Definitive childlessness in women with multiple sclerosis: a multicenter study

The frequency of definitive childlessness in women with multiple sclerosis (MS) may be higher than in the general population. MS may also affect decisions on the delivery procedure and on breast-feeding issues. Aim of the study was to assess the frequency of childlessness and its possible causes, the proportion of cesarean deliveries (CD), and the frequency of breast-feeding in patients and controls who have reached the end of their reproductive period. Female MS patients (>43 years) and controls (>45 years) filled out a questionnaire. We enrolled 303 patients and 500 controls. MS was associated with a higher frequency of childlessness (22 vs 13%) and less patients were in a stable relationship (83 vs 89%). There was no difference in the reported rates of infertility and miscarriages, while elective abortions were more frequent in patients (20 vs 12%). MS did not significantly affect the frequency of CD or of breast-feeding. MS-related reasons for childlessness, reported by 16% of childless patients, included disability/fear of future disability, fear of genetically transmitting MS, fear of not starting/discontinuing treatments, and discouragement by physician. Definitive childlessness is more frequent in women with MS compared to controls. A portion of voluntary childlessness may be avoided through correct/tailored information to patients

Characterization of a Novel Polymorphism in PPARG Regulatory Region Associated with Type 2 Diabetes and Diabetic Retinopathy in Italy

Peroxisome proliferator-activated receptor gamma polymorphisms have been widely associated with type 2 diabetes, although their role in the pathogenesis of vascular complications is not yet demonstrated. In this study, a cohort of 211 type 2 diabetes, 205 obese, and 254 control individuals was genotyped for Pro12Ala, C1431T, C-2821T polymorphisms, and for a newly identified polymorphism (A-2819G). The above-mentioned polymorphisms were analyzed by gene-specific PCR and direct sequencing of all samples. A significant difference was found for -2819G frequency when patients with type 2 diabetes—particularly diabetic women with the proliferative retinopathy—were compared with healthy control individuals. In conclusion, we identified a novel polymorphism, A-2819G, in PPARG gene, and we found it to be associated with type 2 diabetes and proliferative retinopathy in diabetic females. In the analyzed population, this variant represents a genetic risk factor for developing the diabetic retinopathy, whereas Pro12Ala and C1431T do not

Investigating the molecular mechanisms involved in KIF5A-related neurodegeneration

Mutations targeting the neuron-specific kinesin KIF5A lead to neurodegenerative diseases (NDs), including amyotrophic lateral sclerosis (ALS). Distinct phenotypes develop according to which of the three KIF5A domains is affected by mutations, but the reasons behind such heterogeneity are not known yet. Our aim is to gain insight into the molecular mechanisms underlying KIF5A-related NDs by functionally characterizing four domain-specific KIF5A mutants (R17Q, R280C, R864*, N999Vfs*39). Overexpression in SH-SY5Y cells evidenced altered protein turnover for R17Q KIF5A and the ALS-related N999Vfs*39 mutant with respect to wild-type (WT) KIF5A, with the two mutants displaying shorter half-life upon cycloheximide chase. Higher accumulation was observed for R17Q and N999Vfs*39 KIF5A compared to WT KIF5A and the other KIF5A variants following proteasomal blockage, indicating that the ubiquitin-proteasome system might represent the main degradation route for the two mutants. R17Q and N999Vfs*39 KIF5A also displayed preferential partitioning in the detergent-insoluble protein fraction upon proteasome inhibition, which suggests they may form harmful inclusions when proteostasis is impaired. Altered intracellular distribution was evidenced for R864* and N999Vfs*39 KIF5A overexpressed in NSC-34 cells, with the two mutants mainly localizing at cell periphery instead of being diffused within the whole motoneuron like WT KIF5A. In particular, the ALS-related N999Vfs*39 mutant formed puncta inside cell processes, which hints at reduced protein solubility even in basal conditions, and partially sequestered WT KIF5A within them. The abnormal distribution displayed by R864* and N999Vfs*39 KIF5A was paralleled by limited colocalization between the two mutants and mitochondria, whose axonal transport is largely reliant on WT KIF5A in motoneurons. Taken together, our preliminary observations indicate that both unique and shared mechanisms might underlie the pathogenesis of KIF5A-related NDs

Lesiones precancerosas en pacientes concurrentes a la FOLP año 2014

El cáncer bucal constituye una enfermedad con implicancias no solo físicas, sino también psicológicas y sociales. Con el objetivo de Identificar las lesiones premalignas o precancerosas relacionándolas con edad, sexo, factores de riesgo y localización se realizó una investigación observacional, descriptiva, transversal; la información se obtuvo a través del examen bucal de de pacientes que acudieron a la Asignatura de Cirugía A de la FOUNLP (año 2014),todas las variables de nuestro trabajo: Edad, sexo, ocupación, nivel educacional, hábitos, higiene bucal, lesiones precancerosas, características clínicas y localización de las lesiones se volcaron en planillas confeccionadas para tal efecto. Son los grupos de edades más afectados los de 45 a 54 años El tabaquismo fue el hábito más predominante como factor de nesgo. La ocupación laboral que estuvo con mayor presencia en estos pacientes afectados fue la del sector obrero, y el nivel educacional el de secundaria. La localización más frecuente de estas lesiones fue en el labio inferior con un 30,95 %. Se concluye, que se deben intensificar los controles de los factores de riesgo predisponentes para lograr mejorar y conservar la salud de la población por medio de la prevendón de estas patologías.Oral cancer is a disease with not only physical but also psycho- logical and sodal implications. With the aim of linking them identrfy premalignant or precancerous lesions with age, sex, risk factors and location an obseTvational descriptive and cross-sectional study was conducted. Information was obtained through oral examination of patients who carne to the subject of Surgery in FOLP (2014), all of our work variables: age, sex, oc cupation, education level, habits, oral hygiene, precancerous injuries, clinical characteristics and location of the lesions were tumed in forms tailored to that effect. The most affected age groups of 45 to 54years. Smoking was the most prevalent habit as a risk factor.The oc cupation that was more present in these affected patients was the labor sector and the secondary education level. The most common location of these lesions was on the lower lip with a 30.95%. The conclusión is that it must step up Controls predisposing risk factors in order to improve and maintain the health of the population through prevention of these diseases.Facultad de Odontologí

Development of a Nomogram Predicting the Risk of Persistence/Recurrence of Cervical Dysplasia

Background: Cervical dysplasia persistence/recurrence has a great impact on women's health and quality of life. In this study, we investigated whether a prognostic nomogram may improve risk assessment after primary conization. Methods: This is a retrospective multi-institutional study based on charts of consecutive patients undergoing conization between 1 January 2010 and 31 December 2014. A nomogram assessing the importance of different variables was built. A cohort of patients treated between 1 January 2015 and 30 June 2016 was used to validate the nomogram. Results: A total of 2966 patients undergoing primary conization were analyzed. The median (range) patient age was 40 (18-89) years. At 5-year of follow-up, 6% of patients (175/2966) had developed a persistent/recurrent cervical dysplasia. Median (range) recurrence-free survival was 18 (5-52) months. Diagnosis of CIN3, presence of HR-HPV types, positive endocervical margins, HPV persistence, and the omission of HPV vaccination after conization increased significantly and independently of the risk of developing cervical dysplasia persistence/recurrence. A nomogram weighting the impact of all variables was built with a C-Index of 0.809. A dataset of 549 patients was used to validate the nomogram, with a C-index of 0.809. Conclusions: The present nomogram represents a useful tool for counseling women about their risk of persistence/recurrence after primary conization. HPV vaccination after conization is associated with a reduced risk of CIN2+

Practice patterns and 90-day treatment-related morbidity in early-stage cervical cancer

To evaluate the impact of the Laparoscopic Approach to Cervical Cancer (LACC) Trial on patterns of care and surgery-related morbidity in early-stage cervical cancer

The Control Unit of the KM3NeT Data Acquisition System

The KM3NeT Collaboration runs a multi-site neutrino observatory in the Mediterranean Sea. Water Cherenkov particle detectors, deep in the sea and far off the coasts of France and Italy, are already taking data while incremental construction progresses. Data Acquisition Control software is operating off-shore detectors as well as testing and qualification stations for their components. The software, named Control Unit, is highly modular. It can undergo upgrades and reconfiguration with the acquisition running. Interplay with the central database of the Collaboration is obtained in a way that allows for data taking even if Internet links fail. In order to simplify the management of computing resources in the long term, and to cope with possible hardware failures of one or more computers, the KM3NeT Control Unit software features a custom dynamic resource provisioning and failover technology, which is especially important for ensuring continuity in case of rare transient events in multi-messenger astronomy. The software architecture relies on ubiquitous tools and broadly adopted technologies and has been successfully tested on several operating systems

Erratum to: EuPRAXIA Conceptual Design Report – Eur. Phys. J. Special Topics 229, 3675-4284 (2020), https://doi.org/10.1140/epjst/e2020-000127-8

International audienceThe online version of the original article can be found at http://https://doi.org/10.1140/epjst/e2020-000127-8</A

gSeaGen: The KM3NeT GENIE-based code for neutrino telescopes

Program summary Program Title: gSeaGen CPC Library link to program files: http://dx.doi.org/10.17632/ymgxvy2br4.1 Licensing provisions: GPLv3 Programming language: C++ External routines/libraries: GENIE [1] and its external dependencies. Linkable to MUSIC [2] and PROPOSAL [3]. Nature of problem: Development of a code to generate detectable events in neutrino telescopes, using modern and maintained neutrino interaction simulation libraries which include the state-of-the-art physics models. The default application is the simulation of neutrino interactions within KM3NeT [4]. Solution method: Neutrino interactions are simulated using GENIE, a modern framework for Monte Carlo event generators. The GENIE framework, used by nearly all modern neutrino experiments, is considered as a reference code within the neutrino community. Additional comments including restrictions and unusual features: The code was tested with GENIE version 2.12.10 and it is linkable with release series 3. Presently valid up to 5 TeV. This limitation is not intrinsic to the code but due to the present GENIE valid energy range. References: [1] C. Andreopoulos at al., Nucl. Instrum. Meth. A614 (2010) 87. [2] P. Antonioli et al., Astropart. Phys. 7 (1997) 357. [3] J. H. Koehne et al., Comput. Phys. Commun. 184 (2013) 2070. [4] S. Adrián-Martínez et al., J. Phys. G: Nucl. Part. Phys. 43 (2016) 084001.The gSeaGen code is a GENIE-based application developed to efficiently generate high statistics samples of events, induced by neutrino interactions, detectable in a neutrino telescope. The gSeaGen code is able to generate events induced by all neutrino flavours, considering topological differences between tracktype and shower-like events. Neutrino interactions are simulated taking into account the density and the composition of the media surrounding the detector. The main features of gSeaGen are presented together with some examples of its application within the KM3NeT project.French National Research Agency (ANR) ANR-15-CE31-0020Centre National de la Recherche Scientifique (CNRS)European Union (EU)Institut Universitaire de France (IUF), FranceIdEx program, FranceUnivEarthS Labex program at Sorbonne Paris Cite ANR-10-LABX-0023 ANR-11-IDEX-000502Paris Ile-de-France Region, FranceShota Rustaveli National Science Foundation of Georgia (SRNSFG), Georgia FR-18-1268German Research Foundation (DFG)Greek Ministry of Development-GSRTIstituto Nazionale di Fisica Nucleare (INFN)Ministry of Education, Universities and Research (MIUR)PRIN 2017 program Italy NAT-NET 2017W4HA7SMinistry of Higher Education, Scientific Research and Professional Training, MoroccoNetherlands Organization for Scientific Research (NWO) Netherlands GovernmentNational Science Centre, Poland 2015/18/E/ST2/00758National Authority for Scientific Research (ANCS), RomaniaMinisterio de Ciencia, Innovacion, Investigacion y Universidades (MCIU): Programa Estatal de Generacion de Conocimiento, Spain (MCIU/FEDER) PGC2018-096663-B-C41 PGC2018-096663-A-C42 PGC2018-096663-BC43 PGC2018-096663-B-C44Severo Ochoa Centre of Excellence and MultiDark Consolider (MCIU), Junta de Andalucia, Spain SOMM17/6104/UGRGeneralitat Valenciana: Grisolia, Spain GRISOLIA/2018/119GenT, Spain CIDEGENT/2018/034La Caixa Foundation LCF/BQ/IN17/11620019EU: MSC program, Spain 71367