Determinants of 6-month maternal satisfaction with breastfeeding experience in a multicenter prospective cohort study

Although a personally defined experience, successful breastfeeding is usually measured with regard to duration. This study investigated the determinants of maternal satisfaction with breastfeeding experience for 907 mothers enrolled in a prospective cohort study. Despite a median breastfeeding duration (18 weeks) that fell short of recommendations, 822 mothers (90.6%) rated their breastfeeding experience as very or fairly satisfactory. Anticipated breastfeeding duration was a determinant of satisfaction only for women who actually breastfeed < 2 months; in this subgroup of mothers, satisfaction rates ranged from 84.6% for those who anticipated breastfeeding < 2 months to 69.8% for those who anticipated breastfeeding > 4 months (P = .01). Smoking during pregnancy and experiencing breastfeeding difficulties after discharge were independently associated with decreased satisfaction. Eliciting the mother's expectations regarding breastfeeding duration may help the lactation consultant in providing appropriate guidance. Future studies should assess maternal satisfaction using validated instruments.     

Persistent activation of the Fyn/ERK kinase signaling axis mediates imatinib resistance in chronic myelogenous leukemia cells through upregulation of intracellular SPARC

SPARC is an extracellular matrix protein that exerts pleiotropic effects on extracellular matrix organization, growth factor availability, cell adhesion, differentiation, and immunity in cancer. Chronic myelogenous leukemia (CML) cells resistant to the BCR-ABL inhibitor imatinib (IM-R cells) were found to overexpress SPARC mRNA. In this study, we show that imatinib triggers SPARC accumulation in a variety of tyrosine kinase inhibitor (TKI)-resistant CML cell lines. SPARC silencing in IM-R cells restored imatinib sensitivity, whereas enforced SPARC expression in imatinib-sensitive cells promoted viability as well as protection against imatinib-mediated apoptosis. Notably, we found that the protective effect of SPARC required intracellular retention inside cells. Accordingly, SPARC was not secreted into the culture medium of IM-R cells. Increased SPARC expression was intimately linked to persistent activation of the Fyn/ERK kinase signaling axis. Pharmacologic inhibition of this pathway or siRNA-mediated knockdown of Fyn kinase resensitized IM-R cells to imatinib. In support of our findings, increased levels of SPARC mRNA were documented in blood cells from CML patients after 1 year of imatinib therapy compared with initial diagnosis. Taken together, our results highlight an important role for the Fyn/ERK signaling pathway in imatinib-resistant cells that is driven by accumulation of intracellular SPARC.     

Dose-dependent biphasic leptin-induced proliferation is caused by non-specific IL-6/NF-κB pathway activation in human myometrial cells

Background and Purpose

Leptin, an adipokine synthesized by the placenta during pregnancy, has been proposed for the management of preterm labour (PTL), as it is able to prevent in vitro uterine contractility and remodelling associated with labour onset. Another common feature of labour onset is the phenotypic switch of myometrial smooth muscle cells from a proliferative to a hypertrophic state. As proliferative effects have been demonstrated for leptin in other tissues, we aimed to investigate its ability to induce myometrial proliferation and thus to maintain uterine quiescence.

Experimental Approach

We stimulated human primary myometrial smooth muscle cells with leptin in the presence or absence of receptor antagonists or signalling pathway inhibitors.

Key Results

Leptin induced myometrial cell proliferation in a biphasic manner. At 6.25 ng·mL⁻¹, leptin-induced proliferation was mediated by the leptin receptor and required the early activation of ERK1/2. At a concentration above 25 ng·mL⁻¹, leptin induced direct non-specific stimulation of the IL-6 receptor, leading to NF-κB activation, and exerted anti-proliferative effects. However, at 50 ng·mL⁻¹, leptin re-induces proliferation via IL-6 receptor stimulation that requires STAT3 and delayed ERK1/2 activation.

Conclusions and Implications

These data bring new insights into leptin signalling-induced myometrial proliferation and its interrelationship with the IL-6/IL-6 receptor axis. In the light of our previous work, the present study emphasizes the potential value of leptin in the pharmacological management of PTL and it also strengthens the hypothesis that leptin might be a contributory factor in the parturition-related disorders observed in obese women.     

Pharmacological agents for nonalcoholic steatohepatitis

The rationale for specific pharmacologic therapy in nonalcoholic steatohepatitis (NASH) is determined by the potential for disease progression and the difficulties, in many patients, to successfully implement diet and lifestyle changes in the long term. Because they correct insulin resistance, insulin-sensitizing agents are attractive candidates for the treatment of NASH. However, two randomized studies have shown that vitamin E, despite having no effect on insulin sensitivity, achieves interesting histological and biochemical efficacy. This review provides an insight into the therapeutic efficacy and safety issues of different pharmacological agents tested in human NASH.     

Early Miocene hippopotamids (Cetartiodactyla) constrain the phylogenetic and spatiotemporal settings of hippopotamid origin

The affinities of the Hippopotamidae are at the core of the phylogeny of Cetartiodactyla (even-toed mammals: cetaceans, ruminants, camels, suoids, and hippos). Molecular phylogenies support Cetacea as sister group of the Hippopotamidae, implying a long ghost lineage between the earliest cetaceans (∼53 Ma) and the earliest hippopotamids (∼16 Ma). Morphological studies have proposed two different sister taxa for hippopotamids: suoids (notably palaeochoerids) or anthracotheriids. Evaluating these phylogenetic hypotheses requires substantiating the poorly known early history of the Hippopotamidae. Here, we undertake an original morphological phylogenetic analysis including several “suiform” families and previously unexamined early Miocene taxa to test previous conflicting hypotheses. According to our results, Morotochoerus ugandensis and Kulutherium rusingensis, until now regarded as the sole African palaeochoerid and the sole African bunodont anthracotheriid, respectively, are unambiguously included within the Hippopotamidae. They are the earliest known hippopotamids and set the family fossil record back to the early Miocene (∼21 Ma). The analysis reveals that hippopotamids displayed an unsuspected taxonomic and body size diversity and remained restricted to Africa during most of their history, until the latest Miocene. Our results also confirm the deep nesting of Hippopotamidae within the paraphyletic Anthracotheriidae; this finding allows us to reconstruct the sequence of dental innovations that links advanced selenodont anthracotheriids to hippopotamids, previously a source of major disagreements on hippopotamid origins. The analysis demonstrates a close relationship between Eocene choeropotamids and anthracotheriids, a relationship that potentially fills the evolutionary gap between earliest hippopotamids and cetaceans implied by molecular analyses.     

Asthma exacerbations and socio-economic status in French adults with persistent asthma: A prospective cohort study

Introduction: Adults disadvantaged by poor socio-economic status (SES) are more severely affected by asthma compared to those with better SES. We aimed to determine whether the frequency of asthma exacerbations (AEx), as well as aspects related to AEx management, differed based on SES in patients treated with daily treatments. Methods: This study, part of the prospective observational cohort ASTRO-LAB, included French adult patients with persistent asthma. Patients were considered as low SES if they benefited from publicly funded special health insurance and/or were perceived as low SES by their general practitioner. AEx was defined as at least one of the following: asthma-related oral corticosteroid course, medical contact, hospitalization, and death. We examined associations between SES and AEx frequency, perceived triggering factors and type of medical contact after AEx. Results: In our sample of 255 patients, 11.40% were considered as low SES. Patients with low SES did not report significantly more AEx than medium/high SES patients during one-year follow-up (0.79 versus 0.55, p = 0.38). The type of medical contact during AEx differed significantly between the two groups (p = 0.03): patients with medium/high SES consulted their general practitioner more frequently (OR = 2.23, 95% CI = 0.91–5.50, p = 0.08) and were less likely to visit an emergency department or be hospitalized (OR = 0.27, 95% CI = 0.09–0.84, p = 0.02). Conclusions: AEx frequency did not differ significantly between low and medium/high SES patients, but differences were found in the management of AEx. Studies are needed to better understand the relation between precariousness and management of asthma.     

Lessons from “real life experience” of rifaximin use in the management of recurrent hepatic encephalopathy

BACKGROUND Hepatic encephalopathy(HE) is a major complication of cirrhosis with independent prognostic significance. The current management of HE is mainly based on lactulose. Rifaximin has been shown to decrease the risk of HE recurrence in patients with episodic forms. HE can also be persistent. However,there is no drug support recommendation for rifaximin use in this setting.AIM To assess the effectiveness of rifaximin in the management of recurrent episodes of HE and recurrent acute exacerbations on persistent HE, in real life conditions.METHODS In this retrospective study, using a within-subjects design, we collected data of patients treated with rifaximin for HE in two liver diseases centers, during the six-month period before and during the six-month period after the initiation of rifaximin. The primary effectiveness endpoint was the total number of HE events involving hospitalization.RESULTSRifaximin was introduced for prevention of recurrent HE episodes in 29 out of 62 patients with normal mental status between episodes and for prevention of recurrent acute exacerbations on persistent HE in 33 out of 62 patients. In theprevention of recurrent HE episodes group, fewer HE events(0.79 vs 1.78; P =0.013) were reported during the period of time when rifaximin was used. In theprevention of recurrent acute exacerbations on persistent HE group, there was no significant difference in the number of HE-events(1.48 vs 1.77; P = 0.582).CONCLUSION In this real-life experience, the effectiveness of rifaximin was confirmed in the prevention of HE episodes recurrence but was not proved in the prevention of acute exacerbations recurrence on persistent HE.