The Genetic Architecture of Chemosensory Cues Involved in Species Recognition: A Behavioral Approach in the House Mouse

The genetics of chemical signals is poorly understood. We addressed this issue in two subspecies of mice, Mus musculus musculus and M. m. domesticus, comparing their odor phenotypes with that of their hybrids. Earlier studies indicated that these subspecies could be discriminated on the basis of their urinary odor. We assessed male odor phenotypes from perception of musculus mice acting as olfactometers. Our results point to a complex genetic determinism. Reciprocal F1 hybrids produced a distinct odor phenotype, with shared characteristics distinguishing them from their parents, and stronger similarity to domesticus than to musculus. These results are consistent with implications of genes with partial dominance and a parent of origin effect. Further, similarities between reciprocal F2 allowed us to reject a direct role of the Y-chromosome in shaping the odor phenotype. However we show that the X-chromosome could be involved in explaining domesticus phenotype, while epistasis between genes on the sex chromosomes and the autosomes might influence musculus phenotype.     

Maternally acquired genotoxic Escherichia coli alters offspring’s intestinal homeostasis

The neonatal gut is rapidly colonized by a newly dominant group of commensal Escherichia coli strains among which a large proportion produces a genotoxin called colibactin. In order to analyze the short- and long-term effects resulting from such evolution, we developed a rat model mimicking the natural transmission of E. coli from mothers to neonates. Genotoxic and non-genotoxic E. coli strains were equally transmitted to the offspring and stably colonized the gut across generations. DNA damage was only detected in neonates colonized with genotoxic E. coli strains. Signs of genotoxic stress such as anaphase bridges, higher occurrence of crypt fission and accelerated renewal of the mature epithelium were detected at adulthood. In addition, we observed alterations of secretory cell populations and gut epithelial barrier. Our findings illustrate how critical is the genotype of E. coli strains acquired at birth for gut homeostasis at adulthood.     

Diabetes is associated with high risk of severe adverse events during chemotherapy for cancer patients: A single-center study

Diabetes mellitus (DM) is a common comorbidity among cancer patients, but its impact on chemotherapy tolerance has not been widely studied. We aimed to compare the occurrence of severe grade 3/4 adverse events (G3/4 AEs) within 90 days of starting chemotherapy between patients with and without diabetes. We conducted a retrospective single-center study in Lille University Hospital Oncology Department, France. Patients who received the first cycle of chemotherapy for gastrointestinal, gynecological or cancer of unknown primary source between 1 May 2013 and 1 May 2016, were included. Overall, 609 patients were enrolled: 490 patients without diabetes (80.5%) and 119 patients with diabetes (19.5%). Within 90 days of starting chemotherapy, patients with diabetes had a significantly higher occurrence of AEs G3/4 compared to those with no diabetes (multivariate odds ratio [OR]: 1.57 [1.02-2.42], P = .04). More frequent G3/4 AEs in patients with diabetes were infection (26%), hematological disorders (13%), endocrine disorders (13%) and deterioration of the general condition (13%). In the year following the beginning of chemotherapy, patients with diabetes were twice as likely to be hospitalized as those without diabetes (univariate OR: 2.1 [1.40-3.15], P = .0003). After multivariate adjustment, diabetes was no longer significantly associated with the risk of hospitalization (P = .051). There were no differences between patients with and without diabetes regarding dose reduction and chemotherapy treatment delays (P = .61 and P = .30, respectively). Our study suggests the need for better consideration of DM in the personalized care plan to improve chemotherapy tolerance and quality of life of patients with DM.     

EXPLORATION OF MIGRAINE PAIN,DISABILITY, DEPRESSIVE SYMPTOMATOLOGY,AND COPING: A PILOT STUDY

As many as 29% of women suffer from migraine headache, yet it remains a poorly understood phenomenon. Our purpose in conducting this pilot study was to determine the relationships among migraine pain, disability, depressive symptomatology, and coping in women. A convenience sample of 34 women was recruited from university and workplace populations. Nineteen women met the International Headache Society criteria for migraine, while 15 women served as a nonmigraine comparison group. Participants completed eight instruments measuring migraine pain, disability, depressive symptomatology, and coping. The two groups of women were not significantly different on demographic variables. Migraineurs scored significantly higher for pain characteristics, disability, depressive symptomatology, and total coping scores.     

Patient acceptable symptom state and minimal clinically important difference for patient-reported outcomes in systemic sclerosis: A secondary analysis of a randomized controlled trial comparing personalized physical therapy to usual care

Background

To estimate patient acceptable symptom state (PASS) and minimal clinically important difference (MCID) for patient-reported outcomes in systemic sclerosis (SSc).

Prognostic value of aerobic capacity and exercise oxygen pulse in postaortic dissection patients

BackgroundAlthough recommendations encourage daily moderate activities in post aortic dissection, very little data exists regarding cardiopulmonary exercise testing (CPET) to personalize those patient''s physical rehabilitation and assess their cardiovascular prognosis.DesignWe aimed at testing the prognostic insight of CPET regarding aortic and cardiovascular events by exploring a prospective cohort of patients followed‐up after acute aortic dissection.MethodsPatients referred to our department after an acute (type A or B) aortic dissection were prospectively included in a cohort between September 2012 and October 2017. CPET was performed once optimal blood pressure control was obtained. Clinical follow‐up was done after CPET for new aortic event and major cardio‐vascular events (MCE) not directly related to the aorta.ResultsAmong the 165 patients who underwent CPET, no adverse event was observed during exercise testing. Peak oxygen pulse was 1.46(1.22‐1.84) mlO2/beat, that is, 97 (83–113) % of its predicted value, suggesting cardiac exercise limitation in a population under beta blockers (92% of the population). During a follow‐up of 39(20‐51) months from CPET, 42 aortic event recurrences and 22 MCE not related to aorta occurred. Low peak oxygen pulse (<85% of predicted value) was independently predictive of aortic event recurrence, while low peak oxygen uptake (<70% of predicted value) was an independent predictor of MCE occurrence.ConclusionCPET is safe in postaortic dissection patients should be used to not only to personalize exercise rehabilitation, but also to identify those patients with the highest risk for new aortic events and MCE not directly related to aorta.     

Pediatric patients who receive antibiotics for fever and neutropenia in less than 60 min have decreased intensive care needs

Background

Antibiotic delivery to patients with fever and neutropenia (F&N) in <60 min is an increasingly important quality measure for oncology centers, but several published reports indicate that a time to antibiotic delivery (TTA) of <60 min is quite difficult to achieve. Here we report a quality improvement (QI) effort that sought to decrease TTA and assess associated clinical outcomes in pediatric patients with cancer and F&N.

Procedure

We used Lean‐Methodology and a Plan‐Do‐Study‐Act approach to direct QI efforts and prospectively tracked TTA measures and associated clinical outcomes (length of stay, duration of fever, use of imaging studies to search for occult infection, bacteremia, intensive care unit (ICU) consultation or admission, and mortality). We then performed statistical analysis to determine the impact of our QI interventions on total TTA, sub‐process times, and clinical outcomes.

Results

Our QI interventions significantly improved TTA such that we are now able to deliver antibiotics in <60 min nearly 100% of the time. All TTA sub‐process times also improved. Moreover, achieving TTA <60 min significantly reduced the need for ICU consultation or admission (P = 0.003) in this population.

Conclusion

Here we describe our QI effort along with a detailed assessment of several associated clinical outcomes. These data indicate that decreasing TTA to <60 min is achievable and associated with improved outcomes in pediatric patients with cancer and F&N. Pediatr Blood Cancer 2015;62:807–815. © 2015 The Authors. Pediatric Blood & Cancer, published by Wiley Periodicals, Inc.     

Incorporation of resident macrophages in engineered tissues: Multiple cell type response to microenvironment controlled macrophage‐laden gelatine hydrogels

The success of tissue engineering strategy is strongly related to the inflammatory response, mainly through the activity of macrophages that are key cells in initial immune response to implants. For engineered tissues, the presence of resident macrophages can be beneficial for maintenance of homeostasis and healing. Thus, incorporation of macrophages in engineered tissues can facilitate the integration upon implantation. In this study, an in‐vitro model of interaction was developed between encapsulated naive monocytes, macrophages induced with M1/M2 stimulation and incoming cells for immune assisted tissue engineering applications. To mimic the wound healing cascade, naive THP‐1 monocytes, endothelial cells and fibroblasts were seeded on the gels as incoming cells. The interaction was first monitored in the absence of the gels. To mimic resident macrophages, THP‐1 cells were encapsulated in the presence or absence of IL‐4 to control their phenotype and then these hydrogels were seeded with incoming cells. Without encapsulation, activated macrophages induce apoptosis in endothelial cells. Once encapsulated no adverse effects were seen. Macrophage‐laden hydrogels attracted more endothelial cells and fibroblasts compared to monocytes‐laden hydrogels. The induction (M2 stimulation) of encapsulated macrophages did not change the overall number of attracted cells; but significantly affected their morphology. M1 stimulation by a defined media resulted in more secretion of both pro‐ and anti‐inflammatory cytokines compared to M2 stimulation. It was demonstrated that there is a distinct effect of encapsulated macrophages on the behaviour of the incoming cells; this effect can be harnessed to establish a microenvironment more prone to regeneration upon implantation.