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[EN] A thermal method of synthesis and fixation of Pt nanoparticles (Pt NPs) on carbon paper is proposed in this paper. Carbon paper was coated with H2PtCl6 by simple immersion in an ethanol solution containing the Pt precursor. Thereafter, H2PtCl6 was decomposed in inert atmosphere into Pt NPs by applying a temperature of 600 °C. Formed Pt NPs were able to oxidize the surrounding carbon fiber surface. This local thermal oxidation of carbon promoted the generation of nano-roughness and Pt NPs were embedded in the carbon fiber, thus favoring their fixation on carbon paper. Pt load can be easily controlled by the number of coating processes applied. The proposed method combines the advantage of achieving small size nanoparticles (5¿10 nm) with enhanced fixation of Pt NPs when compared with electrochemical synthesis. The optimal number of coatings applied was three, which produced a complete coverage of carbon paper surface (with a Pt load of 0.18 mg cm¿2)., This work was supported by the Instituto Valenciano de Competitividad Empresarial (IVACE) (project references IMDECA/2016/50, IMDEEA/2017/116, IMDEEA/2018/26) and European Union (FEDER funds). Electron Microscopy Service of the UPV (Universitat Politecnica de Val encia) is gratefully acknowledged for help with FESEM and EDX characterization.

Background Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome. Results Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation. Conclusions Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.

Early detection of invaders requires finding small numbers of individuals across large landscapes. It has been argued that the only feasible way to achieve the sampling effort needed for early detection of an invader is to involve volunteer groups (citizen scientists, passive surveyors, etc.). A key concern is that volunteers may have a considerable false-positive and false-negative rate. The question then becomes whether verification of a report from a volunteer is worth the effort. This question is the topic of this paper.We show that the maximum plausible incidence when the expert samples on its own, , and the maximum plausible incidence when the expert only verifies cases reported by the volunteer surveyor to be infected, , are related as Where θfp and θfn are the false positive and false negative rate of the volunteer surveyor, respectively. We also show that the optimal monitoring programme consists of verifying only the cases reported by the volunteer surveyor if Where TN is the cost of a sample taken by the expert and TX is the cost of an expert verifying a case reported by a volunteer surveyor.

Emerging pests and pathogens of plants are a major threat to natural and managed ecosystems worldwide. Whilst it is well accepted that surveillance activities are key to both the early detection of new incursions and the ability to identify pest-free areas, the performance of these activities must be evaluated to ensure they are fit for purpose. This requires consideration of the number of potential hosts inspected or tested as well as the epidemiology of the pathogen and the detection method used. In the case of plant pathogens, one particular concern is whether the visual inspection of plant hosts for signs of disease is able to detect the presence of these pathogens at low prevalences, given that it takes time for these symptoms to develop. One such pathogen is the ST53 strain of the vector-borne bacterial pathogen Xylella fastidiosa in olive hosts, which was first identified in southern Italy in 2013. Additionally, X. fastidiosa ST53 in olive has a rapid rate of spread, which could also have important implications for surveillance. In the current study, we evaluate how well visual surveillance would be expected to perform for this pathogen and investigate whether molecular testing of either tree hosts or insect vectors offer feasible alternatives. Our results identify the main constraints to each of these strategies and can be used to inform and improve both current and future surveillance activities.

In the midst of the COVID-19 pandemic, different vaccines in front of SARS-CoV-2 have been approved and administered in different vulnerable populations. As patients with cancer were excluded from pivotal trials of vaccination, little is known on their immunogenic response to these vaccines, particularly in patients with severely impaired immune system. In response to that uncertainty, the Spanish Society of Hematology and Hemotherapy launched an initiative aimed to provide recommendations for vaccination of the main hematological conditions. This document is based on the available information on COVID-19 outcomes, prior knowledge on vaccination in hematological patients, recent published data on serological response in oncohematological patients and expert opinions. New information about SARS-CoV-2 vaccination will be gathered in the near future, providing new scientific grounds to delineate the most adequate management of vaccination in patients with hematological diseases. The current limited data on SARS-CoV-2 vaccines in hematological patients represents a major limitation of this expert consensus opinion. In fact, the speed in which this field evolves may reduce their validity in the near future.

ObjectivesTo investigate whether MTX should be combined with an additional DMARD and bridging glucocorticoids as initial treatment for patients with early RA to induce an effective long-term response.MethodsThe Care in early RA study is a two-year investigator-initiated pragmatic multicentre randomized trial. Early RA patients, naïve to DMARDs and glucocorticoids, were stratified based on prognostic factors. High-risk patients were randomized to COBRA-Classic (n = 98): MTX, sulfasalazine, prednisone step-down from 60 mg; COBRA-Slim (n = 98): MTX, prednisone step-down from 30 mg; or COBRA-Avant-Garde (n = 93): MTX, leflunomide, prednisone step-down from 30 mg. Low-risk patients were randomized to COBRA-Slim (n = 43); or Tight Step Up (TSU) (n = 47): MTX without prednisone. Clinical/radiological outcomes at year 2, sustainability of response, safety and treatment adaptations were assessed.ResultsIn the high-risk group 71/98 (72%) patients achieved a DAS28-CRP < 2.6 with COBRA-Slim compared with 64/98 (65%) with COBRA-Classic and 69/93 (74%) with COBRA-Avant-Garde (P = 1.00). Other clinical/radiological outcomes and sustainability of response were similar. COBRA-Slim treatment resulted in less therapy-related adverse events compared with COBRA-Classic (P = 0.02) or COBRA-Avant-Garde (P = 0.005). In the low-risk group, 29/43 (67%) patients on COBRA-Slim and 34/47 (72%) on TSU achieved a DAS28-CRP < 2.6 (P = 1.00). On COBRA-Slim, low-risk patients had lower longitudinal DAS28-CRP scores over 2 years, a lower need for glucocorticoid injections and a comparable safety profile compared with TSU.ConclusionAll regimens combining DMARDs with glucocorticoids were effective for patients with early RA up to 2 years. The COBRA-Slim regimen, MTX monotherapy with glucocorticoid bridging, provided the best balance between efficacy and safety, irrespective of patients’ prognosis.Trial registrationClinicalTrials.gov, http://www.clinicaltrials.gov, NCT01172639.

The emergence of Xylella fastidiosa in Europe has highlighted the importance of surveillance for protection of host plants against exotic pathogens. However, surveillance for such pathogens is resource intensive and must therefore be efficient and sustainable. Using the example of the Apulian outbreak, we consider here how best to conduct surveillance in pest-free areas which are at a high risk of infection due to spread from adjacent outbreaks. To do this, we consider where inspection and survey sites should be, which diagnostic test to use during surveillance, and whether to sample hosts or insect vectors. We identify the optimal locations of surveillance sites by linking together an epidemiological model of pathogen spread and a statistically-informed sampling model with a computational optimisation routine. This approach allows us to demonstrate the considerable differences in survey deployment in order to maximise the number of infected hosts detected compared with maximising the overall probability of detection. We go on to consider the impact of the ""detection lag"" before infected hosts become detectable on both the detection probability and the expected prevalence of infection at the time of first detection. Finally, we consider whether sampling of hosts or sampling of vectors would be expected to facilitate earlier detection, and discuss some of the challenges associated with these strategies. As well as providing specific recommendations for improving surveillance activities for X. fastidiosa in Apulia, our methods are generic and can be applied in other areas and for a range of pests and pathogens.

Purpose: Despite the remarkable activity of BTK inhibitors (BTKi) in relapsed B-cell non-Hodgkin lymphoma (B-NHL), no clinically-relevant biomarker has been associated to these agents so far. The relevance of phosphoproteomic profiling for the early identification of BTKi responders remains underexplored. Experimental Design: A set of six clinical samples from an ongoing phase I trial dosing patients with chronic lymphocytic leukemia (CLL) with TG-1701, a novel irreversible and highly specific BTKi, were characterized by phosphoproteomic and RNA sequencing (RNA-seq) analysis. The activity of TG-1701 was evaluated in a panel of 11 B-NHL cell lines and mouse xenografts, including two NF-kappa B-and BTKC481S-driven BTKi-resistant models. Biomarker validation and signal transduction analysis were conducted through real-time PCR, Western blot analysis, immunostaining, and gene knockout (KO) experiments. Results: A nonsupervised, phosphoproteomic-based clustering did match the early clinical outcomes of patients with CLL and separated a group of "early-responders" from a group of "late-responders." This clustering was based on a selected list of 96 phosphosites with Ikaros-pSer442/445 as a potential biomarker for TG-1701 efficacy. TG-1701 treatment was further shown to blunt Ikaros gene signature, including YES1 and MYC, in early-responder patients as well as in BTKi-sensitive B-NHL cell lines and xenografts. In contrast, Ikaros nuclear activity and signaling remained unaffected by the drug in vitro and in vivo in late-responder patients and in BTKC481S, BTKKO, and noncanonical NF-kappa B models. Conclusions: These data validate phosphoproteomic as a valuable tool for the early detection of response to BTK inhibition in the clinic, and for the determination of drug mechanism of action.

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.

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Acquired von Willebrand syndrome (AVWS) is a rare hemorrhagic condition that poses both a diagnostic and a therapeutic challenge. Here we report a singular case of AVWS with two associated conditions, small lymphocytic lymphoma (SLL) and Sjogren's syndrome. The patient presented with recurrent and severe digestive bleeding that forced us to raise a curative attempt of AVWS. A first immunosuppressive therapy with immunoglobulins was unsuccessful and it was later decided to treat lymphoproliferative entity with bendamustine and rituximab effectively achieving SLL and AVWS remission. On the basis of our case and through literature review, we discuss potential strategies to achieve AVWS remission when it appears in the setting of several causative associated conditions. Copyright (C) 2019 Wolters Kluwer Health, Inc. All rights reserved.

Aim: To analyze the effectiveness and safety of direct oral anticoagulants (DOACs) in atrial fibrillation (AF) patients attended in clinical practice. Methods: Observational and prospective study of AF patients that started treatment with DOACs. Results: 1443 patients (age 77.2 +/- 9.7 years, CHA(2)DS(2)-VASc=4.1 +/- 1.5) were included. 46.0% were taking rivaroxaban, 24.4% dabigatran, 22.5% apixaban and 7.1% edoxaban. Patients taking dabigatran were younger, had lower CHA(2)DS(2)-VASc and lesser renal insufficiency. Patients taking apixaban had higher CHA(2)DS(2)-VASc and more renal insufficiency. Rates of stroke/major bleeding/intracranial bleeding were 0.7/1.3/0.2 events/100 patient-years, respectively. Conclusion: This was the first prospective study that analyzed the use of all DOACs in AF patients in Spain, showing a good profile in terms of safety and effectiveness in accordance with pivotal studies.

Burkitt's monomorphic posttransplant lymphoproliferative disorder (B-PTLD) is an uncommon subtype of PTLD. Owing to the paucity of this complication, clinical characteristics and outcome has not been fully described. Clinical characteristics and outcomes of 20 patients diagnosed with B-PTLD from 10 transplant centers belonging to the GEL/TAMO group were reviewed. Median time from transplant to B-PTLD was 7.2 years. All the cases fulfill the morphologic and genetic criteria of B-PTLD, whereas Epstein-Barr virus (EBV) was detected in 70% of cases. Patients were treated with different chemotherapy combinations, and three patients received upfront rituximab monotherapy. The great majority of patients receiving CHOP-like regimens attained a complete response (CR) (73%), similar to that obtained with dose-intensive chemotherapy (83% CR). In contrast, patients receiving upfront rituximab monotherapy required subsequent chemotherapy. Two patients (10%) died during treatment due to infection. The median progression-free survival and overall survival (OS) were 16 months and 139 months, respectively. When analyzing variables predicting for OS, we found that patients with bone marrow involvement had an adverse prognosis, with a median OS of 6 months (p = 0.008). In conclusion, B-PTLD is an uncommon complication usually associated with EBV infection and with an aggressive clinical course, particularly in patients with bone marrow involvement. High-dose chemoimmunotherapy obtained similar responses to R-CHOP, suggesting that R-CHOP could be an adequate alternative for these patients. In contrast, rituximab monotherapy does not seem to be effective enough to control the disease.

This deposit is composed by a publication in which the IGC' authors have had the role of collaboration (it's a collaboration publication). This type of deposit in ARCA is in restrictedAccess (it can't be in open access to the public), and could only be accessed by two ways: either by requesting a legal copy to the author (the email contact present in this deposit) or by visiting the following link: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4383977/ The laboratory mouse is a key model organism to investigate mechanism and therapeutics of human disease. The number of targeted genetic mouse models of disease is growing rapidly due to high-throughput production strategies employed by the International Mouse Phenotyping Consortium (IMPC) and the development of new, more efficient genome engineering techniques such as CRISPR based systems. We have previously described the European Mouse Mutant Archive (EMMA) resource and how this international infrastructure provides archiving and distribution worldwide for mutant mouse strains. EMMA has since evolved into INFRAFRONTIER (http://www.infrafrontier.eu), the pan-European research infrastructure for the systemic phenotyping, archiving and distribution of mouse disease models. Here we describe new features including improved search for mouse strains, support for new embryonic stem cell resources, access to training materials via a comprehensive knowledgebase and the promotion of innovative analytical and diagnostic techniques. European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI).

AIMS/HYPOTHESIS: The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry. METHODS: Sample 1 comprised 845 non-diabetic offspring of type 2 diabetes patients recruited in five European centres participating in the EUGENE2 study. Samples 2 and 3 comprised, respectively, 864 and 524 Italian non-diabetic participants. All individuals underwent an OGTT. Screening for the rs10811661 polymorphism was performed using a TaqMan allelic discrimination assay. RESULTS: The rs10811661 polymorphism did not show a significant association with age, BMI and insulin sensitivity. Participants carrying the TT genotype showed a significant reduction in insulin release, measured by an OGTT-derived index, compared with carriers of the C allele, in the three samples. When these results were pooled with those of three published studies, and meta-analysed with a random-effects model, the T allele was significantly associated with reduced insulin secretion (-35.09 [95% CI 14.68-55.52], p = 0.0008 for CC+CT vs TT; and -29.45 [95% CI 9.51-49.38], p = 0.0038, for the additive model). In addition, in our three samples, participants carrying the TT genotype exhibited an increased risk for impaired glucose tolerance (IGT) compared with carriers of the C allele (OR 1.55 [95% CI 1.20-1.95] for the meta-analysis of the three samples). CONCLUSIONS/INTERPRETATION: Our data, together with the meta-analysis of previously published studies, show that the rs10811661 polymorphism is associated with impaired insulin release and IGT, suggesting that this variant may contribute to type 2 diabetes by affecting beta cell function.

This paper focuses on constraining the erosion rate in the area of the Allchar Sb-As-Tl-Au deposit (Macedonia). It contains the largest known reserves of lorandite (TlAsS2), which is essential for the LORanditeEXperiment (LOREX), aimed at determining the long-term solar neutrino flux. Because the erosion history of the Allchar area is crucial for the success of LOREX, we applied terrestrial in situ cosmogenic nuclides including both radioactive (26Al and 36Cl) and stable (3He and 21Ne) nuclides in quartz, dolomite/calcite, sanidine, and diopside. The obtained results suggest that there is accordance in the values obtained by applying 26Al, 36Cl, and 21Ne for around 85% of the entire sample collection, with resulting erosion rates varying from several tens of m/Ma to ∼165 m/Ma. The samples from four locations (L-8 CD, L1b/R, L1c/R, and L-4/ADR) give erosion rates between 300 and 400 m/Ma. Although these localities reveal remarkably higher values, which may be explained by burial events that occurred in part of Allchar, the erosion rate estimates mostly in the range between 50 and 100 m/Ma. This range further enables us to estimate the vertical erosion rate values for the two main ore bodies Crven Dol and Centralni Deo. We also estimate that the lower and upper limits of average paleo-depths for the ore body Centralni Deo from 4.3 Ma to the present are 250–290 and 750–790 m, respectively, whereas the upper limit of paleo-depth for the ore body Crven Dol over the same geological age is 860 m. The estimated paleo-depth values allow estimating the relative contributions of 205Pb derived from pp-neutrino and fast cosmic-ray muons, respectively, which is an important prerequisite for the LOREX experiment.

Congenital plasminogen deficiency is a rare autosomal recessive disorder, characterized by chronic mucosal membranous lesions. Although the most common clinical manifestation is eye involvement as ligneous conjunctivitis, extra-ocular lesions affecting other mucosal surfaces indicates a systemic disease. In this report we describe two cases with atypical extra-ocular involvement that includes pericarditis and recurrent hematocolpos, and one with paradoxical correlation between ocular lesions and plasminogen levels. In ligneous conjunctivitis, although different treatment strategies have been tried with mild success, the only effective therapy is topical or systemic plasminogen concentrates that are not commercially available. Unfortunately there is not either effective management for cases with multisystemic disease. Hence, treatment for plasminogen deficiency is still a challenge and the variability of the clinical spectrum in this pathology makes necessary a multidisciplinary approach.

LOREX, the acronym of LORandite EXperiment, is the only long-time solar neutrino experiment still actively pursued. It addresses the long-time detection of the solar neutrino flux with the thallium-bearing mineral lorandite, TlAsS2 at the mine of Allchar, FYRMacedonia, via the neutrino-capture reaction 205Tl+νe→205Pb+e−. The final step of LOREX would be the extraction of lorandite samples and the quantitative determination of the ratio of 205Pb/205Tl atoms providing the product of solar neutrino flux and neutrino-capture cross-section, integrated over the age of lorandite (about 4.3×106 y). There is an unprecedented low threshold of only 50 keV for solar pp-neutrinos, to be compared with 232 keV of the GALLEX and SAGE experiments. Moreover, LOREX would be unique in view of providing the mean luminosity of the sun over the last 4.3 million years. This paper presents new data providing an accurate geological age of mineralization at Allchar, and in particular a lower limit of 36 m/106 y for the erosion rate, based on Accelerator Mass Spectrometry of 26Al and 53Mn samples taken from the mine of Allchar. This data allow first realistic conclusions on the feasibility of the LOREX project. The amount of 205Pb due to fast cosmic rays (e.g. muons), strongly depends on the depth at which the mineral existed from the time of its formation to the present day. For the mineral mined at the present-day depth this contribution then depends upon the average erosion rate at this particular location. A reliable determination of the erosion rate is, therefore, indispensable for a proper estimate of the background of 205Pb induced by cosmic radiation. Provided that this lower limit of 36 m/106 y can be corroborated by the mandatory measurement of additional probes, it is expected to reach a signal-to-background ratio equal or better than one. Finally, it is discussed how to get the still unknown capture probability of solar pp-neutrinos from 205Tl into 205Pb, in particular into its first excited state at E*=2.3 keV.

Schottky Mass Spectrometry (SMS) and Isochronous Mass Spectrometry (IMS) have been successfully applied for direct mass measurements of exotic nuclides at FRS-ESR facility at GSI. Both experimental methods are sensitive to single stored ions and can cover very efficiently a large number of nuclides in one run. Presently, more than 1100 masses of different nuclides have been covered by SMS and IMS in several FRS-ESR experiments whereby about 350 of them have been determined for the first time. In this paper, we present the status of our experimental program and use the experimental mass values to test the predictive power of modern mass models.

Nederlands Dagblad

A $^{238}$U projectile beam was used to create cadmium isotopes via abrasion-fission at 410 MeV/u in a beryllium target at the entrance of the in-flight separator FRS at GSI. The fission fragments were separated with the FRS and injected into the isochronous storage ring ESR for mass measurements. The Isochronous Mass Spectrometry (IMS) was performed under two different experimental conditions, with and without B$\rho$-tagging at the dispersive central focal plane of the FRS. In the experiment with B$\rho$-tagging the magnetic rigidity of the injected fragments was determined by an accuracy of $2\times 10^{-4}$. A new method of data analysis, using a correlation matrix for the combined data set from both experiments, has provided mass values for 25 different isotopes for the first time. The high selectivity and sensitivity of the experiment and analysis has given access even to rare isotopes detected with a few atoms per week. In this letter we present for the $^{129,130,131}$Cd isotopes mass values directly measured for the first time. The Cd results clearly show a very pronounced shell effect at $N=82$ which is in agreement with the conclusion from $\gamma$-ray spectroscopy of $^{130}$Cd and confirms the assumptions of modern shell-model calculations., Comment: 7 pages, 5 figures, 3 tables

The pathogenetic mechanisms underlying gastrointestinal dysmotility in diabetic patients remain poorly understood, although enteric neuropathy, damage to interstitial cells of Cajal (ICC) and smooth muscle cell injury are believed to play a role.The aim of this study was to investigate the morphological and functional changes underlying intestinal dysmotility in RIP-I ⁄ hIFNb transgenic mice treated with multiple very low doses of streptozotocin (20 mg⁄ kg, i.p., 5 days). Compared with vehicle-treated mice, streptozotocin-treated animals developed type 1 diabetes mellitus, with sustained hyperglycaemia for 3.5 months, polyphagia, polydipsia and increased faecal output without changes in faecal water content (metabolic cages). Diabetic mice had a longer intestine, longer ileal villi and wider colonic crypts (conventional microscopy) and displayed faster gastric emptying and intestinal transit. Contractility studies showed selective impaired neurotransmission in the ileum and mid-colon of diabetic mice. Compared with controls, the ileal and colonic myenteric plexus of diabetic mice revealed ultrastructural features of neuronal degeneration and HuD immunohistochemistry on whole-mount preparations showed 15% reduction in neuronal numbers. However, no immunohistochemical changes in apoptosis-related markers were noted. Lower absolute numbers of neuronal nitric oxide synthase- and choline acetyltransferase-immunopositive neurons and enhanced vasoactive intestinal polypeptide and substance P immunopositivity were observed. Ultrastructural and immunohistochemical analyses did not reveal changes in the enteric glial or ICC networks. In conclusion, this model of diabetic enteropathy shows enhanced intestinal transit associated with intestinal remodelling, including neuroplastic changes, and overt myenteric neuropathy. Such abnormalities are likely to reflect neuroadaptive and neuropathological changes occurring in this diabetic model.

Theoretical studies are presented how the electric dipole moment (EDM) of the electron in H-like ions in electrostatic storage rings can sensitively be determined. With the proposed experiments a new constraint of about $10^{-29}$ e cm for the electron EDM can be established what is by an order of magnitude more restrictive than the existing bounds. Experiments with H-like ions may provide a possibility to distinguish between the electron EDM effect and the effect of P,T violating interaction between the atomic electron and the nucleus.

Recommendations for Sudden Infant Death Syndrome (SIDS) are available, although it is uncertain the degree of adherence to these measures. The aim of the study is to assess the adherence to recommendations to reduce the risk of SIDS, seeking factors associated to the noncompliance with these recommendations.468 infants were enrolled in two maternity hospitals, one public and one private. Postpartum and 4-month assessments were performed. A questionnaire was used adapting a model validated by the International Child Care Practices Study.Adherence to obstetric recommendations was higher (75.4%) than to pediatric recommendations (53.3%). Regarding pediatric recommendations, a compliance decrease was detected after 4 months. Follow-ups showed decrease in breastfeeding (p0.001 84.9% vs 48.6%) and supine position (61.2% vs 21.2%, p0.001).The decreased adherence to recommendations for SIDS prevention was mainly observed in younger and less educated women, who were not in a relationship and living in poor housing quality and crowded environments.

Background Human papillomavirus (HPV) contribution in vulvar intraepithelial lesions (VIN) and invasive vulvar cancer (IVC) is not clearly established. This study provides novel data on HPV markers in a large series of VIN and IVC lesions. Methods Histologically confirmed VIN and IVC from 39 countries were assembled at the Catalan Institute of Oncology (ICO). HPV-DNA detection was done by polymerase chain reaction using SPF-10 broad-spectrum primers and genotyping by reverse hybridisation line probe assay (LiPA 25 ) (version 1). IVC cases were tested for p16 INK4a by immunohistochemistry (CINtec histology kit, ROCHE). An IVC was considered HPV driven if both HPV-DNA and p16 INK4a overexpression were observed simultaneously. Data analyses included algorithms allocating multiple infections to calculate type-specific contribution and logistic regression models to estimate adjusted prevalence (AP) and its 95% confidence intervals (CI). Results Of 2296 cases, 587 were VIN and 1709 IVC. HPV-DNA was detected in 86.7% and 28.6% of the cases respectively. Amongst IVC cases, 25.1% were both HPV-DNA and p16 INK4a positive. IVC cases were largely keratinising squamous cell carcinoma (KSCC) ( N = 1234). Overall prevalence of HPV related IVC cases was highest in younger women for any histological subtype. SCC with warty or basaloid features (SCC_WB) ( N = 326) were more likely to be HPV and p16 INK4a positive (AP = 69.5%, CI = 63.6–74.8) versus KSCC (AP = 11.5%, CI = 9.7–13.5). HPV 16 was the commonest type (72.5%) followed by HPV 33 (6.5%) and HPV 18 (4.6%). Enrichment from VIN to IVC was significantly high for HPV 45 (8.5-fold). Conclusion Combined data from HPV-DNA and p16 INK4a testing are likely to represent a closer estimate of the real fraction of IVC induced by HPV. Our results indicate that HPV contribution in invasive vulvar cancer has probably been overestimated. HPV 16 remains the major player worldwide.

The periodic time modulations, found recently in the two-body orbital electron-capture (EC) decay of both, hydrogen-like $^{140}$Pr$^{58+}$ and $^{142}$Pm$^{60+}$ ions, with periods near to 7s and amplitudes of about 20%, were re-investigated for the case of $^{142}$Pm$^{60+}$ by using a 245 MHz resonator cavity with a much improved sensitivity and time resolution. We observed that the exponential EC decay is modulated with a period $T = 7.11(11)$s, in accordance with a modulation period $T = 7.12(11)$ s as obtained from simultaneous observations with a capacitive pick-up, employed also in the previous experiments. The modulation amplitudes amount to $a_R = 0.107(24)$ and $a_P = 0.134(27)$ for the 245 MHz resonator and the capacitive pick-up, respectively. These new results corroborate for both detectors {\it exactly} our previous findings of modulation periods near to 7s, though with {\it distinctly smaller} amplitudes. Also the three-body $��^+$ decays have been analyzed. For a supposed modulation period near to 7s we found an amplitude $a = 0.027(27)$, compatible with $a = 0$ and in agreement with the preliminary result $a = 0.030(30)$ of our previous experiment. These observations could point at weak interaction as origin of the observed 7s-modulation of the EC decay. Furthermore, the data suggest that interference terms occur in the two-body EC decay, although the neutrinos are not directly observed., In memoriam of Prof. Paul Kienle, 9 pages, 1 table, 5 figures Phys. Lett. B (2013) online

Comunicación presentada en el SIRCOVA-OFTARED Congress (Society for Research in Retina) celebrado del 6 al 8 de junio de 2013 en Valencia (España), publicado en "Ophthalmic Research" 50:49 (2013). DOI: 10.1159/000351623, Purpose: The retina, as the rest of the central nervous system, is subjected to normal, as well as to pathological aging processes. Among others, age-related macular degeneration is a highly prevalent complication of aging and it has been recently connected to Alzheimer disease. We look for common molecular and cellular mechanisms underlying physiopathological aging in the retina and the CNS, as well as for potential therapies to delay the process. Material and Methods: Immunohistochemistry and electrophysiology were used to evaluate the effects of normal aging in C57Bl/6 mouse retinas. As model for pathological aging, SAMP8 mouse retinas were also studied. To assess the effects of a proinsulin treatment in retinal degeneration, we employed intramuscular injection of adenoasociated vectors (AAV) expressing human proinsulin.