Modèle quadratique de Treynor-Mazuy et régimes de marché : une étude empirique du comportement des portefeuilles dans un contexte canadien

Le modèle quadratique de Treynor et Mazuy (1966) est utilisé depuis longtemps pour mesurer l'habileté d'un gestionnaire à anticiper le marché. Certains auteurs ont toutefois démontré que le coefficient du terme quadratique (gamma) peut être positif sans pour autant que le gestionnaire n'ait eu à anticiper avec succès les fluctuations du marché. L'étude actuelle fait pour sa part ressortir le manque d'information sur la nature de la sousperformance d'un portefeuille présentant un gamma négatif. En élevant la prime de rendement d'un portefeuille au carré, le modèle traite les rendements excédentaires négatifs et positifs de la même façon, ignorant ainsi l'asymétrie qui existe entre les différents régimes de marché. L' étude du rendement de 21 portefeuilles d' actions canadiennes entre décembre 1998 et janvier 2006 réaffirme que le modèle de Treynor et Mazuy (1966) ne peut être utilisé pour identifier avec certitude les gestionnaires ayant anticipé avec succès les baisses de marché

Chronic aortic regurgitation in rats

Objectives: Aortic regurgitation (AR) induces left ventricular (LV) eccentric hypertrophy in response to chronic volume overload. Patients suffering from this disease often remain asymptomatic for decades before progressive LV dysfunction develops silently. Because of this slow evolution, large clinical trials with long-term follow-up on subjects with chronic AR are hard to perform. To overcome this problem, animal models have been developed in the past but results were very heterogeneous. Methods: Helped by echocardiography, we refined a known technique to induce homogenous degrees of severe AR in Wistar-Kyoto rats. The effects on LV function without treatment and with nifedipine (25 mg/kg daily) (a drug currently recommended in humans with chronic AR) were evaluated by echocardiography. Results: Over 6 months, nontreated animals developed progressive LV dilatation and eccentric hypertrophy, characteristic of chronic LV volume overload. The animals also developed progressive LV systolic dysfunction, mimicking closely the evolution of the disease in humans. Abnormal filling parameters were also detected in the majority of animals. Systolic and diastolic abnormalities were prevented but only partially in the group treated with nifedipine. Conclusion: This model can be used to study chronic AR and LV dysfunction associated with the disease. Nifedipine seems to protect the LV against chronic volume overload but only partially. Treatment strategies currently used in humans deserve further investigation

Early LV signaling events in pressure overload

The early events leading to the establishment of left ventricular hypertrophy associated to pressure overload (PO) are not well characterized. To explore these early events, aortic banding (AB) was performed in rats to induce left ventricle (LV) PO. Animals were sacrificed after 24, 48 h or 14 days. An echocardiogram was performed before the procedure and at sacrifice. LVs were preserved for the evaluation of fibrosis, angiotensin II (AT) receptors expression and stress-related MAP kinases (ERK 1/2, JNK and p38) pathways. We observed that concentric LV hypertrophy was established after only 14 days. Collagen I and fibronectin gene expressions were decreased the first 2 days after AB induction whereas AT receptors mRNA levels were sharply increased. ERK 1/2 and JNK activities in LV homogenates were decreased 24 h after AB but came back to normal after 14 days. p38 activity however was stable during the period studied. We also evaluated the presence of two phosphorylated transcription factors related to JNK signaling pathway (ATF-2 and c-Jun) in cardiomyocyte nuclei. The proportion of LV cell nuclei positive for these two activated transcription factors was significantly reduced in AB rats compared to sham. These results suggest that the early response of the LV to acute PO is to attenuate the expression of some pro-fibrotic and pro-hypertrophic signaling pathways and possibly AT signaling by decreasing ERK 1/2 and JNK relative activities

Bacteriocins as a new generation of antimicrobials : toxicity aspects and regulations

In recent decades, bacteriocins have received substantial attention as antimicrobial compounds. Although bacteriocins have been predominantly exploited as food preservatives, they are now receiving increased attention as potential clinical antimicrobials and as possible immune-modulating agents. Infections caused by antibiotic-resistant bacteria have been declared as a global threat to public health. Bacteriocins represent a potential solution to this worldwide threat due to their broad- or narrow-spectrum activity against antibiotic-resistant bacteria. Notably, despite their role in food safety as natural alternatives to chemical preservatives, nisin remains the only bacteriocin legally approved by regulatory agencies as a food preservative. Moreover, insufficient data on the safety and toxicity of bacteriocins represent a barrier against the more widespread use of bacteriocins by the food and medical industry. Here, we focus on the most recent trends relating to the application of bacteriocins, their toxicity and impacts

Hypertension and aortic valve regurgitation in rats

Background : Hypertension (HT) and aortic valve regurgitation (AR) often coexist but the specific impacts of AR + HT on the left ventricle (LV) are still unknown. The best treatment strategy for this combination of diseases is also unclear. The objectives of this study were 1) to evaluate LV function, remodeling and 2) to assess the effects of the angiotensin-converting enzyme (ACE) inhibitor captopril (C) in rats with AR ± HT in spontaneously hypertensive rats (SHR). Methods : Animals were grouped as follows: normotensive (NT) Wistar-Kyoto, NT + AR, hypertensive SHR (HT), and HT + AR receiving or not captopril (150 mg/kg/d). Hearts were evaluated in vivo by echocardiography and harvested for tissue analysis after 6 months of evolution. Results : The HT + AR rats had the worst LV hypertrophy (LVH), subendocardial fibrosis, and lowest ejection fraction. Captopril normalized BP in HT and HT + AR, but could not prevent LVH in HT + AR as well as it did in isolated HT. The LV ejection fraction remained below normal in HT + AR + captopril compared to HT alone + captopril. Cardiomyocyte hypertrophy remained in HT + AR + captopril but was normalized in HT + captopril. Subendocardial fibrosis was reduced by captopril in HT + AR. Conclusions : The AR + HT rats had the most severe myocardial abnormalities. High dose captopril was effective to slow LVH and preserve normal LV ejection fraction in isolated HT or AR, but was less effective when both pathologies were combined. Prohypertrophic stimuli clearly remain active in HT + AR despite ACE inhibition. These results suggest that a very aggressive medical treatment strategy may be required to optimize LV protection when AR and HT co-exist

Plasma concentrations of perfluoroalkyl acids and their determinants in youth and adults from Nunavik, Canada

Perfluoroalkyl acids (PFAAs), a subset of per- and poly-fluoroalkyl substances (PFAS), are environmentally stable, mobile and bioaccumulative compounds. This leads to high concentrations in wildlife species essential to the cultural identity and subsistence of Arctic populations. Our objective was to characterize the distribution and exposure determinants of PFAAs among Nunavik Inuit adults. The study included up to 1322 Nunavik residents aged 16–80 years who participated in the Qanuilirpitaa? 2017 Nunavik Inuit Health Survey (Q2017). Plasma concentrations were compared to those the general Canadian population using data from the Canadian Health Measures Survey Cycle 5 (2016–2017). Associations between plasma concentrations of nine PFAAs, determined by liquid chromatography-tandem mass spectrometry, and sociodemographic factors and traditional activity participation were examined using multiple linear regression models. Overall exposure to PFAAs was twice as high compared to the general Canadian population and less regulated perfluorononanoic acid (PFNA) and perfluoroundecanoic acid (PFUnDA) concentrations were 7-fold higher, and perfluorodecanoic acid (PFDA) concentrations were 4-fold higher. Males had higher concentrations of perfluorooctanoic acid (PFOA) and perfluorohexane sulfonate (PFHxS), whereas females had higher concentrations of PFDA and PFUnDA. PFAAs concentrations increased with age and were highest among those aged 60+ years. PFNA and PFO

Examination of Urinary Pesticide Concentrations, Protective Behaviors, and Risk Perceptions Among Latino and Latina Farmworkers in Southwestern Idaho

Introduction: Studies have documented high levels of pesticide exposure among men farmworkers; however, few have examined exposures or the experiences of women farmworkers. Data gaps also exist regarding farmworkers’ perceived risk and control related to pesticides, information that is critical to develop protective interventions. Objective: We aimed to compare urinary pesticide biomarker concentrations between Latino and Latina farmworkers and examine associations with occupational characteristics, risk perceptions, perceived control, and protective behaviors. Methods: We enrolled a convenience sample of 62 farmworkers (30 men and 32 women) during the pesticide spray season from April–July 2022 in southwestern Idaho. Participants were asked to complete two visits within a seven-day period; at each visit, we collected a urine sample and administered a questionnaire assessing demographic and occupational information. Urine samples were composited and analyzed for 17 biomarkers of herbicides and of organophosphate (OP) and pyrethroid insecticides. Results: Ten pesticide biomarkers (TCPy, MDA, PNP, 3-PBA, 4-F-3-PBA, cis- and trans-DCCA, 2,4-D, Glyphosate, AMPA) were detected in \u3e80% of samples. Men and women had similar urinary biomarker concentrations (p = 0.19–0.94); however, women worked significantly fewer hours than men (p = 0.01), wore similar or greater levels of Personal Protective Equipment (PPE), and were slightly more likely to report having experienced an Acute Pesticide Poisoning (26% of women vs. 14% of men; p = 0.25). We observed inconsistencies in risk perceptions, perceived control, and protective behaviors among men. Discussion: Our study is one the first to examine pesticide exposure and risk perceptions among a cohort of farmworkers balanced on gender. Taken with previous findings, our results suggest that factors such as job tasks, biological susceptibility, or access to trainings and protective equipment might uniquely impact women farmworkers’ exposure and/or vulnerability to pesticides. Women represent an increasing proportion of the agricultural workforce, and larger studies are needed to disentangle these findings

Sternal reentry in a patient with previous deep sternal wound infection managed with horizontal titanium plate fixation

Redo open-heart surgery and sternal reentry in patients with previous deep sternal wound infection (DSWI) and absence of sternal integrity can be a delicate and morbid task due the lack of a dissection plane between the heart and the surrounding soft tissues. Delayed sternal reconstruction and osteosynthesis with horizontal titanium plating fixation (Synthes) following vacuum assisted therapy (KCI) has recently been proposed and adopted for the treatment of DSWI. We present such a case of a patient who was successfully reoperated for valve replacement three years after coronary artery bypass grafting complicated by DSWI and initially treated with titanium plate fixation

Formation of stress-specific p53 binding patterns is influenced by chromatin but not by modulation of p53 binding affinity to response elements†

The p53 protein is crucial for adapting programs of gene expression in response to stress. Recently, we revealed that this occurs partly through the formation of stress-specific p53 binding patterns. However, the mechanisms that generate these binding patterns remain largely unknown. It is not established whether the selective binding of p53 is achieved through modulation of its binding affinity to certain response elements (REs) or via a chromatin-dependent mechanism. To shed light on this issue, we used a microsphere assay for protein–DNA binding to measure p53 binding patterns on naked DNA. In parallel, we measured p53 binding patterns within chromatin using chromatin immunoprecipitation and DNase I coupled to ligation-mediated polymerase chain reaction footprinting. Through this experimental approach, we revealed that UVB and Nutlin-3 doses, which lead to different cellular outcomes, induce similar p53 binding patterns on naked DNA. Conversely, the same treatments lead to stress-specific p53 binding patterns on chromatin. We show further that altering chromatin remodeling using an histone acetyltransferase inhibitor reduces p53 binding to REs. Altogether, our results reveal that the formation of p53 binding patterns is not due to the modulation of sequence-specific p53 binding affinity. Rather, we propose that chromatin and chromatin remodeling are required in this process