Distribution and dynamics of Anopheles gambiae s.l. larval habitats in three Senegalese cities with high urban malaria incidence.

Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November-December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP).

Dietary Quality and Associated Factors among Women of Reproductive Age in Six Sub-Saharan African Countries.

The burden of micronutrient malnutrition is high among women of reproductive age (WRA) in sub-Saharan Africa. We examined the dietary quality and associated factors for WRA in Cameroon, Côte d'Ivoire, Kenya, Nigeria, Senegal, and Tanzania. Data were collected from women aged 15-49 years using representative Diet Quality Questionnaire surveys. The Minimum Dietary Diversity for Women (MDD-W), All-5 (key food group) consumption, noncommunicable disease risk (NCD-Risk), and Global Dietary Recommendation (GDR) indicators were assessed. Participants included N = 16,584 women [Cameroon: N = 2073; Côte d'Ivoire: N = 242; Kenya: N = 864; Adamawa State (Nigeria): N = 1283; Benue State (Nigeria): N = 1047; Nasarawa State (Nigeria): N = 1151; Senegal: N = 7232; Tanzania: N = 2692]. The MDD-W ranged from 43.0% in Tanzania to 81.4% in Côte d'Ivoire and was higher in urban, compared to rural, areas in Cameroon, Kenya, Nasarawa, Senegal, and Tanzania (p < 0.001). Increased education and wealth were positively associated with MDD-W in Kenya, Benue, Senegal, and Tanzania. Fewer than half of all women attained All-5 consumption. NCD-Risk scores ranged from 1.13 (95% CI: 1.08, 1.17) in Tanzania to 2.28 (95% CI: 2.16, 2.40) in Nasarawa, and women's GDR scores ranged from 10.47 (95% CI: 10.40, 10.54) in Cameroon to 11.45 (95% CI: 11.25, 11.64) in Côte d'Ivoire. Our findings highlight key aspects of women's diets in sub-Saharan African settings to enable greater awareness and more targeted responses to the specific areas needing the most improvement.

Vitamin A supplementation coverage and associated factors for children aged 6 to 59 months in integrated and campaign-based delivery systems in four sub-Saharan African countries.

BACKGROUND: Vitamin A deficiency (VAD) is a leading contributor to the poor health and nutrition of young children in sub-Saharan Africa. Funding constraints are compelling many countries to shift from longstanding campaigns to integrating vitamin A supplementation (VAS) into routine health services. We assessed child VAS coverage and associated factors for integrated delivery systems in Mozambique, Senegal, and Sierra Leone and for a campaign-based delivery strategy in Tanzania. METHODS: Data were obtained using representative household surveys administered to primary caregivers of N = 16,343 children aged 6-59 months (Mozambique: N = 1,659; Senegal: N = 7,254; Sierra Leone: N = 4,149; Tanzania: N = 3,281). Single-dose VAS coverage was assessed and bivariate and multivariable associations were examined for child VAS receipt with respect to rural or urban residence; child age and sex; maternal age, education, and VAS program knowledge; and household wealth. RESULTS: VAS coverage for children aged 6-59 months was 42.8% (95% CI: 40.2, 45.6) in Mozambique, 46.1% (95% CI: 44.9, 47.4) in Senegal, 86.9% (95% CI: 85.8, 87.9) in Sierra Leone, and 42.4% (95% CI: 40.2, 44.6) in Tanzania and was significantly higher for children 6-11 vs. 24-59 months in Mozambique, Senegal, and Tanzania. In Sierra Leone, children aged 12-23 months (aOR = 1.86; 95% CI: 1.20, 2.86) and 24-59 months (aOR = 1.55; 95% CI: 1.07, 2.25) were more likely to receive VAS, compared to those 6-11 months. Maternal awareness of VAS programs was associated with higher uptake in Mozambique (aOR = 4.00; 95% CI: 2.81, 5.68), Senegal (aOR = 2.72; 95% CI: 2.35, 3.15), and Tanzania (aOR = 14.50; 95% CI: 10.98, 19.17). Increased household wealth was associated with a higher likelihood of child VAS in Senegal and Tanzania. CONCLUSIONS: Our findings indicate routine delivery approaches for VAS are not achieving the level of coverage needed for public health impact in these settings. Intensive outreach efforts contributed to the higher coverage in Sierra Leone and highlight the importance of reducing the burdens associated with seeking supplementation at health facilities. As countries move towards incorporating VAS into routine health services, the essentiality of informed communities and potential losses for older children and socio-economically disadvantaged populations are key considerations in the sub-Saharan African context.

Urban malaria vector bionomics and human sleeping behavior in three cities in Senegal.

BACKGROUND: Malaria is endemic in Senegal, with seasonal transmission, and the entire population is at risk. In recent years, high malaria incidence has been reported in urban and peri-urban areas of Senegal. An urban landscape analysis was conducted in three cities to identify the malaria transmission indicators and human behavior that may be driving the increasing malaria incidence occurring in urban environments. Specifically, mosquito vector bionomics and human sleeping behaviors including outdoor sleeping habits were assessed to guide the optimal deployment of targeted vector control interventions. METHODS: Longitudinal entomological monitoring using human landing catches and pyrethrum spray catches was conducted from May to December 2019 in Diourbel, Kaolack, and Touba, the most populous cities in Senegal after the capital Dakar. Additionally, a household survey was conducted in randomly selected houses and residential Koranic schools in the same cities to assess house structures, sleeping spaces, sleeping behavior, and population knowledge about malaria and vector control measures. RESULTS: Of the 8240 Anopheles mosquitoes collected from all the surveyed sites, 99.4% (8,191) were An. gambiae s.l., and predominantly An. arabiensis (99%). A higher number of An. gambiae s.l. were collected in Kaolack (77.7%, n = 6496) than in Diourbel and Touba. The overall mean human biting rate was 14.2 bites per person per night (b/p/n) and was higher outdoors (15.9 b/p/n) than indoors (12.5 b/p/n). The overall mean entomological inoculation rates ranged from 3.7 infectious bites per person per year (ib/p/y) in Diourbel to 40.2 ib/p/y in Kaolack. Low anthropophilic rates were recorded at all sites (average 35.7%). Of the 1202 households surveyed, about 24.3% of household members slept outdoors, except during the short rainy season between July and October, despite understanding how malaria is transmitted and the vector control measures used to prevent it. CONCLUSION: Anopheles arabiensis was the primary malaria vector in the three surveyed cities. The species showed an outdoor biting tendency, which represents a risk for the large proportion of the population sleeping outdoors. As all current vector control measures implemented in the country target endophilic vectors, these data highlight potential gaps in population protection and call for complementary tools and approaches targeting outdoor biting malaria vectors.

The Synthesis, Characterization, and Fluxional Behavior of a Hydridorhodatetraborane.

The octahydridotriborate anion plays a crucial role in the field of polyhedral boron chemistry, facilitating the synthesis of higher boranes and the preparation of diverse transition metal complexes. Among the stable forms of this anion, CsB3H8 (or (n-C4H9)4N)[B3H8] have been identified. These salts serve as valuable precursors for the synthesis of metallaboranes, wherein the triborate anion acts as a ligand coordinating to the metal center. In this study, we have successfully synthesized a novel rhodatetraborane dihydride, [Rh(η2-B3H8)(H)2(PPh3)2] (1), which represents a Rh(III) complex featuring a bidentate chelate ligand fasormed by B3H8-. Extensive characterization of this rhodatetraborane complex has been performed using NMR spectroscopy in solution and X-ray diffraction analysis in the solid state. Notably, the complex exhibits intriguing fluxional behavior, which has been investigated using NMR techniques. Moreover, we have explored the reactivity of complex 1 towards pyridine (py) and dimethylphenylphosphine (PMe2Ph). Our findings highlight the labile nature of this four-vertex rhodatetraborane as it undergoes disassembly upon attack from the corresponding Lewis base, resulting in the formation of borane adducts, LBH3, where L = py, PMe2Ph. Furthermore, in these reactions, we report the characterization of new cationic hydride complexes, such as [Rh(H)2(PPh3)2 (py)]+ (2) and [Rh(H)2(PMe2Ph)4]+. Notably, the latter complex has been characterized as the octahydridotriborate salt [Rh(H)2(PMe2Ph)4][B3H8] (3), which extends the scope of rhodatetraborane derivatives.

COVID-19 concerns among caregivers and vitamin A supplementation coverage among children aged 6-59 months in four countries in Western sub-Saharan Africa.

OBJECTIVE: To assess child vitamin A supplementation (VAS) coverage in 2019 and 2020 and explore key factors, including COVID-19 concerns, that influenced VAS status in four sub-Saharan African countries. DESIGN: Data from eight representative household surveys were used to assess VAS coverage. Multivariable logistic regression models examined the effect of rural/urban residence, child sex and age, caregiver education, COVID-19 concern and household wealth on VAS status. SETTING: Nine (2019) and 12 (2020) districts in Burkina Faso, Côte d'Ivoire, Guinea and Mali. PARTICIPANTS: 28 283 caregivers of children aged 6-59 months. RESULTS: Between 2019 and 2020, VAS coverage increased in Burkina Faso (82·2-93·1 %), Côte d'Ivoire (90·3-93·3 %) and Mali (76·1-79·3 %) and decreased in Guinea (86·0 % to 81·7 %). Rural children had a higher likelihood of VAS uptake compared with urban children in Burkina Faso (adjusted OR (aOR) = 4·22; 95 % CI: 3·11, 5·72), Côte d'Ivoire (aOR = 5·19; 95 % CI: 3·10, 8·70) and Mali (aOR = 1·41; 95 % CI: 1·15, 1·74). Children aged 12-59 months had a higher likelihood of VAS uptake compared with children aged 6-11 months in Côte d'Ivoire (aOR = 1·67; 95 % CI: 1·12, 2·48) and Mali (aOR = 1·74; 95 % CI: 1·34, 2·26). Moderate-to-high COVID-19 concern was associated with a lower likelihood of VAS uptake in Côte d'Ivoire (aOR = 0·55; 95 % CI: 0·37, 0·80). CONCLUSION: The increase in VAS coverage from 2019 to 2020 suggests that COVID-19 concerns may not have limited VAS uptake in some African countries, though geographic inequities should be considered.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia

Abstract Objective We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. Methods In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. Results The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p= 0.0009), CD38 expression (p= 0.039), unmutated IGVH status (p= 0.0009) and presence of cytogenetic abnormalities (for del 13q, p= 0.0012, while for other cytogenetic aberrations, p= 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r= -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p= 0.41) or gender (median, 19% for males vs. 20% for females; p= 0.76). Conclusion When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Smudge cells percentage on blood smear is a reliable prognostic marker in chronic lymphocytic leukemia.

OBJECTIVE: We evaluated the relevance of using the smudge cell percentage in the blood smear as a prognostic marker in CLL. METHODS: In this prospective study, 42 untreated Senegalese patients with CLL were enrolled. The diagnosis was established, based on the peripheral blood count and flow cytometry using the Matutes score. Cytogenetic aberrations, assessed by fluorescence in situ hybridization (FISH), were available for 30 patients, while the immunoglobulin heavy chain genes (IGVH) mutation status was performed by next-generation sequencing (NGS) in 24 patients. The SC percentage was determined in the blood smear, as previously described. Statistical analyses were executed using the GraphPad Prism 8. RESULTS: The mean age was 63 years (48 - 85) and the male: female sex ratio was 4.66. A low SC (< 30%) percentage was correlated with Binet stage B/C (p = 0.0009), CD38 expression (p = 0.039), unmutated IGVH status (p = 0.0009) and presence of cytogenetic abnormalities (for del 13q, p = 0.0012, while for other cytogenetic aberrations, p = 0.016). An inverse correlation was found between the SC percentage and the absolute lymphocyte count (r = -0.51) and patients with higher percentage of SCs had a prolonged survival. However, there was no correlation between the SC percentage and age (p = 0.41) or gender (median, 19% for males vs. 20% for females; p = 0.76). CONCLUSION: When less than 30%, the SC was associated with a poor prognosis in CLL. Easy and affordable, the percentage of SCs in a blood smear could be a reliable prognostic marker, accessible to all CLL patients, mainly those in developing countries.

Adult Hemophagocytic Lymphohistiocytosis in Sub-Saharan Area: A Retrospective Study of 26 cases.

Introduction and background Hemophagocytic lymphohistiocytosis (HLH) is a condition caused by inappropriate stimulation of macrophage cells with hemophagocytosis. This paper aims to describe its diagnostic specifics and etiology and seeks to identify the factors that affect its prognosis in the black African adult population. Methods  A retrospective multicentre study was carried out in three medical units in Senegal: Department of Internal Medicine at Pikine Teaching Hospital, and Department of Internal Medicine and Department of Nephrology at Aristide Le Dantec Teaching Hospital; the study covered the period from January 1, 2012 to March 30, 2015. This study included patients aged 18 years and older with a Hemophagocytosis Score (HScore) of ≥202 (with probabilities of acquired HLH of >90%). The data was obtained through medical records. Results In total, 26 patient files were included. The average age of the patients was 41 years, with a male-to-female ratio of 2.25:1. Fever and cytopenia were frequent. Other clinical signs included peripheral lymphadenopathy (69.2%), hepatomegaly (53.8%), splenomegaly (34.6%), neurological disorders (34.5%), and respiratory disorders (15.3%). Thrombocytosis was noted in three cases. Renal involvement was present in eight patients, with one case of collapsing glomerulopathy. The bone marrow aspirate revealed myelodysplasia in 12 patients. The dominant etiologies of HLH were hematological malignancies and infections. The mortality rate of HLH was 73%. Male gender and non-etiological targeted therapy were significantly associated with mortality. However, the age of <40 years in patients and current systemic disease in some cases were correlated with survival. The use of etoposide had no significant impact on the prognosis of our patients. Conclusion A high rate of male predominance, important central nervous system disorders, myelodysplasia, and paradoxical thrombocytosis were found to be the distinct features of adult HLH in our study population.

The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward.

BACKGROUND: Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for understanding how these genetic loci physiologically impact disease development. METHODS: We performed a PCR-free expression assay targeting genes located nearby the GWAS-identified SNPs associated with BMI/obesity in a large panel of human tissues. Furthermore, we analyzed several genetic risk scores (GRS) summing GWAS-identified alleles associated with increased BMI in 4236 individuals. RESULTS: We found that the expression of BMI/obesity susceptibility genes was strongly enriched in the brain, especially in the insula (p = 4.7 × 10-9) and substantia nigra (p = 6.8 × 10-7), which are two brain regions involved in addiction and reward. Inversely, we found that top obesity/BMI-associated loci, including FTO, showed the strongest gene expression enrichment in the two brain regions. CONCLUSIONS: Our data suggest for the first time that the susceptibility genes for common obesity may have an effect on eating addiction and reward behaviors through their high expression in substantia nigra and insula, i.e., a different pattern from monogenic obesity genes that act in the hypothalamus and cause hyperphagia. Further epidemiological studies with relevant food behavior phenotypes are necessary to confirm these findings.

Impact of Highly Active Antiretroviral Therapy on Chronic Hepatitis B Serological Markers among Senegalese HIV Co-infected Children.

BACKGROUND: Coinfection with human immunodeficiency virus (HIV) and hepatitis B virus (HBV) causes complex interactions. The aim of this study was to evaluate the seroprevalence and HBV evolution among HIV coinfected children receiving highly active antiretroviral therapy (HAART). METHODS: A descriptive cross-sectional study was carried out among 252 HIV infected children enrolled in the Hôpital d'enfants Albert Royer, Dakar, Senegal, from April 2013 to March 2015. Clinical characteristics, immuno-virological status, alanine aminotransferase (ALT) levels, and HBV serological marker were taken from the patients' medical records. RESULTS: Overall, 7 children were HBsAg positive with a determinate prevalence rate of 2.8%. Median age at HIV diagnosis was 3.5 years (1.3-14.4 years). According to World Health Organization (WHO) staging, 40.1% of children were stage 4 and 25.8% were stage 3. Of the 7 HIV/HBV-co-infected children, 6 (86%) received lamivudine alone at initiation of treatment, and only one child received tenofovir associated with emtricitabine. Overall median HAART duration treatment including lamivudine alone or tenofovir+lamivudine (or emtricitabine) was 7.7 years (3.3-11.3). Only the two children (29%) receiving lamivudine during follow-up had high HBV DNA load despite having good immuno-virological status. Suppression of HBV DNA replication was achieved in 5 (71.4%) of 7 children. CONCLUSION AND GLOBAL HEALTH IMPLICATION: HIV/HBV coinfection prevalence was low in our study. HBsAg and HBeAg loss were low while suppression of HBV DNA replication was still higher on tenofovir. Screening and monitoring HBV infection among all HIV infected children are required to direct treatment in order to improve children HBV/HIV coinfected outcome.

Impact of vegetation on the methane budget of a temperate forest.

Upland forest soils are known to be the main biological sink for methane, but studies have shown that net methane uptake of a forest ecosystem can be reduced when methane emissions by vegetation are considered. We estimated the methane budget of a young oak plantation by considering tree stems but also the understorey vegetation. Automated chambers connected to a laser-based gas analyser, on tree stems, bare soil and soil covered with understorey vegetation, recorded CH4 fluxes for 7 months at 3 h intervals. Tree stem emissions were low and equated to only 0.1% of the soil sink. Conversely, the presence of understorey vegetation increased soil methane uptake. This plant-driven enhancement of CH4 uptake occurred when the soil was consuming methane. At the stand level, the methane budget shifted from -1.4 ± 0.4 kg C ha-1 when we upscaled data obtained only on bare soil, to -2.9 ± 0.6 kg C ha-1 when we considered soil area that was covered with understorey vegetation. These results indicate that aerenchymatous plant species, which are known to reduce the methane sink in wetlands, actually increase soil methane uptake two-fold in an upland forest by enhancing methane and oxygen transport and/or by promoting growth of methanotrophic populations.

Poor Sensitivity of Commercial Rapid Diagnostic Tests for Hepatitis B e Antigen in Senegal, West Africa.

Limited access to nucleic acid tests for hepatitis B virus (HBV) DNA is a significant barrier to the effective management of chronic HBV infection in resource-poor countries. Alternatively, HBV e antigen (HBeAg) may accurately indicate high viral replication. We assessed the diagnostic performance of three commercially available rapid diagnostic tests (RDTs) for HBeAg (SD Bioline, Insight and OneStep) against a quantitative chemiluminescent immunoassay (CLIA, Architect). Using stored sera from adults with chronic HBV infection, we tested RDTs in three groups in Senegal (48 HBeAg-positive, 196 HBeAg-negative, and 117 cases with high HBV DNA (≥ 106 IU/mL)) and one group in France (17 HBeAg-positive East Asians). In Senegal, the sensitivity and specificity for HBeAg detection were 29.8% and 100% for SD Bioline, 31.1% and 100% for Insight, and 42.5% and 98.4% for OneStep, respectively. The lower limits of detection of these RDTs were very high (> 2.5 log10 Paul Ehrlich Institut units/mL). Their low sensitivity was also confirmed in HBeAg-positive Asian samples (35.3-52.9%). The prevalence of HBeAg in highly viremic (≥ 106 IU/mL) Senegalese patients was low: 58.1% using CLIA and 24.5-37.5% using RDTs. Hepatitis B e antigen prevalence was similarly low in a subgroup of 28 Senegalese women of childbearing age with a high viral load (≥ 106 IU/mL). Approximately, half of highly viremic adults do not carry HBeAg in Africa, and HBeAg RDTs had remarkably poor analytical and diagnostic sensitivity. This implies that HBeAg-based antenatal screening, particularly if using the currently available HBeAg RDTs, may overlook most pregnant women at high risk of mother-to-child transmission in Africa.

[Diagnostic and evolutionary profile of multiple myeloma in Senegal: monocentric study conducted from 2005 to 2016]. / Profil diagnostique et évolutif du myélome multiple au Sénégal: étude monocentrique de 2005 à 2016.

INTRODUCTION: Accessibility to innovative multiple myeloma therapies is limited in sub-Saharan Africa. This study aimed to describe the diagnostic and evolutionary features observed during treatment of our patients with myeloma. METHODS: We conducted a retrospective, descriptive, analytical study (2005 - 2016) of patients with myeloma included in the study based on International Myeloma Working Group (IMWG) Criteria (2003,2014) at the Hopital Aristide Le Dantec (Senegal). RESULTS: We collected data from 136 medical records (69 men, 67 women) of patients with an average age of 59 years ± 10.1 years, who were less than 65 years of age in 69.1% of cases. Tell-tale signs included bone pain (96.3%), renal failure (36.8%), infection (23.5%), pathological fracture (17.6%), spinal cord compression (16.9%) and malignant hypercalcaemia (16.2%). Isotopic antiglobulin test showed that anti-IgG could be detected in 61.3% of cases and Kappa in 65% of cases. Patients were classified stage III (59.4%) and I-II (40.6%)of the index staging system. The median survival of patients under conventional traitement (Méphalan-Prédnisone: 67.6%, innovative: 5.9%) was 20 months (1-78 months). Survival rates are better in the absence of neurological and infectious complications and for patients with score I-II of the index Staging System. CONCLUSION: In our study, multiple myeloma was frequently diagnosed before age 65, at advanced stage of tumor mass. Early detection and access to adequate therapies could improve overall survival.

Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion.

OBJECTIVES: Genome-wide association studies (GWAS) have identified >100 loci independently contributing to type 2 diabetes (T2D) risk. However, translational implications for precision medicine and for the development of novel treatments have been disappointing, due to poor knowledge of how these loci impact T2D pathophysiology. Here, we aimed to measure the expression of genes located nearby T2D associated signals and to assess their effect on insulin secretion from pancreatic beta cells. METHODS: The expression of 104 candidate T2D susceptibility genes was measured in a human multi-tissue panel, through PCR-free expression assay. The effects of the knockdown of beta-cell enriched genes were next investigated on insulin secretion from the human EndoC-ßH1 beta-cell line. Finally, we performed RNA-sequencing (RNA-seq) so as to assess the pathways affected by the knockdown of the new genes impacting insulin secretion from EndoC-ßH1, and we analyzed the expression of the new genes in mouse models with altered pancreatic beta-cell function. RESULTS: We found that the candidate T2D susceptibility genes' expression is significantly enriched in pancreatic beta cells obtained by laser capture microdissection or sorted by flow cytometry and in EndoC-ßH1 cells, but not in insulin sensitive tissues. Furthermore, the knockdown of seven T2D-susceptibility genes (CDKN2A, GCK, HNF4A, KCNK16, SLC30A8, TBC1D4, and TCF19) with already known expression and/or function in beta cells changed insulin secretion, supporting our functional approach. We showed first evidence for a role in insulin secretion of four candidate T2D-susceptibility genes (PRC1, SRR, ZFAND3, and ZFAND6) with no previous knowledge of presence and function in beta cells. RNA-seq in EndoC-ßH1 cells with decreased expression of PRC1, SRR, ZFAND6, or ZFAND3 identified specific gene networks related to T2D pathophysiology. Finally, a positive correlation between the expression of Ins2 and the expression of Prc1, Srr, Zfand6, and Zfand3 was found in mouse pancreatic islets with altered beta-cell function. CONCLUSIONS: This study showed the ability of post-GWAS functional studies to identify new genes and pathways involved in human pancreatic beta-cell function and in T2D pathophysiology.

Formes familiales du syndrome de Gougerot-Sjögren : étude de 22 familles multiplex

Introduction : Les facteurs génétiques du SGS, outre les modèles animaux, sont déterminés par le biais de leurs formes familiales. L'objectif de ce travail était d'étudier les aspects phénotypiques des formes familiales du SGS. Patients et méthodes : Etude réalisée dans le service de Rhumatologie du CHU Aristide Le Dantec de Dakar entre Janvier 2013 et Mars 2016, où nous avons colligé les observations de familles multiplex de SGS répondant aux critères de consensus de 2002.Résultats : Vingt-deux familles ont été colligées à partir de 22 propositus (17 femmes et 5 hommes), d'âge moyen de 31,5 ans au début apparent de la maladie. Le SGS chez ces propositus était primitif dans 8 cas et secondaire à une PR dans 14 cas. Les familles totalisaient 921 membres. Soixante- quinze (54 femmes et 21 hommes), y compris les cas index présentaient un SGS (54 primitifs et 21 secondaires), soit une prévalence de 8,14 %. Les apparentés de premiers degré atteints étaient au nombre de 46 (85%). Les autres maladies auto- immunes associées étaient une PR (16 cas), un lupus systémique (1 cas), une polymyosite (1 cas), une sclérodermie systémique (1 cas), un vitiligo (1 cas) et une maladie de Basedow (1 cas). Les autres affections répertoriées étaient : lymphome oculaire (1 cas), cancer du col de l'utérus (1 cas). L'évolution sous traitement fut favorable, sauf chez 1 cas décédé. Conclusion : Le caractère familial du SGS chez nos malades plaide en faveur de l'implication de facteurs génétiques dans le déterminisme de la maladie

Rosai Dorfman disease diagnosed by fine-needle aspiration cytology in a young man with HIV infection.

RDD (Rosai Dorfman disease) is a rare and benign histiocytic proliferative disorder of unknown etiology. FNAC (Fine-needle aspiration cytology) is a useful and reliable tool for the diagnosis of RDD, and as such, biopsy is avoidable.

Knowledge of and management attitude regarding dentin hypersensitivity among dentists from a West African country.

AIM: The aim of the present study was to assess knowledge of, and management attitude of dentists regarding dentin hypersensitivity. MATERIALS AND METHODS: The study involved all the dentists from private and public sectors, exerting in Senegal. The following data were requested from the surveyed dentists using an anonymous questionnaire; sociodemographics (i.e. age, gender, area of activity, etc.) and knowledge on triggering factor, type of pain, diagnosis, preventive and curative procedures. RESULTS: Out of the 238 dentists who received the questionnaire, 68.9% returned properly filled forms. They were 116 males and 48 females with a mean age of 41.99 ± 8.50 years. Eighty three percent of the participants had a good understanding of the characteristics of pain related to DH and 92% recognized chemical and thermal stimuli as triggering factor while mechanical stimulus was not evoked. Many responders (90.9%) did not have any idea of the mechanism for pain transmission across the dentin. Regarding diagnosis technique, 68% use mechanical stimuli to elicit DH pain. Regarding management procedure, the use of desensitizing tooth paste is the mostly chosen option followed by professional topical application of fluoride. More than 1/3rd of the surveyed dentists confess resorting to root canal to manage DH. CONCLUSION: We recommend incorporation of basic science knowledge on orofacial pain and competencies to manage painful conditions like dentin hypersensitivity. Also, health regulatory institutions should make continuing dental education a requirement to preserve the dental licensure.

Evaluation of mineral trioxide aggregate (MTA) versus calcium hydroxide cement (Dycal(®) ) in the formation of a dentine bridge: a randomised controlled trial.

AIM: To assess the effectiveness of mineral trioxide aggregate (MTA) used as an indirect pulp-capping material in human molar and premolar teeth. METHODOLOGY: We conducted a clinical evaluation of 60 teeth, which underwent an indirect pulp-capping procedure with either MTA or calcium hydroxide cement (Dycal(®) ). Calcium hydroxide was compared with MTA and the thickness of the newly formed dentine was measured at regular time intervals. The follow-up was at 3 and 6 months, and dentine formation was monitored by radiological measurements on digitised images using Mesurim Pro(®) software. RESULTS: At 3 months, the clinical success rates of MTA and calcium hydroxide were 93% and 73%, respectively (P = 0.02). At 6 months, the success rate was 89.6% with MTA, and remained steady at 73% with calcium hydroxide (P = 0.63). The mean initial residual dentine thickness was 0.23 mm, and increased by 0.121 mm with MTA and by 0.136 mm with calcium hydroxide at 3 months. At 6 months, there was an increase of 0.235 mm with MTA and of 0.221 mm with calcium hydroxide. CONCLUSIONS: A higher success rate was observed in the MTA group relative to the Dycal(®) group after 3 months, which was statistically significant. After 6 months, no statistically significant difference was found in the dentine thickness between the two groups. Additional histological investigations are needed to support these findings.

Anti-oxidant, anti-inflammatory and immunomodulating properties of an enzymatic protein hydrolysate from yellow field pea seeds.

PURPOSE: Enzymatic protein hydrolysates of yellow pea seed have been shown to possess high anti-oxidant and anti-bacterial activities. The aim of this work was to confirm the anti-oxidant, anti-inflammatory and immunomodulating activities of an enzymatic protein hydrolysate of yellow field pea seeds. METHODS: The anti-oxidant and anti-inflammatory properties of peptides from yellow field pea proteins (Pisum sativum L.) were investigated in LPS/IFN-γ-activated RAW 264.7 NO⁻ macrophages. The immunomodulating potential of pea protein hydrolysate (PPH) was then studied in a murine model. RESULTS: Pea protein hydrolysate, after a 12 h pre-treatment, showed significant inhibition of NO production by activated macrophages up to 20%. Moreover, PPH significantly inhibited their secretion of pro-inflammatory cytokines, TNF-α- and IL-6, up to 35 and 80%, respectively. Oral administration of PPH in mice enhanced the phagocytic activity of their peritoneal macrophages and stimulated the gut mucosa immune response. The number of IgA+ cells was elevated in the small intestine lamina propria, accompanied by an increase in the number of IL-4+, IL-10+ and IFN-γ+ cells. This was correlated to up-regulation of IL-6 secretion by small intestine epithelial cells (IEC), probably responsible for B-cell terminal differentiation to IgA-secreting cells. Moreover, PPH might have increased IL-6 production in IECs via the stimulation of toll-like receptors (TLRs) family, especially TLR2 and TLR4 since either anti-TLR2 or anti-TLR4 was able to completely abolish PPH-induced IL-6 secretion. CONCLUSIONS: Enzymatic protein degradation confers anti-oxidant, anti-inflammatory and immunomodulating potentials to pea proteins, and the resulted peptides could be used as an alternative therapy for the prevention of inflammatory-related diseases.