Celiac disease in children and adolescents with Down syndrome: behavioural, adaptive and sleep profiles.

BACKGROUND: Individuals with Down syndrome (DS) exhibit higher risk for celiac disease (CD) than general population. Although literature suggests CD could be associated with behavioural problems in both paediatric and adult age, such association has been poorly explored in children and adolescents DS. Therefore, the current study aimed to investigate differences in emotional/behavioural difficulties, adaptive skills and sleep problems between children with DS with and without CD. METHODS: Data were retrospectively collected from a database including data from 381 individuals with DS (3-18 years). The final sample included 65 participants, 27 with co-occurring CD and 38 age, IQ, sex and body mass index-matched controls without CD. Emotional/behavioural difficulties, adaptive skills and sleep problems were assessed through parent report questionnaires. RESULTS: No group differences emerged in emotional/behavioural difficulties, whereas participants in the CD group showed better adaptive skills in the practical domain than control group. Weak differences emerged in sleep problems. CONCLUSIONS: Youth with DS and co-occurring CD do not exhibit more emotional and behavioural problems than youth with DS without co-occurring CD but exhibit better adaptive skills in the practical domain.

Phase-field modeling of constrained interactive fungal networks.

Fungi develop structures that interact with their surroundings and evolve adaptively in the presence of geometrical constraints, finding optimal solutions for complex combinatorial problems. The pathogenic fungus Ophiocordyceps constitutes a perfect model for the study of constrained interactive networks. Modeling these networks is challenging due to the highly coupled physics involved and their interaction with moving boundaries. In this work, we develop a computational phase-field model to elucidate the mechanics of the emerging properties observed in fungal networks. We use a variational approach to derive the equations governing the evolution in time of the mycelium biomass and the nutrients in the medium. We present an extensive testing of our model, reproduce growing and decaying phenomena, and capture spatial and temporal scales. We explore the variables interplay mechanism that leads to different colony morphologies, and explain abrupt changes of patterns observed in the laboratory. We apply our model to simulate analogous processes to the evolution of Ophiocordyceps as it grows through confined geometry and depletes available resources, demonstrating the suitability of the formulation to study this class of biological networks.

Endocrine toxicity in cancer patients treated with nivolumab or pembrolizumab: results of a large multicentre study.

INTRODUCTION: The immune checkpoint inhibitors (ICPIs) agents anti-T lymphocytes-associated antigen 4 (CTLA-4) and anti-programmed cell death protein-1 (PD-1) and its ligands (PD-L1/PD-L2) have opened a new scenario in the treatment of cancer. These agents can induce immuno-related adverse events (irAEs), which may affect the endocrine system. PURPOSE: The aim of this study was to analyze the occurrence and the course of endocrine irAEs in cancer patients treated with anti-PD-1 immunotherapy. METHODS: This was a retrospective, multicentre study, involving cancer patients treated with the PD-1 inhibitors nivolumab or pembrolizumab at reference Oncology Centres. One hundred and seventy-nine consecutive patients with different types of cancer (mostly non-small cell lung cancer, melanoma, kidney cancer) were included in the study. Patients had received nivolumab (70.9%) or pembrolizumab (29.1%) for 2-33 months. The study evaluated clinical data records until the established date of July 15, 2018. The primary end point was the assessment of endocrine toxicity and possible predictive factors. RESULTS: Endocrine toxicity occurred in 54 out of 179 patients (30.2%) and was related to thyroid dysfunction, with the exception of one case of diabetes mellitus. Thyroid toxicity occurred mostly within 2 months from the initiation of immunotherapy (83% of cases). A pre-existing thyroid dysfunction was a significant predictor of disease flare. CONCLUSIONS: Thyroid alterations are frequently associated with anti PD-1 treatment in cancer patients. Regular thyroid assessment should be performed, particularly in the first months of treatment and in patients with a pre-existing thyroid disease.

hERG1 channels drive tumour malignancy and may serve as prognostic factor in pancreatic ductal adenocarcinoma.

BACKGROUND: hERG1 channels are aberrantly expressed in human cancers. The expression, functional role and clinical significance of hERG1 channels in pancreatic ductal adenocarcinoma (PDAC) is lacking. METHODS: hERG1 expression was tested in PDAC primary samples assembled as tissue microarray by immunohistochemistry using an anti-hERG1 monoclonal antibody (α-hERG1-MoAb). The functional role of hERG1 was studied in PDAC cell lines and primary cultures. ERG1 expression during PDAC progression was studied in Pdx-1-Cre,LSL-Kras(G12D/+),LSL-Trp53(R175H/+) transgenic (KPC) mice. ERG1 expression in vivo was determined by optical imaging using Alexa-680-labelled α-hERG1-MoAb. RESULTS: (i) hERG1 was expressed at high levels in 59% of primary PDAC; (ii) hERG1 blockade decreased PDAC cell growth and migration; (iii) hERG1 was physically and functionally linked to the Epidermal Growth Factor-Receptor pathway; (iv) in transgenic mice, ERG1 was expressed in PanIN lesions, reaching high expression levels in PDAC; (v) PDAC patients whose primary tumour showed high hERG1 expression had a worse prognosis; (vi) the α-hERG1-MoAb could detect PDAC in vivo. CONCLUSIONS: hERG1 regulates PDAC malignancy and its expression, once validated in a larger cohort also comprising of late-stage, non-surgically resected cases, may be exploited for diagnostic and prognostic purposes in PDAC either ex vivo or in vivo.

A proteomics-driven assay defines specific plasma protein signatures in different stages of Ménière's disease.

Ménière's disease (MD) is a common disorder of the inner ear whose hallmarks are vertigo, tinnitus, aural fullness, and progressive hearing loss. The degree of severity of the disease is quite heterogeneous, and so is its pathogenesis. A multifactorial inheritance of intrinsic and extrinsic factors has been described, but there is not a common agreement on the molecular basis of MD. In a recent article, we have demonstrated that patients suffering from MD share a common plasma proteomic signature, characterized by the presence of several up- and down-regulated proteins. In this study, we have further extended our analysis and show that the differential expression of plasma proteins can identify specific subsets of MD-affected individuals, depending on their stage. Our findings confirm our plasma proteomics-driven approach as a powerful tool for early diagnosis of MD and uncover a potentially starring role for some proteins in the development and fate of this frustrating disease, whose pathogenesis still remains unclear.

Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer.

BACKGROUND: Some trial have demonstrated a benefit of adjuvant fluoropirimidine with or without platinum compounds compared with surgery alone. ITACA-S study was designed to evaluate whether a sequential treatment of FOLFIRI [irinotecan plus 5-fluorouracil/folinic acid (5-FU/LV)] followed by docetaxel plus cisplatin improves disease-free survival in comparison with 5-FU/LV in patients with radically resected gastric cancer. PATIENTS AND METHODS: Patients with resectable adenocarcinoma of the stomach or gastroesophageal junction were randomly assigned to either FOLFIRI (irinotecan 180 mg/m(2) day 1, LV 100 mg/m(2) as 2 h infusion and 5-FU 400 mg/m(2) as bolus, days 1 and 2 followed by 600 mg/m(2)/day as 22 h continuous infusion, q14 for four cycles) followed by docetaxel 75 mg/m(2) day 1, cisplatin 75 mg/m(2) day 1, q21 for three cycles (sequential arm) or De Gramont regimen (5-FU/LV arm). RESULTS: From February 2005 to August 2009, 1106 patients were enrolled, and 1100 included in the analysis: 562 in the sequential arm and 538 in the 5-FU/LV arm. With a median follow-up of 57.4 months, 581 patients recurred or died (297 sequential arm and 284 5-FU/LV arm), and 483 died (243 and 240, respectively). No statistically significant difference was detected for both disease-free [hazard ratio (HR) 1.00; 95% confidence interval (CI): 0.85-1.17; P = 0.974] and overall survival (OS) (HR 0.98; 95% CI: 0.82-1.18; P = 0.865). Five-year disease-free and OS rates were 44.6% and 44.6%, 51.0% and 50.6% in the sequential and 5-FU/LV arm, respectively. CONCLUSIONS: A more intensive regimen failed to show any benefit in disease-free and OS versus monotherapy. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01640782.

New fracture patterns distal epiphysis femur in youth: Update of current classification.

INTRO: Distal growth core fractures of the femur are the third most common fracture in patients older than 10 years. These fractures result from high-energy trauma and have a high risk of evolving into growth disorders. The classification most used to describe these types of fractures is that described by Salter and Harris. Special clinical cases often occur in clinical practice that are not described in the classifications used. In our study, we analyzed and further focused on new fracture patterns related to pediatric epiphyseal detachments not easily described by the normal classifications currently used in the literature. MATERIALS AND METHODS: From January 2020 to December 2022, we treated 2 male clinical cases with epiphyseal detachments of the distal femur that could not be classified according to the Salter and Harris classification. age of the patients was 10 and 11 years, respectively; for both patients, the traumatic mechanism was a direct trauma to the right knee at high speed using an electric scooter; Serious clinical and radiographic follow-ups were performed at month 1, month 3, month 6, month 12, and month 24 from the date of surgery. DISCUSSION: Distal femur fractures represent a challenge for the orthopedics because they have a high incidence of complications. In our experience, there has been an increase in this type of injury caused using recently developed electric vehicles, which can reach considerable speeds. The Salter Harris classification is among the most widely used for fractures involving the growth physis. This classification proved to be rather limiting in the present case, so we decided to classify the fracture as 'Salter Harris III equivalent'. CONCLUSIONS: The fracture examined is a very rare fracture of the distal femur and is not reflected in the classifications currently in use. The patient presented an excellent clinical and radiographic result after surgery with the presence of a shortening of the affected femur in relation to the contralateral one, which suggests that the growth deficit may continue and increase over time for which reason future studies until skeletal maturity will be necessary to quantify the damage to the growth physis.

Postmenopausal women with carotid atherosclerosis: potential role of the serum calcium levels.

BACKGROUND AND AIM: Studies on the association between serum calcium levels and cardiovascular diseases suggested a causative role for hypercalcemia but other studies showed that even serum calcium levels within normal range could be involved in atherosclerosis. However, while dietary calcium intake does not seem to be related to adverse cardiovascular effects, the association between calcium supplementation and the cardiovascular events has not been fully proven. Our aim was to determine the relation between serum calcium levels, within normal range, and the presence of carotid atherosclerosis in a population in whom investigations on this topic are lacking, the postmenopausal women. METHODS AND RESULTS: In this retrospective study, participants were recruited from women aged 49-65 years who underwent an ultrasonography evaluation of the carotid arteries between years 2008-2012. The study included 413 subjects with serum calcium level available, without symptomatic cardiovascular disease. A physical examination, including the evaluation of body mass index, waist and hip circumferences and the blood pressure, as well as, a collection of a venous blood sample was performed. The mean age was 56 ± 7 years. The prevalence of the carotid atherosclerosis was 50.8%. The comparison between women with and without carotid atherosclerosis showed differences for the classical risk factors and for serum calcium levels (p = 0.001). The logistic regression analysis, adjusting for these risk factors, confirmed the association between serum calcium levels and carotid atherosclerosis (p = 0.011). Furthermore, we showed an increasing prevalence of carotid atherosclerosis from lower to higher calcium quartiles (p = 0.016). CONCLUSION: We found a positive relation between serum calcium levels and the carotid atherosclerosis in postmenopausal women. This study may suggest a redetermination of the reference range of calcemia, at least in menopause.

Discontinuation rate and serious adverse events of chemoimmunotherapy as neoadjuvant treatment for triple-negative breast cancer: a systematic review and meta-analysis.

BACKGROUND: The use of combination of chemotherapy with immune checkpoint inhibitors (ICIs) has shown efficacy in triple-negative breast cancer (TNBC), and chemoimmunotherapy has been introduced in clinical practice. However, limited data are available on the discontinuation rate and serious adverse events of these treatments, particularly in the neoadjuvant setting. Herein, we carried out a comprehensive systematic review and meta-analysis to assess discontinuation rate and serious adverse events of chemoimmunotherapy compared to chemotherapy alone in phase II and III neoadjuvant clinical trials in TNBC. MATERIALS AND METHODS: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, EMBASE, Cochrane Library, and PubMed/Medline were searched for articles published from June 2008 to May 2023. The outcomes of interest were the discontinuation rate, serious adverse events, and grade 3-4 adverse events. RESULTS: Four studies were included in the analysis. The pooled odds ratios (ORs) for discontinuation rate and serious adverse events were 1.26 [95% confidence interval (CI) 0.78-2.06] and 1.79 (95% CI 1.4-2.28), respectively, in patients receiving chemoimmunotherapy compared to chemotherapy alone as neoadjuvant treatment for TNBC. The chemoimmunotherapy group had a higher risk of grade 3-4 adverse events (OR 1.30, 95% CI 1.07-1.59). The analysis showed substantial heterogeneity, and the risk of discontinuation rate was heavily influenced by the KEYNOTE-522 trial. CONCLUSIONS: Our findings highlight the need for clinical trials specifically focused on safety, quality of life, and treatment adherence in TNBC patients receiving neoadjuvant treatment. Close monitoring of tolerability remains crucial in this clinical setting.

Triplets versus doublets, with or without cisplatin, in the first-line treatment of stage IIIB-IV non-small cell lung cancer (NSCLC) patients: a multicenter randomised factorial trial (FAST).

BACKGROUND: The FAST is a 2 × 2 factorial trial addressing two questions: (1) the role of replacing cisplatin (P) with a non-platinum agent, vinorelbine (N), and (2) the role of adding a third agent, ifosfamide (I), in a doublet based on gemcitabine (G). METHODS: A total of 433 stage IIIB-IV non-small cell lung cancer (NSCLC) patients were randomised to one of four arms: gemcitabine-cisplatin (GP), gemcitabine-vinorelbine, gemcitabine-ifosfamide-cisplatin or gemcitabine-ifosfamide-vinorelbine. Two comparisons were performed: N- vs P-containing regimens and I-triplets vs non-I doublets. RESULTS: For N- vs P-containing regimens, adjusted overall survival was 9.7 vs 11.3 months (P=0.044), progression-free survival was 4.9 vs 6.4 months (P=0.020) and response rate was 24% vs 31% (P=0.124), respectively. No statistically significant difference was observed between doublets and triplets. Grade 3-4 haematological toxicity was significantly more frequent in P-containing therapy; grade 3-4 leucopenia was significantly more common in triplets. Concerning non-haematological toxicity, grade 3-4 nausea-vomiting was significantly increased in P-containing regimens. CONCLUSIONS: This trial provides evidence of a slight survival superiority of GP-containing regimens over platinum-free N-containing chemotherapy. This trial also confirms that the addition of a third chemotherapy agent (I) to a standard G-based doublet does not improve treatment outcome.

Phase II trial of single-agent oral vinorelbine in elderly (> or =70 years) patients with advanced non-small-cell lung cancer and poor performance status.

BACKGROUND: Elderly patients with advanced non-small-cell lung cancer (NSCLC) with poor performance status (PS) are a special population requiring particular attention. Single-agent oral vinorelbine could be an attractive option. PATIENTS AND METHODS: A total of 43 patients with stage IIIB-IV NSCLC and Eastern Cooperative Oncology Group (ECOG) PS of two or more with good functional status were prospectively recruited. Oral vinorelbine was administered at the dose of 60 mg/m(2) on days 1-8 every 3 weeks. Primary end points were response rate and safety. RESULTS: Overall response rate was 18.6% with 8 partial responses; 18 of 43 (41.8%) experienced stable disease lasting >12 weeks and 17 of 43 (39.6%) disease progression for an overall clinical benefit of 60.4%. Median time to progression was 4.0 (range 2-22) months and median overall survival 8.0 (range 3-35) months. Treatment was well tolerated. Of 187 cycles, we did not observe any grade 3/4 toxicity with the exception of a single not-febrile G3 neutropenia. Regardless of severity, main toxic effects observed were nausea in 48.1% and vomiting in 22.9% of patients, anemia in 43.2%, fatigue in 32.6% and leukopenia in 23.2%. CONCLUSION: Single-agent oral vinorelbine is extremely safe in elderly patients with advanced NSCLC and ECOG PS of two or more and may represent a valid option in this very special population.

Executive functions in individuals with Williams syndrome.

BACKGROUND: The present study was aimed at investigating working memory (WM) and executive functions capacities in individuals with Williams syndrome (WS) as compared with mental-age matched typically developing (TD) children. METHOD: In order to serve the study goal, a sizeable battery of tasks tapping WM as well as attention, memory, planning, categorisation, shifting and inhibition abilities was administered to 15 individuals with WS (mean chronological age of 19.11 and mean mental age of 6.10), and to a group of 15 TD children (mean chronological age of 7.6 and mean mental age of 6.9). RESULTS: Participants with WS showed deficits in both verbal and visual-spatial modalities for selective and sustained attention, short-term memory and WM, planning and inhibition. However, considering categorisation and shifting abilities, relatively unimpaired performance emerged on those tasks relying on verbal materials. CONCLUSIONS: These findings are both relevant to improve our knowledge about certain qualitative aspects of the anomalous cognitive development in WS as well as for its eventual clinical implications.

Pemetrexed in combination with oxaliplatin as a first-line therapy for advanced gastric cancer: a multi-institutional phase II study.

BACKGROUND: This clinical trial assessed the efficacy of pemetrexed combined with oxaliplatin (PEMOX) in patients with advanced gastric cancer (AGC). PATIENTS AND METHODS: Forty-four patients with untreated AGC were enrolled to evaluate response rate (RR). Patients received pemetrexed (500 mg/m(2)) with vitamin supplementation and oxaliplatin (120 mg/m(2)) every 21 days for six cycles or until disease progression occurred. RESULTS: Median age was 62 years (range 26-76). The majority of patients (93%) had metastatic disease. Sixteen of the 44 patients achieved confirmed response [RR 36%; 95% confidence interval (CI) 22% to 52%]; four complete responses and 12 partial responses (complete and partial responses according to the RECIST guidelines are the confirmed-responses observed in the study population). Median time to tumor progression (TTP) was 6.2 months (95% CI 4.3-7.5) and median survival was 10.8 months (95% CI 7.7-17.2). A total of 220 cycles were administered, with a median of six cycles. Most common grade 3/4 toxic effects were neutropenia in 41% of patients (19% of cycles) and thrombocytopenia in 11% of patients (4% of cycles). Treatment delays or dose reductions for toxicity occurred in 10% and 5% of cycles, respectively. CONCLUSIONS: PEMOX is active and well tolerated in AGC. RR, TTP, and survival were comparable to those achieved in studies using different 5-fluorouracil (5-FU)-oxaliplatin combinations, without the inconvenience of prolonged 5-FU schedules.

Accreditation for colorectal cancer surgery in Italy. Preliminary results of a new program in a district hospital.

Accreditation for colorectal (CR) cancer surgery has become a major issue in Italy. This study aimed to analyze the early results of a newly structured program for the treatment of CR cancer in a rural district hospital. Between 2017 and 2018, a total of 214 consecutive patients underwent a CR procedure for malignancy. There were 113 men and 101 women of a mean age of 74 years. Primary CR adenocarcinoma was diagnosed in 210 patients (98%). The incidence of stage I, II, III, and IV disease was 26%, 31%, 24%, and 19% respectively. Hospital volume increased tenfold compared to previous years. Anatomical resection was performed in 204 patients. Right-sided resection and resection of the transverse colon or left angle were performed in 76 (37%) and 14 (7%) patients, respectively. A restorative left sided CR resection was performed in 80 patients (39%), whereas Hartmann procedure and Miles abdominal-perineal resection were performed in 27 (13%) and 6 (3%) patients, respectively. Total colectomy with ileorectal anastomosis was performed in one patient, and two more patients underwent atypical resection. Emergency cecostomy was performed in 15 patients and a colic endoprosthesis was implanted in one patient for obstruction and seven underwent resection afterwards. Laparoscopic resection was performed in 118 patients (57.8%), and the conversion rate was 2%. Overall morbidity, reintervention, and mortality rates were 24.6%, 3,7%, and 3.2%, respectively. The incidence of AL was 4.6%, and two patients died of the consequences of it after right hemicolectomy. Five more elderly patients died for non-surgical related medical complications. The median hospital stay was ten days, and early unplanned readmission rate was 2%. Hospital and surgeon requirements, in terms of minimum volume, organization, and surgical outcome were fulfilled. A rural district hospital can become a tertiary referral center for the surrounding districts without imposing unreasonable travel burdens for patients. CR surgery represents a capital investment for the hospital administration since it shows the effectiveness and quality of care.

Impact of recent legislative bills regarding clinical research on Italian ethics committee activity.

AIMS AND BACKGROUND: The present work assessed the impact of two decrees on ethics committees in Italy, aimed at bringing the national laws on the conduct of clinical trials into line with the rest of the EC, and regulating and facilitating not-for-profit research. MATERIAL AND METHODS: Prospectively collected data from an Italian multicentre study were examined with respect to the ethics review process. Administrative and time elements of the review process were audited. Main outcome measures were time between the application submission and the ethics committee definitive opinion, type and number of application submission forms, number of ethics committees that refused fee exemption, and time between the ethics committee approval and the administrative authorisation. RESULTS: A total of 134 local research ethics committees (LRECs) were approached. Application submission procedures and application forms varied greatly; paper submission was mandatory. The median time from submission to approval was 72 days. Only two LRECs refused the fee exemption. The median time from LREC approval to administrative agreement was 50 days and only 9.6% of local authorities came to a verbal agreement with the sponsor. CONCLUSIONS: Italian LRECs are still not sufficiently efficient in complying with the Directive 2001/20/EC requirement (60 days). Better coordination of LRECs work is needed although the optimal level of coordination between them is still not known. In the meantime, national guidelines are needed concerning the application of Directive 2001/20/EC. The behaviour of Italian LRECs towards not-for-profit research was excellent although only the fee exemption was requested.

Phylloporus and Phylloboletellus are no longer alone: Phylloporopsis gen. nov. (Boletaceae), a new smooth-spored lamellate genus to accommodate the American species Phylloporus boletinoides.

The monotypic genus Phylloporopsis is described as new to science based on Phylloporus boletinoides. This species occurs widely in eastern North America and Central America. It is reported for the first time from a neotropical montane pine woodland in the Dominican Republic. The confirmation of this newly recognised monophyletic genus is supported and molecularly confirmed by phylogenetic inference based on multiple loci (ITS, 28S, TEF1-α, and RPB1). A detailed morphological description of P. boletinoides from the Dominican Republic and Florida (USA) is provided along with colour images of fresh basidiomata in habitat, line drawings of the main anatomical features, transmitted light microscopic images of anatomical features and scanning electron microscope images of basidiospores. The taxonomic placement, ecological requirements and distribution patterns of P. boletinoides are reviewed and the relationships with phylogenetically related or morphologically similar lamellate and boletoid taxa such as Phylloporus, Phylloboletellus, Phyllobolites and Bothia are discussed.

shRNA targeting of ferritin heavy chain activates H19/miR-675 axis in K562 cells.

PURPOSE: The heavy subunit of the iron storage protein ferritin (FHC) is essential for the intracellular iron metabolism and, at the same time, it represents a central hub of iron-independent pathways, such as cell proliferation, angiogenesis, p53 regulation, chemokine signalling, stem cell expansion, miRNAs expression. In this work we have explored the ability of FHC to modulate gene expression in K562 cells, through the up-regulation of the lncRNA H19 and its cognate miR-675. MATERIALS AND METHODS: Targeted silencing of FHC was performed by lentiviral-driven shRNA strategy. FHC reconstitution was obtained by full length FHC cDNA transfection with Lipofectamine 2000. ROS amounts were determined with the redox-sensitive probe H2DCFDA. H19, miR-675, miR-107, Twist1, ID3, EPHB6, GNS, ANK1 and SMAD6 mRNA amounts were quantified by Taqman assay and qPCR analysis. RESULTS: FHC silencing in K562 cells modulates gene expression through the up-regulation of the lncRNA H19 and its cognate miR-675. Experimental findings demonstrate that the molecular mechanism underlying this phenomenon is represented by an FHC knock-down-triggered increase in reactive oxygen species (ROS) production. CONCLUSIONS: In this paper we uncover a so far not described function of the ferritin heavy subunit in the control of lncRNA pathways.

Mechanisms behind the enhancement of thermal properties of graphene nanofluids.

While the dispersion of nanomaterials is known to be effective in enhancing the thermal conductivity and specific heat capacity of fluids, the mechanisms behind this enhancement remain to be elucidated. Herein, we report on highly stable, surfactant-free graphene nanofluids, based on N,N-dimethylacetamide (DMAc) and N,N-dimethylformamide (DMF), with enhanced thermal properties. An increase of up to 48% in thermal conductivity and 18% in specific heat capacity was measured. The blue shift of several Raman bands with increasing graphene concentration in DMF indicates that there is a modification in the vibrational energy of the bonds associated with these modes, affecting all the molecules in the liquid. This result indicates that graphene has the ability to affect solvent molecules at long-range, in terms of vibrational energy. Density functional theory and molecular dynamics simulations were used to gather data on the interaction between graphene and solvent, and to investigate a possible order induced by graphene on the solvent. The simulations showed a parallel orientation of DMF towards graphene, favoring π-π stacking. Furthermore, a local order of DMF molecules around graphene was observed suggesting that both this special kind of interaction and the induced local order may contribute to the enhancement of the fluid's thermal properties.

Adjuvant treatment of early breast cancer: do the St Gallen recommendations influence clinical practice? Results from the NORA study.

BACKGROUND: The NORA study is a prospective longitudinal cohort study aiming at investigating treatment in patients with early breast cancer. Here, we present the impact of the St Gallen recommendations on clinical practice. PATIENTS AND METHODS: We compared adjuvant strategies in patients enrolled in 2000-2002 to those in 2003-2004 to verify the impact of the 2003 St Gallen recommendations. RESULTS: The use of aromatase inhibitors (AIs) doubled: 65/629 patients (10.3%) vs 100/458 patients (21.8) (P < 0.0001). Following chemotherapy, AIs were administered in 8.5% of the retrospective cohort and in 15.1% of the prospective one (P < 0.0001). The use of taxanes plus hormones dropped (P = 0.0026), but not when used as single agents. A marked increase was observed in the use of anthracycline-based chemotherapy (46.3% vs 65.2%), mainly three-drug regimens (33.3% vs 46.6%). CONCLUSION: Our results suggest that the St Gallen recommendations have had a major impact on clinical practice.

Visceral larvae as a predictive index of the overall level of fish batch infection in European anchovies (Engraulis encrasicolus): A rapid procedure for Food Business Operators to assess marketability.

The European anchovy (Engraulis encrasicolus), one of the most important pelagic fish resources in the Mediterranean Sea, is frequently infected by anisakid larvae. Food Business Operators (FBOs) should use appropriate sampling plans and analytical methods to avoid commercialization of massively infected batches and reduce the risk of transmission of viable zoonotic larvae. In this study, performed at FishLab (Department of Veterinary Sciences of the University of Pisa) during 2016, an official sampling plan was associated with a digestion protocol for the inspection of anchovies. Considering that anisakid larvae are usually located in the fish visceral cavity and in the adjacent muscles (VM), this part was analyzed. In particular, we assessed the reliability of the digestion of a subsample of 150g (±30g) of VM, randomly collected from 29 specimens, in estimating the marketability of the anchovies' batch. Fifty-seven samples of 29 anchovies were collected. Each anchovy was sectioned to separate VM. All the subsamples were digested, and visible larvae counted. A high correlation between the number of larvae in VM regions and in the total batch was observed, indicating a very significant contribution of the VM region on total number of parasites. The Mean Abundance (MA) was used to assess the batch marketability according to a threshold calculated on the basis of the maximum number of nematodes tolerated per sample. Considering that the MA can be calculated only when the number of examined specimens is known, the number of visible Larvae per gram of tissue (LpG) was calculated on 150g (±30g) of VM subsamples. A LpG marketability threshold was calculated dividing the maximum number of tolerated nematodes by the average weight of a sample of 29 anchovies calculated considering data available in literature. To evaluate the diagnostic performance of the LpG threshold, the marketability of 57 batches assessed on the basis of the MA threshold was assumed as the gold standard. The proposed LpG showed very high Specificity and Sensitivity. These findings suggest that the analysis of VM is representative of the overall infestation of the batch, both when considering the absolute number of parasites and the LpG, and may represent a valid alternative to the whole anchovy digestion. In particular, the use of an automated digestive method, coupled with the aforesaid sampling plan, could allow the procedure to be used by FBOs in operational conditions.