Treatment and Imaging Modalities of Giant Coronary Aneurysms Resulting from Kawasaki Disease and Presenting as Acute Inferior Wall Myocardial Infarction.

Giant coronary aneurysms are late sequelae of Kawasaki disease (KD). We describe a 53-year-old patient who presented with acute myocardial infarction and proximal aneurysms of all three coronary arteries. Coronary angiography demonstrated the aneurysms, but CT angiography allowed accurate assessment of the real dimensions of the aneurysms and making the decision on the preferred method of revascularization. The patient underwent coronary bypass surgery and is asymptomatic at follow-up.

Structural maturation of cortical perineuronal nets and their perforating synapses revealed by superresolution imaging.

Parvalbumin-positive (PV+) interneurons play a pivotal role in orchestrating windows of experience-dependent brain plasticity during development. Critical period closure is marked by the condensation of a perineuronal net (PNN) tightly enwrapping subsets of PV+ neurons, both acting as a molecular brake on plasticity and maintaining mature PV+ cell signaling. As much of the molecular organization of PNNs exists at length scales near or below the diffraction limit of light microscopy, we developed a superresolution imaging and analysis platform to visualize the structural organization of PNNs and the synaptic inputs perforating them in primary visual cortex. We identified a structural trajectory of PNN maturation featuring a range of net structures, which was accompanied by an increase in Synaptotagmin-2 (Syt2) signals on PV+ cells suggestive of increased inhibitory input between PV+ neurons. The same structural trajectory was followed by PNNs both during normal development and under conditions of critical period delay by total sensory deprivation or critical period acceleration by deletion of MeCP2, the causative gene for Rett syndrome, despite shifted maturation levels under these perturbations. Notably, superresolution imaging further revealed a decrease in Syt2 signals alongside an increase in vesicular glutamate transporter-2 signals on PV+ cells in MeCP2-deficient animals, suggesting weaker recurrent inhibitory input between PV+ neurons and stronger thalamocortical excitatory inputs onto PV+ cells. These results imply a latent imbalanced circuit signature that might promote cortical silencing in Rett syndrome before the functional regression of vision.

Visualizing and discovering cellular structures with super-resolution microscopy.

Super-resolution microscopy has overcome a long-held resolution barrier-the diffraction limit-in light microscopy and enabled visualization of previously invisible molecular details in biological systems. Since their conception, super-resolution imaging methods have continually evolved and can now be used to image cellular structures in three dimensions, multiple colors, and living systems with nanometer-scale resolution. These methods have been applied to answer questions involving the organization, interaction, stoichiometry, and dynamics of individual molecular building blocks and their integration into functional machineries in cells and tissues. In this Review, we provide an overview of super-resolution methods, their state-of-the-art capabilities, and their constantly expanding applications to biology, with a focus on the latter. We will also describe the current technical challenges and future advances anticipated in super-resolution imaging.

[Intrauterine device and pelvic inflammatory disease: Myth or reality?] / Dispositif intra-utérin et infections génitales hautes : mythe ou réalité ?

INTRODUCTION: Intrauterine device (IUD) is a reliable contraceptive method that is long term reversible, and well tolerated. Numerous studies prove its efficiency and report rare complications that are attributed to it. However, its use is limited due to fear that it can cause a pelvic inflammatory disease (PID). This is based on historical data on infections related to the "Dalkon Shield", which was removed from the market in 1974. METHOD: The analyzed articles were extracted from PUBMED database between 2000 and 2016. In total, 22 studies were retained. A meta-analysis was not possible due to the methodological diversity among the selected articles contributing to this narrative review of the literature. RESULTS: After analysis, the following factors influence the risk of PID linked to IUDs: an advanced age and sexually transmitted infections. CONCLUSION: The risk of PID linked to IUDs is lower than 1%. This is explained by new models of IUD, better screening tests, more frequent follow-up of the patients and the improvement of care PID patients. In the light of our results, the threat of pelvic inflammatory disease should not hinder the use of IUDs.

Tim-3 expression represents dysfunctional tumor infiltrating T cells in renal cell carcinoma.

PURPOSE: Renal cell carcinoma (RCC) is the most common cancer of kidney. Evidences have shown that RCC is sensitive to various immunotherapies. Tim-3 plays a role in suppressing Th1-mediated immune responses. However, no study has yet examined the effect of Tim-3 on tumor infiltrating lymphocytes (TILs) in RCC. METHODS: We investigated the expression and function of Tim-3 on TIL CD4+ T cells and TIL CD8+ T cells from 30 RCC patients. RESULTS: Levels of Tim-3 were significantly increased on both TIL CD4+ T cells and TIL CD8+ T cells and were associated with higher stages of the cancer. Also, GATA-3 and interferon gamma (IFN-γ) were down-regulated, whereas T-bet was up-regulated in TIL Tim-3+ T cells, indicating that Tim-3 expression defined a population of dysfunctional TIL Th1/Tc1 cells. Mechanism analyses showed that TIL Tim-3-expressing CD8+ T cells exhibited impaired Stat5 and p38 signaling pathway. Blocking the Tim-3 pathway restored cell proliferation and increased IFN-γ production in TIL CD4+ and CD8+ T cells of RCC. CONCLUSIONS: These results suggest that Tim-3 may be used as a novel target for increasing immune responses in RCC tumor microenvironment.

[Contraception during the perimenopause: indications, security, and non contraceptive benefits]. / Contraception en période de périménopause: indication, sécurité et avantages non contraceptifs.

Although patients' fertility is diminished in the period of perimenopause, they still need efficient contraception. Thorough knowledge of the physiological changes occuring during this period of transition is essential in order to provide optimal care. Until the age of 50, no contraceptive method is specifically considered unsuitable due to age alone. The choice of contraceptive needs to be adapted to the patient, assessing the individual risk factors and favouring the potential non-contraceptive advantages of the method selected. Long-term contraceptive methods (e.g., the copper intrauterine device (IUD), the Mirena IUD or a subcutaneous implant) offer an excellent solution on both levels.

[An exploration of sexual desire and sexual activities of women with psychosis]. / Désir et pratiques sexueues chez les femm-es souffrant de psychose.

Most clinicians avoid discussing sexuality with patients with severe mental disorders. Sexual disturbances can be related to medication, to psychological issues such as self-stigma and anhedonia, and to the social context. We studied desire and sexual practices in women suffering from schizophrenia, in comparison with healthy women. Contrary to previous research, women with schizophrenia featured dyadic and individual desire similar to women of comparable age. Yet, only half of women with psychosis had sexual practice, either alone or with a partner. They were less satisfied with their activity, both in terms of function and psychological issues such as sexual self-esteem. This finding underscores the stigmatization these women suffer from, which prevents the opportunity of a possible improvement in this important interpersonal domain.

Mapping Synaptic Input Fields of Neurons with Super-Resolution Imaging.

As a basic functional unit in neural circuits, each neuron integrates input signals from hundreds to thousands of synapses. Knowledge of the synaptic input fields of individual neurons, including the identity, strength, and location of each synapse, is essential for understanding how neurons compute. Here, we developed a volumetric super-resolution reconstruction platform for large-volume imaging and automated segmentation of neurons and synapses with molecular identity information. We used this platform to map inhibitory synaptic input fields of On-Off direction-selective ganglion cells (On-Off DSGCs), which are important for computing visual motion direction in the mouse retina. The reconstructions of On-Off DSGCs showed a GABAergic, receptor subtype-specific input field for generating direction selective responses without significant glycinergic inputs for mediating monosynaptic crossover inhibition. These results demonstrate unique capabilities of this super-resolution platform for interrogating neural circuitry.

Regulatory B Cell Function Is Suppressed by Smoking and Obesity in H. pylori-Infected Subjects and Is Correlated with Elevated Risk of Gastric Cancer.

Helicobacter pylori infection occurs in more than half of the world's population and is the main cause for gastric cancer. A series of lifestyle and nutritional factors, such as tobacco smoking and obesity, have been found to elevate the risk for cancer development. In this study, we sought to determine the immunological aspects during H. pylori infection and gastric cancer development. We found that B cells from H. pylori-infected patients presented altered composition and function compared to uninfected patients. IL-10-expressing CD24+CD38+ B cells were upregulated in H. pylori-infected patients, contained potent regulatory activity in inhibiting T cell pro-inflammatory cytokine secretion, and responded directly to H. pylori antigen stimulation. Interestingly, in H. pylori-infected smoking subjects and obese subjects, the number of IL-10+ B cells and CD24+CD38+ B cells were reduced compared to H. pylori-infected asymptomatic subjects. Regulatory functions mediated by CD24+CD38+ B cells were also impaired. In addition, gastric cancer positive patients had reduced IL-10-producing B cell frequencies after H. pylori-stimulation. Altogether, these data suggest that in H. pylori-infection, CD24+CD38+ B cell is upregulated and plays a role in suppressing pro-inflammatory responses, possibly through IL-10 production, a feature that was not observed in smoking and obese patients.

Correlative stochastic optical reconstruction microscopy and electron microscopy.

Correlative fluorescence light microscopy and electron microscopy allows the imaging of spatial distributions of specific biomolecules in the context of cellular ultrastructure. Recent development of super-resolution fluorescence microscopy allows the location of molecules to be determined with nanometer-scale spatial resolution. However, correlative super-resolution fluorescence microscopy and electron microscopy (EM) still remains challenging because the optimal specimen preparation and imaging conditions for super-resolution fluorescence microscopy and EM are often not compatible. Here, we have developed several experiment protocols for correlative stochastic optical reconstruction microscopy (STORM) and EM methods, both for un-embedded samples by applying EM-specific sample preparations after STORM imaging and for embedded and sectioned samples by optimizing the fluorescence under EM fixation, staining and embedding conditions. We demonstrated these methods using a variety of cellular targets.

Effect of estetrol on Beta-Endorphin level in female rats.

INTRODUCTION: Estetrol (E4), a naturally occurring estrogen produced exclusively by human fetal liver, is currently being evaluated for potential use in contraception and menopausal care in humans. The present study was designed to profile E4 effects on the central nervous system, to assess the in vivo effects of E4 administration on Beta-Endorphin (ß-END) release in specific brain structures and to evaluate whether E4 has synergic or antagonistic effects on estradiol-mediated ß-END synthesis. EXPERIMENTAL: Intact female adult rats received different doses of E4 and ovariectomized (OVX) rats received different doses of E4 or E2V or combinations of both drugs. The concentrations of ß-END were assessed in the frontal and parietal cortex, hippocampus, hypothalamus, neurointermediate lobe, anterior pituitary and plasma. RESULTS: E4 at the dose of 1mg/kg/day did not alter ß-END content in most brain areas, as well as, plasma levels of intact animals E4 administered at a dose of 5mg/kg/day decreased ß-END content in the hippocampus, hypothalamus, and in the neurointermediate lobe, as well as, plasma levels, compared to intact animals receiving vehicle. E4 increased ß-END values in the frontal cortex, but not in the plasma, following the administration of 1mg/kg/day in OVX rats, whereas treatment with 5mg/kg/day in OVX rats induced a significant increase in ß-END levels in most brain areas and in the plasma. However, in the presence of estradiol, E4 showed an estrogen-antagonistic effect in selected brain structures at the dose of 5mg/kg/day and in plasma levels of ß-END at the dose of 1mg/kg/day and 5mg/kg/day. CONCLUSION: In OVX rats, E4 increases CNS and peripheral levels of ß-END, behaving as a weak estrogen-agonist. The antagonistic effect observed after combined estradiol and E4 administration further profiles E4 as a natural SERM.

Recipient body mass index and age interact to impact survival after heart transplantation.

Although recipient body mass index (BMI) and age are known risk factors for mortality after heart transplantation, how they interact to influence survival is unknown. Our study utilized the UNOS registry from 1997 to 2012 to define the interaction between BMI and age and its impact on survival after heart transplantation. Recipients were stratified by BMI: underweight (<18.5), normal weight (18.5-24.99), overweight (25-29.99), and either moderate (30-34.99), severe (35-39.99), or very severe (≥40) obesity. Recipients were secondarily stratified based on age: 18-40 (younger recipients), 40-65 (reference group), and ≥65 (advanced age recipients). Among younger recipients, being underweight was associated with improved adjusted survival (HR 0.902; p = 0.010) while higher mortality was seen in younger overweight recipients (HR 1.260; p = 0.005). However, no differences in adjusted survival were appreciated in underweight and overweight advanced age recipients. Obesity (BMI ≥ 30) was associated with increased adjusted mortality in normal age recipients (HR 1.152; p = 0.021) and even more so with young (HR 1.576; p < 0.001) and advanced age recipients (HR 1.292; p = 0.001). These results demonstrate that BMI and age interact to impact survival as age modifies BMI-mortality curves, particularly with younger and advanced age recipients.

Anticholinergic medications: an additional contributor to cognitive impairment in the heart failure population?

BACKGROUND/OBJECTIVES: Patients with congestive heart failure (CHF) have a high prevalence of cognitive impairment and the association is multifactorial. In general, the burden of anticholinergic drugs has consistently been shown to be a risk factor for cognitive impairment in the elderly. The aim of this study was to assess the cognitive burden of medications in patients with CHF. DESIGN: This was a cross-sectional, retrospective, single-center study. SETTING: The study was conducted in an outpatient setting. PARTICIPANTS: Patients who presented to a comprehensive heart failure clinic during a 1-month period were included. MEASUREMENTS: The primary outcomes of interest were mean anticholinergic cognitive burden (ACB) score of all medications and CHF medications (ACB-CHF), calculated based on the ACB Scoring Scale (ACB-SS). The ACB-CHF score was further dichotomized as 0 or 1 (low anticholinergic burden) versus 2 or 3 (high anticholinergic burden). RESULTS: A total of 182 patients were included. The mean ACB and ACB-CHF scores were 2.4 (range 0-13) and 1.0 (range 0-4), respectively, while 25.8 % of patients had an ACB-CHF score of 2 or 3. There was no association found between ejection fraction in patients with systolic heart failure and the ACB (p = 0.28) or ACB-CHF (p = 0.62) score. CONCLUSION: We conclude that patients with CHF have a substantial exposure to anticholinergic medications with adverse cognitive effects. This may be another important contributor to the increased prevalence of cognitive impairment in these patients.

Chronic tubal ectopic pregnancy: a rare but challenging diagnosis.

A 34-year-old woman without any medical history presented to our hospital emergency unit with a history of 4 days of progressively increasing pain in the left iliac fossa, fever and vaginal bleeding for the past 3 weeks. Urine pregnancy test and serum bhCG were negative. CT scan showed a left pelvic mass compatible with a tubo-ovarian abscess. After transfer to our gynaecology unit, transvaginal ultrasound revealed an empty uterus with a heterogeneous mass in the left adnexal area. We performed a laparoscopy, which revealed an enlarged left haematosalpinx with firm adhesions to the surrounding organs, but no abscess. A total left salpingectomy was undertaken and the histopathological examination revealed the presence of chorionic villi, suggesting the diagnosis of chronic ectopic tubal pregnancy. The postoperative course was uneventful.

Impact of donor age on survival after heart transplantation: an analysis of the United Network for Organ Sharing (UNOS) registry.

BACKGROUND: Data are limited regarding the influence of donor age on outcomes after heart transplantation. We sought to determine if advanced donor age is associated with differences in survival after heart transplantation and how this compares to waitlist survival. METHODS: All adult heart transplants from 2000 to 2012 were identified using the United Network for Organ Sharing database. Donors were stratified into four age groups: 18-39 (reference group), 40-49, 50-54, and 55 and above. Propensity scoring was used to compare status IA waitlist patients who did not undergo transplantation with IA recipients who received hearts from advanced age donors. The primary outcome of interest was recipient survival and this was analyzed with multivariate Cox regression analysis and the Kaplan-Meier method. RESULTS: A total of 22,960 adult heart transplant recipients were identified. Recipients of hearts from all three older donor groups had significantly increased risk of mortality (HR, 1.187-1.426, all p < 0.001) compared to recipients from donors age 18 to 39. Additionally, propensity-matched status IA patients managed medically without transplantation had significantly worse adjusted survival than status IA recipients who received hearts from older donors age ≥55 (HR, 1.362, p < 0.001). CONCLUSIONS: Compared to donors aged 18-39, age 40 and above is associated with worse adjusted recipient survival in heart transplantation. This survival difference becomes more pronounced as age increases to above 55. However, the survival rate among status IA patients who receive hearts from advanced age donors (≥55) is significantly better compared to similar status IA patients who are managed without transplantation.

Effects of a typical acute oral calcium load on arterial properties and endothelial function in healthy subjects.

BACKGROUND/OBJECTIVES: Often recommended, calcium supplements have been incriminated as increasing the risk of cardiovascular events, whereas dietary calcium has generally been exonerated. As a first step to address the vascular safety of such dietary measures at the clinical nutritionist toolbox, we sought to determine and compare the acute effects of a typical oral calcium load, provided either as a supplement or as food, on vascular parameters assessed noninvasively in healthy subjects. SUBJECTS/METHODS: In this acute, cross-over, random-order intervention, 11 young and healthy vitamin D-sufficient volunteers (8 women/3 men, 33±6.1 years, body mass index 22.6±2.3 kg/m(2)), ingested 600 mg of calcium twice, once as calcium citrate and the other time from dairy products. Biochemical, vascular and hemodynamic parameters, before and 2 h after each challenge, were compared. Arterial stiffness was studied by measuring pulse wave velocity, augmentation index and large (C1) and small (C2) arterial compliance. Endothelial function was assessed by flow-mediated dilation (FMD). RESULTS: Despite effective calcium loading accompanied by a significant 60% parathyroid hormone level reduction on both occasions, there were no clinically significant changes in the vascular parameters neither in comparison with baseline, nor between the studies. A decrease in heart rate with no change in cardiac output was noticed after the supplement. CONCLUSIONS: An effective calcium load has no clinically significant untoward effect on the vascular properties of young healthy subjects, regardless of its source. Additional studies should determine whether this holds true for chronic calcium supplementation, particularly in subjects with a priori vascular impairment.

Fertility after high-dose testosterone and intracytoplasmic sperm injection in a patient with androgen insensitivity syndrome with a previously unreported androgen receptor mutation.

We report on a case of a man with familial, X-linked, partial androgen insensitivity, in whom a new point mutation in the androgen receptor (AR) ligand-binding domain (causing a valine-to-alanine substitution at codon 686) was identified. High-dose prolonged testosterone therapy resulted in marked progression in patient's appearance and great improvement in sperm count and characteristics. In combination with intracytoplasmic microinjection, treatment resulted in fertility. This is believed to be the first report of such a case. This case supports high-dose testosterone therapeutic trial in this condition. Furthermore, it underscores the possibility of achieving fertility with current endocrine and assisted reproduction modalities, making some of these X-linked AR mutations paternally transmissible.