"Muscle Pics", a new body-checking behavior in muscle dysmorphia?

BACKGROUND AND AIMS: The internalization of ideal hypermuscular body and pro-muscularity media's influence have shown their importance in muscle dysmorphia development. The aim of the current study is to have a better understanding of links between specific body checking behaviors and muscle dysmorphia in social network context. METHODS: In total, 342 students practicing weightlifting at the university gym in Bordeaux answered to a survey with sociodemographic information and body checking symptoms including taking specific selfies of muscles and muscularity "Muscle Pics" and the MDDI (Muscle Dysmorphic Disorder Inventory). RESULTS: Muscle dysmorphia was prevalent in 18.7% of our population (64 students). We observed that muscle dysmorphia was correlated to "Muscle Pics", "Follow-up", "Message", "Selfie", and gym mirror checking with significant results (P<0.01). Also, « Muscle Pics ¼ were linked to APEDs use, pro-muscularity websites, fitness model comparison and gym mirror checking (P<0.01). For muscle dysmorphia, "Muscle Pics" have strong predictive results (OR=5.10, P=0.000) and (OR=4.08, P=0.000) for adjusted. "Follow up" (OR=4.76, P=0.000) and (OR=3.83, P=0.000) for adjusted, "Muscle Pics Selfie" (OR=11.20, P=0.000) and (OR=11.55, P=0.000) for adjusted, "Muscle Pics Message" (OR=4.49, P=0.001) and (OR=5.78, P=0.001) for adjusted. CONCLUSION: "Muscle Pics" showed several links with muscle dysmorphia for global score "drive for size", "functional impairment" but not for "appearance intolerance" dimension. Pro-muscularity websites, fitness model comparisons and gym mirror checking are linked to muscle dysmorphia and "Muscle Pics". Future research on "Muscle Pics" will help to provide a better understanding of muscle dysmorphia and its link with pro-muscularity influence websites.

Comparing the effects of self-selected MUsic versus predetermined music on patient ANXiety prior to gynaecological surgery: the MUANX randomized controlled trial.

BACKGROUND: Anxiety is frequently observed in the preoperative setting. The negative impact of preoperative anxiety is well known. In the context of gynaecological surgery, anxiety is exacerbated by the fact that the intervention can have catastrophic repercussions on a woman's body image, sexuality, and psycho-affective well-being. Music listening is increasingly used as an alternative therapy for minimizing preoperative anxiety. Personal preferences, familiarity, and popularity may be key elements for an optimal relaxation response to music. This study aimed to determine whether listening to self-selected music decreases preoperative anxiety in women scheduled to undergo gynaecologic surgery compared with predetermined music from an application (MUSIC CARE®). METHODS: The MUANX study was a single-blind, monocentric, parallel, superiority, randomized controlled trial. A total of 174 women were included and randomized in two groups between August 2017 and September 2018. Patients in the intervention group listened to the personal music playlist that they had created before being hospitalized. Patients in the control group listened to the predetermined playlist on the MUSIC CARE® application. All patients received standard nursing care and listened to 20 min of music 1 h before surgery. Anxiety scores were assessed before and after the music session using Spielberger's State-Trait Anxiety Inventory (STAI). RESULTS: The mean age of the 171 evaluated patients was 41.5 years (SD = 10.0 years). Before the music session, the STAI state anxiety score was similar in the control group (M = 38.8, SD = 11.9) and the intervention group (M = 39.0, SD = 13.1). After the music session, this score had significantly decreased in both the control group (M = -7.2, SD = 9.0) and the intervention group (M = -5.5, SD = 6.6), with no significant difference in score reduction between groups. Physiological parameters were unchanged after the music session. No significant differences in postoperative measurements (pain intensity, hospitalization duration) were observed between the two groups. CONCLUSION: Self-selected music is as effective as predetermined music for reducing patient anxiety before gynaecological surgery. As it has no side effects and is easily applicable in gynaecological surgical services, this non-drug intervention may be proposed by healthcare professionals in the management of preoperative anxiety. TRIAL REGISTRATION: The MUANX trial (MUsic therapy on ANXiety) is registered at the US National Institutes of Health ( ClinicalTrials.gov ) #NCT03226834. Registered on 24 July 2017. https://clinicaltrials.gov/ct2/show/NCT03226834?term=muanx&draw=2&rank=1.

NLRP7 is increased in human idiopathic fetal growth restriction and plays a critical role in trophoblast differentiation.

Fetal growth restriction (FGR) the leading cause of perinatal mortality and morbidity is highly related to abnormal placental development, and placentas from FGR pregnancies are often characterized by increased inflammation. However, the mechanisms of FGR-associated inflammation are far from being understood. NLRP7, a member of a family of receptors involved in the innate immune responses, has been shown to be associated with gestational trophoblastic diseases. Here, we characterized the expression and the functional role of NLRP7 in the placenta and investigated its involvement in the pathogenesis of FGR. We used primary trophoblasts and placental explants that were collected during early pregnancy, and established trophoblast-derived cell lines, human placental villi, and serum samples from early pregnancy (n = 38) and from FGR (n = 40) and age-matched controls (n = 32). Our results show that NLRP7 (i) is predominantly expressed in the trophoblasts during the hypoxic period of placental development and its expression is upregulated by hypoxia and (ii) increases trophoblast proliferation ([3H]-thymidine) and controls the precocious differentiation of trophoblasts towards syncytium (syncytin 1 and 2 and ß-hCG production and xCELLigence analysis) and towards invasive extravillous trophoblast (2D and 3D cultures). We have also demonstrated that NLRP7 inflammasome activation in trophoblast cells increases IL-1ß, but not IL-18 secretion. In relation to the FGR, we demonstrated that major components of NLRP7 inflammasome machinery are increased and that IL-1ß but not IL-18 circulating levels are increased in FGR. Altogether, our results identified NLRP7 as a critical placental factor and provided evidence for its deregulation in FGR. NLRP7 inflammasome is abundantly expressed by trophoblast cells. It is regulated by a key parameter of placental development, hypoxia. It controls trophoblast proliferation, migration, and invasion and exhibits anti-apoptotic role. NLRP7 machinery is deregulated in FGR pregnancies. KEY MESSAGES: NLRP7 inflammasome is abundantly expressed by trophoblast cells. It is regulated by a key parameter of placental development, hypoxia. It controls trophoblast proliferation, migration, and invasion and exhibits anti-apoptotic role. NLRP7 machinery is deregulated in FGR pregnancies.

The signaling axis atypical protein kinase C λ/ι-Satb2 mediates leukemic transformation of B-cell progenitors.

Epigenetically regulated transcriptional plasticity has been proposed as a mechanism of differentiation arrest and resistance to therapy. BCR-ABL leukemias result from leukemic stem cell/progenitor transformation and represent an opportunity to identify epigenetic progress contributing to lineage leukemogenesis. Primary human and murine BCR-ABL+ leukemic progenitors have increased activation of Cdc42 and the downstream atypical protein kinase C (aPKC). While the isoform aPKCζ behaves as a leukemic suppressor, aPKCλ/ι is critically required for oncogenic progenitor proliferation, survival, and B-cell differentiation arrest, but not for normal B-cell lineage differentiation. In vitro and in vivo B-cell transformation by BCR-ABL requires the downregulation of key genes in the B-cell differentiation program through an aPKC λ/ι-Erk dependent Etv5/Satb2 chromatin repressive signaling complex. Genetic or pharmacological targeting of aPKC impairs human oncogenic addicted leukemias. Therefore, the aPKCλ/ι-SATB2 signaling cascade is required for leukemic BCR-ABL+ B-cell progenitor transformation and is amenable to non-tyrosine kinase inhibition.

[Care pathway diversity of patients with multiple sclerosis between French regions]. / Diversité des prises en charge des patients atteints de sclérose en plaques entre régions françaises.

BACKGROUND: The aim of this study is to analyze and to compare data from 2015, focusing on hospital care for patients with multiple sclerosis from three French regions with different characteristics in terms of prevalence, size and number of multiple sclerosis competencies and resource centers. METHODS: All hospital admissions from the PMSI MCO 2015 database, with a principal or related diagnosis (PD-RD) of G35* ("multiple sclerosis") were extracted. We also extracted chemotherapy treatments administered in hospital, during admissions with a significant associated diagnosis (SAD) of G35*, if the PD or RD was coded Z512 ("non-tumor chemotherapy"). The analyzed regions corresponded to those of 2015, some of which have since merged. RESULTS: There were 95,359 hospital admissions for multiple sclerosis in France in 2015 among a total cohort of 21,102 patients, resulting in a total cost of € 54.1m. Patients with MS were managed mainly in the ambulatory setting, which accounted for 88.5 % of all admissions. The Rhône-Alpes region represented 7.6 % of national admissions for MS, 9.6 % of patients, and 14 % of inpatient days, contributing 10.4 % of the national cost of MS care. 58.4 % of stays were managed by the two main multiple sclerosis centers. The Nord-Pas-de-Calais region represented 9.8 % of national admissions, 10 % of patients, 6.6 % of inpatient days, and 9.1 % of the national cost. 29.8 % of stays were managed by the main multiple sclerosis center. The Centre region represented 2.7 % of stays, 2.8 % of patients, 3.1 % of inpatient days, and 2.8 % of the national cost. 28.4 % of stays were managed by the main multiple sclerosis center. CONCLUSION: This study highlights the diversity of multiple sclerosis hospital management and care between these three regions.

Hepoxilin analogs, potential new therapeutics in disease.

We have chemically synthesized several stable analogs of the naturally occurring hepoxilins, 12-LO products derived from arachidonic acid, which we found to have promising actions in a variety of test systems of disease. The analogs, PBTs, afford chemical and biological stability to the hepoxilin molecule. This article reviews some of our latest observations with the PBTs in the areas of inflammation (inhibition of the bleomycin-evoked lung fibrosis in mice in vivo), platelet aggregation (antagonism of the thromboxane receptor in human platelets in vitro) and thrombosis (inhibitors in vivo), and cancer (apoptosis of the human leukemia cell line, K562 in vitro and in vivo). The demonstration that the PBTs are active in vivo suggests that they can serve as a platform for their further development as novel therapeutics in disease.

[Two cases of polyarteritis nodosa with a good prognosis?]. / Deux périartérites noueuses de bon pronostic?

INTRODUCTION: Polyarteritis nodosa is a systemic necrotizing vasculitis that may become serious, even with no usual poor prognosis factors. EXEGESIS: We report two cases of polyarteritis nodosa with negative histology, starting only with an extensive necrosis of the extremities. The treatment, associating corticosteroids and, secondarily, immunosuppressors, did not prevent a bilateral half-leg amputation for the two patients. In the first case the disease stabilized, but in the second one, it worsened, leading to death within 2 years. CONCLUSION: This clinical aspect of the disease is unusual and should be identified because of its bad prognosis. It might benefit from a treatment from the outset associating corticosteroids and immunosuppressors, even with no usual bad prognosis factors.

The hepoxilin analog PBT-3 inhibits heparin-activated platelet aggregation evoked by ADP.

We have previously shown that PBT-3, a stable synthetic analog of hepoxilins, inhibits the aggregation of human platelets in vitro evoked by collagen through inhibition of thromboxane A(2) formation and action on the TP receptor. We now show that PBT-3 is capable of potently inhibiting the second phase of aggregation evoked by ADP in both washed human platelets and platelet-rich plasma (PRP), a phase associated with thromboxane formation. Aspirin blocks this second phase as well; so does the thromboxane receptor antagonist SQ 29,548. When ADP-evoked aggregation in PRP is activated by heparin through an enhancement of thromboxane formation, PBT-3, aspirin as well as SQ 29,548 block this activation through different mechanisms. These data confirm the inhibitory action of PBT-3 on aggregation of human platelets through inhibition of both thromboxane formation and blockade of thromboxane receptor action and suggest that this family of compounds may be useful in the treatment of thrombotic disorders in combination with heparin.

Improved high-performance liquid chromatographic method for the combined analysis of phospholipase, lipoxygenase and cyclooxygenase activities.

We report herein an improved method for the high-performance liquid chromatographic separation and analysis of eicosanoids formed during the stimulation of human platelets in vitro with collagen. Since the products of interest, excepting arachidonic acid, contain hydroxyl groups (one to several), our method involves the conversion of the hydroxyl groups into acetates (pyridine/acetic anhydride) after derivatization with anthryl diazomethane (ADAM) rendering the compounds with much decreased polarity for separation on a reversed-phase column. This procedure is superior to that involving ADAM esters only, i.e. with free hydroxyl groups, as it leads to the excellent separation of the desired compounds from each other and from extraneous peaks observed due to the ADAM reagent and sharpens the peak of thromboxane. We have successfully applied the method to investigate the formation of thromboxane B2 and 12-hydroxyheptadecatrienoic acid (HHT) (products of cyclooxygenase and thromboxane A2 synthase), 12-hydroxyeicosatetraenoic acid (12-HETE, a 12-lipoxygenase product) and arachidonic acid (AA, product of phospholipase A2) formed during the in vitro aggregation of human platelets induced by collagen. A correlation between the inhibition of aggregation by aspirin and thromboxane/HHT formation was observed. All four compounds can be chromatographed in a single run. We employed prostaglandin B1 (PGB1) as internal reference standard to quantify the products. The method is useful to investigate selectivity of drugs which may affect either or all of these enzyme pathways at the same time.

Novel platelet antiaggregating substances.

We describe herein a novel action of four stable analogs of the hepoxilins. These analogs inhibit to different degrees, the aggregation of washed human platelets evoked by collagen. One of the analogs, PBT-3, is particularly effective with an IC(50) = 8 x 10(-7) M. The other analogs are about 5-fold less active, but all analogs are about 500-fold more active than the native hepoxilins. The PBT analogs inhibit the collagen-enhanced formation of thromboxane A(2) and HHT but do not affect the formation of 12-HETE or the release of arachidonic acid except at doses higher than those needed to block platelet aggregation. These results demonstrate that these novel compounds may have potential for development into drugs in the treatment of thromboxane-mediated cardiovascular disease.

[Peri-aortic fibrosis: unusual case of jaundice]. / La fibrose péri-aortique: une cause rare d'ictère.

Periaortic fibrosis is defined as the development of aortic perianeuvrysmal fibrosis either resulting from a focal inflammatory reaction or a self-perpetuating process. Compression of neighboring organs is a possible complication. Bile duct obstruction is exceptional.

[Association between polymyositis and hepatitis C infection. Treatment-related difficulties]. / Association entre polymyosite et infection par le virus de l'hépatite C. Les difficultés du traitement.

INTRODUCTION: Chronic hepatitis C virus infection is often associated with various auto-immune disorders. We report four cases of an association between polymyositis and hepatitis C virus infection. The course and the difficulties of therapy are discussed. EXEGESIS: Among 510 consecutive patients infected by viral hepatitis C, we report four cases of polymyositis. Corticosteroids increased serum alanine aminotransferase levels in two cases, leading to severe liver injury in one patient. Worsening of polymyositis under interferon-alpha therapy was observed in one case. Clinical and biological stability were reported in another case. Aggravation of polymyositis with severe muscle weakness and dyspnea occurred in two patients after disruption of interferon-alpha treatment. Intravenous gamma globulins subsequently improved their condition, without biological worsening of viral hepatitis. CONCLUSION: These observations suggest an association between hepatitis C virus infection and polymyositis. Because corticosteroids can induce adverse effects in the liver, intravenous gamma globulins could be used for the treatment of this particular form of polymyositis.

[Cardiac amyloidosis: a restrictive cardiopathy with no single prognosis]. / L'amylose cardiaque: une cardiopathie restrictive au pronostic non univoque.

Cardiac amyloidosis is expressed as a restrictive myocardiopathy. Echocardiography suggests the diagnosis. There is a great difference between the prognosis of senile cardiac amyloidosis and "AL" amyloidosis. We illustrate this point with two case reports.

Formation of 14,15-hepoxilins of the A(3) and B(3) series through a 15-lipoxygenase and hydroperoxide isomerase present in garlic roots.

We report herein for the first time the formation by freshly grown garlic roots and the structural characterization of 14,15-epoxide positional analogs of the hepoxilins formed via the 15-lipoxygenase-induced oxygenation of arachidonic acid. These compounds are formed through the combined actions of a 15(S)-lipoxygenase and a hydroperoxyeicosatetraenoic acid (HPETE) isomerase. The compounds were formed when either arachidonic acid or 15-HPETE were used as substrates. Both the "A"-type and the "B"-type products are formed although the B-type compounds are formed in greater relative quantities. Chiral phase high performance liquid chromatography analysis confirmed the formation of hepoxilins from 15(S)- but not 15(R)-HPETE, indicating high stereoselectivity of the isomerase. Additionally, the lipoxygenase was of the 15(S)-type as only 15(S)-hydroxyeicosatetraenoic acid was formed when arachidonic acid was used as substrate. The structures of the products were confirmed by gas chromatography-mass spectrometry of the methyl ester trimethylsilyl ether derivatives as well as after characteristic epoxide ring opening catalytically with hydrogen leading to dihydroxy products. That 15(S)-lipoxygenase activity is of functional importance in garlic was shown by the inhibition of root growth by BW 755C, a dual cyclooxygenase/lipoxygenase inhibitor and nordihydroguaiaretic acid, a lipoxygenase inhibitor. Additional biological studies were carried out with the purified intact 14(S), 15(S)-hepoxilins, which were investigated for hepoxilin-like actions in causing the release of intracellular calcium in human neutrophils. The 14,15-hepoxilins dose-dependently caused a rise in cytosolic calcium, but their actions were 5-10-fold less active than 11(S), 12(S)-hepoxilins derived from 12(S)-HPETE. These studies provide evidence that 15(S)-lipoxygenase is functionally important to normal root growth and that HPETE isomerization into the hepoxilin-like structure may be ubiquitous; the hepoxilin-evoked release of calcium in human neutrophils, which is receptor-mediated, is sensitive to the location within the molecule of the hydroxyepoxide functionality.

Biochemical, hemodynamic, and vascular evidence concerning the free radical hypothesis of nitrate tolerance.

Tolerance to nitroglycerin (NTG) may be due to increased superoxide anion production. Hemodynamic parameters and biochemical markers of free radical production were measured in 20 healthy male subjects at baseline, 3 h after acute transdermal NTG (0.6 mg/h), and after 5 days of continuous therapy. Transdermal NTG therapy was continued, and 2 days later all subjects received 2 g of oral vitamin C, or placebo, in a double-blind, randomized, crossover fashion. In another study of eight male subjects, forearm plethysmography was used to assess the venous responses to sublingual NTG at baseline, after 5 days of sustained transdermal NTG therapy (0.6 mg/h), and after 2 g of oral vitamin C or placebo. Systolic blood pressure decreased in response to acute transdermal NTG therapy but returned to normal after sustained NTG therapy, indicating the development of tolerance. The venous volume responses to sublingual NTG were significantly diminished after sustained therapy with transdermal NTG. Plasma lipid peroxidation products, 8-iso-PGF2 alpha, and vitamin C were unchanged by acute and sustained therapy with transdermal NTG. Vitamin C failed to restore either the hemodynamic or venous effects of NTG. These results do not support the hypothesis that nitrate therapy and tolerance is associated with increased free radical production.

The GM2 activator protein, a novel inhibitor of platelet-activating factor.

The GM2 activator protein is required as a substrate-specific cofactor for beta-hexosaminidase A to hydrolyze GM2 ganglioside. The GM2 activator protein reversibly binds and solubilizes individual GM2 ganglioside molecules, making them available as substrate. Although GM2 ganglioside is the strongest binding ligand for the activator protein, it can also bind and transport between membranes a series of other glycolipids, even at neutral pH. Biosynthetic studies have shown that a large portion of newly synthesized GM2 activator molecules are not targeted to the lysosome, but are secreted and can then be recaptured by other cells through a carbohydrate independent mechanism. Thus, the GM2 activator protein may have other in vivo functions. We found that the GM2 activator protein can inhibit, through specific binding, the ability of platelet activating factor (PAF) to stimulate the release of intracellular Ca2+ pools by human neutrophils. PAF is a biologically potent phosphoacylglycerol. Inhibitors for PAF's role in the pathogenesis of inflammatory bowel disease and asthma have been sought as potential therapeutic agents. The inherent stability and protease resistance of the small, monomeric GM2 activator protein, coupled with the ability to produce large quantities of the functional protein in transformed bacteria, suggest it may serve as such an agent.

Hepoxilin signaling in intact human neutrophils: biphasic elevation of intracellular calcium by unesterified hepoxilin A3.

We have previously shown that the methyl ester of hepoxilin A3 causes a receptor-induced rise in intracellular calcium through the release from intracellular stores in suspended human neutrophils. The corresponding free acid was devoid of activity. We now report that the action of the free acid form of hepoxilin A3 is dependent on the type of vehicle used, i.e. it is active in releasing calcium when used in an ethanol vehicle but not in DMSO. The methyl ester is equally active in either vehicle. The pattern of calcium release between the free acid and the methyl ester is qualitatively different. Both compounds show a biphasic pattern, i.e. an initial rapid phase followed by a slow decline in calcium levels but never reaching pre-hepoxilin A3 baseline levels. The methyl ester appears slightly more potent in the initial phase of calcium release than the free acid (methyl = 188+/-14 S.D., free acid = 135+/-11 S.D. nM, P < 0.0005). Both compounds appear to reach the same calcium levels at the plateau of the second prolonged phase (methyl = 88+/-8 S.D., free acid = 107+/-15 S.D. nM, not significant). Lanthanum chloride (an inhibitor of calcium influx) interfered with the second phase of the curve causing calcium levels to return to normal pre-hepoxilin levels for both compounds. Addition of lanthanum chloride prior to the hepoxilin addition or carrying out the experiments in calcium-free medium, eliminated the second phase completely, with the calcium peak returning rapidly to normal baseline levels, suggesting that the second phase is due to calcium influx. Again the methyl ester is more active than the free acid (methyl, 189+/-12; free acid, 145+/-6 S.D. nM, P<0.005). Additional experiments with tritium-labelled methyl ester of hepoxilin A3 demonstrated that the compound is hydrolyzed into the free acid intracellularly. These experiments demonstrate that DMSO interacts with hepoxilin free acid, interfering with its entry into the cell while ethanol does not. Once inside the cell, hepoxilin interacts with its own receptor to release calcium rapidly from stores, but it also causes a more prolonged influx of calcium from the extracellular milieu.