n = 20) and advanced (n = 25) disease. ROC curve was constructed to evaluate prognostic performance. RESULTS: MiR-30b-5p was differentially expressed in primary tumors and paired metastatic lesions, with bone metastases displaying significantly higher miR-30b-5p expression levels, paralleling the corresponding primary tumors. Interestingly, patients with advanced disease disclosed increased circulating miR-30b-5p expression compared to patients with localized BrC. CONCLUSIONS: MiR-30b-5p might identify BrC patients at higher risk of disease progression, thus, providing a useful clinical tool for patients' monitoring, entailing earlier and more effective treatment. Nonetheless, validation in larger multicentric cohorts is mandatory to confirm these findings.

Is dual-phase C-arm CBCT sufficiently accurate for the diagnosis of colorectal cancer liver metastasis during liver intra-arterial treatment?

PURPOSE: This study aimed to estimate the accuracy of dual-phase C-arm cone beam computed tomography (CBCT) for the detection of colorectal cancer liver metastases, as compared with multidetector computed tomography (MDCT). MATERIALS AND METHODS: Between March 2014 and December 2016, 49 consecutive patients referred for intra-arterial treatment for colorectal cancer liver metastases were enrolled in a single-center observational study. All patients were examined with MDCT and with dual-phase C-arm cone beam computed tomography performed after iodine injection in the proper hepatic artery before intra-arterial treatment. Two blinded observers independently reviewed all examinations. Diagnostic accuracy was determined using both a six-cell matrix method and a "worst-case scenario." RESULTS: Readers identified at MDCT 264 colorectal liver metastases and 43 other liver lesions. The early and late arterial phase showed 240 and 277 liver lesions respectively. A certainty of the diagnosis was obtained in 63% and 85% at the early (EAP) and late arterial phase (LAP), respectively. Streak artifacts or liver segment truncation, or inadequate enhancement was responsible for the inability to see or to correctly adjudicate a lesion to a diagnosis in 27% and 15% of the cases at the EAP and LAP. The "worst-case scenario" yielded a Se and Sp of 58% and 51%, respectively, at EAP and 84% and 70%, respectively, at LAP. CONCLUSION: On CBCT, EAP showed limited accuracy. LAP provided the best tumor detectability. KEY POINTS: • The early arterial phase (EAP) yielded poor accuracy: Se = 58% and Sp = 51% (p < 0.0001). • The late arterial phase (LAP) phase yielded good accuracy: Se = 84% and Se = 70% (p = 0.02). • The probability of a correct diagnosis at the EAP was 60%.

Can cone-beam CT tumor blood volume predicts the response to chemoembolization of colorectal liver metastases? Results of an observational study.

PURPOSE: To determine whether intraprocedural C-arm cone-beam CT (CBCT) parenchymal blood volume (PBV) can predict the response of colorectal cancer liver metastases (CRCLM) 2 months after irinotecan drug-eluting bead (DEBIRI) chemoembolization. MATERIALS AND METHODS: This single-center observational study was compliant with the Helsinki Declaration and approved by our institutional review board. Thirty-four consecutive CRCLM patients referred for DEBIRI chemoembolization were enrolled between March 2015 and December 2016. Tumor size was assessed at baseline and 2 months after DEBIRI chemoembolization by multidetector CT (Response Evaluation Criteria in Solid Tumors RECIST 1.0), and PBV was measured before and after DEBIRI chemoembolization. Two independent readers reviewed all data. We determined the potential correlation (Spearman's rank correlation) between intraprocedural PBV values and tumor response at 2 months. The relationship between tumor response and PBV was studied using a mixed model. A logistic regression model was applied to study the relationship between patient "Responder/Non-responder" and PBV. RESULTS: There was a strong correlation between baseline PBV or the percent change of PBV and the 2-month tumor response (rho = - 0.8587 (p = 0.00001) and rho = 0.8027 (p = 0.00001), respectively). The mixed model showed that an increase of 1 ml/1000 ml in PBV of a tumor before DEBIRI chemoembolization led to a 0.54 mm decrease in diameter (p < 0.005). A 1% decrease in PBV after DEBIRI chemoembolization resulted in tumor shrinkage of 0.75 mm (p < 0.005). The logistic regression model showed that patients with a 1% smaller mean decrease of PBV after DEBIRI chemoembolization had a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493). CONCLUSION: Intraprocedural PBV may predict tumor response to DEBIRI chemoembolization. KEY POINTS: • There is a strong relationship between the parenchymal blood volume (PBV) of colorectal liver metastases before DEBIRI chemoembolization and tumor response at 2 months. • Higher PBV values before DEBIRI chemoembolization correlate with greater tumor shrinkage, but only if the PBV decreases by more than 70% after DEBIRI chemoembolization. • Each increase of 1% in the mean decrease of PBV after DEBIRI chemoembolization resulted in a 10% lower likelihood of achieving disease control (OR = 0.9, 95% confidence interval (CI) = 0.81-1; p = 0.0493).

A methodological approach for the simultaneous quantification of glycerol and fatty acids from cork suberin in a single GC run.

INTRODUCTION: Suberin, as part of plant protective barriers, is one of the most important natural polymers after cellulose and lignin. For a full elucidation of suberin structure the quantification of glycerol, fatty α,ω-diacids and ω-hydroxyacids, the major building blocks of suberin, is of primary importance. Glycerol is often lost in the most used analytical procedures or rarely determined by deficient or too laborious techniques. OBJECTIVES: Propose a simple, accessible and reliable methanolysis work-up procedure for an accurate and simultaneous quantification of glycerol and suberin fatty monomers in the same GC run. MATERIAL AND METHODS: Cork from Quercus suber L. was depolymerised by methanolysis. Glycerol was derivatised to an organic soluble form before the suberin monomers recovery in water/organic solvent partition. Gas chromatography flame ionisation detector (GC-FID) response factors were determined for glycerol, ferulic acid and one for each fatty monomer substructure. Additionally, 1,2,4-butanetriol and methyl nonadecanoate were used as internal standards. RESULTS: The proposed experimental approach allowed the glycerol and all the fatty suberin monomers in the same GC run to be quantified accurately. Glycerol represented 30.6 area%, 14.2 mass% and 38.4 molar% of suberin and the COOH/OH groups ratio was 0.6:1 in the proposed experimental approach in contrast with 0.10 area% and COOH/OH ratio of 3:1 in the most used protocol. Furthermore, ω-hydroxyacids/α,ω-diacids mass ratio was 1:1 as opposed to an area ratio of 1.5:1. CONCLUSION: The proposed work-up procedure revealed to be a reliable analytical tool for the complete analysis of suberin allowing the future knowledge to grow towards a better understanding of suberin structure throughout its range and variability.

Transcriptional profiling of cork oak phellogenic cells isolated by laser microdissection.

MAIN CONCLUSION: The phenylpropanoid pathway impacts the cork quality development. In cork of bad quality, the flavonoid route is favored, whereas in good quality, cork lignin and suberin production prevails. Cork oaks develop a thick cork tissue as a protective shield that results of the continuous activity of a secondary meristem, the cork cambium, or phellogen. Most studies applied to developmental processes do not consider the cell types from which the samples were extracted. Here, laser microdissection (LM) coupled with transcript profiling using RNA sequencing (454 pyrosequencing) was applied to phellogen cells of trees producing low- and good quality cork. Functional annotation and functional enrichment analyses showed that stress-related genes are enriched in samples extracted from trees producing good quality cork (GQC). This process is under tight transcriptional (transcription factors, kinases) regulation and also hormonal control involving ABA, ethylene, and auxins. The phellogen cells collected from trees producing bad quality cork (BQC) show a consistent up-regulation of genes belonging to the flavonoid pathway as a response to stress. They also display a different modulation of cell wall genes resulting into a thinner cork layer, i.e., less meristematic activity. Based on the analysis of the phenylpropanoid pathway regulating genes, in GQC, the synthesis of lignin and suberin is promoted, whereas in BQC, the same pathway favors the biosynthesis of free phenolic compounds. This study provided new insights of how cell-specific gene expression can determine tissue and organ morphology and physiology and identified robust candidate genes that can be used in breeding programs aiming at improving cork quality.