Drivers of Anemia Reduction among Women of Reproductive Age in Senegal: A Country Case Study.

BACKGROUND: In Senegal, anemia prevalence among women of reproductive age (WRA) decreased from 59% in 2005 to 54% in 2017. However, determinants of reduction in disease burden under challenging public health conditions have not been studied. OBJECTIVE: To conduct a systematic in-depth assessment of the quantitative and qualitative determinants of anemia reduction among WRA in Senegal between 2005 and 2017. METHODS: Standard Exemplars in Global Health methodology was used for quantitative analyses using Senegal's Demographic and Health Surveys. Qualitative analyses included a systematic literature review, program/policy analysis, and interviews with key stakeholders. A final Oaxaca-Blinder decomposition analysis (OBDA) evaluated the relative contribution of direct and indirect factors. RESULTS: Among non-pregnant women (NPW), mean hemoglobin (Hb) increased from 11.4 g/dL in 2005 to 11.7 g/dL in 2017 (p<0.0001), corresponding to a 5%-point decline in anemia prevalence (58% to 53%). However, inequities by geographical region, household wealth, women's educational attainment, urban compared to rural residence, and antenatal care (ANC) during last pregnancy continue to persist. During this time period, several indirect nutrition programs were implemented, with stakeholders acknowledging the importance of these programs, but agreeing there needs to be more consistency, evaluation, and oversight for them to be effective. Our OBDA explained 59% of the observed change in mean Hb, with family planning (25%), malaria prevention programs (17%), use of iron and folic acid (IFA) during last pregnancy (17%), and improvement in women's empowerment (12%) emerging as drivers of anemia decline, corroborating our qualitative and policy analyses. CONCLUSIONS: Despite a reduction in anemia prevalence, anemia remains a severe public health problem in Senegal. To protect the gains achieved to date, as well as accelerate reduction in WRA anemia burden, focused efforts to reduce gender and social disparities, and improve coverage of health services, such as family planning, IFA, and antimalarial programs, are needed.

Relapse after intermittent access to cocaine: Discriminative cues more effectively trigger drug seeking than do conditioned cues.

RATIONALE: When people with drug addiction encounter cues associated with drug use, this can trigger cravings and relapse. These cues can include conditioned stimuli (CSs) signaling drug delivery and discriminative stimuli (DSs) signaling drug availability. Compared to CS effects, DS effects are less explored in preclinical studies on cue-induced relapse. OBJECTIVE: We compared CS and DS effects on reward seeking following abstinence from intermittent-access cocaine (or sucrose) self-administration. METHODS: During 15-20 intermittent-access sessions, rats self-administered i.v. cocaine or sucrose pellets paired with a light-tone CS. Cocaine/sucrose was available for 5-min (signalled by a light; DS+) and unavailable for 25 min (signalled by different lighting conditions; DS-), and this cycled for 4 h/session. Following abstinence, we measured cocaine/sucrose seeking under extinction triggered by CS and DS presentation, and instrumental responding reinforced by these cues. RESULTS: Across intermittent-access sessions, rats increased lever pressing for cocaine or sucrose during DS+ periods and decreased responding during DS- periods. On days 2 and 21 of abstinence, only presentation of the DS+ or DS+ and CS combined elicited increased cocaine/sucrose-seeking behaviour (i.e., increased active lever presses). Presenting the DS- alongside the DS+ suppressed the increased cocaine-seeking behaviour otherwise produced by the DS+ . Finally, on day 21 of abstinence, rats showed equivalent levels of lever pressing reinforced by the DS+ , CS and by the DS+ and CS combined, suggesting comparable conditioned reinforcing value. CONCLUSIONS: After intermittent self-administration, cocaine-associated DSs and CSs acquire similar conditioned reinforcing properties, but DSs more effectively trigger increases in drug seeking.

The intentions of French health university students to recommend and to receive the HPV vaccine are mainly influenced by vaccine knowledge, confidence in vaccines and personal HPV vaccination.

INTRODUCTION: Despite documented effectiveness in preventing several cancers, genital warts and safety of Human Papillomavirus (HPV) vaccine, immunization coverage among French adolescents remains far from the 80 % target. University health students (HS) in France may promote HPV vaccine through a national service (Service Sanitaire des Etudiants en Santé). We aimed to evaluate intentions to recommend the HPV vaccine to friends and relatives, to receive HPV vaccine, and to identify factors associated with these attitudes. METHODS: We conducted a cross-sectional survey in five French Universities from October 2019 to February 2020, using a self-administered online questionnaire. We used bivariable and multivariable logistic regression models to identify determinants of behavior around HPV vaccine: (i) individual intention for vaccination, and (ii) vaccine recommendation to friends and relatives. RESULTS: Among the 732 respondents (180 men, 552 women), 305 (41.7%) reported previous HPV vaccination (54.5 % among women), 504 (68.9%) would recommend the HPV vaccine to friends and relatives, 532 (72.7%) respondents would be vaccinated today if it was recommended for them. Intentions to recommend or to receive the HPV vaccine were less frequent in nursing students compared to medical and pharmacy students. After adjustment for demographical factors, HPV vaccine knowledge was associated with intention [aOR 1.30 (95%-confidence interval, 1.15-1.47)] and recommendation [1.26 (1.10-1.45)], respectively. Additionally, adjusting for knowledge about HPV infections, and confidence in vaccines in general was associated with vaccine intention [1.55, (1.30-1.84)] and recommendation [1.52 (1.24-1.86)]. HPV-vaccinated HS were more prone to recommend the HPV vaccine to friends and relatives [10.9 (6.6-17.9)]. CONCLUSION: A majority of HS would accept and/or recommend HPV vaccines. HS with greater knowledge about the HPV vaccine were more prone to recommend it. Strengthening knowledge about HPV and its vaccination is probably necessary before their Involvement in a HPV immunization program.

Sexuality of adolescent girls born with HIV in Senegal: an anthropological analysis.

Objectives: In Senegal, the dominant social norm upholds virginity before marriage and edifies abstinence for adolescents as a cardinal moral value. Currently, sex outside of marriage remains socially condemned. The onset of sex for adolescent girls born with HIV in Senegal brings up several challenges. In Dakar, initiatives, especially through digital applications, are being developed to support these young people. These programs are much rarer in rural settings. A study conducted in 2021 explored how adolescent girls born with HIV who live outside of Dakar experience sexuality, what socio-health constraints they face, and what support they receive from the healthcare system. Method: An anthropological study titled 'Treatment Failure among Children and Adolescents Living with HIV in Senegal, Outside Dakar' (ETEA-VIH, ANRS 12421) was conducted in 2021 in 14 regional hospitals and health centers. Semi-structured interviews were conducted with 87 HIV-positive children and adolescents, 95 parents/guardians, and 47 health care workers. Adolescent girls' onset of sexuality was specifically analyzed for 40 adolescent girls age 12-19 years old. Results: Generally, parents feign oblivion about their children's sexual lives. Mothers dread a pregnancy out of marriage because they are responsible for overseeing sex education and would be 'blamed' for the transgression. The occurrence of an unintended pregnancy can lead to exclusion from the family and a risk of transmitting HIV to the child due to the lack of medical and social support. HIV remains a stigmatizing disease that families keep secret. The risk of disclosure is a major concern. Despite sexual and reproductive health (SRH) programs, most healthcare workers are reluctant to discuss sexuality or to offer contraception to adolescent girls. Information spaces have been set up in some regional hospitals by associations trained in SRH. They are rarer in health centers. Accessibility to digital applications and discussion forums is limited due to the lack of smartphones and Internet access. Conclusion: In rural settings, HIV-positive adolescent girls are confronted with the silence that surrounds sexuality and HIV. An individualized approach and confidential access to contraception should be prioritized to support them with assistance from PLHIV associations.

Deep Dive Into MicroRNAs in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease, is thought to develop in genetically predisposed individuals as a consequence of complex interactions between dysregulated inflammatory stimuli, immunological responses, and environmental factors. The pathogenesis of IBD has yet to be fully understood. The global increase in the incidence of IBD suggests a gap in the current understanding of the disease. The development of a new diagnostic tool for inflammatory bowel disease that is both less invasive and more cost-effective would allow for better management of this condition. MicroRNAs (miRNAs) are a class of noncoding RNAs with important roles as posttranscriptional regulators of gene expression, which has led to new insights into understanding IBD. Using techniques such as microarrays and real-time polymerase chain reactions, researchers have investigated the patterns in which patients with Crohn's disease and ulcerative colitis show alterations in the expression of miRNA in tissue, blood, and feces. These miRNAs are found to be differentially expressed in IBD and implicated in its pathogenesis through alterations in autophagy, intestinal barrier, and immune homeostasis. In this review, we discuss the miRNA expression profiles associated with IBD in tissue, peripheral blood, and feces and provide an overview of the miRNA mechanisms involved in IBD.

We review the published studies on microRNA (miRNA) expression in inflammatory bowel disease, including miRNAs extracted from blood, tissue, and stool samples. We discuss the main mechanisms of miRNA involvement in inflammatory bowel disease and their potential use as biomarkers.

Treatment success or failure in children and adolescents born with HIV in rural Senegal: An anthropological perspective.

Due to the efficacy of antiretrovirals (ARVs), mortality and morbidity related to the AIDS epidemic has declined considerably in recent decades. Nevertheless in Africa, the persistence of new infections and the concerning development of ARV drug resistance reflect the challenges in preventing and treating HIV infection. These problems are especially affecting children and adolescents living with HIV (CALHIV). In 1998, Senegal was the first West African country to implement a government program for access to ARV drugs. However, care for CALHIV remains challenging. A national survey conducted in 2015 showed that 64% of CALHIV (0-19 years) in follow-up in sites outside of Dakar were in treatment failure. The article presents the results of an anthropological study that aims to examine the modalities of medical and social care for CALHIV, identify the various structural and social determinants of treatment failure or success, and ascertain their respective influence. The ethnographic survey was conducted between July 2020 and November 2021 in 11 of the 14 regions of Senegal and in 15 health facilities (11 health centers and 4 regional hospitals). The interviews and observations were conducted with 65 children and adolescents, 63 parents or guardians, and 47 health workers providing their care. The results show that situations of treatment failure or success are the result of favorable or unfavorable configurations that bring into play various actors-children, parents, health care professionals-and their interactions with and in varying sociocultural and structural contexts. This research underscores the contribution of anthropology to the analysis and understanding of care systems. From a public health perspective, our analyses argue for a differentiated approach to strengthening the skills of health facility staff, taking into account the specificity of each site.

D-amphetamine maintenance therapy reduces cocaine use in female rats.

RATIONALE: D-amphetamine maintenance therapy is a promising strategy to reduce drug use in cocaine use disorder (addiction). In both male rats and human cocaine users, d-amphetamine treatment reduces cocaine-taking and -seeking. However, this has not been examined systematically in female animals, even though cocaine addiction afflicts both sexes, and the sexes can differ in their response to cocaine. OBJECTIVES: We determined how d-amphetamine maintenance therapy during cocaine self-administration influences cocaine use in female rats. METHODS: In experiment 1, two groups of female rats received 14 intermittent access (IntA) cocaine self-administration sessions. One group received concomitant d-amphetamine maintenance treatment (COC + A rats; 5 mg/kg/day, via minipump), the other group did not (COC rats). After discontinuing d-amphetamine treatment, we measured responding for cocaine under a progressive ratio schedule, responding under extinction, and cocaine-primed reinstatement of drug-seeking. In experiment 2, we assessed the effects of d-amphetamine maintenance on these measures in already IntA cocaine-experienced rats. Thus, rats first received 14 IntA cocaine self-administration sessions without d-amphetamine. They then received 14 more IntA sessions, now either with (COC/COC + A rats) or without (COC/COC rats) concomitant d-amphetamine treatment. RESULTS: In both experiments, d-amphetamine treatment did not significantly influence ongoing cocaine self-administration behaviour. After d-amphetamine treatment cessation, cocaine-primed reinstatement of cocaine-seeking was also unchanged. However, after d-amphetamine treatment cessation, rats responded less for cocaine both under progressive ratio and extinction conditions. CONCLUSIONS: D-amphetamine treatment can both prevent and reverse increases in the motivation to take and seek cocaine in female animals.

Impact of the Exposome on the Epigenome in Inflammatory Bowel Disease Patients and Animal Models.

Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract that encompass two main phenotypes, namely Crohn's disease and ulcerative colitis. These conditions occur in genetically predisposed individuals in response to environmental factors. Epigenetics, acting by DNA methylation, post-translational histones modifications or by non-coding RNAs, could explain how the exposome (or all environmental influences over the life course, from conception to death) could influence the gene expression to contribute to intestinal inflammation. We performed a scoping search using Medline to identify all the elements of the exposome that may play a role in intestinal inflammation through epigenetic modifications, as well as the underlying mechanisms. The environmental factors epigenetically influencing the occurrence of intestinal inflammation are the maternal lifestyle (mainly diet, the occurrence of infection during pregnancy and smoking); breastfeeding; microbiota; diet (including a low-fiber diet, high-fat diet and deficiency in micronutrients); smoking habits, vitamin D and drugs (e.g., IBD treatments, antibiotics and probiotics). Influenced by both microbiota and diet, short-chain fatty acids are gut microbiota-derived metabolites resulting from the anaerobic fermentation of non-digestible dietary fibers, playing an epigenetically mediated role in the integrity of the epithelial barrier and in the defense against invading microorganisms. Although the impact of some environmental factors has been identified, the exposome-induced epimutations in IBD remain a largely underexplored field. How these environmental exposures induce epigenetic modifications (in terms of duration, frequency and the timing at which they occur) and how other environmental factors associated with IBD modulate epigenetics deserve to be further investigated.

Long-Term Overconsumption of Fat and Sugar Causes a Partially Reversible Pre-inflammatory Bowel Disease State.

Nutrition appears to be an important environmental factor involved in the onset of inflammatory bowel diseases (IBD) through yet poorly understood biological mechanisms. Most studies focused on fat content in high caloric diets, while refined sugars represent up to 40% of caloric intake within industrialized countries and contribute to the growing epidemics of inflammatory diseases. Herein we aim to better understand the impact of a high-fat-high-sucrose diet on intestinal homeostasis in healthy conditions and the subsequent colitis risk. We investigated the early events and the potential reversibility of high caloric diet-induced damage in mice before experimental colitis. C57BL/6 mice were fed with a high-fat or high-fat high-sucrose or control diet before experimental colitis. In healthy mice, a high-fat high-sucrose diet induces a pre-IBD state characterized by gut microbiota dysbiosis with a total depletion of bacteria belonging to Barnesiella that is associated with subclinical endoscopic lesions. An overall down-regulation of the colonic transcriptome converged with broadly decreased immune cell populations in the mesenteric lymph nodes leading to the inability to respond to tissue injury. Such in-vivo effects on microbiome and transcriptome were partially restored when returning to normal chow. Long-term consumption of diet enriched in sucrose and fat predisposes mice to colitis. This enhanced risk is preceded by gut microbiota dysbiosis and transcriptional reprogramming of colonic genes related to IBD. Importantly, diet-induced transcriptome and microbiome disturbances are partially reversible after switching back to normal chow with persistent sequelae that may contribute to IBD predisposition in the general population.

NOD2/CARD15 polymorphisms (P268S, IVS8+158, G908R, L1007fs, R702W) among Kuwaiti patients with Crohn's disease: A case-control study.

Background: Nucleotide-binding oligomerization domain-containing two (NOD2/CARD15) gene polymorphisms are implicated in the pathogenesis of Crohn's disease (CD). Aim: To describe the allelic frequency of NOD2/CARD15 gene variants among Kuwaiti patients with CD and investigate potential genotype/phenotype associations. Methods: Adult Kuwaiti citizens with an established diagnosis of CD and healthy controls were enrolled from October 2018 to May 2020. Three common NOD2/CARD15 polymorphisms (R702W, G908R, and L1007fs) and P268S and IVS8+158 polymorphisms were screened by polymerase chain reaction/restriction analysis length polymorphism (PCR/RFLP). Results: Ninety adult Kuwaiti patients with CD and 210 healthy subjects (as controls) were recruited. P268S, IVS8+158, G908R, and R702W minor alleles were identified in 38.9%, 21.1%, 12.2%, and 4.4% of CD patients, respectively. NOD2/CARD15 polymorphisms coexisted in 35 healthy controls (16.7%) and 21 CD patients (23.3%). Individuals with either a single or multiple polymorphism were approximately two times more likely to have CD than those with no polymorphism. Patients with multiple polymorphisms had significantly more stricturing and penetrating disease. Conclusion: NOD2/CARD15 gene polymorphisms were significantly associated with an increased risk of disease and aggressive phenotypes among the Kuwaiti CD population.

Telomeres: New players in immune-mediated inflammatory diseases?

Telomeres are repetitive DNA sequences located at the ends of linear chromosomes that preserve the integrity and stability of the genome. Telomere dysfunctions due to short telomeres or altered telomere structures can ultimately lead to replicative cellular senescence and chromosomal instability, both mechanisms being hallmarks of ageing. Chronic inflammation, oxidative stress and finally telomere length (TL) dynamics have been shown to be involved in various age-related non-communicable diseases (NCDs). Immune-mediated inflammatory diseases (IMIDs), including affections such as inflammatory bowel disease, psoriasis, rheumatoid arthritis, spondyloarthritis and uveitis belong to this group of age-related NCDs. Although in recent years, we have witnessed the emergence of studies in the literature linking these IMIDs to TL dynamics, the causality between these diseases and telomere attrition is still unclear and controversial. In this review, we provide an overview of available studies on telomere dynamics and discuss the utility of TL measurements in immune-mediated inflammatory diseases.

Investigating ADR mechanisms with Explainable AI: a feasibility study with knowledge graph mining.

BACKGROUND: Adverse drug reactions (ADRs) are statistically characterized within randomized clinical trials and postmarketing pharmacovigilance, but their molecular mechanism remains unknown in most cases. This is true even for hepatic or skin toxicities, which are classically monitored during drug design. Aside from clinical trials, many elements of knowledge about drug ingredients are available in open-access knowledge graphs, such as their properties, interactions, or involvements in pathways. In addition, drug classifications that label drugs as either causative or not for several ADRs, have been established. METHODS: We propose in this paper to mine knowledge graphs for identifying biomolecular features that may enable automatically reproducing expert classifications that distinguish drugs causative or not for a given type of ADR. In an Explainable AI perspective, we explore simple classification techniques such as Decision Trees and Classification Rules because they provide human-readable models, which explain the classification itself, but may also provide elements of explanation for molecular mechanisms behind ADRs. In summary, (1) we mine a knowledge graph for features; (2) we train classifiers at distinguishing, on the basis of extracted features, drugs associated or not with two commonly monitored ADRs: drug-induced liver injuries (DILI) and severe cutaneous adverse reactions (SCAR); (3) we isolate features that are both efficient in reproducing expert classifications and interpretable by experts (i.e., Gene Ontology terms, drug targets, or pathway names); and (4) we manually evaluate in a mini-study how they may be explanatory. RESULTS: Extracted features reproduce with a good fidelity classifications of drugs causative or not for DILI and SCAR (Accuracy = 0.74 and 0.81, respectively). Experts fully agreed that 73% and 38% of the most discriminative features are possibly explanatory for DILI and SCAR, respectively; and partially agreed (2/3) for 90% and 77% of them. CONCLUSION: Knowledge graphs provide sufficiently diverse features to enable simple and explainable models to distinguish between drugs that are causative or not for ADRs. In addition to explaining classifications, most discriminative features appear to be good candidates for investigating ADR mechanisms further.

Enhanced Electrochemical Behavior of Peanut-Shell Activated Carbon/Molybdenum Oxide/Molybdenum Carbide Ternary Composites.

Biomass-waste activated carbon/molybdenum oxide/molybdenum carbide ternary composites are prepared using a facile in-situ pyrolysis process in argon ambient with varying mass ratios of ammonium molybdate tetrahydrate to porous peanut shell activated carbon (PAC). The formation of MoO2 and Mo2C nanostructures embedded in the porous carbon framework is confirmed by extensive structural characterization and elemental mapping analysis. The best composite when used as electrodes in a symmetric supercapacitor (PAC/MoO2/Mo2C-1//PAC/MoO2/Mo2C-1) exhibited a good cell capacitance of 115 F g-1 with an associated high specific energy of 51.8 W h kg-1, as well as a specific power of 0.9 kW kg-1 at a cell voltage of 1.8 V at 1 A g-1. Increasing the specific current to 20 A g-1 still showcased a device capable of delivering up to 30 W h kg-1 specific energy and 18 kW kg-1 of specific power. Additionally, with a great cycling stability, a 99.8% coulombic efficiency and capacitance retention of ~83% were recorded for over 25,000 galvanostatic charge-discharge cycles at 10 A g-1. The voltage holding test after a 160 h floating time resulted in increase of the specific capacitance from 74.7 to 90 F g-1 at 10 A g-1 for this storage device. The remarkable electrochemical performance is based on the synergistic effect of metal oxide/metal carbide (MoO2/Mo2C) with the interconnected porous carbon. The PAC/MoO2/Mo2C ternary composites highlight promising Mo-based electrode materials suitable for high-performance energy storage. Explicitly, this work also demonstrates a simple and sustainable approach to enhance the electrochemical performance of porous carbon materials.

Calorie Restriction as a New Treatment of Inflammatory Diseases.

Immoderate calorie intake coupled with a sedentary lifestyle are major determinants of health issues and inflammatory diseases in modern society. The balance between energy consumption and energy expenditure is critical for longevity. Excessive energy intake and adiposity cause systemic inflammation, whereas calorie restriction (CR) without malnutrition, exerts a potent anti-inflammatory effect. The objective of this review was to provide an overview of different strategies used to reduce calorie intake, discuss physiological mechanisms by which CR might lead to improved health outcomes, and summarize the present knowledge about inflammatory diseases. We discuss emerging data of observational studies and randomized clinical trials on CR that have been shown to reduce inflammation and improve human health.

Characteristics of Lymphoma in Patients with Inflammatory Bowel Disease: A Systematic Review.

BACKGROUND: Lymphoma is a dreaded complication of inflammatory bowel diseases [IBD]. Knowledge about lymphoma in patients with IBD is limited to epidemiological data and the description of risk factors. We performed a systematic review to describe the clinical characteristics and prognosis of lymphoma in patients with IBD. METHODS: Electronic databases were searched up to June 1, 2020. All published clinical characteristics of lymphoma occurring in patients with IBD were collected. RESULTS: Eleven studies were included. A total of 589 lymphomas were described in patients with IBD. As seen in de novo lymphoma, non-Hodgkin's lymphoma [NHL] was the most common histological subtype [83.9%]. Diffuse large B-cell lymphoma [DLBCL] and follicular lymphoma were the most well-represented NHL in patients with IBD [30% and 13% respectively]. Two main differences were observed in comparison with de novo lymphoma: primary intestinal lymphoma [PIL] represented a large proportion of lymphoma in patients with IBD [22-75%] whereas mucosa-associated lymphoid tissue [MALT] lymphoma was under-represented. Epstein-Barr virus [EBV]-positive status was observed in a large proportion of tumours [44-75%]. Survival data of lymphoma in patients with IBD were similar to those of de novo lymphoma. DISCUSSION: This systematic review first highlights that PIL [especially DLBCL subtype] is significantly more frequent in patients with IBD and represents the most common entity. Conversely, MALT lymphoma is extremely rare in the IBD population. However, the overall quality of the evidence is low. Further studies are required to better define lymphoma characteristics in patients with IBD.

Parallel Social Information Processing Circuits Are Differentially Impacted in Autism.

Parallel processing circuits are thought to dramatically expand the network capabilities of the nervous system. Magnocellular and parvocellular oxytocin neurons have been proposed to subserve two parallel streams of social information processing, which allow a single molecule to encode a diverse array of ethologically distinct behaviors. Here we provide the first comprehensive characterization of magnocellular and parvocellular oxytocin neurons in male mice, validated across anatomical, projection target, electrophysiological, and transcriptional criteria. We next use novel multiple feature selection tools in Fmr1-KO mice to provide direct evidence that normal functioning of the parvocellular but not magnocellular oxytocin pathway is required for autism-relevant social reward behavior. Finally, we demonstrate that autism risk genes are enriched in parvocellular compared with magnocellular oxytocin neurons. Taken together, these results provide the first evidence that oxytocin-pathway-specific pathogenic mechanisms account for social impairments across a broad range of autism etiologies.

Genomic and molecular alterations in human inflammatory bowel disease-associated colorectal cancer.

Patients with inflammatory bowel disease are at increased risk of colorectal cancer, which has worse prognosis than sporadic colorectal cancer. Until recently, understanding of pathogenesis in inflammatory bowel disease-associated colorectal cancer was restricted to the demonstration of chromosomic/microsatellite instabilities and aneuploidy. The advance of high-throughput sequencing technologies has highlighted the complexity of the pathobiology and revealed recurrently mutated genes involved in the RTK/RAS, PI3K, WNT, and TGFß pathways, leading to potentially new targetable mutations. Moreover, alterations of mitochondrial DNA and the dysregulation of non-coding sequences have also been described, as well as several epigenetic modifications. Although recent studies have brought new insights into pathobiology and raised the prospect of innovative therapeutic approaches, the understanding of colorectal carcinogenesis in inflammatory bowel disease and how it differs from sporadic colorectal cancer remains not fully elucidated. Further studies are required to better understand the pathogenesis and molecular alterations leading to human inflammatory bowel disease-associated colorectal cancer.

Obesity status modifies the association between rs7556897T>C in the intergenic region SLC19A3-CCL20 and blood pressure in French children.

Background Growing evidence reports an association between inflammatory markers, obesity and blood pressure (BP). Specifically, the intergenic single nucleotide polymorphism (SNP) rs7556897T > C (MAF = 0.34) located between SLC19A3 and the CCL20 was shown to be associated with chronic inflammatory diseases. In addition, CCL20 expression was found increased in pancreatic islets of obese rodents and human pancreatic ß cells under the influence of inflammation. In this study, we hypothesized that SNP rs7556897 could affect BP levels, thus providing a link between inflammation, BP and obesity. Methods BP was measured under supine position with a manual sphygmomanometer; values reported were the means of three readings. We analyzed rs7556897 in 577 normal weight and 689 obese French children. Using real-time polymerase chain reaction (PCR), we quantified CCL20 and SLC19A3 expression in adipose tissue and peripheral blood mononuclear cells (PBMCs) of normal weight and overweight children. Results The rs7556897C allele was negatively associated with diastolic BP in normal weight children (ß = -0.012 ± 0.004, p = 0.006) but positively associated in obese children (ß = 2.178 ± 0.71, p = 0.002). A significant interaction between rs7556897T > C and the obesity status (obese or normal weight) was detected (ß = 3.49, p = 9.79 × 10-5) for BP in a combined population analysis. CCL20 mRNA was only expressed in the adipose tissue of overweight children, and its expression levels were 10.7× higher in PBMCs of overweight children than normal weight children. Finally, CCL20 mRNA levels were positively associated with rs7556897T > C in PBMCs of 58 normal weight children (ß = 0.43, p = 0.002). SLC19A3 was not expressed in PBMCs, and in adipose tissue, it showed same levels of expression in normal weight and overweight children. The gene expression results may highlight a specific involvement of CCL20 via communicating obesity/inflammation pathways that regulate BP. Conclusions Childhood obesity reverses the effect of rs7556897T > C on diastolic BP, possibly via the modulation of CCL20 expression levels.

Ex-situ nitrogen-doped porous carbons as electrode materials for high performance supercapacitor.

Nitrogen (N) doping of porous carbon materials is an effective strategy for enhancing the electrochemical performance of electrode materials. Herein, we report on ex-situ (post) nitrogen-doped porous carbons prepared using a biomass waste, peanut shell (PS) as a carbon source and melamine as the nitrogen source. The synthesis method involved a two-step mechanism, initial chemical activation of the PS using KOH and post N-doping of the activated carbon. The effect of the activating agent/precursor ratio and the ex-situ N-doping on the structural, textural, electrochemical properties of the porous carbons was studied. The ex-situ N-doped porous carbon with an optimum amount of KOH to PS exhibited the best capacitance performance with a specific surface area (SSA) of 1442 m2 g-1 and an enriched nitrogen content (3.2 at %). The fabricated symmetric device exhibited a 251.2 F g-1 specific capacitance per electrode at a gravimetric current of 1 A g-1 in aqueous electrolyte (2.5 M KNO3) at a wide cell voltage of 2.0 V. A specific energy of 35 Wh kg-1 with a corresponding specific power of 1 kW kg-1 at 1 A g-1 was delivered with the device still retaining up to 22 Wh kg-1 and a 20 kW kg-1 specific power even at 20 A g-1. Moreover, long term device stability was exhibited with an 83.2% capacity retention over 20 000 charge/discharge cycles and also a good rate capability after 180 h of floating at 5 A g-1. This great performance of the symmetric supercapacitor can be correlated to the surface porosity and post nitrogen-doping effect which increased the electrochemically-active sites resulting in a remarkable charge storage capability.

Polyphenol-rich tea decreases iron absorption from fortified wheat bread in Senegalese mother-child pairs and bioavailability of ferrous fumarate is sharply lower in children.

BACKGROUND/OBJECTIVES: Fractional iron absorption (FAFe) from ferrous fumarate (FeFum) and ferrous sulfate (FeSO4) in adults is generally comparable. While FeFum is commonly used to fortify infant foods, FAFe from FeFum in young children and infants may be decreased compared with FeSO4 and this effect has not been assessed in inhibitory vs noninhibitory meals. Previous studies also reported FAFe to be strongly correlated in mother-child pairs. Our objective was to measure FAFe from fortified bread labeled with 58FeSO4 and 57FeFum in mother-child pairs with and without a commonly consumed herbal tea of Combretum micranthum (Tisane Kinkéliba, TK). METHODS: Senegalese mother-child pairs (n = 17) were randomly assigned to receive, in a 2 × 2 factorial design, fortified bread with 58FeSO4 or 57FeFum consumed with TK or water. FAFe was assessed by measuring erythrocyte incorporation of stable iron-isotopes 14 days after administration. RESULTS: In children, relative bioavailability (RBV) from FeFum was 51 and 64% compared with FeSO4 when served with TK or water (both, P < 0.05). In mothers, the presence of TK decreased FAFe by 56% (P < 0.05) and 50% (P = 0.077) and in children by 65 and 72% (both, P < 0.0001), in the meals with 58FeSO4 and 57FeFum, respectively. After adjustment for plasma ferritin, there was a positive correlation between FAFe in mothers and children (r = 0.4142, P = 0.001). CONCLUSIONS: In Senegalese women and children, herbal tea decreased FAFe from a wheat-based meal. The RBV of FeFum was low in children but not in their mothers. FAFe was modestly correlated in mother-child pairs, possibly due to shared genetic, epigenetic or environmental background.