Transcriptomic basis of sex loss in the pea aphid.

BACKGROUND: Transitions from sexual to asexual reproduction are common in eukaryotes, but the underlying mechanisms remain poorly known. The pea aphid-Acyrthosiphon pisum-exhibits reproductive polymorphism, with cyclical parthenogenetic and obligate parthenogenetic lineages, offering an opportunity to decipher the genetic basis of sex loss. Previous work on this species identified a single 840 kb region controlling reproductive polymorphism and carrying 32 genes. With the aim of identifying the gene(s) responsible for sex loss and the resulting consequences on the genetic programs controlling sexual or asexual embryogenesis, we compared the transcriptomic response to photoperiod shortening-the main sex-inducing cue-of a sexual and an obligate asexual lineage of the pea aphid, focusing on heads (where the photoperiodic cue is detected) and embryos (the final target of the cue). RESULTS: Our analyses revealed that four genes (one expressed in the head, and three in the embryos) of the region responded differently to photoperiod in the two lineages. We also found that the downstream genetic programs expressed during embryonic development of a future sexual female encompass ∼1600 genes, among which miRNAs, piRNAs and histone modification pathways are overrepresented. These genes mainly co-localize in two genomic regions enriched in transposable elements (TEs). CONCLUSIONS: Our results suggest that the causal polymorphism(s) in the 840 kb region somehow impair downstream epigenetic and post-transcriptional regulations in obligate asexual lineages, thereby sustaining asexual reproduction.

From guidelines to current practices: Suboptimal hypertension management in France.

In France, the prevalence of hypertension is higher than 30%. Although treatment guidelines have been well established over the last twenty years, the national blood pressure control rate is below the average of high-income countries. This observational study aimed to describe the antihypertensive prescription behaviours of primary care physicians (PCPs) in France and to assess their compliance with current French guidelines, focusing on three specific prescription issues and their potential repercussions on blood pressure control: treatment initiation, treatment renewal or change and type of triple therapy. Prescription data were retrieved using the IQVIA longitudinal patient database (LPD), which delivers real-world data insights from French primary care electronic medical records (EMR). The average number of prescribed therapeutic agents was 1.9 per patient, with 39.3% monotherapy prescriptions. Treatment initiation represented 7.2% of all antihypertensive prescriptions. At treatment initiation, 22.5% of patients were prescribed dual therapy. The proportion of treatment renewal in the same therapeutic class was 74.3% while the proportion of treatment change was 18.5%. Of these, only 6.3% of patients received an additional therapy. Lastly, 35.7% of triple therapies were consistent with the recommended combinations. In conclusion, this study provides evidence of therapeutic gaps in hypertension management in France. The low blood control rate may be attributed to PCPs' therapeutic inertia and lack of knowledge of treatment guidelines. All stakeholders should commit to rapid corrective action in order to provide patients with the best care.

[Burnout syndrome in health professionals at a university hospital in Spain]. / Síndrome de Burnout en profesionales sanitarios en un hospital universitario de España.

OBJECTIVE: To evaluate the risk of Burnout in the health professionals of the Huesca University Hospital, 50 years after its inauguration, to investigate the variables related to the work motivation of the hospital health personnel and to assess the predisposing and protective factors of the risk of Burnout. MATERIAL AND METHODS: An observational, analytical, prospective and unicentric study was conducted from September 2017 to April 2019, evaluating all the health professionals who worked at the Hospital San Jorge de Huesca (n=209). RESULTS: The mean age was 42.86 years. 72.2% were women. 12.4% had moderate risk of burnout. There was 12.4% of high emotional exhaustion, 36.8% of high depersonalization and 44.5% of low personal accomplishment. Burnout was statistically significant associated with the professional category (P=.010), work experience (P=.026), hours of work per week (P=.036), choice of the same profession (P=.001) and recommendation to the offspring (P<.001). CONCLUSIONS: One tenth of the sample had a moderate risk of burnout. Almost half of the health workers confirmed a high degree of satisfaction with the work environment and the majority expressed an adequate use of well-being strategies and a high degree of autonomy, recognition and satisfaction at work.

Efficacy of extended infusion of ß-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE).

BACKGROUND: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal ß-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. METHODS: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. DISCUSSION: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. TRIAL REGISTRATION: European Clinical Trials Database: EudraCT 2018-001476-37. ClinicalTrials.gov, ID: NCT04233996.

[Night workers' exposure to harshness factors in France: Lessons learned from the 2010 SUMER Survey]. / L'exposition des travailleurs de nuit aux facteurs de pénibilité en France : les enseignements de l'enquête SUMER 2010.

BACKGROUND: Despite the fact that French laws state that night work should be exceptional, the number of night workers has sharply increased in the past 20 years. At the same time, empirical and epidemiological studies indicate that night work has negative effects on workers' health. This is why the 2010 French pension act considered night work to be a drudgery. The aim of this study is to investigate whether night workers are more subject to other factors defined as contributing to the drudgery of work than are day workers. This article focuses on exposure to physical constraints (manual manipulation of heavy loads, awkward posture, exposure to mechanical vibrations) and aggressive physical environment (carcinogenic, mutagenic and reprotoxic chemicals [CMR], extreme temperature and noise). METHODS: Our study used the 2010 Medical Monitoring Survey of Occupational Risks [Surveillance médicale des expositions aux risques professionnels, (SUMER)] that was conducted among a sample of around 50,000 employees representative of 21.7 million French employees. We used logistic regressions to explore the potential influence of night work on the probabilities of exposure to at least one CMR, noise, thermal nuisance and physical constraints. RESULTS: Even though descriptive statistics suggest that night workers are more exposed to drudgery of work than day workers, our multivariate logistic models indicate that the exposure is not always positively correlated with the number of nights worked. Moreover, the exposure differs according to gender and socio-occupational category. CONCLUSION: Our findings suggest that night workers are more exposed to several factors defined as contributing to the drudgery of work than are day workers. Thus, they seem to face multiple disadvantages in the labor market. Preventive measures in favor of night workers should be targeted at job content as much as work organization.

Smoking does influence disease behaviour and impacts the need for therapy in Crohn's disease in the biologic era.

BACKGROUND: Recently, the notion that smoking may adversely affect Crohn's disease (CD) outcomes has been challenged by the suggestion that the widespread use of immunosuppressants and anti-TNF drugs might offset the adverse effects of tobacco. AIM: To reassess the influence of tobacco smoking on disease phenotype and complications on a time-dependent analysis, taking into account the different therapeutic interventions. METHODS: We designed a retrospective cohort study of 3224 patients with Crohn's disease. The data were collected from the Spanish national inflammatory bowel disease registry (ENEIDA), including information regarding demographics, clinical characteristics, disease complications, therapeutic interventions and smoking status. Patients were classified as nonsmokers, smokers and former smokers, according to their present and past smoking habits. RESULTS: In the univariate analysis, smokers had more strictures (22.6% vs. 19.3%, P < 0.05) and less colonic involvement (7.2% vs. 10.9%, P < 0.05), and were more frequently under treatment with steroids (91.6% vs. 85.8%, P < 0.05), immunosuppressants (73.5% vs. 63.6% P < 0.05) or anti-TNF drugs (31.4% vs. 25.1%, P < 0.05) than nonsmokers. In the time-dependent multivariate analysis, smokers were found to have a significantly decreased survival free of stricturing disease (HR: 1.5, CI 95% 1.18-1.90) or perianal complications (HR: 1.50, CI 95% 1.01-1.46), and had a higher risk for requiring thiopurine therapy (HR: 1.20, CI 95% 1.05-1.30). CONCLUSION: These results suggest that, despite the widespread use of immunosuppressants and anti-TNF drugs, smokers with Crohn's disease still have a more severe disease course, with increased therapeutic requirements when compared with nonsmokers.

Cardiac motion estimation by joint alignment of tagged MRI sequences.

Image registration has been proposed as an automatic method for recovering cardiac displacement fields from tagged Magnetic Resonance Imaging (tMRI) sequences. Initially performed as a set of pairwise registrations, these techniques have evolved to the use of 3D+t deformation models, requiring metrics of joint image alignment (JA). However, only linear combinations of cost functions defined with respect to the first frame have been used. In this paper, we have applied k-Nearest Neighbors Graphs (kNNG) estimators of the α-entropy (H(α)) to measure the joint similarity between frames, and to combine the information provided by different cardiac views in an unified metric. Experiments performed on six subjects showed a significantly higher accuracy (p<0.05) with respect to a standard pairwise alignment (PA) approach in terms of mean positional error and variance with respect to manually placed landmarks. The developed method was used to study strains in patients with myocardial infarction, showing a consistency between strain, infarction location, and coronary occlusion. This paper also presents an interesting clinical application of graph-based metric estimators, showing their value for solving practical problems found in medical imaging.

Realistic simulation of cardiac magnetic resonance studies modeling anatomical variability, trabeculae, and papillary muscles.

Simulated magnetic resonance imaging brain studies have been generated for over a decade. Despite their useful potential, simulated cardiac studies are only emerging. This article focuses on the realistic simulation of cardiac magnetic resonance imaging datasets. The methodology is based on the XCAT phantom, which is modified to increase realism of the simulated images. Modifications include the modeling of trabeculae and papillary muscles based on clinical measurements and published data. To develop and evaluate our approach, the clinical database included 40 patients for anatomical measurements, 10 patients for papillary muscle modeling, and 10 patients for local gray value statistics. The virtual database consisted of 40 digital voxel phantoms. Histograms from different tissues were obtained from the real datasets and compared with histograms of the simulated datasets with the Chi-square dissimilarity metric (χ(2)) and Kullback-Leibler divergence. For the original phantom, χ(2) values averaged 0.65 ± 0.06 and Kullboek-Leibler values averaged 0.69 ± 0.38. For the modified phantom, χ(2) values averaged 0.34 ± 0.12 and Kullboek-Leibler values averaged 0.32 ± 0.15. The proposed approach demonstrated a noticeable improvement of the local appearance of the simulated images with respect to the ones obtained originally.

Simulation of late gadolinium enhancement cardiac magnetic resonance studies.

In this study we propose a pipeline for simulation of late gadolinium enhancement images. We used a modified version of the XCAT phantom to improve simulation realism. Modifications included the modeling of trabeculae and papillary muscles, and the increase of sublabels to resemble tissue intensity variability. Magnetic properties for each body tissue were sampled in three settings: from Gaussian distributions, combining Rayleigh-Gaussian distributions, and from Rayleigh distributions. Thirty-two simulated datasets were compared with 32 clinical datasets from infarcted patients. Histograms were obtained for five tissues: lung, pericardium, myocardium, blood and hyper-enhanced area. Real and simulated histograms were compared with the Chi-square dissimilarity metric (χ(2)) and Kullback-Leibler divergence (KL). The generated simulated images look similar to real images according to both metrics. Rayleigh and the Rayleigh-Gaussian models obtained comparable average results (respectively: χ(2)= 0.16 ± 0.12 and 0.18 ± 0.11; KL=0.15 ± 0.17 and 0.16 ± 0.18).

3D mesh based wall thickness measurement: identification of left ventricular hypertrophy phenotypes.

Left ventricular hypertrophy (LVH) is a complex cardiac condition mainly identified by the thickening of the myocardial wall. Although most of the contemporary cardiac imaging modalities provide high resolution 3D images, the wall thickness (WT) is still measured within the acquired planes. This way of measurement may introduce an error as cardiac wall is not necessarily orthogonal to the plane. In this study we analyze how different approaches to measure WT can affect an automatic identification of hypertrophy. The compared approaches are: WT measured along surface normal and the one provided by a medial surface. For both approaches we evaluated their ability to identify LVH phenotypes by testing with two classifiers: Transductive Confidence Machine-k Nearest Neighbor (TCM-kNN) and Linear Discriminant Analysis (LDA). Fifty three subjects were included in this study: 18 patients with hypertrophic cardiomyopathy (HCM), 13 patients with hypertensive heart disease (HDD) and 22 sedentary subjects (CG). Medial surface based approach allowed obtaining higher classification accuracy in HDD patients, while normal based approach allowed for higher classification accuracy in HCM patients.

[Task delegation in primary care: new roles to the nursing personnel in Catalunya]. / La delegation de taches en soins primaires: les nouveaux roles des infirmieres en Catalogne.

A model of provision of primary care is experimented in a Catalan health centre. The model implies more varied roles and greater autonomy to nurses. They are the first contact of the patients coming to the health center. They base their decisions on a Guide for interventions on emergencies. The latter are distributed into 3 groups: (i) the cases which can be dealt with and finalized by the misusing the protocols previously established; (ii) the cases which require immediate care from the nurse, later intervention from the physician and common finalization at the end; (iii) the cases which require immediate intervention from the physician and, if the physician is not available, an evaluation from the nurse in the meanwhile. On 202 patients requesting a consultation on the same day, the data below are obtained:--70% cases have been resolved by the nurse using the Guide--14% cases have been resolved by the nurse after a telephone conversation with the physician--16% have been orientated to the relevant departments. Moreover, the on duty physician has been consulted in 6% The Guide appears therefore extremely useful. However, in the long range, the need for additional training in some specific domains were emerging, and that of constant interchange between physicians and nurses as well.

[Acalculous cholecystitis: an uncommon form of presentation of Q fever]. / Colecistitis alitiásica: una forma infrecuente de presentación de fiebre Q.

Acute acalculous cholecystitis is a very rare clinical presentation of Q fever. We report the case of a 38-year-old man who presented with fever associated with elevation of liver enzyme levels and thickening of the gallbladder wall on abdominal ultrasonography and who was initially diagnosed with acute acalculous cholecystitis. Due to the persistence of fever and transaminase elevation despite antibiotic treatment, a liver biopsy was performed. Characteristic "doughnut" epithelioid granulomas were observed, suggesting a diagnosis of granulomatous hepatitis caused by Q fever, which was confirmed by serological methods. Treatment with doxycycline was commenced and the patient subsequently showed rapid clinical improvement, with disappearance of fever and normalization of liver enzyme levels. We review 8 cases of acute cholecystitis associated with Q fever published in the literature and stress the importance of liver biopsy in the etiological diagnosis of patients with prolonged fever and abnormal liver function tests.

[Resolution of Ménétrier's disease after eradication of Helicobacter pylori infection]. / Resolución de la enfermedad de Ménétrier tras la erradicación de la infección por Helicobacter pylori.

Ménétrier's disease is an infrequent clinical entity characterized by thickening of the gastric folds secondary to hyperplasia of the foveolar mucosa cells, frequently associated with loss of enteric proteins and hypoalbuminemia. Its etiology is unknown, although in the last few years it has been related to Helicobacter pylori infection. We present the case of a 38-year-old man with protein-losing gastroenteropathy caused by Ménétrier's disease, in whom eradication of H. pylori infection was followed by symptom improvement and resolution of hypoalbuminemia. In agreement with the criteria of other authors, we investigate the presence of H. pylori infection in all patients with Ménétrier's disease. When positive, the first-line treatment consists of eradication therapy.

A PCR-RFLP test to detect allelic variants of the bovine kappa-casein gene.

Point mutations in exon IV of bovine kappa-casein gene (kappaCn, CASK, CSN3) determine nine allelic variants (A, B, C, E, F, G, H, I, and A1) for the gene. These variants are associated with major differences in composition and manufacturing properties of milk (i.e., cheese yield). A PCR-RFLP test was developed in order to distinguish the different alleles. Polymorphisms are detected by digestion with the endonucleases HindIII, HaeIII, and MaeII followed by electrophoresis in agarose gels stained with ethidium bromide. Twenty eight DNA samples from different breeds of Argentina were analyzed for the A, B, and E variants. This simple PCR-RFLP test makes feasible the inclusion of kappa-casein genotypes in breeding plans.

Unprecedented oxidation of a phenylglycinol-derived 2-pyridone: enantioselective synthesis of polyhydroxypiperidines.

[reaction: see text]. The phenylglycinol-derived 2-pyridone 1 undergoes m-CPBA oxidation steroselectively leading to the chiral nonracemic unsaturated bicyclic hydroxylactam 2, from which the enantioselective synthesis of (3R,5R)-3,4,5-trihydroxypiperidine (16) and the formal synthesis of the azasugar epiisofagomine are described. The enantioselective synthesis of (S)-N-Boc-3-hydroxypiperidine and (3R,4S)-3,4-dihydroxypiperidine is also reported.

The value of endorectal MR imaging to predict positive biopsies in clinically intermediate-risk prostate cancer patients.

The aim of this study was to assess the effectiveness of endorectal MR imaging in predicting the positive biopsy results in patients with clinically intermediate risk for prostate cancer. We performed a prospective endorectal MR imaging study with 81 patients at intermediate risk to detect prostate cancer between January 1997 and December 1998. Intermediate risk was defined as: prostatic specific antigen (PSA) levels between 4 and 10 ng/ml or PSA levels in the range of 10-20 ng/ml but negative digital rectal examination (DRE) or PSA levels progressively higher (0.75 ng/ml year(-1)). A transrectal sextant biopsy was performed after the endorectal MR exam, and also of the area of suspicion detected by MR imaging. The accuracies were measured, both singly for MR imaging and combined for PSA level and DRE, by calculating the area index of the receiver operating characteristics (ROC) curve. Cancer was detected in 23 patients (28%). Overall sensitivity and specificity of endorectal MRI was 70 and 76%, respectively. Accuracy was 71% estimated from the area under the ROC curve for the total patient group and 84% for the group of patients with PSA level between 10-20 ng/ml. Positive biopsy rate (PBR) was 63% for the group with PSA 10-20 ng/ml and a positive MR imaging, and 15% with a negative MR exam. The PBR was 43% for the group with PSA 4-10 ng/ml and a positive MR study, and 13% with a negative MR imaging examination. We would have avoided 63% of negative biopsies, while missing 30% of cancers for the total group of patients. Endorectal MR imaging was not a sufficient predictor of positive biopsies for patients clinically at intermediate risk for prostate cancer. Although we should not avoid performing systematic biopsies in patients with endorectal MR imaging negative results, as it will miss a significant number of cancers, selected patients with a PSA levels between 10-20 ng/ml or clinical-biopsy disagreement might benefit from endorectal MR imaging.

In vitro anti-Toxoplasma gondii antibody production by peripheral blood mononuclear cells in the diagnosis and the monitoring of toxoplasmic encephalitis in AIDS-related brain lesions.

The spontaneous secretion in vitro of anti-Toxoplasma gondii antibodies by peripheral blood mononuclear cells was assessed in 69 patients with AIDS-related brain lesions. The sensitivity and specificity of this assay in the diagnosis of toxoplasmic encephalitis (TE) were found to be 85.4% and 92.8%, respectively. Twenty-four patients with TE were observed during 1-year follow-up after initiation of anti-Toxoplasma treatment and classified on the basis of their clinical and radiologic responses as sustained responders (SR; n = 11), incomplete responders (IR; n = 7) or transient responders (TR; n = 6). In vitro anti-T. gondii antibody secretion decreased as early as the first month after initiation of treatment and disappeared within the year in SRs, persisted in IRs, and decreased but rebounded at relapse in the TR patients. In vitro anti-T. gondii antibody, which reflects immune system activation by parasitic antigens, could be a surrogate marker of TE in AIDS patients.

Cytokines and cell surface molecules independently induce CXCR4 expression on CD4+ CCR7+ human memory T cells.

In the present study, we show that IL-2, IL-4, IL-7, and IL-15 are able to induce functional CXCR4 surface expression on resting in vitro-generated CD4+ CXCR4- CCR7+ memory T cells. Cytokine-mediated induction of CXCR4 expression was associated with an increase in CXCR4 transcription, enhanced stromal-derived factor-1-induced T cell migration in vitro, and increased susceptibility of these cells to infection with X4 strains of HIV-1. CXCR4 expression could also be induced through an alternative pathway, following coculture of these cells with CD40-activated, autologous, CD34+ progenitor-derived dendritic cells. Although these dendritic cells express transcripts for IL-7 and IL-15, addition of neutralizing anti-IL-7R and IL-15 mAbs did not block induction of CXCR4 expression. Indeed, dendritic cell-mediated up-regulation of CXCR4 expression was found to depend on CD40/CD154 and CD134/CD134L interactions. Whereas activated autologous dendritic cells induced the expression of both CXCR4 and CD25 on a portion of CCR7+ memory T cells, concomitant CD3-mediated activation of these cells further enhanced CD25 expression, but, in contrast, prevented induction of CXCR4 expression. This observation suggests that triggering of the CD134 and CD154 molecules, in contrast to TCR/CD3 complex-mediated stimulation, results in simultaneous T cell activation and CXCR4 expression. Taken together, these results show that common gamma-chain-interacting cytokines as well as signals mediated via noncognate interactions between activated dendritic cells and memory T cells are involved in the up-regulation of CXCR4 expression.