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In this paper, we investigate the harmonicity of a tangent map ϕ : (TM,g) → (TN,h), in the case when the tangent bundles TM and TN are endowed with natural Riemannian metrics g, h. In this work we generalize previous results related to the article of A. Sanini [24]. [ABSTRACT FROM AUTHOR]

In this paper, we investigate the harmonicity and biharmonicity of a tangent map Φ: (TM; gs) → (TN; hs) in the case where the tangent bundles TM; TN are endowed with Sasaki Riemannian metrics gs; hs. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To estimate the prevalence of Behçet's disease (BD) in a multiethnic population living in France, with particular focus on disease risk among immigrants. METHODS: The study was conducted in a county in the Paris metropolitan area that is home to 1,094,412 adults (ages >/=15 years), of whom 26% are of non-European ancestry. Patients with BD living in this area during 2003 were identified using 3 sources (hospitals, community physicians, and the National Health Insurance database), and diagnoses were verified using the International Study Group criteria. Standardized, year-2003 prevalence rates were computed for the overall population and for each ethnic group. Stratified prevalence rates according to age at immigration to France were calculated to investigate the relationship between age at immigration and BD risk. RESULTS: Seventy-nine subjects fulfilled our search criteria. The overall prevalence per 100,000 adults was 7.1 (95% confidence interval [95% CI] 3.5-14.4), and the prevalence for populations of European, North African, and Asian ancestry was 2.4 (95% CI 0.6-7.2), 34.6 (95% CI 24.4-47.5), and 17.5 (95% CI 10.7-27.2), respectively. Within the migrant population of either North African or Asian ancestry, BD prevalences were similar for residents born in France, residents <15 years old at immigration, and residents >/=15 years old at immigration. CONCLUSION: Our findings indicate that the prevalence of BD among immigrants of North African or Asian ancestry is significantly higher than that in the European-origin population, and comparable with rates reported from North Africa and Asia. Moreover, our results suggest that BD risk is not related to age at immigration. These findings support the hypothesis that BD has a primarily hereditary basis. [ABSTRACT FROM AUTHOR]

A convenient and effective synthesis of imidazo[1,2- a ]pyrimidine derivatives has been developed under microwave irradiations using Al 2 O 3 as a catalyst in solvent-free conditions. The functionalized imidazo[1,2- a ]pyrimidine derivatives are useful in biochemistry and medical science. In our investigation, the antimicrobial activity of the synthesized compounds was evaluated against 13 microorganisms, including 6 Gram-positive bacteria, 4 Gram-negative bacteria, and 3 pathogenic fungi. Bioactivity tests revealed that the majority of the compounds exhibited good antimicrobial activity. Finally, molecular docking simulations and ADME-T predictions were performed, showing that the most active compounds have good binding modes with microbial targets and promising pharmacokinetic safety profiles.

Background: PRIMVAC is a VAR2CSA-derived placental malaria vaccine candidate aiming to prevent serious clinical outcomes of Plasmodium falciparum infection during pregnancy. We assessed the safety and immunogenicity of PRIMVAC adjuvanted with Alhydrogel or glucopyranosyl lipid adjuvant in stable emulsion (GLA-SE) in French and Burkinabe women who were not pregnant., Methods: This first-in-human, randomised, double-blind, placebo-controlled, dose escalation trial was done in two staggered phases, a phase 1A trial in 18-35-year-old women who were malaria naive in a hospital in France and a subsequent phase 1B trial in women who were naturally exposed to P falciparum and nulligravid in the clinical site of a research centre in Burkina Faso. Volunteers were recruited into four sequential cohorts receiving PRIMVAC intramuscularly at day 0, 28, and 56: two cohorts in France receiving 20 μg or 50 μg of PRIMVAC and then two in Burkina Faso receiving 50 μg or 100 μg of PRIMVAC. Volunteers were randomly assigned (1:1) to two groups (PRIMVAC adjuvanted with either Alhydrogel or GLA-SE) in France and randomly assigned (2:2:1) to three groups (PRIMVAC adjuvanted with either Alhydrogel, GLA-SE, or placebo) in Burkina Faso. Randomisation was centralised, using stratification by cohort and blocks of variable size, and syringes were masked by opaque labels. The primary endpoint was the proportion of participants with any grade 3 or higher adverse reaction to vaccination up until day 35. Safety at later time points as well as humoral and cellular immunogenicity were assessed in secondary endpoints. This trial is registered with ClinicalTrials.gov, NCT02658253., Findings: Between April 19, 2016, and July 13, 2017, 68 women (18 in France, 50 in Burkina Faso) of 101 assessed for eligibility were included. No serious adverse event related to the vaccine occurred. PRIMVAC antibody titres increased with each dose and seroconversion was observed in all women vaccinated with PRIMVAC (n=57). PRIMVAC antibody titres reached a peak (geometric mean 11 843·0, optical density [OD] 1·0, 95% CI 7559·8-18 552·9 with 100 μg dose and GLA-SE) 1 week after the third vaccination (day 63). Compared with Alhydrogel, GLA-SE tended to improve the PRIMVAC antibody response (geometric mean 2163·5, OD 1·0, 95% CI 1315·7-3557·7 with 100 μg dose and Alhydrogel at day 63). 1 year after the last vaccination, 20 (71%) of 28 women who were vaccinated with PRIMVAC/Alhydrogel and 26 (93%) of 28 women who were vaccinated with PRIMVAC/GLA-SE still had anti-PRIMVAC antibodies, although antibody magnitude was markedly lower (452·4, OD 1·0, 95% CI 321·8-636·1 with 100 μg dose and GLA-SE). These antibodies reacted with native homologous VAR2CSA expressed by NF54-CSA infected erythrocytes (fold change from baseline at day 63 with 100 μg dose and GLA-SE: 10·74, 95% CI 8·36-13·79). Limited cross-recognition, restricted to sera collected from women that received the 100 μg PRIMVAC dose, was observed against heterologous VAR2CSA variants expressed by FCR3-CSA (fold change from baseline at day 63: 1·49, 95% CI 1·19-1·88) and 7G8-CSA infected erythrocytes (1·2, 1·08-1·34)., Interpretation: PRIMVAC adjuvanted with Alhydrogel or GLA-SE had an acceptable safety profile, was immunogenic, and induced functional antibodies reacting with the homologous VAR2CSA variant expressed by NF54-CSA infected erythrocytes. Cross-reactivity against heterologous VAR2CSA variants was limited and only observed in the higher dose group. An alternate schedule of immunisation, antigen dose, and combinations with other VAR2CSA-based vaccines are envisaged to improve the cross-reactivity against heterologous VAR2CSA variants., Funding: Bundesministerium für Bildung und Forschung, through Kreditanstalt für Wiederaufbau, Germany; Inserm, and Institut National de Transfusion Sanguine, France; Irish Aid, Department of Foreign Affairs and Trade, Ireland., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: Sub-optimal penetration of antiretroviral drugs in genital compartments might promote local HIV persistence and increase the risk of HIV transmission., Objectives: To describe the penetration of maraviroc, raltegravir, raltegravir glucuronide and rilpivirine in seminal plasma and cervico-vaginal secretions (CVS) and to assess local antiretroviral efficacy in HIV-1-positive patients., Methods: This was a prospective, multicentre study. Inclusion criteria were HIV-1 positive, age >18 years, receiving regimens containing maraviroc and/or raltegravir and/or rilpivirine for >1 month, and good self-reported adherence. Paired blood and genital samples were collected 12 h (raltegravir and maraviroc) or 24 h (rilpivirine) post-dose. These concentrations were determined (UPLC-MS/MS) in blood and seminal plasma (total and unbound) and CVS (total, dried spots) and HIV-RNA was quantified in paired blood and genital samples., Results: Among the 54 enrolled patients, 15 received maraviroc (6 men), 27 received raltegravir (14 men) and 20 received rilpivirine (10 men), corresponding to 54 total and 52 unbound plasma concentrations, 29 total CVS samples and 23 total and 18 unbound seminal plasma samples. Maraviroc and raltegravir displayed a ratio of genital fluids/plasma concentrations >0.5 in both male and female genital tracts. Conversely, rilpivirine displayed a low ratio. Antiretroviral free fractions were consistent with historical data. Nine patients had blood plasma HIV-RNA >50 copies/mL (2/9 had sub-optimal antiretroviral blood plasma exposure) and two other patients had detectable HIV-RNA in genital fluids., Conclusions: Maraviroc and raltegravir demonstrated good penetration in genital compartments, yielding good local virological response in genital compartments, whereas rilpivirine presented a low penetration profile but good local response., (© The Author 2017. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Preterm birth (PTB) is commonly accompanied by in utero fetal inflammation, and existing tocolytic drugs do not target fetal inflammatory injury. Of the candidate proinflammatory mediators, IL-1 appears central and is sufficient to trigger fetal loss. Therefore, we elucidated the effects of antenatal IL-1 exposure on postnatal development and investigated two IL-1 receptor antagonists, the competitive inhibitor anakinra (Kineret) and a potent noncompetitive inhibitor 101.10, for efficacy in blocking IL-1 actions. Antenatal exposure to IL-1β induced Tnfa , Il6 , Ccl2 , Pghs2 , and Mpges1 expression in placenta and fetal membranes, and it elevated amniotic fluid IL-1β, IL-6, IL-8, and PGF 2α , resulting in PTB and marked neonatal mortality. Surviving neonates had increased Il1b , Il6 , Il8 , Il10 , Pghs2 , Tnfa , and Crp expression in WBCs, elevated plasma levels of IL-1β, IL-6, and IL-8, increased IL-1β, IL-6, and IL-8 in fetal lung, intestine, and brain, and morphological abnormalities: e.g., disrupted lung alveolarization, atrophy of intestinal villus and colon-resident lymphoid follicle, and degeneration and atrophy of brain microvasculature with visual evoked potential anomalies. Late gestation treatment with 101.10 abolished these adverse outcomes, whereas Kineret exerted only modest effects and no benefit for gestation length, neonatal mortality, or placental inflammation. In a LPS-induced model of infection-associated PTB, 101.10 prevented PTB, neonatal mortality, and fetal brain inflammation. There was no substantive deviation in postnatal growth trajectory or adult body morphometry after antenatal 101.10 treatment. The results implicate IL-1 as an important driver of neonatal morbidity in PTB and identify 101.10 as a safe and effective candidate therapeutic., (Copyright © 2017 by The American Association of Immunologists, Inc.)

Plasma and cervicovaginal secretion (CVS) samples were collected from 19 human immunodeficiency virus type 1-infected women on lopinavir- or indinavir-containing regimens. Lopinavir and indinavir were detectable in 29 and 93% of CVS samples, respectively, a finding that may be ascribed to these drugs' differences in protein binding and pK(a). The relationship between lopinavir and indinavir pharmacodynamics and viral evolution in the female genital tract should be assessed over time.

Malignant fibrous histiocytoma (MFH) and giant cells sarcoma arise from fibrous tissue and histiocytic cells evenly distributed in all age group, except children much less common than osteosarcoma and chondrosarcoma. They most commonly localize in the major long bones (femur, tibia, humerus) and in pelvis. Pain and sometimes swelling are the most frequent symptoms but pathologic fractures are rather common. Medical imaging shows a purely osteolytic tumor centrally or eccentrically located, ill defined with a permeative or even moth eaten patterns. Periosteal reaction is scarce or absent. Osteogenic reaction or tumor calcifications are absent. Outcome was historically better than those of osteosarcoma but hangs on the grading of tumors; low grade sarcoma have a regional evolution while high grade malignant histiocytofibroma are threatened with metastases. Therapy must be adapted to the histological grading and the extent of the illness. Low grade localized MFH are best treated by wide resection. High grade MFH are preferentially treated by a comprehensive multidisciplinary approach with preoperative chemotherapy including high dose methotrexate, wide resection and postoperative chemotherapy. With such a treatment, nearly 80% of patients seen with localized tumor of the limb can be cured and keep a functional limb.