A French community-based intervention for parents of French-Canadian children with behavior problems: The EQUIPE program.

OBJECTIVES: Behavior problems are one of the most common reasons for seeking mental health services in pediatric populations. The objectives are to evaluate the effects of the EQUIPE program (Étude Québécoise d'Intervention pour les Parents d'Enfants avec des problèmes de comportement) and to analyze the impact of the severity of behavior problems and of parental characteristics. METHODS: This program was translated from the Community Parent Education Program. The effects of EQUIPE, as compared to a control group, were evaluated by using Child Behavior Checklist and Parent Stress Index questionnaires before (T0) and after the intervention program (T1), and at 6 (T2) and 12months (T3) follow-up visits. RESULTS: In total, 533 participants were enrolled in intervention (n=465) (with "severe" or "mild" subgroups according to CBCL-T score) and a control group (n=68). In the two groups, the results showed a statistically significant decrease in Child Behavior Checklist and Parent Stress Index total scores at T1, T2 and T3, with the exception of Child Behavior Checklist total scores in the control group at T2. In the intervention group Child Behavior Checklist total scores were significantly higher in the "severe"; which was not the case for Parent Stress Index total scores at T2 and T3. DISCUSSION: Socioeconomic characteristics, family details, parental medical history and the age of the children appeared to influence changes in Child Behavior Checklist and Parent Stress Index total scores. CONCLUSION: The EQUIPE program is an effective intervention for reducing behavior problems and parents' stress in a French-Canadian population.

Impact on testicular function of a single ablative activity of 3.7 GBq radioactive iodine for differentiated thyroid carcinoma.

STUDY QUESTION: What are the consequences of radioactive iodine (RAI) therapy for testicular function? SUMMARY ANSWER: A single activity of 3.7 GBq RAI for differentiated thyroid carcinoma (DTC) treatment in young men transiently altered Sertoli cell function and induced sperm chromosomal abnormalities. WHAT IS KNOWN ALREADY: Few studies, mainly retrospective, have reported the potential impacts of RAI on endocrine and exocrine testicular function. STUDY DESIGN, SIZE, DURATION: A longitudinal prospective multi-center study on testicular function performed in DTC patients before a single 131I ablative activity of 3.7 GBq (V0) and at 3 months (V3) and 13 months (V13) after treatment. PARTICIPANTS/MATERIALS, SETTING, METHODS: Forty male patients, aged 18-55 years, with DTC participated. Hormonal analysis included FSH, LH, testosterone and inhibin B serum levels at V0, V3 and V13. Furthermore, sperm parameters, DNA fragmentation and sperm chromosomal abnormalities were evaluated at each time points. The differences in all parameters, between V0-V3, V0-V13 and V3-V13, were analyzed, using a Wilcoxon test. MAIN RESULTS AND THE ROLE OF CHANCE: Prior to RAI administration, all patients had normal gonadal function. At V3, a statistically significant increase in FSH levels and a decrease in inhibin B levels were observed and sperm concentration, as well as the percentage of morphologically normal spermatozoa, were significantly decreased (P < 0.0001). These modifications were transient as both sperm concentration and normal morphology rate returned to baseline values at V13. However, at this later time point, FSH and inhibin B levels were still impacted by RAI administration but remained in the normal range. Although no DNA fragmentation was observed at V3 nor V13, our study revealed a statistically significant increase in the number of sperm chromosomal abnormalities both at V3 (P < 0.001) and V13 (P = 0.01). LIMITATIONS, REASONS FOR CAUTION: Among the 40 patients included in the study, only 24 had all the parameters available at all visits. WIDER IMPLICATIONS OF THE FINDINGS: Prospective studies with longer term follow up would be helpful to determine whether the chromosome abnormalities persist. These studies would be required before sperm banking should be suggested for all patients. However, sperm preservation for DTC patients who require cumulative radioiodine activities higher than 3.7 GBq should be proposed. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by the Programme Hospitalier de Recherche Clinique, AP-HP (No. P040419). The authors report no conflict of interest in this work. TRIAL REGISTRATION NUMBER: NCT01150318.

Differences between inflammatory and catabolic mediators of peri-implantitis and periodontitis lesions following initial mechanical therapy: An exploratory study.

BACKGROUND AND OBJECTIVE: The aim of this study was to analyze the differences in inflammatory and catabolic mediators expressed in peri-implantitis compared to periodontitis lesions after non-surgical therapy. Peri-implantitis is associated with a faster rate of bone loss when compared with periodontitis, and peri-implant non-surgical therapy is ineffective to cure peri-implantitis. This may be due to persistent inflammation in peri-implantitis tissues after initial mechanical treatment. MATERIAL AND METHODS: Eleven patients with peri-implantitis and 10 with severe chronic periodontitis received non-surgical therapy. They were included at re-evaluation (8 weeks) if they presented pocket depth ≥6 mm with bleeding on probing, and the indication for open flap debridement surgery. Connective tissues were harvested during surgery from diseased sites. Healthy gingiva were harvested during third molar extraction in a third group of healthy patients (n=10). Explants were incubated for 24 hours in media culture and the release of cytokines, chemokines, growth factors, osteoprotegerin, receptor activator of nuclear factor kappa-B ligand (RANKL), matrix metalloproteinase and tissue inhibitors of matrix metalloproteinase (TIMP) in the conditioned media was analyzed by an exploratory multiplex immunoassay. When difference was found in the conditioned media, an immunohistochemistry was performed to compare expression in the tissues. RESULTS: Connective tissues from non-stabilized peri-implantitis exhibited a distinct cytokine profile compared to periodontitis lesions that did not respond to initial therapy. Indeed, TIMP-2 was significantly increased in media from peri-implantitis (P≤.05). In addition, the in situ expression of TIMP-2, interleukin-10 and RANKL was also significantly increased in peri-implantitis tissues (P≤.05). However, the ratio of RANKL/osteoprotegerin-positive cells did not vary (P≥.05). CONCLUSION: This study suggests that peri-implantitis and periodontitis connective tissues exhibit differences in response to non-surgical treatment, which may contribute to a different pattern of disease evolution.

Selective progesterone receptor modulators: current applications and perspectives.

Selective progesterone receptor modulators (SPRMs) are steroid progesterone receptor ligands able to induce agonistic or antagonistic activities. Mifepristone, the class leader, was primarily used for pregnancy termination from the 1980s. Emergency contraception with extended activity was the second major development 30 years later, with mifepristone in some countries and ulipristal acetate world-wide. More recently, ulipristal acetate was released for the treatment of myoma-related uterine bleeding. In addition to a very rapid cessation of bleeding, SPRMs allow a decrease in myoma volume, as do gonadotropin releasing hormone analogs. However, estradiol secretion is not blunted by SPRMs. This offers new alternatives for myoma treatment, especially in women close to menopause. In conclusion, use of SPRMs has allowed significant progress in emergency contraception and treatment of myoma-related symptoms. Numerous future perspectives in women's health care are currently under evaluation.

New lithium metal polymer solid state battery for an ultrahigh energy: nano C-LiFePO4 versus nano Li1.2V3O8.

Novel lithium metal polymer solid state batteries with nano C-LiFePO4 and nano Li1.2V3O8 counter-electrodes (average particle size 200 nm) were studied for the first time by in situ SEM and impedance during cycling. The kinetics of Li-motion during cycling is analyzed self-consistently together with the electrochemical properties. We show that the cycling life of the nano Li1.2V3O8 is limited by the dissolution of the vanadium in the electrolyte, which explains the choice of nano C-LiFePO4 (1300 cycles at 100% DOD): with this olivine, no dissolution is observed. In combination with lithium metal, at high loading and with a stable SEI an ultrahigh energy density battery was thus newly developed in our laboratory.

Discovery and development of therapeutic aptamers.

Therapeutic aptamers are single-stranded structured oligonucleotides that bind to protein targets with high affinity and specificity and modulate protein function. Aptamers are discovered by iterative rounds of selection for binding to the target protein, partitioning, and amplification of binding clones from a diverse starting library (SELEX). Postselection optimization of clones using chemical modification is directed at improving affinity, potency, and metabolic stability. A key attribute of therapeutic aptamers is the ability to tailor the pharmacokinetic profile by modulating the degree of metabolic stability and modulating renal clearance and rate of distribution by conjugation to various sizes of polyethylene glycol (PEG). In toxicology studies, therapeutic aptamers have been largely devoid of the previously reported oligonucleotide class effects of immune stimulation, complement activation, and anticoagulation; and the principal finding is the histologically visible accumulation of drug-related material in mononuclear phagocytes, a finding generally not considered an adverse effect. Good safety margins between the pharmacologically effective dose and toxicologically established no-adverse-effect levels have been observed consistently. There are presently seven aptamers either on the market or in clinical trials, but there is still much to be demonstrated in terms of chronic systemic use to fully realize the potential of this promising new class of drugs.

Randomized placebo- and active-controlled study of desvenlafaxine for menopausal vasomotor symptoms.

OBJECTIVE: To evaluate the efficacy and safety of desvenlafaxine (administered as desvenlafaxine succinate) vs. tibolone and placebo for menopausal vasomotor symptoms and the incidence of uterine bleeding. METHODS: This 12-week, double-blind, randomized, controlled trial was conducted at 35 sites in Europe, two sites in South Africa, and one site in Mexico. Postmenopausal women with ≥50 moderate or severe hot flushes per week (n = 485) were randomized to desvenlafaxine 100 mg/day, tibolone 2.5 mg/day, or placebo. Reduction in the average daily number of moderate and severe hot flushes at weeks 4 and 12 (primary endpoint) was evaluated using analysis of covariance. Safety assessments included incidence of uterine bleeding, adverse events, laboratory values, and vital signs. RESULTS: At week 12, no statistically significant difference was observed in reduction of the average daily number of moderate and severe hot flushes for desvenlafaxine (-5.78) vs. placebo (-5.82; p = 0.921), although time to 50% reduction was significantly less than placebo (13 vs. 26 days, p = 0.006). Hot flush reduction with tibolone (-8.21) was significantly greater than placebo (p < 0.001). Nausea was the most common adverse event with desvenlafaxine, was generally mild to moderate, and resolved within the first 2 weeks. Significantly more subjects experienced bleeding with tibolone (23%) vs. desvenlafaxine (12%; p < 0.024) or placebo (9%; p < 0.001). CONCLUSIONS: Desvenlafaxine did not separate from placebo in reducing the number of moderate to severe hot flushes at week 12, although it did allow women to achieve 50% reduction sooner than placebo. Tibolone did separate from placebo, but with smaller than expected effect. The placebo effect was high (57%). Adverse drug reactions were consistent with the known safety profile of desvenlafaxine, and significantly more women who received tibolone experienced episodes of bleeding compared with women who received desvenlafaxine or placebo.

[Revision of of the subfamily of Metaracoelophryinae de Puytorac 1972 (Oligohymenophora: Hoplytophryida: Hoplytophryidae), astome ciliates of the digestive tract of Oligochaeta worms of Africa: description of five new species]. / Révision de la sous-famille des Metaracoelophryinae de Puytorac 1972 (Oligohymenophora : Hoplytophryida : Hoplytophryidae), ciliés astomes du tube digestif d'oligochètes terricoles d'Afrique : description de cinq espèces nouvelles.

Five new species belonging to the astome ciliates, living in the digestive tract of Oligochaeta worms belonging to the genus Alma from Cameroon, have been described. The techniques used are: vital staining, staining of the nucleus with Diamidino Phenyl Indol (DAPI), scanning electron microscopy and silver staining method (Fernandez Galiano, 1976, 1994). This work confirms the presence of the genus Paracoelophrya and Dicoelophrya in the digestive track of the oligochaete Alma from Gabon and Cameroon; it helps to understand the general taxonomy of this Metaracoelophryinae subfamily. Moreover, the homogeneity of this group is confirmed and the phylogenetic relationship inside the Hoplitophryida order need more studies to be solved.

Oral Condition and Incident Coronary Heart Disease: A Clustering Analysis.

Poor oral health has been linked to coronary heart disease (CHD). Clustering clinical oral conditions routinely recorded in adults may identify their CHD risk profile. Participants from the Paris Prospective Study 3 received, between 2008 and 2012, a baseline routine full-mouth clinical examination and an extensive physical examination and were thereafter followed up every 2 y until September 2020. Three axes defined oral health conditions: 1) healthy, missing, filled, and decayed teeth; 2) masticatory capacity denoted by functional masticatory units; and 3) gingival inflammation and dental plaque. Hierarchical cluster analysis was performed with multivariate Cox proportional hazards regression models and adjusted for age, sex, smoking, body mass index, education, deprivation (EPICES score; Evaluation of Deprivation and Inequalities in Health Examination Centres), hypertension, type 2 diabetes, LDL and HDL serum cholesterol (low- and high-density lipoprotein), triglycerides, lipid-lowering medications, NT-proBNP and IL-6 serum level. A sample of 5,294 participants (age, 50 to 75 y; 37.10% women) were included in the study. Cluster analysis identified 3,688 (69.66%) participants with optimal oral health and preserved masticatory capacity (cluster 1), 1,356 (25.61%) with moderate oral health and moderately impaired masticatory capacity (cluster 2), and 250 (4.72%) with poor oral health and severely impaired masticatory capacity (cluster 3). After a median follow-up of 8.32 y (interquartile range, 8.00 to 10.05), 128 nonfatal incident CHD events occurred. As compared with cluster 1, the risk of CHD progressively increased from cluster 2 (hazard ratio, 1.45; 95% CI, 0.98 to 2.15) to cluster 3 (hazard ratio, 2.47; 95% CI, 1.34 to 4.57; P < 0.05 for trend). To conclude, middle-aged individuals with poor oral health and severely impaired masticatory capacity have more than twice the risk of incident CHD than those with optimal oral health and preserved masticatory capacity (ClinicalTrials.gov NCT00741728).

Quality assessment of induced spermatogenesis in hypogonadotrophic hypogonadic men treated with gonadotrophins.

Hypogonadotrophic hypogonadism (HH) is characterized by deficient gonadotrophin secretion, resulting from pituitary or hypothalamic defects. In order to induce spermatogenesis, HH patients are treated with commercially available gonadotrophins. As far as is known, quality and genetic integrity of induced sperm cells have never been investigated, although they represent an important issue, since the ultimate goal of this treatment is to have competent spermatozoa in order to achieve paternity. In order to evaluate the nuclear integrity of induced sperm cells, sperm samples from treated HH patients were compared with sperm samples from normospermic control donors. Sperm cells were analysed by fluorescence in-situ hybridization, using probes specific for chromosomes 13, 21, 18, X and Y, and by TdT (terminal deoxynucleotidyl transferase)-mediated dUDP nick-end labelling assay. Results showed that the rate of aneuploid and diploid sperm cells in patients was not statistically different from controls and that the rate of sperm cells with fragmented DNA was within the normal values. Spermatozoa obtained by gonadotrophin treatment in HH patients are likely to have a balanced chromosomal content and a normal DNA integrity but this conclusion needs to be confirmed by further studies dealing with a greater number of patients.

Interleukin 12-mediated prevention of spontaneous mammary adenocarcinomas in two lines of Her-2/neu transgenic mice.

The ability of interleukin (IL)-12 to prevent tumors when administered to individuals with a genetic risk of cancer was studied in two lines of transgenic mice expressing rat HER-2/neu oncogene in the mammary gland. Female BALB/c (H-2(d)) mice carrying the activated HER-2/ neu oncogene show no morphological abnormalities of the mammary gland until 3 wk of age. They then progress through atypical hyperplasia to in situ lobular carcinoma and at 33 wk of age all 10 mammary glands display invasive carcinomas. Adult FVB mice (H-2(q)) carrying the HER-2/neu protooncogene develop mammary carcinomas with a longer latency (38-49 wk) and a lower multiplicity (mean of 2.6 tumors/mice). Treatment with IL-12 (5 daily intraperitoneal injections, 1 wk on, 3 wk off; the first course with 50 ng IL-12/day, the second with 100 ng IL-12/day) begun at 2 wk of age in BALB/c mice and at 21 wk of age in FVB mice markedly delayed tumor onset and reduced tumor multiplicity. Analogous results were obtained in immunocompetent and permanently CD8(+) T lymphocyte-depleted mice. In both transgenic lines, tumor inhibition was associated with mammary infiltration of reactive cells, production of cytokines and inducible nitric oxide synthase, and reduction in microvessel number, in combination with a high degree of hemorrhagic necrosis.

Tooth extraction decision model in periodontitis patients.

OBJECTIVE: The purpose of this study was to build, around several types of input data, a decision analysis model for dental extraction strategy in periodontitis patients. MATERIALS AND METHODS: The decision analysis was based on the following scenario: a fictitious adult chronic periodontitis patient with no chief complaint, being referred to make a decision of extraction on one single tooth presenting a periodontal defect that may affect the decision-making process. A decision tree was used to identify the treatment options within the next 5 years. Scientific evidences were based on probabilities given by a literature analysis using a systematic approach. Clinical expertize was based on subjective utilities (SUs) assigned by an experts' panel. Expected utilities (EUs) were used to rank the following options: no treatment (EU(1)) or periodontal treatment (EU(2)); extraction followed by a tooth-supported fixed partial denture - FPD - (EU(3)) or an implant-supported single crown - ISC - (EU(4)). RESULTS: The robustness analysis calculation indicates that the probability of tooth survival needed to be equal to 0.78 in order that the passive option becomes optimal. However, EU(1) was impossible to calculate due to the lack of available probabilities. The EU intervals were 79-96, 86-89 and 94-95 for EU(2), EU(3) and EU(4), respectively. Consequently, the FPD option is dominated by the ISC option, and it is not possible to conclude to a difference between the periodontal and the ISC therapy. CONCLUSIONS: Within the limits of this model, tooth extraction followed by FPD is the worst strategy compared with ISC or periodontal therapies.

[Morphological variations of the nuclear apparatus of astome ciliates Almophrya bivacuolata and A. maediovacuolata (protozoa: ciliophora) endocommensal of terricolous oligochaetes in Cameroon]. / Variations morphologiques de l'appareil nucléaire chez les ciliés Astomes Almophrya bivacuolata et A. mediovacuolata (protozoa: ciliophora) endocommensaux d'oligochites terricoles du Cameroun.

The silver impregnation supplemented by DAPI and Feulgen nuclear coloration enabled us to study the morphological variations of the nuclear apparatus of two species of endocommensal Astome ciliates, Almophrya bivacuoloata (de Puytorac & Dragesco, 1968) and A. mediovocuolata (Ngassam, 1983). We highlighted important digitations and the presence of dark bands in the structure of the "H" macronucleus of the small cellular types as well as the presence of intermediate forms between "H" and "X" in these two species.

Masticatory Capacity and Mortality: The Preventive and Clinical Investigation Center (IPC) Cohort Study.

Poor oral health (OH) has been associated with mortality, but the association between OH components and mortality remains imprecise. The present observational study aimed to investigate if there is an association between oral masticatory efficiency and cardiovascular (CV) mortality in a large French subject cohort. The study was based on a cohort of 85,830 subjects aged between 16 and 94 y at recruitment. The follow-up extended from 2001 to 2014 and the mean follow-up was 8.06 ± 2.73 y. The number of deaths totaled 1,670. Full-mouth examinations were performed. Dental plaque, dental calculus, gingival inflammation, missing teeth, and masticatory units were recorded. Masticatory units represent the number of natural or prosthetic opposing premolars and molar pairs and can be considered an accurate indicator for masticatory efficiency. Causes of death were ascertained from death certificates. Cox regression analyses were used to calculate hazard ratios (HRs). In the fully adjusted model, the number of masticatory units <5 is associated with an HR of 1.72 (95% confidence interval [CI], 1.54 to 1.91) for all-cause mortality, HR of 1.41 (95% CI, 1.01 to 1.99) for CV mortality, HR of 1.76 (95% CI, 1.44 to 2.15) for cancer mortality, and HR of 1.85 (95% CI, 1.55 to 2.20) for non-CV and noncancer mortality. Significant statistical associations with the other oral variables were also found for all-cause mortality, cancer mortality, and non-CV and noncancer mortality in the adjusted models. Our study indicates that after full adjustment, all oral parameters are associated with all-cause, cancer, and non-CV and noncancer mortality. However, the low number of masticatory units is associated with an increased risk of CV mortality. We highlight the association of masticatory units and CV mortality.

A 6.78-MHz Robust WPT System with Inductive Link Bandwidth Extended for cm-Sized Implantable Medical Devices.

This paper presents a new technique to design a robust inductive link for Wireless Power Transmission (WPT) to centimeter-sized (cm-sized) Implantable Medical Devices (IMDs). The consequence of this methodology is the bandwidth extension of utilized link to maximize both Power Delivered to Load (PDL) and Power Transfer Efficiency (PTE). Design, circuit implementation, and In-vivo validation experimental results are reported. Different conditions of tests, including three misalignment experiments, are performed with the proposed WPT system to prove the concept of a robust inductive link. The geometry of the Transmitter (Tx) and Receiver (Rx) coils are considered as well as the operating frequency (fp) of the WPT system. The Tx and Rx coils are crafted in a circulated shape with the diameters of 5 and 2.5 cm, respectively. Achieved PTE and PDL are in the range of 0.82%-25.7% and 44.4mW-720mW, respectively. The distance between Tx and Rx coils varies in the range of 1.5 to 4cm.

Periodontitis and Cardiovascular Diseases. Consensus Report.

Background: In Europe cardiovascular disease (CVD) is responsible for 3.9 million deaths (45% of deaths), being ischaemic heart disease, stroke, hypertension (leading to heart failure) the major cause of these CVD related deaths. Periodontitis is also a chronic non-communicable disease (NCD) with a high prevalence, being severe periodontitis, affecting 11.2% of the world's population, the sixth most common human disease. Material and Methods: There is now a significant body of evidence to support independent associations between severe periodontitis and several NCDs, in particular CVD. In 2012 a joint workshop was held between the European Federation of Periodontology (EFP) and the American Academy of Periodontology to review the literature relating periodontitis and systemic diseases, including CVD. In the last five years important new scientific information has emerged providing important emerging evidence to support these associations. Results and Conclusions: The present review reports the proceedings of the workshop jointly organised by the EFP and the World Heart Federation (WHF), which has updated the existing epidemiological evidence for significant associations between periodontitis and CVD, the mechanistic links and the impact of periodontal therapy on cardiovascular and surrogate outcomes. This review has also focused on the potential risk and complications of periodontal therapy in patients on anti thrombotic therapy and has made recommendations for dentists, physicians and for patients visiting both the dental and medical practices.

The localization of protein carboxyl-methylase in sperm tails.

Protein carboxyl-methylase (PCM), an enzyme known to be involved in exocytotic secretion and chemotaxis, has been studied in rat and rabbit spermatozoa. PCM activity and its substrate methyl acceptor protein(s) (MAP) were demonstrated in the supernate after solubilization of the sperm cell membrane by detergent (Triton X-100). A protein methylesterase that hydrolyzes methyl ester bonds created by PCM was demonstrated in rabbit but not in rat spermatozoa. This enzyme was not solubilized by nonionic detergent. The specific activities of PCM in rat spermatozoa from caput and cauda epididymis were similar and lower than that found in testis. By contrast, MAP substrates were low in testis and increased in parallel with sperm maturation in the epididymis. Multiple MAP were demonstrated in spermatozoa by polyacrylamide gel electrophoresis. The pattern of these proteins was similar in spermatozoa from different portions of the reproductive tract. Fractionation of heads and tails of rat spermatozoa on sucrose gradients indicated that PCM was found exclusively in the tail fraction, whereas MAP was detected both in head and tail fractions. The presence of all the components of the protein carboxyl-methylation system in spermatozoa and the localization of PCM and some of its substrates in the sperm tail are consistent with their involvement in sperm cell motility.

Cost-effectiveness modeling of dental implant vs. bridge.

AIMS: We assess the cost-effectiveness of dental implant first-line strategy vs. fixed partial denture strategy in patients suffering from one single missing tooth. MATERIALS AND METHODS: The model used a simulation decision framework over a 20-year period. Potential treatment switches can occur every 5 years. Transition probabilities come from literature, epidemiological reports or expert opinions. They have been programmed using specific distribution ranges to simulate the patients' and practice variability, and to take into account parameter uncertainty. Direct medical costs have been assessed according to a cost survey. Probabilistic sensitivity analyses were conducted using 5000 Monte-Carlo simulations, generating confidence intervals of model outcomes. RESULTS: We found that mean cost-effectiveness of the bridge strategy is higher than the implant strategy. CONCLUSION: Implant as the first-line strategy appears to be the 'dominant' strategy, considering the lower overall costs and the higher success rate.

Multivisceral Resection for Locally Advanced Gastric and Gastroesophageal Junction Cancers-11-Year Experience at a High-Volume North American Center.

INTRODUCTION: The oncologic benefit of multivisceral en bloc resections for T4 gastroesophageal tumors has been questioned, given the increased morbidity associated. We thus sought to investigate the surgical and oncologic outcomes of curative-intent en bloc multivisceral resections for T4 gastroesophageal carcinomas. METHODS: Between 2005 and 2016, 35 of the 525 patients who had gastric or EGJ carcinomas underwent curative-intent multivisceral resections for direct invasion or adhesion to adjacent organs. RESULTS: Postoperative complications occurred in 16(46%), 10 of which were Clavien-Dindo ≥ 3 (29%). Ninety-day mortality was 3%. The R0 resection rate was 94% (33). Direct organ invasion (pT4b) was confirmed on pathological analysis in 14 (40%) and did not affect survival. The majority (28, 80%) had lymph node involvement with a high nodal disease burden and was associated with decreased survival. Overall 5-year survival rate was 34%, and the vast majority of recurrences were distant/peritoneal (81%). On multivariate analysis, positive lymph nodes (H.R. 21.2; 95%CI 2.34-192) and R1 resection (H.R. 5.6; 95%CI 1.02-30.9) were predictors of survival. CONCLUSION: Multivisceral resections for T4 gastric and GEJ adenocarcinomas, in combination with effective systemic therapy, result in prolonged long-term survival with acceptable morbidity. Complete resection to negative margins should remain a mainstay of curative-intent treatment in carefully selected patients.

Persistence of an intact endometrial matrix and vessels structure in women exposed to VA-2914, a selective progesterone receptor modulator.

BACKGROUND: VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity that induces amenorrhea, whereas progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by an increase in naked vessel size and density. OBJECTIVE: Our objective was to quantify the effects of VA-2914 on endometrial vascularization, fibrillar matrix, and vascular endothelial growth factor (VEGF)-A expression in endometrial biopsies from 41 women before and after 12 wk daily treatment with a placebo, or 2.5, 5, or 10 mg VA-2914. METHODS: Collagen fibrillar network was stained by silver impregnation. Vessel area, density, and structure were quantified with a computer-assisted image analysis system after double immunostaining using an anti-von Willebrand factor (endothelial cells) and an anti-alpha smooth muscle actin (vascular smooth muscle cells) marker antibody. VEGF-A mRNAs were quantified by RT-PCR and localized by immunohistochemistry. RESULTS: The endometrial vessels, collagen network, and mRNA levels of VEGF-A were identical during the luteal phase at baseline and in VA-2914 treated women. VEGF-A distribution was unchanged. CONCLUSIONS: VA-2914 does not alter the endometrial matrix and cells, and does not modify the endometrial vessel morphology as compared with baseline biopsies.