Validation of an algorithm for identifying incident cancer cases based on long-term illness and diagnosis related group program data from the French National Health Insurance Information System (SNDS).

PURPOSE: Three generic claims-based algorithms based on the Illness Classification of Diseases (10th revision- ICD-10) codes, French Long-Term Illness (LTI) data, and the Diagnosis Related Group program (DRG) were developed to identify retirees with cancer using data from the French national health insurance information system (Système national des données de santé or SNDS) which covers the entire French population. The present study aimed to calculate the algorithms' performances and to describe false positives and negatives in detail. METHODS: Between 2011 and 2016, data from 7544 participants of the French retired self-employed craftsperson cohort (ESPrI) were first matched to the SNDS data, and then toFrench population-based cancer registries data, used as the gold standard. Performance indicators, such as sensitivity and positive predictive values, were estimated for the three algorithms in a subcohort of ESPrI. RESULTS: The third algorithm, which combined the LTI and DRG program data, presented the best sensitivities (90.9%-100%) and positive predictive values (58.1%-95.2%) according to cancer sites. The majority of false positives were in fact nearby organ sites (e.g., stomach for esophagus) and carcinoma in situ. Most false negatives were probably due to under declaration of LTI. CONCLUSION: Validated algorithms using data from the SNDS can be used for passive epidemiological follow-up for some cancer sites in the ESPrI cohort.

Applying Gestalt approach as a method for teaching computer science practice in the classroom: A case study in primary schools in Brazil.

The use of information technology in the academic environment has grown. Building different didactic techniques to help students learn and practice with Information Technology (IT) resources is common. However, applying these techniques does not necessarily mean that students may acquire knowledge. The differential idea of this work is to create an approach in which students are protagonists and not just absorbers of IT. Based on this perspective, we applied a Gestalt approach to assist students in practicing these technological resources. They produce new hardware and software tools during classes based on their personal needs and worldviews. We analyzed applications of this novel way of computer science teaching in three different schools. It was possible to observe greater motivation from the students to experience new knowledge from technological resources. The common aspect was that solutions were conceived and developed from students' needs. The development followed a Gestalt approach, which combines the idea of form and imagination. Thus, with this approach, reactivity towards IT was reduced. It helped construct technological tools to acquire propaedeutic knowledge.

To what extent do age, stage and treatment influence survival after invasive cervical cancer: a French population-based study.

PURPOSE: In an attempt to understand why cervical cancer (CC) survival is decreasing with diagnosis period among older women in France, this study aimed to estimate the effects of main prognostic factors on net survival in CC according to age. METHODS: French cancer registries databases were used to retrospectively analyze women diagnosed with CC in 2011-2012. Net survival was estimated with the Pohar-Perme method and prognostic factors (socio-demographic, clinical variables, stage at diagnosis, therapeutic management) were analyzed with Lambert and Royston's flexible parametric model. RESULTS: One thousand one hundred fifty three women with CC were identified. 30.4% were < 45, 41.4% 45-64, and 28.3% ≥ 65 years. Older women were diagnosed at a more advanced stage than younger women: 54.8% regional (FIGO IB2-IVA), 33.0% distant (IVB) in women ≥ 65 years vs 33.7% and 8.0%, respectively in women < 45 years. Half of women with regional stage of CC received recommended treatment; this rate decreased with increasing age (< 45: 66.1%, 45-64: 62.7%, ≥ 65: 29.2%). Older age was significantly associated with increased risk of death: hazard ratio 1.89 for age ≥ 65, as were regional stage (2.81), distant stage (15.99), and not receiving recommended treatment (2.26). CONCLUSION: Older women with CC diagnosed at advanced stage who do not receive standard of care are at markedly increased risk of death. Special attention to the management of older women is warranted in France, not only to diagnose cancer at an earlier stage (via gynecological follow-up in these menopaused women who remain at risk of CC), but also to ensure they receive standard of care, taking into account their overall state of health.

Design and synthesis of naphthylchalcones as novel anti-leukaemia agents.

A series of new hydroxylated chalcone derivatives with different substitution patterns on a phenyl ring A and B, were prepared by Claisen-Schmidt condensation in an aqueous alkaline base. The antiproliferative activity of the studied compounds was evaluated against the human leukaemia cell line U-937. The structure-activity relationship of these naphthylchalcones was investigated by the introduction of one methoxy or two methyl groups on the A ring, the introduction of a methoxy group on the naphthyl ring or by varying the position of the methoxy group on the A ring. The results revealed that the naphthylchalcone containing a methoxy group in position 6́ of the A ring was the most cytotoxic compound, with an IC50 value of 4.7 ± 0.5 µM against U-937 cells. This synthetic chalcone induced S and G2-M cell cycle arrest, a time-dependent increase in sub-G1 ratio and annexin-V positive cells, caspase activation and poly(ADP-ribose) polymerase cleavage. Apoptosis induction was blocked by a pan-caspase inhibitor and by the selective caspase-3/7 inhibitor and attenuated by the inhibition of c-jun N-terminal kinases / stress-activated protein kinases (JNK/SAPK) and phosphoinositide 3-kinase. The structure-activity relationship of naphthylchalcones against human leukaemia cells reveals that the major determining in cytotoxicity is the presence of a methoxy group in position 6́ of the A ring that suggest the potential of this compound or derivatives in the development of new anti-leukaemia drugs.

Bacterial Nanocellulose toward Green Cosmetics: Recent Progresses and Challenges.

In the skin care field, bacterial nanocellulose (BNC), a versatile polysaccharide produced by non-pathogenic acetic acid bacteria, has received increased attention as a promising candidate to replace synthetic polymers (e.g., nylon, polyethylene, polyacrylamides) commonly used in cosmetics. The applicability of BNC in cosmetics has been mainly investigated as a carrier of active ingredients or as a structuring agent of cosmetic formulations. However, with the sustainability issues that are underway in the highly innovative cosmetic industry and with the growth prospects for the market of bio-based products, a much more prominent role is envisioned for BNC in this field. Thus, this review provides a comprehensive overview of the most recent (last 5 years) and relevant developments and challenges in the research of BNC applied to cosmetic, aiming at inspiring future research to go beyond in the applicability of this exceptional biotechnological material in such a promising area.

Upgrading the Topical Delivery of Poorly Soluble Drugs Using Ionic Liquids as a Versatile Tool.

Numerous studies are continuously being carried out in pursuit of formulations with higher performance. Problems such as poor drug solubility, which hinders drug incorporation into delivery systems and bioavailability, or limitations concerning the stability and performance of the formulations may cause difficulties, since solving all these drawbacks at once is a huge challenge. Ionic liquids (ILs), due to their tunable nature, may hypothetically be synthesized for a particular application. Therefore, predicting the impact of a particular combination of ions within an IL in drug delivery could be a useful strategy. Eight ILs, two choline amino acid ILs, two imidazole halogenated ILs, and four imidazole amino acid ILs, were prepared. Their applicability at non-toxic concentrations, for improving solubility and the incorporation of the poorly soluble, ferulic, caffeic, and p-coumaric acids, as well as rutin, into topical emulsions, was assessed. Next, the impact of the ILs on the performance of the formulations was investigated. Our study showed that choosing the appropriate IL leads to a clear upgrade of a topical emulsion, by optimizing multiple features of its performance, such as improving the delivery of poorly soluble drugs, altering the viscosity, which may lead to better sensorial features, and increasing the stability over time.

(Bio)Technological aspects of microalgae pigments for cosmetics.

Photosynthetic microorganisms convert carbon dioxide and solar radiation into interesting bioactive compounds not yet entirely explored. Several species of microalgae are known to be rich in colored high-valuable components that, although remarkable, are poorly explored as natural sources of pigments for cosmetics. Pigments associated to photosynthetic activity include chlorophyll, ß-carotene, astaxanthin, xanthophylls, and phycobiliproteins, many of which have shown high potential as cosmetic actives due to their antioxidant, immune-enhancing, and anti-inflammatory properties. In the last decade, concern with a young and beautiful appearance has emerged, encouraging many consumers to use anti-aging cosmetics daily. As a result, the cosmetic market has been growing and evolving rapidly to meet consumer expectations. However, due to regular use and the sensitive nature of facial skin, local adverse reactions may often occur, such as irritation, sensitization, or photoreactions, and safety evaluation is mandatory prior to marketing. It is, therefore, understandable that new actives from natural sources, such as microalgae, are perceived as attractive alternatives for consumers who seek ingredients without allergenic potential. Thus, the cosmetic industry has recently started to explore the inclusion of compounds extracted from microalgae and cyanobacteria in innovative formulations. Herein, we revised nontraditional microalgae species for pigment production with cosmetic applications, indicating those that could also be considered potential ingredients for innovative cosmetics. KEY POINTS: • Extraction methods for pigments from photosynthetic microorganisms were compiled. • Innovative cosmeceuticals could be developed with natural pigments. • Safety features of such natural pigments were also described.

Topical Drug Delivery Systems Based on Bacterial Nanocellulose: Accelerated Stability Testing.

Bacterial nanocellulose (BNC) membranes have enormous potential as systems for topical drug delivery due to their intrinsic biocompatibility and three-dimensional nanoporous structure, which can house all kinds of active pharmaceutical ingredients (APIs). Thus, the present study investigated the long-term storage stability of BNC membranes loaded with both hydrophilic and lipophilic APIs, namely, caffeine, lidocaine, ibuprofen and diclofenac. The storage stability was evaluated under accelerated testing conditions at different temperatures and relative humidity (RH), i.e., 75% RH/40 °C, 60% RH/25 °C and 0% RH/40 °C. All systems were quite stable under these storage conditions with no significant structural and morphological changes or variations in the drug release profile. The only difference observed was in the moisture-uptake, which increased with RH due to the hydrophilic nature of BNC. Furthermore, the caffeine-loaded BNC membrane was selected for in vivo cutaneous compatibility studies, where patches were applied in the volar forearm of twenty volunteers for 24 h. The cutaneous responses were assessed by non-invasive measurements and the tests revealed good compatibility for caffeine-loaded BNC membranes. These results highlight the good storage stability of the API-loaded BNC membranes and their cutaneous compatibility, which confirms the real potential of these dermal delivery systems.

Self-regulation in oral hygiene behaviours in adults with gingivitis: The mediating role of coping planning and action control.

AIM: This study investigates the joint role of volitional predictors of oral hygiene behaviours of flossing and brushing in adults with gingivitis, framed by the Health Action Process Approach model (HAPA). MATERIALS AND METHODS: In a longitudinal online survey, 201 participants aged 18-75, of which 56.7% were women, completed assessments at baseline(T1), 2 weeks(T2) and 4 months(T3). Oral hygiene behaviours(OH) (brushing and flossing) and social cognitive determinants of behaviour in the HAPA: action and maintenance self-efficacy(ASE & MSE), intention(INT), coping planning(CP) and action control(AC) were evaluated. Structural equation modelling was used to test a series of three nested models. In Model 1, action self-efficacy would determine MSE and INT, and INT would determine OH; in Model 2, INT would determine both CP and AC and the two OH behaviours; and in Model 3, CP and AC would be sequential mediators between INT and OH. RESULTS: Model 3, predicting a mediating process from intention to behaviour via coping planning and action control, showed the best fit according to the fit indices and explained more of the variance in dental hygiene. The mediating role of coping planning and action control between intention and oral hygiene behaviours was thus confirmed. Importantly, coping planning did not mediate between intention and oral hygiene behaviours, which means that oral hygiene intention influences action control through coping planning, and both sequentially mediate this influence on behaviour. CONCLUSIONS: For individuals who are not yet following the recommendations for specific oral hygiene behaviours, coping planning and action control represent psychological mechanisms by which intentions are put into practice.

Plasmodium falciparum merozoite surface antigen-specific cytophilic IgG and control of malaria infection in a Beninese birth cohort.

BACKGROUND: Substantial evidence indicates that cytophilic IgG responses to Plasmodium falciparum merozoite antigens play a role in protection from malaria. The specific targets mediating immunity remain unclear. Evaluating antibody responses in infants naturally-exposed to malaria will allow to better understand the establishment of anti-malarial immunity and to contribute to a vaccine development by identifying the most appropriate merozoite candidate antigens. METHODS: The study was based on parasitological and clinical active follow-up of infants from birth to 18 months of age conducted in the Tori Bossito area of southern Benin. For 399 infants, plasma levels of cytophilic IgG antibodies with specificity for five asexual stage malaria vaccine candidate antigens were determined by ELISA in infants' peripheral blood at 6, 9, 12 and 15 months of age. Multivariate mixed logistic model was used to investigate the association between antibody levels and anti-malarial protection in the trimester following the IgG quantification. Moreover, the concentrations of merozoite antigen-specific IgG were compared between a group of infants apparently able to control asymptomatic malaria infection (CAIG) and a group of infants with no control of malaria infection (Control group (NCIG)). Protective effect of antibodies was also assessed after 15 months of malaria exposure with a Cox regression model adjusted on environmental risk. RESULTS: Cytophilic IgG responses to AMA1, MSP1, MSP2-3D7, MSP2-FC27, MSP3 and GLURP R2 were associated with increasing malarial infection risk in univariate analysis. The multivariate mixed model showed that IgG1 and IgG3 to AMA1 were associated with an increased risk of malarial infection. However infants from CAIG (n = 53) had significantly higher AMA1-, MSP2-FC27-, MSP3-specific IgG1 and AMA1-, MSP1-, MSP2-FC27-, MSP3 and GLURP-R2-specific IgG3 than those from NCIG (n = 183). The latter IgG responses were not associated with protection against clinical malaria in the whole cohort when protective effect is assessed after 15 months of malaria exposition. CONCLUSION: In this cohort, merozoite antigen-specific cytophilic IgG levels represent a marker of malaria exposure in infants from 6 to 18 months of age. However, infants with resolution of asymptomatic infection (CAIG) seem to have acquired naturally immunity against P. falciparum. This observation is encouraging in the context of the development of multitarget P. falciparum vaccines.

Modelling the impact of different front-of-package nutrition labels on mortality from non-communicable chronic disease.

BACKGROUND: Front-of-Package nutrition labels (FoPLs) are intended to help reduce the incidence of nutrition-related non-communicable diseases through an improvement in diet quality. FoPLs have been shown to improve the nutritional quality of purchases and have been associated with improved diet quality, which is in turn associated with reduced risk of non-communicable diseases. However, the potential impact of FoPLs on reducing mortality from chronic diseases has never been estimated. METHODS: Data from a laboratory experimental economics test were used to investigate the effects of five different FoPLs (Nutri-Score, Health Star Rating system, Multiple Traffic lights, Reference intakes and SENS (Système d'Etiquetage Nutritionnel Simplifié)) on the nutritional quality of household purchases. The relative differences in nutrient content and composition of food purchases were then applied to dietary intakes using data from an observational study, thus yielding estimates for 'reference' and 'labelled' diets. A macro-simulation study using the PRIME model was then conducted to estimate the impact of the modification in dietary intake as a result of FoPL use on mortality from diet-related non-communicable diseases. RESULTS: The use of FoPLs led to a substantial reduction in mortality from chronic diseases. Approximately 3.4% of all deaths from diet-related non-communicable diseases was estimated to be avoidable when the Nutri-Score FoPL was used. The remaining FoPLs likewise resulted in mortality reduction, although to a lesser extent: Health Star Rating system (2.8%), Reference Intakes (1.9%), Multiple Traffic Lights (1.6%), and SENS (1.1%). CONCLUSIONS: FoPLs have the potential to help decrease mortality from diet-related non-communicable diseases, and the Nutri-Score appears to be the most efficient among the five formats tested.

Cytotoxic activity of the seaweed compound fucosterol, alone and in combination with 5-fluorouracil, in colon cells using 2D and 3D culturing.

Colorectal cancer (CRC) is one of the most frequently occurring carcinomas which require effective therapies. Fucosterol is a sterol present in marine brown seaweeds with several biological activities. However, the influence of fucosterol in CRC remains to be determined. Thus, the aim of this study was to examine the anticancer activity of fucosterol alone and in combination with 5-fluorouracil (5-Fu) on two human CRC cell lines (HCT116 and HT29) and compared with cytotoxicity in one normal colon fibroblast cell line (CCD-18co) in monolayer (2D). The effect of fucosterol alone or in combination with 5-Fu was further assessed using HT29 multicellular spheroids (3D). Data demonstrated that fucosterol alone or combined with 5-Fu decreased cell viability in HT29 cells in 2D cultures without inducing cytotoxic in normal colon cells. The combination, fucosterol, and 5-Fu, also inhibited cell proliferation, clonogenic potential and cell migration without producing cell death in 2D. In multicellular spheroids, the combination fucosterol plus 5-Fu at the same concentrations used in 2D was not effective demonstrating that under the tested conditions the 3D model was more resistant than the 2D model. Taken together, these findings suggest that fucosterol might be a promising alternative to enhance the cytotoxic and anti-invasive actions of 5-Fu in colon cancer cells without consequent major adverse effects in normal cells. Our results also reinforce the need to include more complex 3D culture models in the initial stages of drug screening.

Adolescent and young adult oncology patients in France: Heterogeneity in pathways of care.

BACKGROUND: In order to evaluate at the population level the impact of the actions developed in France since 2004 to organize the care of adolescents and young adults (AYAs) with cancer, we conducted the present study to provide an unbiased view of the pathway of care of these patients. METHODS: Using a population-based registry, we conducted a review of all cases of cancer diagnosed during 2012 and 2013 in 15- to 24-year-old patients living in nineteen French administrative areas. RESULTS: The median times for diagnosis and treatment of the 993 included AYAs were 9 weeks (3-22) and 1 day (0-20), respectively. Delays in diagnosis were significantly longer in young adults than in adolescents, especially for soft-tissue sarcomas (48.7 weeks vs. 15.4 weeks, P = 0.04) and bone tumors (21.4 weeks vs. 10.1 weeks, P = 0.04). The first physicians seen by patients were mostly general practitioners (67.4%). Most patients (77.5%) were treated in adult units. Management decisions were taken within the context of a multidisciplinary team (MDT) in 85.3% of cases. MDT meetings that involved both pediatric and adult oncologists were uncommon (15.7% of patients). Twenty-six percent of patients were included in randomized or nonrandomized clinical studies. The proportion of inclusion was significantly higher in adolescents (39.5%) than in young adults (16.8%). CONCLUSION: In France, pathways of care for AYAs are heterogeneous. It is necessary to organize a national network of expert centers with adequate medical skills and specific psychosocial support and facilities to provide the best possible care for these patients.

Choline- versus imidazole-based ionic liquids as functional ingredients in topical delivery systems: cytotoxicity, solubility, and skin permeation studies.

BACKGROUND: Poor drug solubility represents a problem for the development of topical formulations. Since ionic liquids (ILs) can be placed in either lipophilic or hydrophilic solutions, they may be advantageous vehicles in such delivery systems. Nonetheless, it is vital to determine their usefulness when used at concentrations were cell viability is maintained, which was considered herein. METHOD: Five different ILs were prepared-three imidazole-based ILs: [C2mim][Br], [C4mim][Br], and [C6mim][Br]; and two choline-based ILs: [Cho][Phe] and [Cho][Glu]. Their cytotoxicity in human keratinocytes (HaCat cells), their influence in drug solubility and in percutaneous permeation, using pig skin membranes, was evaluated. RESULTS: Caffeine and salicylic acid were used as model actives. Choline-based ILs proved to be more suitable as functional ingredients, since they showed higher impact on drug solubility and a lower cytotoxicity. The major solubility enhancement was observed for caffeine and further solubility studies were carried out with this active in several concentrations of the choline-based ILs (0.1; 0.2; 0.5; 1.0; 3.0 and 5.0%, w/w) at 25 °C and 32 °C. Solubility was greatly influenced by concentrations up to 0.5%. The choline-based ILs showed no significant impact on the skin permeation, for both actives. The size of the imidazole-based ILs alkyl chain enhances the caffeine solubility and permeation, but also the ILs cytotoxicity. Stable O/W emulsions and gels were prepared containing the less toxic choline-based ILs and caffeine. CONCLUSIONS: Our results indicate that the choline-based ILs were effective functional ingredients, since, when used at nontoxic concentrations, they allowed a higher drug loading, while maintaining the stability of the formulations.

Quality by design (QbD), Process Analytical Technology (PAT), and design of experiment applied to the development of multifunctional sunscreens.

Multifunctional formulations are of great importance to ensure better skin protection from harm caused by ultraviolet radiation (UV). Despite the advantages of Quality by Design and Process Analytical Technology approaches to the development and optimization of new products, we found in the literature only a few studies concerning their applications in cosmetic product industry. Thus, in this research work, we applied the QbD and PAT approaches to the development of multifunctional sunscreens containing bemotrizinol, ethylhexyl triazone, and ferulic acid. In addition, UV transmittance method was applied to assess qualitative and quantitative critical quality attributes of sunscreens using chemometrics analyses. Linear discriminant analysis allowed classifying unknown formulations, which is useful for investigation of counterfeit and adulteration. Simultaneous quantification of ethylhexyl triazone, bemotrizinol, and ferulic acid presented at the formulations was performed using PLS regression. This design allowed us to verify the compounds in isolation and in combination and to prove that the antioxidant action of ferulic acid as well as the sunscreen actions, since the presence of this component increased 90% of antioxidant activity in vitro.

Evolution of the levels of human leukocyte antigen G (HLA-G) in Beninese infant during the first year of life in a malaria endemic area: using latent class analysis.

BACKGROUND: HLA-G, a non-classical HLA class I antigen, is of crucial interest during pregnancy by inhibiting maternal immune response. Its role during infections is discussed, and it has been described that high levels of soluble HLA-G during childhood increase the risk of malaria. To explore more precisely interactions between soluble HLA-G and malaria, latent class analysis was used to test whether distinct sub-populations of children, each with distinctive soluble HLA-G evolutions may suggest the existence of groups presenting variable malaria susceptibility. METHOD: A study was conducted in Benin from 2010 to 2013 and 165 children were followed from birth to 12 months. Evolution of soluble HLA-G was studied by the latent class method. RESULTS: Three groups of children were identified: one with consistently low levels of soluble HLA-G during follow-up, a second with very high levels and a last intermediate group. In all groups, low birth weight, high number of malaria infections and high exposure to malaria transmission were associated with high level of soluble HLA-G. Placental malaria was not. Presence of soluble HLA-G in cord blood increased the probability of belonging to the highest trajectory. CONCLUSION: These results, together with previous ones, confirm the important role of HLA-G in the individual susceptibility to malaria. Assaying soluble HLA-G at birth could be a good indicator of newborns more fragile and at risk of infections during childhood.

Long-term Results of Domino Liver Transplantation for Hepatocellular Carcinoma Using the "Double Piggy-back" Technique: A 13-Year Experience.

OBJECTIVES: The aim of this study was to evaluate the long-term outcome of liver transplantation (LT) for hepatocellular carcinoma (HCC) with Domino LT (DLT) using the "Double Piggy-back" technique. BACKGROUND DATA: DLT using livers from familial amyloidotic polyneuropathy (FAP) patients is a well-described technique and useful for expanding the donor pool. However, data on long-term results for HCC are limited, particularly regarding the use of the "Double Piggy-back" technique. METHODS: Between 2001 and 2014, a total of 260 patients undergoing LT for HCC were analyzed from a prospective database. Of those, 114 were submitted to DLT. Comparisons between groups were performed using propensity score matching. RESULTS: Median follow-up was 34 months (1-152). Overall and disease-free 5-year survival rates for the whole population were 58% and 56%, respectively. There were 177 (68%) patients within Milan Criteria and an additional 26 (10%) within University of California San Francisco (UCSF) criteria. Patients older than 50 years were more likely to receive an FAP liver [odds ratio (OR) 1.94, confidence interval (CI) 1.02-3.69]. DLT patients had more major complications (23.7% vs 13.0%, P = 0.025). Only patients undergoing DLT presented with piggy-back syndrome (7% vs 0%, P = 0.001). After adjusting for potential confounders, DLT and cadaveric LT had a similar 5-year survival rate (59% vs 44%, respectively, P = 0.117). Thirteen patients (11.4%) evidenced FAP disease but not before 6 years after DLT. CONCLUSIONS: DLT for HCC is feasible and achieves equivalent results to cadaveric LT. The benefit of expanding the donor pool must be balanced against higher morbidity and a real risk of disease transmission.

A comprehensive assessment of the transcriptome of cork oak (Quercus suber) through EST sequencing.

BACKGROUND: Cork oak (Quercus suber) is one of the rare trees with the ability to produce cork, a material widely used to make wine bottle stoppers, flooring and insulation materials, among many other uses. The molecular mechanisms of cork formation are still poorly understood, in great part due to the difficulty in studying a species with a long life-cycle and for which there is scarce molecular/genomic information. Cork oak forests are of great ecological importance and represent a major economic and social resource in Southern Europe and Northern Africa. However, global warming is threatening the cork oak forests by imposing thermal, hydric and many types of novel biotic stresses. Despite the economic and social value of the Q. suber species, few genomic resources have been developed, useful for biotechnological applications and improved forest management. RESULTS: We generated in excess of 7 million sequence reads, by pyrosequencing 21 normalized cDNA libraries derived from multiple Q. suber tissues and organs, developmental stages and physiological conditions. We deployed a stringent sequence processing and assembly pipeline that resulted in the identification of ~159,000 unigenes. These were annotated according to their similarity to known plant genes, to known Interpro domains, GO classes and E.C. numbers. The phylogenetic extent of this ESTs set was investigated, and we found that cork oak revealed a significant new gene space that is not covered by other model species or EST sequencing projects. The raw data, as well as the full annotated assembly, are now available to the community in a dedicated web portal at http://www.corkoakdb.org. CONCLUSIONS: This genomic resource represents the first trancriptome study in a cork producing species. It can be explored to develop new tools and approaches to understand stress responses and developmental processes in forest trees, as well as the molecular cascades underlying cork differentiation and disease response.

High plasma levels of HLA-G are associated with low birth weight and with an increased risk of malaria in infancy.

BACKGROUND: The immunosuppressive properties of HLA-G protein can create a tolerogenic environment that may allow Plasmodium falciparum to avoid host immune responses. There are known associations between high levels of circulating soluble HLA-G (sHLA-G) and either parasite or viral infections and it has been suggested that the induction of sHLA-G expression could be a mechanism via which infectious agents subvert host immune defence. The study presented here is the first to investigate the possible association between sHLA-G and malaria or malaria related risk factors in Benin. METHODS: A parasitological and clinical follow-up of 165 mothers and their newborns from delivery through to one year of age was conducted in the Tori Bossito area of southern Benin. Plasma levels of sHLA-G were determined by ELISA in maternal peripheral and cord blood and again in infants' peripheral blood at 3, 6, 9 and 12 months of age. The associations between the levels of sHLA-G and malaria risk factors were investigated through multivariate mixed models. RESULTS: Strong correlations were observed between the maternal and cord plasma concentrations of sHLA-G. In multivariate analyses, high cord plasma levels of sHLA-G were independently associated with (i) low birth weight and (ii) an increased risk of P. falciparum infection in infancy. CONCLUSION: These results show for the first time the possible involvement of sHLA-G in generating immune tolerance during pregnancy-associated malaria. Soluble HLA-G may represent a useful marker of susceptibility to malaria in infants and be associated with the higher susceptibility to infection observed for LBW children.

Forced Expiratory Volume in One Second Quotient (FEV1Q) as a Prognostic Factor in Amyotrophic Lateral Sclerosis Patients: Comparing Its Predictive Value to Other Lung Function Measurements.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder affecting the first and second motor neurons. Forced vital capacity (FVC) and forced expiratory volume in one second (FEV1) have conventionally served as indicators of respiratory muscle strength. Recently, FEV1Q (FEV1 divided by the sex-specific first percentile values of absolute FEV1 in adults with lung disease) has been suggested as a predictor of mortality. While FVC has been utilized as a prognostic factor, FEV1Q has not yet been examined. METHODS: This retrospective unicenter study evaluated FEV1Q as a predictor of mortality in ALS patients, comparing its predictive efficacy with other measurements, including FEV1, FVC, sniff nasal inspiratory pressure, and maximal inspiratory pressure. The study utilized univariate analysis for each variable employing the Cox proportional hazards model to determine the statistical significance and predictive power of each measurement. RESULTS: Forty-five patients were included, female predominant (60%) and an average age at diagnosis of 69.2 ± 11 years. Almost all (95%) met the criteria for non-invasive ventilation (NIV) and initiated (93%) during the study period, a mean of 137 days after diagnosis. The mortality rate observed was 57%, occurring at a median of 398 days post-diagnosis. On average, patients underwent 1.7 pulmonary function tests, revealing a decline in various parameters, including FEV1, FEV1Q, and FVC. However, only FEV1Q was a statistically significant predictor of mortality (p < 0.0083) in a Cox regression analysis. A negative coefficient for FEV1Q indicated that higher values were associated with a reduced mortality risk, with an average FEV1Q of 2.68 observed at the time of death. CONCLUSION: FEV1Q emerged as the only statistically significant predictor of mortality among the evaluated respiratory measurements in ALS patients. This study is the first to focus on applying FEV1Q in the clinical evaluation of ALS, marking an initial step in understanding its potential role in patient follow-up. However, further studies are needed before these findings can be incorporated into clinical practice.