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Hyperinflammation present in individuals with severe COVID-19 has been associated with an exacerbated cytokine production and hyperactivated immune cells. Endoplasmic reticulum stress leading to the unfolded protein response has been recently reported as an active player in inducing inflammatory responses. Once unfolded protein response is activated, GRP78, an endoplasmic reticulum–resident chaperone, is translocated to the cell surface (sGRP78), where it is considered a cell stress marker; however, its presence has not been evaluated in immune cells during disease. Here we assessed the presence of sGRP78 on different cell subsets in blood samples from severe or convalescent COVID-19 patients. The frequency of CD45+sGRP78+ cells was higher in patients with the disease compared to convalescent patients. The latter showed similar frequencies to healthy controls. In patients with COVID-19, the lymphoid compartment showed the highest presence of sGRP78+ cells versus the myeloid compartment. CCL2, TNF-α, C-reactive protein, and international normalized ratio measurements showed a positive correlation with the frequency of CD45+sGRP78+ cells. Finally, gene expression microarray data showed that activated T and B cells increased the expression of GRP78, and peripheral blood mononuclear cells from healthy donors acquired sGRP78 upon activation with ionomycin and PMA. Thus, our data highlight the association of sGRP78 on immune cells in patients with severe COVID-19.

Biologics are recommended to treat paediatric ulcerative colitis (UC) that is chronically active or steroid-dependent despite aminosalicylic acids (5-ASA) and thiopurine treatments. Anti-tumour necrosis factor inhibitors (Anti-TNF inhibitors) are the agents of choice and vedolizumab could be considered as second-line biologic therapy.In the current case, we aim to describe a successful long-term treatment with vedolizumab in a 9-year-old boy with severe UC and primary non-response to infliximab. Concomitant azathioprine was used, and steroid refractoriness was also detected. Drug and anti-drug antibody levels were negative after infliximab induction so a switch to a 6-week-induction vedolizumab regimen followed by a maintenance regimen as a monotherapy was decided. The clinical response and tolerability to vedolizumab allowed long-term disease remission. Vedolizumab is currently non-authorised to treat paediatric patients and there is limited data on long-term treatments to date. This case contributes to the literature by adding evidence on the long-term efficacy and safety of vedolizumab in paediatric UC.

Background: Post-stroke oropharyngeal dysphagia (PS-OD) and its complications increase healthcare costs, suggesting that its appropriate management is cost-effective. We aimed to assess the efficiency of healthcare interventions in PS-OD management. Methods: A systematic review was conducted following PRISMA recommendations. Four databases were searched from inception through 30 June 2021. Outcome measures were cost-effectiveness and cost-savings of healthcare interventions. English and Spanish literature were included. Narrative and tables were used to present and synthesise evidence. Quality was evaluated using the CHEERS Statement. Results: A total of 244 studies were identified, and 10 were included. Screening and diagnosis of PS-OD studies found: (1) adjusted reduction in hospitalisation costs when assessed during the first admission day; (2) non-significant reduction in hospitalisation costs with OD management after thrombolysis; and (3) videofluoroscopy as the most cost-effective screening method (compared to bedside evaluation and a combination of both). Two studies showed cost-effective rehabilitation programmes, including OD management. Pelczarska et al. showed an incremental cost–utility ratio of texture-modified diets using a gum-based thickener of 20,977 PLN (4660€) following a dynamic model, and Kotecki et al. commercially prepared thickened fluids that were 44% to 59% less expensive than in situ prepared fluids. Elia et al. showed home enteral nutrition was cost-effective (£12,817/QALY), and Beavan et al. showed higher nutrient intake and low increase in hospitalisation costs using looped-nasogastric tubes (£5.20 for every 1% increase). Heterogeneity between studies precluded a quantitative synthesis. Conclusions: Included studies suggest that healthcare interventions aiming to prevent OD complications are cost-effective. However, studies assessing novel strategies are needed.

Background and objectives While randomised controlled trials in HIV-infected patients have shown that certain dual antiretroviral therapy (DAT) regimens are non-inferior in terms of efficacy compared with classical triple-drug regimens, few real clinical experiences have been described. The aim of the study was to investigate, in real clinical practice, DAT effectiveness, durability, and risk factors for treatment discontinuation. Methods This was a prospective cohort study that included HIV-infected patients treated with DAT (2015-2020). DAT was considered effective when patients achieved or maintained virological suppression and was assessed at 24 and 48 weeks. DAT durability was evaluated using the Kaplan-Meier method. Adherence and treatment cost were compared with patients' previous antiretroviral regimens. Results 51 patients were included, 27.5% with HIV-1 RNA >= 50 copies/mL at baseline, treated with a wide range of dual combinations. At 48 weeks follow-up, 83.8% and 50.0% of patients who started DAT with HIV-1 RNA = 50 copies/mL, respectively, were suppressed. 39 out of 51 patients (76.5%) maintained DAT for a mean treatment duration of 40.5 +/- 14.8 weeks. Full adherence was observed in 78.4% of patients compared with 70.2% in the previous regimen. Mean daily cost was euro18.6 +/- 4.3 compared with euro16.1 +/- 7.9 in the previous regimen (p=0.008). Conclusion DAT effectiveness and durability were higher in patients who were virologically suppressed at baseline. DAT is a possible alternative for virologically non-suppressed patients who cannot be treated with a triple-drug regimen.

Background/Aims Fecal incontinence (FI) is a prevalent condition among women. While biomechanical motor components have been thoroughly researched, anorectal sensory aspects are less known. We studied the pathophysiology of FI in community-dwelling women, specifically, the conduction through efferent/afferent neural pathways. Methods A cross-sectional study was conducted on 175 women with FI and 19 healthy volunteers. The functional/structural study included anorectal manometry/endoanal ultrasound. Neurophysiological studies including pudendal nerve terminal motor latency (PNTML) and sensory-evoked-potentials to anal/rectal stimulation (ASEP/RSEP) were conducted on all healthy volunteers and on 2 subgroups of 42 and 38 patients, respectively. Results The main conditions associated with FI were childbirth (79.00%) and coloproctological surgery (37.10%). Cleveland score was 11.39 ± 4.09. Anorectal manometry showed external anal sphincter and internal anal sphincter insufficiency in 82.85% and 44.00%, respectively. Sensitivity to rectal distension was impaired in 27.42%. Endoanal ultrasound showed tears in external anal sphincter (60.57%) and internal anal sphincter disruptions (34.80%). Abnormal anorectal sensory conduction was evidenced through ASEP and RSEP in 63.16% and 50.00% of patients, respectively, alongside reduced activation of brain cortex to anorectal stimulation. In contrast, PNTML was delayed in only 33.30%. Stools were loose/very loose in 56.70% of patients. Conclusions Pathophysiology of FI in women is mainly associated with mechanical sphincter dysfunctions related to either muscle damage or, to a lesser extent, impaired efferent conduction at pudendal nerves. Impaired conduction through afferent anorectal pathways is also very prevalent in women with FI and may play an important role as a pathophysiological factor and as a potential therapeutic target. (J Neurogastroenterol Motil 2019;25:423-435)

Background and purpose Oropharyngeal dysphagia (OD) affects 40–81% of patients after stroke. A recent systematic review on the costs of OD and its main complications showed higher acute and long-term costs for those patients who developed OD, malnutrition and pneumonia after stroke. These results suggest that appropriate management of post-stroke OD could reduce clinical complications and costs. The purpose of this systematic review is to assess the available literature for healthcare interventions that are efficient or cost-effective in the management of OD. Methods A systematic review on economic evaluations of health care interventions will be performed on post-stroke patients with OD following PRISMA recommendations. Four bibliographic databases will be searched and a subsequent reference check will be done. English and Spanish literature will be included without date restrictions. Studies will be included if they refer to economic evaluations or in which cost savings were reported in post-stroke patients suffering OD. Studies will be excluded if they are partial economic evaluation studies, if they refer to esophageal dysphagia, or if OD is caused by causes different from stroke. Evidence will be presented and synthetised with a narrative method and using tables. Quality evaluation will be done using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) statement. Discussion The protocol for this systematic review is the first step to assess the cost-effectiveness of the healthcare interventions that have been described as potential treatments for post-stroke OD. This systematic review will summarise the current evidence on the relation between cost and benefits associated with the appropriate management of OD in post-stroke patients. Trial registration PROSPERO CRD42020136245

Background: The effect of oropharyngeal dysphagia (OD) and thickened fluid (TF) therapy on hydration status has not been well defined in the literature. We aimed to assess the hydration status in patients with OD and the effect TF therapy has on it. Methods: Two literature reviews following PRISMA methodology (each one including a systematic and a scoping review) were performed: (R1) hydration status in adult patients with OD; (R2) effect of TF therapy on fluid intake and dehydration. Narrative and descriptive methods summarized both reviews. Quality assessment was assessed by Joanna Briggs Institute tools and GRADE. Results: (R1) Five out of twenty-two studies using analytical parameters or bioimpedance showed poorer hydration status among OD and 19–100% prevalence of dehydration; (R2) two high quality studies (total of 724 participants) showed positive effects of TF on hydration status. Among the articles included, nine out of ten studies that evaluated fluid intake reported a reduced TF intake below basal water requirements. Conclusions: Dehydration is a highly prevalent complication in OD. There is scientific evidence on the positive effect of TF therapy on the hydration status of patients with OD. However, strict monitoring of fluid volume intake is essential due to the low consumption of TF in these patients.

Altres ajuts: acords transformatius de la UAB Financial support received from research grants from Nutricia Danone Advanced Medical Nutrition (HESDY Grant); Fundació Salut del CSdM, Strategic Action Grant in Oropharyngeal Dysphagia provided by the Centro de Investigación Biomédica en Red en el Área de Enfermedades Hepáticas y Digestivas (CIBERehd), Instituto de Salud Carlos III, DJO Global, and la Fundació la Marató de TV3 (11/2310). Background and purpose: The healthcare economic costs of post-stroke oropharyngeal dysphagia (OD) are not fully understood. The purpose of this study was to assess the acute, subacute and long-term costs related to post-stroke OD and its main complications (malnutrition and respiratory infections). Methods: A cost of illness study of patients admitted to Mataró Hospital (Catalonia, Spain) from May 2010 to September 2014 with a stroke diagnosis was performed. OD, malnutrition and respiratory infections were assessed during hospitalization and follow-up (3 and 12 months). Hospitalization and long-term costs were measured from hospital and healthcare system perspectives. Multivariate linear regression analysis was performed to assess the independent effect of OD, malnutrition and respiratory infections on healthcare costs during hospitalization, and at 3 and 12 months' follow-up. Results: In all, 395 patients were included of whom 178 had OD at admission. Patients with OD incurred major total in-hospital costs (€5357.67 ± €3391.62 vs. €3976.30 ± €1992.58, p < 0.0001), 3-month costs (€8242.0 ± €5376.0 vs. €5320.0 ± €4053.0, p < 0.0001) and 12-month costs (€11,617.58 ± €12,033.58 vs. €7242.78 ± €7402.55, p < 0.0001). OD was independently associated with a cost increase of €789.68 (p = 0.011) during hospitalization and of €873.5 (p = 0.084) at 3 months but not at 12 months. However, patients with OD who were at risk of malnutrition or malnourished and suffered respiratory infections incurred major mean costs compared with those patients without OD (€19,817.58 ± €13,724.83 vs. €7242.8 ± €7402.6, p < 0.0004) at 12 months' follow-up. Conclusion: Oropharyngeal dysphagia causes significant high economic costs during hospitalization that strongly and significantly increase with the development of malnutrition and respiratory infections at long-term follow-up.

ObjectivesTo assess the healthcare costs associated with poststroke oropharyngeal dysphagia (OD) and its complications (malnutrition, dehydration, pneumonia and death).DesignSystematic review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses recommendations.Data sourcesMEDLINE, Embase and the National Health Service Economic Evaluation Database were searched up to 31 December 2019.ParticipantsPatients with poststroke.Primary outcome measuresThe costs associated to poststroke OD and its complications.Data analysisData were synthetised narratively, quality evaluation was done using an adaptation of Drummond’s checklist and Grading of Recommendations Assessment, Development and Evaluation recommendations were used to assess strength of evidence.ResultsA total of 166 articles were identified, of which 10 studies were included. The cost of OD during the hospitalisation was assessed in four studies. One prospective study showed an increase of US$6589 for patients requiring tube feeding. Two retrospective studies found higher costs for those patients who developed OD, (US$7329 vs US$5939) among patients with haemorrhagic stroke transferred to inpatient rehabilitation and an increase of €3000 (US$3950) and SFr14 000 (US$15 300) in hospitalisation costs. One study did not found OD as a predictor for total medical costs in the multivariate analysis. One retrospective study showed an increase of US$4510 during the first year after stroke for those patients with OD. For pneumonia, five retrospective studies showed an increase in hospitalisation costs after stroke of between US$1456 and US$27 633. One prospective study showed an increase in hospitalisation costs during 6 months after stroke in patients at high malnutrition risk. Strength of evidence was considered moderate for OD and pneumonia and low for malnutrition.ConclusionsThis systematic review shows moderate evidence towards higher costs for those patients who developed OD after stroke. The available literature is heterogeneous, and some important aspects have not been studied yet. Further studies are needed to define the specific cost of poststroke OD.PROSPERO registration numberCRD42018099977.

Hereditary hemochromatosis, one of the commonest genetic disorder in Caucasians, is mainly associated to homozygosity for the C282Y mutation in the HFE gene, which is highly prevalent (allele frequency up to near 10% in Northern Europe) and easily detectable through a widely available "first level" molecular test. However, in certain geographical regions like the Mediterranean area, up to 30% of patients with a HH phenotype has a negative or non-diagnostic (i.e. simple heterozygosity) test, because of a known heterogeneity involving at least four other genes (HAMP, HJV, TFR2, and SLC40A1). Mutations in such genes are generally rare/private, making the diagnosis of atypical HH essentially a matter of exclusion in clinical practice (from here the term of "non-HFE" HH), unless cumbersome traditional sequencing is applied. We developed a Next Generation Sequencing (NGS)-based test targeting the five HH genes, and applied it to patients with clinically relevant iron overload (IO) and a non-diagnostic first level genetic test. We identified several mutations, some of which were novel (i.e. HFE W163X, HAMP R59X, and TFR2 D555N) and allowed molecular reclassification of "non-HFE" HH clinical diagnosis, particularly in some highly selected IO patients without concurring acquired risk factors. This NGS-based "second level" genetic test may represent a useful tool for molecular diagnosis of HH in patients in whom HH phenotype remains unexplained after the search of common HFE mutations.

IntroductionOropharyngeal dysphagia (OD) is a major disorder following stroke. OD can produce alterations in both the efficacy and safety of deglutition and may result in malnutrition, dehydration, frailty, respiratory infections and pneumonia. These complications can be avoided by early detection and treatment of OD in poststroke patients, and hospital stays, medication and mortality rates can be reduced. In addition to acute in-hospital costs from OD complications, there are other costs related to poststroke OD such as direct non-healthcare costs or indirect costs. The objective of this systematic review is to assess and summarise literature on the costs related to OD in poststroke patients.Methods and analysisA systematic review of studies on the cost of OD and its complications (aspiration, malnutrition, dehydration, aspiration pneumonia and death) in patients who had a stroke will be performed from the perspectives of the hospital, the healthcare system and/or the society. The main outcomes of interest are the costs related to poststroke OD. We will search MEDLINE, Embase and the National Health Service Economic Evaluation Database. Studies will be included if they are partial economic evaluation studies, studies that provide information on costs in adult (>17 years) poststroke patients with OD and/or its complications (malnutrition, dehydration, frailty, respiratory infections and pneumonia) or economic evaluation studies in which the cost of this condition has been estimated. Studies will be excluded if they refer to oesophageal dysphagia or OD caused by causes other than stroke. Main study information will be presented and summarised in tables, separately for studies that provide incremental costs attributable to OD or its complications and studies that report the effect of OD or its complications on total costs of stroke, and according to the perspective from which costs were measured.Ethics and disseminationThe results of this systematic review will be published in a peer-reviewed journal.PROSPERO registration numberCRD42018099977.

Nanomaterials based sensing systems provide a new class of rapid and low cost detection alternatives with interest in the field of safety and security applications. In this review we report the recent trends in the use of various nanomaterials such as nanoparticles, carbon nanotubes, nanowires and graphene to detect different safety and security related analytes (i.e. microorganisms, toxins, pesticides and explosives). Nanomaterials are used either as modifiers of the electrochemical transducers or as labels with the objective to enhance the electrochemical signal, improve the stability and in general the performance of the detection systems including their cost-efficiency. Most of the developed systems are shown to bring excellent improvements while being used in the laboratory. Their application in real sample and during in-field monitoring still needs a long way while issues such as the reproducibility, stability, mass production capability of the designed devices etc. shouldn’t still yet be resolved.

Simple strategies for producing silver and gold nanoparticles (AgNP and AuNP) along with the corresponding core shell nanoparticles (Au–Ag and Ag–Au) by reduction of the metal salts AgBF4 and HAuCl4 by NaBH4 in water will be presented. The morphologies of the obtained nanoparticles are determined by the order of addition of reactants. The obtained NPs, with sizes in the range 3–40 nm, are characterized by transmission electronic microscopy (TEM) and UV–Vis absorption spectroscopy, so as to evaluate their qualities. Moreover, a direct electrochemical detection protocol based on a cyclic voltammetry in water solution that involves the use of glassy carbon electrode is also applied to characterize the prepared NPs. The developed NPs and the related electroanalytical method seem to be with interest for future sensing and biosensing applications including DNA sensors and immunosensors.

Different methods of synthesis for the production of electroactive nanocrystals (NCs) for use as labels in DNA sensing systems are presented. They are based on two general ways of controlling the formation and growth of the nanoparticles: (a) physical restriction of the volume available for the growth of the individual nanoparticles by using templates such as reverse micelles; (b) arrested precipitation that depends on exhaustion of one of the reactants. The water dispersed nanocrystals thus obtained are then characterized by optical or electrochemical techniques so as to evaluate the quality of the prepared NCs. A novel direct electrochemical stripping detection protocol that involves the use of a bismuth modified graphite epoxy composite electrode is developed and applied so as to quantify the CdS NCs. The electrochemical study revealed a linear dependency of the stripping current upon the concentration of CdS NCs with a detection limit of around 10(15) CdS NCs cm(-3). The obtained NCs are of great interest for future applications in electrochemical genosensors.

We present recent trends and challenges in the use of nanoparticles as DNA labels in electrochemical detection systems. We discuss nanoparticle synthesis procedures and methods for attaching biological molecules that enable their application in genosensors. We also discuss typical electrochemical procedures based on gold nanoparticles and quantum dots (QDs), along with QD carriers, such as carbon nanotube or polystyrene beads. High sensitivity and selectivity, simultaneous detection of various DNA sequences, and cost-efficient detection are advantages that seem to come using these novel labels in DNA electrochemical detection schemes.

A flexible hybrid polydimethylsiloxane (PDMS)-polycarbonate (PC) microfluidic chip with integrated screen printed electrodes (SPE) was fabricated and applied for electrochemical quantum dots (QDs) detection. The developed device combines the advantages of flexible microfluidic chips, such as their low cost, the possibility to be disposable and amenable to mass production, with the advantages of electrochemistry for its facility of integration and the possibility to miniaturize the analytical device. Due to the interest in biosensing applications in general and particularly the great demand for labelling alternatives in affinity biosensors, the electrochemistry of cadmium sulfide quantum dots (CdS QDs) is evaluated. Square wave anodic stripping voltammetry (SWASV) is the technique used due to its sensitivity and low detection limits that can be achieved. The electrochemical as well as the microfluidic parameters of the developed system are optimized. The detection of CdS QDs in the range between 50 to 8000 ng mL(-1) with a sensitivity of 0.0009 μA/(ng mL(-1)) has been achieved. In addition to the single in-chip flow through measurements, the design of a recirculation system with the aim of achieving lower detection limits using reduced volumes (25 μL) of sample was proposed as a proof-of-concept.

The detection of non-amplified DNA sequences plays a crucial role in the rapid diagnosis of genetic-related diseases especially for early stage treatment. Among the various biosensors that have been used for DNA detection, electrochemical sensors show great promise because they present efficient signal transduction and are capable of precise DNA recognition at a relatively low cost in addition to the broad range of designs with interest to be applied in different kinds of samples. Advancements in micro- and nanotechnologies, specifically fabrication techniques and new nanomaterials, have enabled for the development of highly sensitive, highly specific electrochemical sensors making them attractive for the detection of small sequence variations. Furthermore, the integration of sensors with sample preparation and fluidic processes enables for rapid, multiplexed electrochemical DNA detection essential for point of care clinical diagnostics.

6 páginas, 3 figuras., The use of square wave voltammetry to monitor the cellular uptake, in HeLa cells, of quantum dots (QD) decorated with sweet arrow peptide (SAP) is reported. A SAP derivative containing an additional N-terminal cysteine residue (C-SAP) was synthesized using the solid-phase method and conjugated to QDs. The obtained results show that QDs-SAP either interact with the extracellular cell membrane matrix or translocate the bilayer. The first situation, membrane adsorption, is probably a transient state before cellular uptake. Both confocal microscopy and SWV results support the detection of this cellular internalization process. The developed electrochemical investigation technique can provide valuable insights into the study of peptide-mediated delivery, as well as the design and development of nanoparticle probes for intracellular imaging, diagnostic, and therapeutic applications. In addition, the described electrochemical interrogation is low cost, is easy to use, and offers future interest for diagnostics including cell analysis., This work was supported by MAT2008-03079/NAN (MEC, Madrid); MCI-FEDER (Bio2008-00799, NAN2004-09159-C04- 02 and NANOBIOMED-CONSOLIDER) and the Generalitat de Catalunya (CeRBa and 2005SGR-00663). S. Pujals is supported by a FPU grant from the Ministerio de Ciencia e Innovación of Spain.

The emergence of nanotechnology and nanomaterials has opened up new horizons for the development of improved analytical devices. New synthesis, fabrication, and characterization methods offer the possibility to control the size, shape, and composition of nanometric-scale materials, thereby allowing exquisite control of their properties. The ability to carefully tailor the physical properties of nanomaterials is probably the major achievement of nanoscience and represents an essential element for their application in analytical systems. Among the numerous detecting strategies, electrochemical sensing techniques play a growing role in various fields in which an accurate, low-cost, fast, and online analytical measuring system is required. Besides the relatively low cost compared with optical instrumentation, advantages such as the possibility of miniaturization as well as in-field applications make electrochemical sensing devices very attractive. The properties of nanostructured materials, such as high surface/volume ratio, their ability to be functionalized, favorable electronic and thermal features, and electrocatalytic effect attracted considerable attention for the assembling of novel electrochemical sensing systems. Nanomaterials such as nanoparticles (NPs), nanotubes, nanowires, nanocomposites, and nanochannels of various sizes and compositions have been applied in electroanalysis to improve the immobilization of enzymes, antigens, and nucleic acids on electrochemical transducer surfaces, to promote the direct electron-transfer reactions, and to amplify and orient the analytic signal of biorecognition events. In this article, a general description of the properties of the nanomaterials most commonly used in electroanalysis, along with their integration into electrochemical analytical tools, is given. The analytical performances and the impact such nanomaterial-based devices are expected to have upon clinical diagnostics, environmental monitoring, security surveillance, and food safety are also discussed. Keywords: nanomaterials; nanoparticles; quantum dots; carbon nanotubes; nanowires; nanopores; nanochannels; electroanalysis; sensors; biosensors; immunosensors; protein; DNA

Recent advances of our research in the development of novel nanomaterial based electrochemical transducing platforms for biomedical applications are outlined. The objective has been to design platforms with interest for future applications in low cost, user-friendly and efficient electrochemical based sensors and biosensors that can be used even by non professional people for fast diagnostic at home or doctor’s office as well as other applications where either an emergency exists or an alternative method toward the sophisticated and expensive laboratory instrumentation is being required.

Alagille syndrome (ALGS), or arteriohepatic dysplasia, is a congenital multisystem disease due to Notch signalling pathway mutations, most commonly affecting JAGGED-1 (ALGS type 1), and more rarely NOTCH-2 (ALGS type 2), leading to hepatic, lung, renal and ocular dysfunction (chronic cholestasis, peripheral pulmonary artery stenosis, dysplastic kidneys pigmentary retinopathy), and skeletal abnormalies (minor vertebral segmentation, characteristic facies, posterior embryotoxon/anterior segment defects). ALGS is an autosomal dominant disease, but it is characterized also by variable penetrance and clinical expression and somatic/germline mosaicism. A 20-year-old man with ALGS was admitted to the University Hospital of Verona because of pancytopenia. Following analyses led to the diagnosis of Philadelphia chromosome/bcr-abl-negative, CD10-positive, B-lineage acute lymphoblastic leukemia (common B-ALL). In order to identify the genetic components involved in this complex phenotype, we sequenced the exome of a bone marrow sample collected from the patient. By genome interpretation with Knome pipeline applied to the reference genome UCSC hg19, we found missense variants both in NOTCH-2 (E38K) and JAGGED-1 (P871R) genes that are mainly involved in the syndrome, although their effect on protein function was predicted not to be deleterious. However, we detected putative damaging mutations in genes such as PAX5 (R38H) and NOTCH-1 (K1821N), which might be strongly related to the observed disease. In fact, PAX5 is a member of PAX protein family of transcription factors implicated into regulation of early development that binds NOTCH-2 and likely altering its functionality. On the other hand, NOTCH-1 is involved in cell growth and proliferation and thus the predicted alteration of function of the corresponding protein may have an important role in neoplastic transformation. Disclosures Martinelli: Novartis: Consultancy, Speakers Bureau; BMS: Consultancy, Speakers Bureau; Pfizer: Consultancy; ARIAD: Consultancy.

Alagille syndrome (ALGS), or arteriohepatic dysplasia, is a congenital multisystem disease due to Notch signalling pathway mutations, most commonly affecting JAG1 (ALGS type 1), and more rarely NOTCH2 (ALGS type 2), leading to hepatic, lung, renal and ocular dysfunction (chronic cholestasis, peripheral pulmonary artery stenosis, dysplastic kidneys pigmentary retinopathy), and skeletal abnormalies (minor vertebral segmentation, characteristic facies, posterior embryotoxon/anterior segment defects). ALGS is an autosomal dominant disease, but it is characterized also by variable penetrance and clinical expression and somatic/germline mosaicism. A 20-year-old man with ALGS was admitted to the University Hospital of Verona because of pancytopenia. Following analyses led to the diagnosis of Philadelphia chromosome/bcr-abl-negative, CD10-positive, B-lineage acute lymphoblastic leukemia (common B-ALL). In order to identify the genetic components involved in this complex phenotype, we sequenced the exome of a bone marrow sample collected from the patient. By genome interpretation with Knome pipeline applied to the reference genome UCSC hg19, we found missense variants both in NOTCH2 (E38K) and JAG1 (P871R) genes that are mainly involved in the syndrome, although their effect on protein function was predicted not to be deleterious. However, we detected putative damaging mutations in genes such as PAX5 (R38H) and NOTCH1 (K1821N) which might be strongly related to the observed disease. In fact, PAX5 is a member of PAX protein family of transcription factors implicated into regulation of early development, that binds NOTCH2 and likely altering its functionality. On the other hand, NOTCH1 is involved in cell growth and proliferation and thus the predicted alteration of function of the corresponding protein may have an important role in neoplastic transformation. Disclosures: No relevant conflicts of interest to declare.

not Available.

A simple method based on screen-printed electrodes and a handheld potentiostatic device is reported for the detection of water soluble CdS quantum dots modified with glutathione. The detection method is based on the stripping of electrochemically reduced cadmium at pH 7.0 by using square wave voltammetry. Various parameters that affect the sensitivity of the method are optimized. QD suspension volumes of 20 microl and a number of around 2 x 10(11) CdS quantum dots have been able to be detected. The proposed method should be of special interest for bioanalytical assays, where CdS quantum dots can be used as electrochemical tracers.