Genomic architecture of carcass and pork traits and their association with immune capacity.

Carcass and pork traits have traditionally been considered of prime importance in pig breeding programmes. However, the changing conditions in modern farming, coupled with antimicrobial resistance issues, are raising the importance of health and robustness-related traits. Here, we explore the genetic architecture of carcass and pork traits and their relationship with immunity phenotypes in a commercial Duroc pig population. A total of nine traits related to fatness, lean content and meat pH were measured at slaughter (∼190 d of age) in 378 pigs previously phenotyped (∼70 d of age) for 36 immunity-related traits, including plasma concentrations of immunoglobulins, acute-phase proteins, leukocytes subpopulations and phagocytosis. Our study showed medium to high heritabilities and strong genetic correlations between fatness, lean content and meat pH at 24 h postmortem. Genetic correlations were found between carcass and pork traits and white blood cells. pH showed strong positive genetic correlations with leukocytes and eosinophils, and strong negative genetic correlations with haemoglobin, haematocrit and cytotoxic T cell proportion. In addition, genome-wide association studies (GWASs) pointed out four significantly associated genomic regions for lean meat percentages in different muscles, ham fat, backfat thickness, and semimembranosus pH at 24 h. The functional annotation of genes located in these regions reported a total of 14 candidate genes, with BGN, DPP10, LEPR, LEPROT, PDE4B and SLC6A8 being the strongest candidates. After performing an expression GWAS for the expression of these genes in muscle, two signals were detected in cis for the BGN and SLC6A8 genes. Our results indicate a genetic relationship between carcass fatness, lean content and meat pH with a variety of immunity-related traits that should be considered to improve immunocompetence without impairing production traits.

Self-management interventions for chronically ill patients with limited health literacy: A descriptive analysis.

OBJECTIVES: To support patients with limited health literacy with the challenges they face in the day-to-day management of their disease(s), numerous self-management interventions (SMIs) have been developed. To date, it is unclear to what extent SMIs have been developed for chronically ill patients with limited health literacy. This study aims to provide a description of these SMIs and to provide insight in their methodological components. METHODS: A secondary analysis of the COMPAR-EU database, consisting of SMIs addressing patients with diabetes, chronic obstructive pulmonary disease, obesity and heart failure, was conducted. The database was searched for SMIs addressing health literacy, including cognitive aspects and the capacity to act. RESULTS: Of the 1681 SMIs in the COMPAR-EU database, 35 studies addressed health literacy, describing 39 SMIs. The overview yields a high variety in interventions given, with overlapping information, but also lacking of specific details. DISCUSSION: This descriptive analysis shows that there was a large variety in the extensiveness of the description of intervention characteristics and their justification or explanation. A focus on the broad concept of health literacy, including functional skills, cognitive skills and the capacity to act could improve the effectiveness. This should be taken into account in the future development of SMIs.

Bundles reduce anastomosis leak in patients undergoing elective colorectal surgery. A propensity score-matched study.

Background: anastomosis leak still being a handicap in colorectal surgery. Bowel mechanical preparation and oral antibiotics are not a practice recommended in many clinical practice guides. The aim is to analyse the decrease in frequency and severity of postoperative complications, mainly related to anastomotic leak, after the establishment of a bundle. Methods: Single-center, before-after study. A bundle was implemented to reduce anastomotic leaks and their consequences. The Bundle group were matched to Pre-bundle group by propensity score matching. Mechanical bowel preparation, oral and intravenous antibiotics, inflammatory markers measure and early diagnosis algorithm were included at the bundle. Results: The bundle group shown fewer complications, especially in Clavien Dindós Grade IV complications (2.3% vs. 6.2% p < 0.01), as well as a lower rate of anastomotic leakage (15.5% vs. 2.2% p < 0.01). A significant decrease in reinterventions, less intensive unit care admissions, a shorter hospital stay and fewer readmissions were also observed. In multivariate analysis, the application of a bundle was an anastomotic leakage protective factor (OR 0.121, p > 0.05). Conclusions: The implementation of our bundle in colorectal surgery which include oral antibiotics, mechanical bowel preparation and inflammatory markers, significantly reduces morbidity adjusted to severity of complications, the anastomotic leakage rate, hospital stay and readmissions. Register study: The study has been registered at clinicaltrials.gov Code: nct04632446.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience / Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro

Background Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. Objectives To study whether low-dose rituximab is also effective for bullous pemphigoid. Methods Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. Results Six patients, five males and a female, with a mean age of 78.6 years (range 65–89) and a mean history of BP of 6.7 months (range 2–16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1–3), and 4 weeks (range 3–5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13–20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. Conclusions Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP (AU)

Antecedentes La administración de dosis bajas de rituximab es un protocolo utilizado en diversas enfermedades autoinmunes, que ha demostrado también su eficacia y seguridad para el pénfigo vulgar. Objetivos Determinar si rituximab a dosis bajas es efectivo para el penfigoide ampolloso (PA). Métodos Se trató a los pacientes con PA con un ciclo único de 2 infusiones de rituximab 500 mg con un intervalo de 2 semanas. Se monitorizaron los puntos temprano y final tardío. Resultados Se incluyeron en el estudio 6 pacientes, 5 varones y una mujer, con una edad media de 78,6 años (rango: 65.89) e historia media de PA de 6,7 meses (rango: 2-16). Se observó una respuesta rápida y acusada tras un ciclo único de tratamiento, con un tiempo medio hasta el control de la enfermedad y el final de la fase de consolidación de 1,9 (rango: 1-3) y 4 semanas (rango: 3-5), respectivamente. Cuatro pacientes lograron un punto final tardío a una media de 15,75 semanas (rango: 13-20). Tres de ellos lograron una remisión parcial sin terapia (2 pacientes) o con terapia mínima (un paciente), logrando uno de ellos la remisión completa sin terapia. A un paciente se le realizó un seguimiento de 6 semanas tras la administración de rituximab. El paciente restante sufrió una recaída transcurridas 4 semanas del tratamiento de rituximab, permaneciendo en remisión completa con terapia mínima. Un paciente manifestó gingivoestomatitis herpética relacionada con rituximab. Conclusiones La administración de dosis bajas de rituximab para PA logró tasas de remisión aceptables y reducción de esteroides, con un mejor perfil de seguridad y un menor coste, en comparación con las dosis estándar. Este estudio piloto sugiere que la administración de bajas dosis de rituximab podría ser una opción terapéutica para el PA (AU)

[Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro / Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience

Antecedentes La administración de dosis bajas de rituximab es un protocolo utilizado en diversas enfermedades autoinmunes, que ha demostrado también su eficacia y seguridad para el pénfigo vulgar. Objetivos Determinar si rituximab a dosis bajas es efectivo para el penfigoide ampolloso (PA). Métodos Se trató a los pacientes con PA con un ciclo único de 2 infusiones de rituximab 500 mg con un intervalo de 2 semanas. Se monitorizaron los puntos temprano y final tardío. Resultados Se incluyeron en el estudio 6 pacientes, 5 varones y una mujer, con una edad media de 78,6 años (rango: 65.89) e historia media de PA de 6,7 meses (rango: 2-16). Se observó una respuesta rápida y acusada tras un ciclo único de tratamiento, con un tiempo medio hasta el control de la enfermedad y el final de la fase de consolidación de 1,9 (rango: 1-3) y 4 semanas (rango: 3-5), respectivamente. Cuatro pacientes lograron un punto final tardío a una media de 15,75 semanas (rango: 13-20). Tres de ellos lograron una remisión parcial sin terapia (2 pacientes) o con terapia mínima (un paciente), logrando uno de ellos la remisión completa sin terapia. A un paciente se le realizó un seguimiento de 6 semanas tras la administración de rituximab. El paciente restante sufrió una recaída transcurridas 4 semanas del tratamiento de rituximab, permaneciendo en remisión completa con terapia mínima. Un paciente manifestó gingivoestomatitis herpética relacionada con rituximab. Conclusiones La administración de dosis bajas de rituximab para PA logró tasas de remisión aceptables y reducción de esteroides, con un mejor perfil de seguridad y un menor coste, en comparación con las dosis estándar. Este estudio piloto sugiere que la administración de bajas dosis de rituximab podría ser una opción terapéutica para el PA (AU)

Background Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. Objectives To study whether low-dose rituximab is also effective for bullous pemphigoid. Methods Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. Results Six patients, five males and a female, with a mean age of 78.6 years (range 65–89) and a mean history of BP of 6.7 months (range 2–16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1–3), and 4 weeks (range 3–5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13–20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. Conclusions Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP (AU)

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Low-Dose Rituximab for Bullous Pemphigoid. Protocol and Single-Center Experience. / [Artículo traducido] Baja dosis de rituximab para penfigoide ampolloso. Protocolo y experiencia de un único centro.

BACKGROUND: Low-dose rituximab is a protocol used in several autoimmune diseases, that has also shown to be effective and safe in pemphigus vulgaris. OBJECTIVES: To study whether low-dose rituximab is also effective for bullous pemphigoid. METHODS: Patients with BP were treated with a single cycle of two infusions of rituximab 500 mg at an interval of 2 weeks. Early and late end points were monitored. RESULTS: Six patients, five males and a female, with a mean age of 78.6 years (range 65-89) and a mean history of BP of 6.7 months (range 2-16) were included. A rapid and marked response was observed after a single cycle of treatment, with a mean time to disease control and to end of consolidation phase of 1.9 (range 1-3), and 4 weeks (range 3-5), respectively. Four patients achieved a late end point at a mean of 15.75 weeks (range 13-20). Three of them achieved partial remission with no therapy (two patients) or with minimal therapy (one patient), and one of them achieved complete remission with no therapy. One patient has 6 weeks of clinical follow-up after rituximab administration. The remaining patient relapsed 4 weeks after the rituximab treatment, and remains in complete remission with more than minimal therapy. One patient had a herpetic gingivostomatitis related to rituximab. CONCLUSIONS: Low-dose rituximab for BP achieved acceptable remission rates and steroid-sparing activity, with a better safety profile and a lower cost, compared to standard doses. This pilot study suggests that low-dose rituximab could be a therapeutic option for BP.

Informed consent in dentistry and medicine in Spain: Practical considerations and legality.

BACKGROUND: The healthcare practice of dentistry, as well as medicine, is framed within a legal environment. Patients have the right to know all the information related to any action performed on them and dental or medical doctors are obliged to obtain their patient's prior written informed consent (IC) before undertaking any healthcare procedures. MATERIAL AND METHODS: Here we reviewed the legality and jurisprudence in Spain regarding IC. We also used INFLESZ text readability analysis software to analyse a sample of official Spanish informed consent documents (ICDs) from different surgical and interventional procedures related to dentistry and oral cavity interventions. RESULTS: It is a mistake to confound IC with ICDs. This error prevents physicians from considering the former as a care process in which the patient's authorisation signature is the last link in a chain formed, almost in its entirety, by the informative process and deliberation alongside the patient. Multiple factors can influence communication between practitioners and their patients. Importantly, treatment adherence is greater when patients feel involved and autonomous in shared decision-making and when the circumstances of their lives are adequately considered. We concluded that although the ICDs we analysed conformed to the requirements set out in international law, they were somewhat difficult to read according to the reading habits of the general Spanish population. CONCLUSIONS: Knowledge about the legality of IC helps professionals to understand the problems that may arise from their non-compliance. This is because the omission or defective fulfilment of IC obligations is the origin of legal responsibility for medical practitioners. In this sense, to date, there have been more convictions for defective ICs than for malpractice. The information provided in ICs should include the risks, benefits, and treatment alternatives and must be tailored to the needs and capabilities of the patient to enable autonomous decision-making.

Evidence-Based Network Modelling to Simulate Nucleus Pulposus Multicellular Activity in Different Nutritional and Pro-Inflammatory Environments.

Initiation of intervertebral disc degeneration is thought to be biologically driven. This reflects a process, where biochemical and mechanical stimuli affect cell activity (CA) that compromise the tissue strength over time. Experimental research enhanced our understanding about the effect of such stimuli on different CA, such as protein synthesis or mRNA expression. However, it is still unclear how cells respond to their native environment that consists of a "cocktail" of different stimuli that might locally vary. This work presents an interdisciplinary approach of experimental and in silico research to approximate Nucleus Pulposus CA within multifactorial biochemical environments. Thereby, the biochemical key stimuli glucose, pH, and the proinflammatory cytokines TNF-α and IL1ß were considered that were experimentally shown to critically affect CA. To this end, a Nucleus Pulposus multicellular system was modelled. It integrated experimental findings from in vitro studies of human or bovine Nucleus Pulposus cells, to relate the individual effects of targeted stimuli to alterations in CA. Unknown stimulus-CA relationships were obtained through own experimental 3D cultures of bovine Nucleus Pulposus cells in alginate beads. Translation of experimental findings into suitable parameters for network modelling approaches was achieved thanks to a new numerical approach to estimate the individual sensitivity of a CA to each stimulus type. Hence, the effect of each stimulus type on a specific CA was assessed and integrated to approximate a multifactorial stimulus environment. Tackled CA were the mRNA expressions of Aggrecan, Collagen types I & II, MMP3, and ADAMTS4. CA was assessed for four different proinflammatory cell states; non-inflamed and inflamed for IL1ß, TNF-α or both IL1ß&TNF-α. Inflamed cell clusters were eventually predicted in a multicellular 3D agent-based model. Experimental results showed that glucose had no significant impact on proinflammatory cytokine or ADAMTS4 mRNA expression, whereas TNF-α caused a significant catabolic shift in most explored CA. In silico results showed that the presented methodology to estimate the sensitivity of a CA to a stimulus type importantly improved qualitative model predictions. However, more stimuli and/or further experimental knowledge need to be integrated, especially regarding predictions about the possible progression of inflammatory environments under adverse nutritional conditions. Tackling the multicellular level is a new and promising approach to estimate manifold responses of intervertebral disc cells. Such a top-down high-level network modelling approach allows to obtain information about relevant stimulus environments for a specific CA and could be shown to be suitable to tackle complex biological systems, including different proinflammatory cell states. The development of this methodology required a close interaction with experimental research. Thereby, specific experimental needs were derived from systematic in silico approaches and obtained results were directly used to enhance model predictions, which reflects a novelty in this research field. Eventually, the presented methodology provides modelling solutions suitable for multiscale approaches to contribute to a better understanding about dynamics over multiple spatial scales. Future work should focus on an amplification of the stimulus environment by integrating more key relevant stimuli, such as mechanical loading parameters, in order to better approximate native physiological environments.

How to predict para-aortic node involvement in advanced cervical cancer? Development of a predictive score. A FRANCOGYN study.

INTRODUCTION: Node involvement is one of the main prognostic factors for cervical cancer. Para-aortic lymph node (PALN) assessment is crucial for treating advanced cervical cancer, to define irradiation fields. Objective of this study was to develop a score predicting para-aortic lymph node involvement in patients with advanced cervical cancer. PATIENTS AND METHOD: We performed a multicenter, retrospective, study on 9 French centers from 2000 to 2015, including patients with advanced squamous cell cervix carcinoma who had PALN status assessed by imaging and/or by surgery. Factors associated with a risk of PALN involvement were determined by univariate and multivariate analysis using a logistic regression model. A score was then developed and validated. RESULTS: A total of 1446 patients treated for cervical cancer were included. Of these, 498 had an advanced squamous cell cervical cancer. Ninety-one patients (18.3%) had positive PALN. After univariate and multivariate analysis, tumor size on pelvic MRI, initial SCC, and suspected pelvic node involvement on PET-CT were included in our score. This model allowed the population to be divided into 3 risk groups. Area under the ROC curve of the score was 0.81 (95%CI = 0.72-0.90). In the low-risk group, 9% (28/287) had PALN involvement, whereas in the high-risk group, 43% (22/51) had PALN involvement. CONCLUSION: We developed a simple score predicting PALN involvement in advanced cervical cancers. Three risk groups can be defined, and patients considered to be at low risk may avoid para-aortic staging as well as extensive field irradiation.

Management of borderline ovarian tumours during pregnancy: Results of a French multi-centre study.

OBJECTIVE: To assess the diagnostic and prognostic characteristics of borderline ovarian tumours (BOTs) detected during pregnancy, and to establish an inventory of French practices. MATERIALS AND METHODS: A retrospective multi-centre case study of 14 patients treated for BOTs, diagnosed during pregnancy between 2005 and 2017, in five French pelvic cancerology expert centres, including data on clinical characteristics, histological tumour characteristics, surgical procedure, adjuvant treatments, follow-up and fertility. RESULTS: The mean age of patients was 29.3 [standard deviation (SD) 6.2] years. Most BOTs were diagnosed on ultrasonography in the first trimester (85.7 %), and most of these cases (78.5 %) also underwent magnetic resonance imaging to confirm the diagnosis (true positives 54.5 %). Most patients underwent surgery during pregnancy (57 %), with complete staging surgery in two cases (14.3 %). Laparoscopy was performed more frequently than other procedures (50 %), and unilateral adnexectomy was more common than cystectomy (57.5 %). Tumour size influenced the surgical approach significantly (mean size 7.5 cm for laparoscopy, 11.9 cm for laparoconversion, 14 cm for primary laparotomy; P = 0.08), but the type of resection did not. Most patients were initially diagnosed with International Federation of Gynecology and Obstetrics stage IA (92.8 %) tumours, but many were upstaged after complete restaging surgery (57.1 %). Most BOTs were serous (50 %), two cases had a micropapillary component (28.5 %), and one case had a micro-invasive implant. BOTs were bilateral in two cases (14.2 %). Mean follow-up was 31.4 (SD 14.8) months. Recurrent lesions occurred in two patients (14.2 %) and no deaths have been recorded to date among the study population. CONCLUSION: BOTs remain rare, but this study - despite its small sample size - supports the hypothesis that BOTs during pregnancy have potentially aggressive characteristics.

Prognostic Value and Risk Factors of Peritoneal Carcinomatosis Recurrence for Patients with Endometrial Cancer: A Multicenter Study from the FRANCOGYN Group.

BACKGROUND: The prognosis for patients with endometrial cancer (EC) peritoneal carcinomatosis (PC) recurrence has received little study. This study aimed to determine specific risk factors and prognosis of EC with PC recurrence (PCR) versus no PC recurrence (NPCR). METHODS: Data of all patients with EC who received primary surgical treatment between January 2000 and February 2017 were abstracted from the French FRANCOGYN Research Group database. Clinical and pathologic variables were compared between the two groups (PCR vs. NPCR). Multivariate analysis was performed to define prognostic factors for peritoneal recurrence. Overall survivals (OS) of patients after recurrence were compared using the Kaplan-Meier method. RESULTS: The study analyzed 1466 patients, and 257 of these patients (17.5%) had recurrence. At presentation, 63 of these patients had PC. International Federation of Gynecology and Obstetrics (FIGO) stages 3 and 4 disease were significantly associated with PCR versus NPCR (odds ratio 2.24; 95% confidence interval 1.23-4.07; p = 0.008). The death rate for the patients with PC was 47.6%, with a median survival of 12 months after diagnosis of recurrence. According to the histologic subtype, OS was 29 months (Q1-Q3, 13-NA) for endometrioid carcinomas, 7.5 months (Q1-Q3, 4-15) for serous carcinomas, and 10 months (Q1-Q3, 5-15) for clear cell carcinomas. Chemotherapy for treatment of PCR was associated with improved OS after recurrence (OSAR; p = 0.0025). CONCLUSION: An initial advanced stage of EC is a risk factor for PCR. For women with PCR, a diagnosis of type 1 EC recurrence more than 12 months after the initial treatment and management of PCR with chemotherapy is associated with improved OSAR. Prospective studies are needed to determine the precise optimal management required in this clinical situation and to assess the relevance of biomarkers to predict the risk of PCR for EC patients.

Simulating intervertebral disc cell behaviour within 3D multifactorial environments.

MOTIVATION: Low back pain is responsible for more global disability than any other condition. Its incidence is closely related to intervertebral disc (IVD) failure, which is likely caused by an accumulation of microtrauma within the IVD. Crucial factors in microtrauma development are not entirely known yet, probably because their exploration in vivo or in vitro remains tremendously challenging. In silico modelling is, therefore, definitively appealing, and shall include approaches to integrate influences of multiple cell stimuli at the microscale. Accordingly, this study introduces a hybrid Agent-based (AB) model in IVD research and exploits network modelling solutions in systems biology to mimic the cellular behaviour of Nucleus Pulposus cells exposed to a 3D multifactorial biochemical environment, based on mathematical integrations of existing experimental knowledge. Cellular activity reflected by mRNA expression of Aggrecan, Collagen type I, Collagen type II, MMP-3 and ADAMTS were calculated for inflamed and non-inflamed cells. mRNA expression over long periods of time is additionally determined including cell viability estimations. Model predictions were eventually validated with independent experimental data. RESULTS: As it combines experimental data to simulate cell behaviour exposed to a multifactorial environment, the present methodology was able to reproduce cell death within 3 days under glucose deprivation and a 50% decrease in cell viability after 7 days in an acidic environment. Cellular mRNA expression under non-inflamed conditions simulated a quantifiable catabolic shift under an adverse cell environment, and model predictions of mRNA expression of inflamed cells provide new explanation possibilities for unexpected results achieved in experimental research. AVAILABILITYAND IMPLEMENTATION: The AB model as well as used mathematical functions were built with open source software. Final functions implemented in the AB model and complete AB model parameters are provided as Supplementary Material. Experimental input and validation data were provided through referenced, published papers. The code corresponding to the model can be shared upon request and shall be reused after proper training. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Genome-wide association study for feed efficiency in collective cage-raised rabbits under full and restricted feeding.

Feed efficiency (FE) is one of the most economically and environmentally relevant traits in the animal production sector. The objective of this study was to gain knowledge about the genetic control of FE in rabbits. To this end, GWASs were conducted for individual growth under two feeding regimes (full feeding and restricted) and FE traits collected from cage groups, using 114 604 autosome SNPs segregating in 438 rabbits. Two different models were implemented: (1) an animal model with a linear regression on each SNP allele for growth trait; and (2) a two-trait animal model, jointly fitting the performance trait and each SNP allele content, for FE traits. This last modeling strategy is a new tool applied to GWAS and allows information to be considered from non-genotyped individuals whose contribution is relevant in the group average traits. A total of 189 SNPs in 17 chromosomal regions were declared to be significantly associated with any of the five analyzed traits at a chromosome-wide level. In 12 of these regions, 20 candidate genes were proposed to explain the variation of the analyzed traits, including genes such as FTO, NDUFAF6 and CEBPA previously associated with growth and FE traits in monogastric species. Candidate genes associated with behavioral patterns were also identified. Overall, our results can be considered as the foundation for future functional research to unravel the actual causal mutations regulating growth and FE in rabbits.

Microgravity effects on frozen human sperm samples.

PURPOSE: Microgravity has severe effects on cellular and molecular structures as well as on metabolic interactions. The aim of this study is to investigate the effects of microgravity (µg) exposure on human frozen sperm samples. METHODS: Sibling samples from 15 normozoospermic healthy donors were frozen using glycerol as cryoprotectant and analyzed under microgravity and ground conditions. Microgravity was obtained by parabolic flights using a CAP10B plane. The plane executed 20 parabolic maneuvers with a mean of 8.5 s of microgravity for each parabola. RESULTS: Frozen sperm samples preserved in cryostraws and stored in a secure and specific nitrogen vapor cryoshipper do not suffer significant alterations after µg exposure. Comparing the study group (µg) and the control group (1 g), similar results were obtained in the main parameters studied: sperm motility (M/ml) 13.72 ± 12.57 vs 13.03 ± 12.13 (- 0.69 95% CI [- 2.9; 1.52]), progressive a + b sperm motility (%) 21.83 ± 11.69 vs 22.54 ± 12.83 (0.03 95% CI [- 0.08; 0.15]), sperm vitality (%) 46.42 ± 10.81 vs 44.62 ± 9.34 (- 0.04 95% CI [- 0.13; 0.05]), morphologically normal spermatozoa (%) 7.03 ± 2.61 vs 8.09 ± 3.61 (0.12 95% CI [0.01; 0.24]), DNA sperm fragmentation by SCD (%) 13.33 ± 5.12 vs 13.88 ± 6.14 (0.03 95% CI [- 0.09; 0.16]), and apoptotic spermatozoa by MACS (%) 15.47 ± 15.04 vs 23.80 ± 23.63 (- 0.20 95% CI [- 0.66; 1.05]). CONCLUSION: The lack of differences obtained between frozen samples exposed to µg and those maintained in ground conditions provides the possibility of considering the safe transport of human male gametes to space. Nevertheless, further research is needed to validate the results and to consider the possibility of creating a human sperm bank outside the Earth. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov: NCT03760783.

Prognostic factors of overall survival for patients with FIGO stage IIIc or IVa ovarian cancer treated with neo-adjuvant chemotherapy followed by interval debulking surgery: A multicenter cohort analysis from the FRANCOGYN study group.

INTRODUCTION: The aim of this study was to identify prognostic factors of overall survival in patients with FIGO stage IIIc or IVa ovarian cancer (OC) treated by neo-adjuvant chemotherapy (NAC) followed by interval debulking surgery. MATERIALS AND METHODS: Data from 483 patients with ovarian cancer were retrospectively collected, from January 1, 2000 to December 31, 2016, from the FRANCOGYN database, regrouping data from 11 centers specialized in ovarian cancer treatment. Median overall survival was determined using the Kaplan-Meier method. Univariate and multivariate analysis were performed to define prognostic factors of overall survival. RESULTS: The median overall survival was 52 after a median follow up of 30 months. After univariate analysis, factors significantly associated with decreased overall survival were; no pelvic and/or para-aortic lymphadenectomy (p = 0.002), residual disease (CC1/CC2/CC3) after surgery (p < 0.001), positive cytology after NAC (p < 0.001), omental disease after NAC (p = 0.002), no pathologic complete response (pCR) (p = 0.002). In multivariate analysis, factors significantly associated with decreased overall survival were; residual disease after surgery (HR = 1.93; CI95% (1.16-3.21), p = 0.01) and positive cytology after NAC (HR = 1.59; CI95% (1.01-2.55), p = 0.05). Patients with no residual disease after surgery had a median overall survival of 64 months versus 35 months for patients with residual disease. Patients with negative cytology after NAC had a median overall survival of 71 months versus 43 months for patients with positive cytology after NAC. CONCLUSION: In this first and largest French based retrospective study, complete cytoreductive surgery in ovarian cancer remains the main prognostic factor of overall survival.

[Prognostic significance of groin lymph node ratio in vulvar squamous cell carcinoma]. / Signification pronostique du ratio d'atteinte ganglionnaire inguinale dans le carcinome épidermoide vulvaire.

OBJECTIVES: The aim was to review the clinical impact of lymph node ratio (LNR) of groin metastatic nodal disease in women with vulvar squamous cell carcinoma. MATERIAL AND METHODS: Cohort study of women with vulvar squamous cell carcinoma, managed between January 2005 and December 2015, in five institutions in France with prospectively maintained databases (French multicenter tertiary care centers). POPULATION: In total, 636 women managed for VSCC of whom 508 (79.9%) underwent surgical groin nodal staging. MAIN OUTCOME MEASURES: Comparison of overall and recurrence free survival between women according to LNR. RESULTS: In total, 176 women (34.6%) had at least one positive lymph node (LN). There was a significant differences for the 5-year overall survival and recurrence free survival rates between women with LNR>0.2 and women with LNR<0.2. CONCLUSION: LNR seems to be a significant prognostic factor in women with vulvar squamous cell carcinoma.