Breast cancer time to treatment in Martinique: predictive factors and effect on survival.

BACKGROUND: Martinique is the second French Region with the lowest physician-to-population ratio, which may affect waiting times for access to care. OBJECTIVES: To assess (i) factors influencing waiting times from diagnosis to cancer-related treatments in breast cancer women in Martinique, and (ii) the impact of waiting times on patients' survival. STUDY DESIGN: Retrospective observational study. METHODS: Data on women diagnosed with invasive breast cancer between 1st January 2013 and 31st December 2017 and initially treated by surgery were extracted from the Martinique population-based registry. A cox model was performed to find predictive factors for waiting times. A log-rank test was used to compare time-to-treatment between groups. RESULTS: In total, 713 patients were included (mean age: 58 ± 13). Median time from diagnosis to surgery was 40 [25-60] days. Age at diagnosis was found to predict variations in waiting times. Patients > 75 had longer waiting time to surgery than those < 40 or [40-50] (P = 0.016 and P < 0.001, respectively). Women with a time-to-treatment ≥ 4 months had a significant lower survival (P < 0.01). CONCLUSIONS: Specific interventions are needed to improve waiting time from diagnosis to initial treatment, as they are longer than recommended and affect survival time.

Prevalence and associated risk factors for Kaposi's sarcoma among HIV-positive patients in a referral hospital in Northern Tanzania: a retrospective hospital-based study.

BACKGROUND: Kaposi's sarcoma (KS) is a multifocal angioproliferative tumor involving blood and lymphatic vessels, caused by Human Herpes Virus-8 (HHV-8). KS is an important AIDS-defining tumor with high prevalence in Sub-Saharan Africa, including Tanzania which has high HIV and HHV-8 sero-prevalence. It is critically important to monitor the prevalence of AIDS-defining tumors, such as KS, in the age of HIV/AIDS. We studied the prevalence of KS and associated risk factors among HIV-positive patients at Kilimanjaro Christian Medical Centre (KCMC), a referral hospital in northern Tanzania, over the period from January 2012 to December 2015. METHODS: This was a retrospective hospital-based cross-sectional study to determine the prevalence of KS among HIV/AIDS patients between 2012 and 2015. The study included 1100 HIV patients' data which were collected at the Infectious Disease Clinic (IDC) from patients' files. Stata version 13 (StataCorp LP, Texas 77,845 USA) was used for all statistical analyses. The prevalence of KS was calculated across levels of a number of categorical variables. Logistic regression was performed to determine relative risk of KS for all characteristics. We included all variables with p-values ≤10% in the multivariate analysis, including ART use, as this is considered to have an influence on KS. In the multivariate analysis, statistical significance was established based on a two-tailed p-value ≤5%. All patients' notes were kept confidential as per the Helsinki declaration. RESULTS: Our results revealed a 4.6% prevalence of KS at KCMC hospital, between January 2012 and December 2015, 51(4.6%) patients were diagnosed with KS out of 1100 HIV-positive patients. The study further revealed that KS in HIV patients was most associated with low CD4 cell count (less than or equal to 200 cells/µl). Moreover, women were more likely than men to diagnosed with KS, with higher odds significantly associated with KS (OR 0.42, p < 0.009). Increased age, above 35 years, among the HIV seropositive patients was significantly associated with KS (OR 25.67, p < 0.007). HIV patients who were none smokers were more likely to suffer from KS compared to HIV smokers (OR 0.41, p < 0.010). CONCLUSION: KS remains a common malignant vascular tumor commonly associated with HIV/AIDS in Tanzania. Our study highlights the need for continued efforts to combat HIV, as well as associated diseases such as KS. Continued availability of ART (Anti-Retroviral Therapy) to HIV/AIDS patients, and test reagents for CD4 cell count and viral load determination are important measures to alleviate the suffering of these patients. Furthermore, studies to gather more evidence on ART resistance are highly needed to guide treatment choices.

Teenagers and young adults with cancer in Europe: from national programmes to a European integrated coordinated project.

Over 14 000 patients aged 15-24 are estimated to be diagnosed with cancer in the European Union (EU) each year. Teenagers and young adults (TYA) often fall down gaps between children's and adults cancer services. The specific challenges of providing optimal care to them are described, but we present a summary of recent progress. Progress to overcome these challenges is happening at different rates across Europe. We summarise the European national projects in this field but more recently we have seen the beginnings of European coordination. Within the EU 7th Funding Programme (FP7) European Network for Cancer Research in Children and Adolescents programme (ENCCA), a specific European Network for Teenagers and Young Adults with Cancer has held a series of scientific meetings, including professionals, patients and caregivers. This group has proposed unanswered research questions and agreed key features of a high-quality service that can improve outcomes for TYA with cancer, including the primacy of collaboration between adult and paediatric services to eliminate the gap in the management of TYA with cancer.

Spore traps network: a new tool for predicting epidemics of wheat yellow rust.

A network of Burkard 7-day spore-recording traps was set up in the Walloon Region in Belgium to monitor the airborne inoculum of wheat pathogens. The relationship between the airborne inoculum of Puccinia striiformis f.sp. tritici, the causal agent of stripe rust, and the disease incidence on plants in untreated plots located near each spore traps was studied during the 2008-2009 season. The presence of airborne inoculum was tested in four locations on tapes collected from the Burkard spore traps from 1 April to 14 June 2009. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted. P. striiformis f.sp. tritici was quantified by real-time polymerase chain reaction (PCR) assay using specific primers and SYBRGreen. The airborne inoculum of P. striiformis was first detected between 7 and 13 April 2009, depending on the location in the Walloon Region. The first symptoms of stripe rust were observed in the fields between 15 May and 2 June 2009. The onset of the disease symptoms was always preceded by a higher peak of airborne inoculum about 15 days earlier. When P. striiformis f.sp. tritici was detected, the daily quantities of spores, collected from a volume of air of 14.4 m3, fluctuated between 0.23 and 154.66. This study shows that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of P. striiformis in order to understand and predict stripe rust outbreaks.

MicroRNA-206 expression levels correlate with clinical behaviour of rhabdomyosarcomas.

BACKGROUND: Rhabdomyosarcomas (RMSs) are primarily paediatric sarcomas that resemble developing skeletal muscle. Our aim was to determine the effects of microRNAs (miRNA) that have been implicated in muscle development on the clinical behaviour of RMSs. METHODS: Expression levels of miR-1, miR-206, miR-133a and miR-133b were quantified by RT-PCR in 163 primary paediatric RMSs, plus control tissues, and correlated with clinico-pathological features. Correlations with parallel gene expression profiling data for 84 samples were used to identify pathways associated with miR-206. Synthetic miR-206 was transfected into RMS cell lines and phenotypic responses assessed. RESULTS: Muscle-specific miRNAs levels were lower in RMSs compared with skeletal muscle but generally higher than in other normal tissues. Low miR-206 expression correlated with poor overall survival and was an independent predictor of shorter survival in metastatic embryonal and alveolar cases without PAX3/7-FOXO1 fusion genes. Low miR-206 expression also significantly correlated with high SIOP stage and the presence of metastases at diagnosis. High miR-206 expression strongly correlated with genes linked to muscle differentiation and low expression was associated with genes linked to MAPkinase and NFKappaB pathway activation. Increasing miR-206 expression in cell lines inhibited cell growth and migration and induced apoptosis that was associated with myogenic differentiation in some, but not all, cell lines. CONCLUSION: miR-206 contributes to the clinical behaviour of RMSs and the pleiotropic effects of miR-206 supports therapeutic potential.

Genetic diversity of the mating type and toxin production genes in Pyrenophora tritici-repentis.

Pyrenophora tritici-repentis, the causal agent of tan spot on wheat, is a homothallic loculoascomycete with a complex race structure. The objectives of this study were to confirm the homothallic nature of the pathogen, characterize mating type diversity and toxin production genes in a global collection of strains, and analyze how these traits are associated between each other and with existing races. The pseudothecia production capacity, race identification, mating type locus (MAT), internal transcribed spacer, and glyceraldehyde-3-phosphate dehydrogenase regions were analyzed in a selection of 88 strains originating from Europe, North and South America, North Africa, and Central and South Asia. Some (60%) strains produced pseudothecia containing ascospores, independent of their origin. Race identification obtained using the multiplex polymerase chain reaction targeting host-selective toxin (HST) genes was consistent, overall, with the results based on the inoculation of a set of differential wheat cultivars and confirmed the predominance of race 1/2 strains ( approximately 83%). However, discrepancies in race identification, differences from the reference tester strains, and atypical ToxA profiles suggest the presence of new races and HSTs. The MAT1-1 and MAT1-2 coding regions are consecutively arranged in a single individual, suggesting putative heterothallic origin of P. tritici-repentis. Upstream from the MAT is an open reading frame of unknown function (ORF1) containing a MAT-specific degenerate carboxy-terminus. The phylogenetic analysis of the MAT locus reveals two distinct groups, unlinked to geographical origin or ToxA profile. Group I, the best-represented group, is associated with typical tan spot lesions caused by races 1, 2, 3, and 5 on wheat. It is more homogenous than group II encompassing race 4 strains, as well as isolates associated primarily with small spot lesions on wheat leaves or other hosts. Group II could contain several distinct taxa.

Pomological and nutraceutical properties in apricot fruit: cultivation systems and cold storage fruit management.

We have investigated the effect of cultivation systems and fruit post-harvest management on the antioxidant properties of apricot fruits. Trees of five cultivars 'Tyrinthos', 'Cafona', 'Bella d'Italia', 'Vitillo' and 'Pellecchiella' were cultivated under integrated and organic systems. Fruits were collected at full maturity stage and analyzed either immediately or after storage at 4+/-0.5 degrees C and 85% of relative humidity for seven and 14 days. The main pomological traits (weight, colour, flesh firmness, total soluble sugars, titratable acidity) and antioxidant properties were analyzed. The total antioxidant capacity (TAC by TEAC method), total phenols content (TP by Folin-Ciocalteu method) and carotenoid content by HPLC-DAD were monitored. Cultivar characterization by principal component analysis (PCA) indicated a large variability on pomological and antioxidant properties of apricot fruits. 'Bella d'Italia' showed better TAC and TP values compared to the other cultivars. ANOVA interactions between cultivar and cultivation system (organic/integrated) were found for the antioxidant properties. These interactions may help to select a set of genotypes with better performances under organic system, which in our study might be indicated in 'Cafona' and 'Bella d'Italia'.

[Retroperitoneal mass in children : clinical cases of Wilms tumor and neuroblastoma]. / Le cas clinique du mois. Les masses rétropéritonéales chez l'enfant : a propos d'une tumeur de Wilms et d'un neuroblastome.

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. We present the case-reports of 2 children under the age of 5 years admitted to the University Hospital of Liège, one with a Wilms tumor and one with a neuroblastoma.

[Exploring . . . a retroperitoneal mass in children]. / Comment j'explore ... une masse retroperitoneale chez l'enfant.

Detection of a retroperitoneal mass in children needs a fast and accurate exploration. Wilms tumor and neuroblastoma, the most frequent, will be presented more in detail including their clinical and biological characteristics, their diagnostic tests and their primary therapeutic treatments.

Distribution of airborne Mycosphaerella graminicola inoculum at the field scale.

A network of 10 Burkard 7-day spore-recording traps was set up in the Walloon region in Belgium to monitor the airborne inoculum of wheat pathogens. Three spore traps were used to analyse the distribution of Mycosphaerella graminicola inoculum at the field scale, at 1 m above ground level. Two traps were set up in a wheat field 100 m apart. The third trap was placed 70 m away in a sugar beet field adjacent to the wheat field. Total DNA from each fragment of spore trap tape corresponding to 1 day sampling was extracted and the quantity of M. graminicola was assessed using real-time polymerase chain reaction (PCR) assay. The experiment was conducted from July to October 2009. Positive detections were obtained for between 33 and 36 days, depending on the spore traps. When detected, the daily quantities of cDNA, collected from a volume of 14.4 m3, fluctuated between 4.84E+00 and 6.10E+03. Correlation coefficients higher than 0,82 and no significant differences were observed between the quantities of M. graminicola collected by the three spore traps, indicating that, at 1 m above ground level, the distribution of inoculum can be considered as homogenous at the tested field scale. This study confirms that spore traps coupled with real-time PCR could be used to assess the airborne inoculum of M. graminicola and to understand the development of the disease at this scale.

Percutaneous tumor ablation: microencapsulated echo-guided interstitial chemotherapy combined with cryosurgery increases necrosis in prostate cancer.

This study aimed at confirming the increased growth inhibition (GI) of human prostate tumors produced by a intentionally palliative combination treatment of cryochemotherapy, i.e., partial cryoablation (CA) followed by intratumor partial chemotherapy with injection of microencapsulated 5-fluorouracil (MCC/5FU) at the ice ball (IB) periphery. We report the local effectiveness of cryochemotherapy compared to chemotherapy only with using multiple injections of MCC/5FU spaced out to maximize cumulative effect of sustained release of 5-fluorouracil (5FU) during a 21-day period. Prostate bioluminescent tumor cells - DU145 Luc+ - were implanted sub-cutaneously and bilaterally in each flank of nude mice. Tumors were treated with: (i) cryoablation alone (CA), causing necrosis in approximately 45% of the tumor volume; (ii) cryo-chemotherapy (CA+MCC/5FU), a combined regimen consisting of partial CA followed immediately and on day 14 by ultrasound assisted, intra-tumor injections (40 mul) of MCC/5FU( 0.81 ng/mm3 of tumor) containing Ethiodol (IPO) an imaging contrast agent, on two opposite sides of the unfrozen part of tumor; (iii) intratumor chemotherapy (MCC/5FU), consisting of three successive intra-tumor injections of microencapsulated 5FU on two opposite sides on Day 0, 4, and 11, and (iv) control series (MM), consisting of a single injection of echogenic microcapsules (mucaps) containing IPO but no 5FU. Tumor growth and viability were followed during a 21-day period with using biometric measurements, bioluminescent imaging (BLI) and ultrasonography (US), and then animals were sacrificed. CA, spared 54.4% of the tumor volume and the IB kill ratio was 0.4 +/-0.9. The maximum tumor volume reduction observed by Day 3 was short-lived as re-growth became significant by Day 6. CA+ MCC/5FU spared 55.6% of the tumor volume and the IB kill ratio was 0.54 +/- 0.12. The viable tumor cells, as measured by BLI remained at preoperative levels. After 11 days CA+ MCC/5FU limited the growth of the partially ablated tumors to only 10.6% of the growth of CA treated tumors (p=0.04). By Day 18 the CA+MCC/5FU had inhibited tumor growth by 78% compared to the CA treated tumors (p=0.05) and after 21 days the growth was inhibited by 71% (p=0.04) compared to more than 650% growth in the MM group and 600% growth in the CA treated group. The two injections of MCC/5FU produced a visible focal necrosis in 55% of the tumors. MCC/5FU proved effective by themselves and reduced the growth of prostate tumor volumes by 51% (p=0.025) compared to MM controls during the 21 days. Focal necrosis was macroscopically visible at the site of 66% of the tumors injected only with MCC/5FU. The BLI clearly showed zones of reduced tumor cell viability at the injection sites. The mean number of bioluminescent (viable) tumor cells, remained below preoperative levels for the first 6 days and then increased at a rate approximately 20% that of the growth of control tumor cells. The chemoablative effects of intentionally limited doses of MCC/5FU injected within the IB margin augment the effects of incomplete cryoablation in this prostate tumor model, with dramatic tumor GI and directionally increased necrosis dimensions compared to CA alone, confirming the results of a previous study. Our results indicate the potential advantages of our combination cryochemotherapy that utilizes different mechanisms to kill tumor cells and retard tumor growth in the region surrounding the IB where tumor cells escape the lethal effects of cryosurgery. The study suggests that cryochemotherapy may become a more predictable technique that could be indicated as an adjuvant or an alternative to palliative therapy of hormone refractory prostate cancer (HRPC).

[Acute pericarditis in a sclerodermic patient at the 27th week of pregnancy]. / Péricardite aiguë chez une patiente sclérodermique survenue à la 27ème semaine de grossesse.

A 31-year-old women with a limited cutaneous form of systemic sclerosis (ISSc), developed chest pain at the 27th week of pregnancy, with electric pathognomonic signs of pericarditis. As there was no evidence of another etiology than ISSc, (oral) aspirin and (oral) prednisolone were successively administered and the patient's condition improved rapidly.

Self-crosslinked fibrous collagen/chitosan blends: Processing, properties evaluation and monitoring of degradation by bi-fluorescence imaging.

Porous collagen/chitosan scaffolds with different Collagen:Chitosan (Coll:Ch) ratios were prepared by freeze-drying followed by self-crosslinking via dehydrothermal treatment (DHT) and characterized as biomaterials for tissue engineering. Cy7 and Cy5.5 fluorochromes were covalently grafted to collagen and chitosan, respectively. Thus, it was possible, using optical fluorescence imaging of the two fluorochromes, to simultaneously track their in vivo biodegradation, in a blend scaffold form. The fluorescence signal evolution, due to the bioresorption, corroborated with histological analysis. In vitro cytocompatibility of Coll:Ch blend scaffolds were evaluated with standardized tests. In addition, the scaffolds showed a highly interconnected porous structure. Extent of crosslinking was analyzed by convergent analysis using thermogravimetry, Fourier Transform Infrared Spectroscopy and PBS uptake. The variations observed with these techniques indicate strong interactions between collagen and chitosan (covalent and hydrogen bonds) promoted by the DHT. The mechanical properties were characterized to elucidate the impact of the different processing steps in the sample preparation (DHT, neutralization and sterilization by ß-irradiation) and showed a robust processing scheme with low impact of Coll:Ch composition ratio.

High-throughput screening assay for new ligands at human melatonin receptors.

AIM: Melatonin (MT) is a neurohormone produced and secreted primarily by the pineal gland in a circadian manner, and mainly acts through 2 receptor subtypes: MT1 and MT2 in humans. The diversity in their tissue distribution is in favor of different functions for each receptor subtype. Selective modulators are therefore required to determine the physiological roles of these melatonin receptor subtypes and their implications in pathological processes. METHODS: A homogenous MT1/MT2 receptor binding assay was established for high-throughput screening of new ligands at the hMT1 and/or hMT2 receptors. The functional properties (agonists or antagonists) were assessed by a conventional guanosine-5'[gamma-(35)S] triphosphate (GTP-gammaS) assay. RESULTS: Three hMT1 receptor-selective small molecule antagonists and 1 hMT2 receptor-selective small molecule antagonist with novel structural features were identified following a high-throughput screening campaign of 48,240 synthetic and natural compounds. CONCLUSION: The findings may assist in the expansion of chemical probes to these 2 receptor subtypes.

High-throughput screening of novel antagonists on melanin-concentrating hormone receptor-1.

AIM: To find new antagonists on human melanin-concentrating hormone receptor-1 (MCHR-1) through high-throughput screening (HTS) of a diverse compound library. METHODS: MCHR-1, [3H]SNAP7941, and FlashBlue G-protein-coupled receptor beads were used to measure the receptor-binding activities of various compounds based on scintillation proximity assay (SPA) technology. The guanosine 5'(gamma-[35S]thio) triphosphate ([35S]GTPgammaS) binding assay was subsequently applied to functionally characterize the "hits" identified by the HTS campaign. RESULTS: Of the 48,240 compounds screened with the SPA method, 12 hits were confirmed to possess MCHR-1 binding activities, 8 were functionally studied subsequently with the [35S]GTPgammaS binding assay, and only 1 compound (NC127816) displayed moderate human MCHR-1 binding affinity (Ki=115.7 nmol/L) and relatively potent antagonism (KB=23.8 nmol/L). This compound shares a novel scaffold (1-ethoxy-2H-2-aza-1-phospha-naphthalene 1-oxide) with 3 other analogs in the group. CONCLUSION: Considering the marked difference in molecular shape and electrostatic status between NC127816 and the structures reported elsewhere, we anticipate that its derivatives may represent a new class of potent MCHR-1 modulators.

Survival of Campylobacter jejuni in mineral bottled water according to difference in mineral content: application of the Weibull model.

The aim of the study was to examine the hypothesis proposed by Evans et al. [2003. Hazards of healthy living: bottled water and salad vegetables as risk factors for Campylobacter infection. Emerg. Infect. Dis. 9(10), 1219-1225] that mineral bottled water accidentally contaminated by Campylobacter jejuni would represent a risk factor for Campylobacter infection. Culturability of C. jejuni cells inoculated in low- and high-mineral bottled water during storage at 4 degrees C in the dark was performed by surface plating and modelled using the Weibull model. The loss of C. jejuni culturability observed in all conditions tested was shown to be dependent on strain, preculture condition and water composition. Following inoculation of C. jejuni, the rapid loss of culturability was not correlated to complete cell death as the passage into embryonated eggs enabled recovery of cells from the viable but non-culturable state. In conclusion, the sanitary risk associated with contaminated bottled water cannot be excluded although it is presumably low. Culture conditions, strain and water type must be taken into account in the evaluation of the risk factors as they influence significantly Campylobacter survival in water.

[Clinical characteristics and follow-up of patients with magnetic resonance imaging confirmed myopericarditis: A retrospective study]. / Caractéristiques et suivi clinique d'une cohorte de patients atteints de myopéricardite confirmée en imagerie par résonance magnétique.

INTRODUCTION: Pericarditis are frequently associated with some degree of concomitant myocardial involvement. Predominant pericarditis with limited myocardial involvement are named myopericarditis. Data regarding myopericarditis are scarce. PATIENTS AND METHODS: Retrospective chart review of all patients admitted between 2002 and 2011 with magnetic resonance imaging confirmed myopericarditis. RESULTS: Twenty-seven patients were included. Eighty-one percent were men, with median age of 32 years. Infectious disease preceded hospitalization in 55% of cases. Mean left ventricle ejection fraction at admission was 55% with focal myocardial impairment mainly localized in lateral and inferior walls. Coronary angiogram was performed in 37% of cases to rule out an ischaemic aetiology. We identified 5 cases (19%) of myopericarditis preceded by an episode of streptococcus group A throat infection. Non-sustained ventricular tachycardia was observed in 15% of cases. After a 2-year follow-up period, mortality rate was zero and recurrence rate was 15%. CONCLUSIONS: In our series, myopericarditis was a benign disease affecting mostly young men, and prognosis was good. A significant proportion of cases was preceded by group A streptococcus infection.

[Spontaneous coronary artery dissection on the 10th post-partum day: a case report]. / Dissection spontanée d'une artère coronaire au 10e jour post-partum: observation clinique.

Spontaneous coronary artery dissection is a rare cause of myocardial infarction. It most commonly occurs in young women in the peri-partum period. The aetiology remains obscure. The authors describe the case of a 38 year old woman who suffered an inferior wall myocardial infarction on the 10th post-partum day. After failure of thrombolysis, coronary angiography showed dissection of the right coronary artery. An attempted angioplasty was unsuccessful and the patient was treated medically with a favourable clinical outcome. Spontaneous coronary artery dissection should be considered in all young patients without coronary risk factors presenting with acute myocardial ischaemia, especially young women in the peri-partum period. Emergency coronary angiography should be undertaken to establish the diagnosis and orientate appropriate treatment which may be medical, interventional or surgical.