Knowledge, attitudes, practices about HIV and implications in risk and stigma prevention among French Guianese and Brazilian border inhabitants : Beliefs about HIV among border inhabitants.

BACKGROUND: The border area between French Guiana and Brazil is an active HIV-transmission zone. The aim of the present study was to describe HIV knowledge, risk and the level of stigma among inhabitants of this border area. METHODS: A cross-sectional study was conducted among 621 inhabitants over 18 years of age in the border cities of Saint-Georges-de-l'Oyapock in French Guiana and Oiapoque in Brazil. It was conducted between October 2017 and February 2018. An anonymous standardized questionnaire was filled out by culturally-trained mediators, then analyzed using STATA 12. RESULTS: Almost half (45.9%) of the individuals had a low education level. Participants whose native language was Portuguese or French demonstrated better HIV knowledge than other populations, notably native Amerindian and creole-speaking people. HIV risk behavior was more frequent in men and in younger age groups. People with good HIV knowledge reported having performed more HIV tests in the last year than participants with poor knowledge. The stigma level was high and reported in 74.8% of respondents. CONCLUSIONS: These results illustrate the need for initiatives to improve HIV prevention among autochthonous populations on both sides of this border area. Cross-border collaboration on health policies could produce common key messages adapted to the education level and multi-linguistic populations who live in this area.

Transporters associated with antigen processing (TAP)-independent presentation of soluble insulin to alpha/beta T cells by the class Ib gene product, Qa-1(b).

T cell hybridomas isolated from nonresponder H-2(b) mice immunized with pork insulin were stimulated by insulin in the presence of major histocompatibility complex (MHC)-unmatched antigen presenting cells. The restriction element used by these CD4(-) T cells was mapped to an oligomorphic MHC class Ib protein encoded in the T region and identified as Qa-1(b) using transfectants. The antigenic determinant was localized to the insulin B chain, and experiments with truncated peptides suggested that it is unexpectedly long, comprising most or all of the 30 amino acid B chain. The antigen processing pathway used to present insulin to the Qa-1(b)- restricted T cells does not require transporters associated with antigen processing (TAP), and it is inhibited by chloroquine. A wide variety of cell lines from different tissues efficiently present soluble insulin to Qa-1(b)-restricted T cells, and insulin presentation is not enhanced by phagocytic stimuli. Our results demonstrate that Qa-1(b) can function to present exogenous protein to T cells in a manner similar to MHC class II molecules. Therefore, this class Ib protein may have access to a novel antigen processing pathway that is not available to class Ia molecules.

Randomized open-label trial comparing topical prescription triamcinolone to over-the-counter hydrocortisone for the treatment of phimosis.

BACKGROUND: Phimosis is a common condition affecting most infant boys and generally resolves over time without symptoms. Severe cases of phimosis can lead to balanoposthitis, urinary tract infections, and urinary retention. Medical treatment for symptomatic phimosis includes topical corticosteroids with manual foreskin retraction. OBJECTIVE: Over-the-counter hydrocortisone 1% cream was compared in a randomized controlled fashion with prescription triamcinolone 0.1% cream for the medical management of symptomatic phimosis. METHODS: The study institution conducted a randomized open-label trial for the treatment of grades 4-5 phimosis (phimosis grade scale 0-5). Boys aged 3-13 years were randomized to hydrocortisone 1% cream or triamcinolone 0.1% cream dosed at least twice daily for a course of 12 weeks. Instructions were provided for appropriate application and manual retraction of the foreskin. Evaluations were performed at 4, 8, and 12 weeks. Successful completion of the study was determined by reaching phimosis grade 2 or less or after completing 12 weeks of treatment. RESULTS: A total of 52 boys enrolled in the trial, with a total of 32 boys completing the 12-week duration. Of the 13 boys in the hydrocortisone arm, there was a 30.8% success rate at 4 weeks, 53.8% success rate at 8 weeks, and 61.5% success rate at 12 weeks. Of the 19 boys in the triamcinolone arm, there was a 31.6% success rate at 4 weeks, 52.6% success rate at 8 weeks, and 68.4% success rate at 12 weeks. There was no statistical difference between the two arms at each interval. DISCUSSION: To the study authors' knowledge, this is the first open-label trial with direct comparison of hydrocortisone 1% cream with triamcinolone 0.1% cream. The study results support those reported in other studies when each topical steroid was compared with placebo. Limitations of the study include loss to follow-up, unblinded treatment allocation, and reduced power to detect differences by treatment frequency and duration. CONCLUSION: Over-the-counter hydrocortisone 1% cream is not inferior to triamcinolone 0.1% cream when paired with manual retraction for the treatment of grade 4-5 phimosis. Successful treatment response may be seen up to 12 weeks.

Novel Hydroxamic Acids Incorporating 1-((1H-1,2,3-Triazol-4-yl)methyl)- 3-substituted-2-oxoindolines: Synthesis, Biological Evaluation and SAR Analysis.

BACKGROUND: Histone deacetylases (HDAC) enzymes are emerging as potential targets for cancer treatments. In this study, several series of novel hydroxamic acids incorporating 1-((1H- 1,2,3-triazol-4-yl)methyl)-3-substituted-2-oxoindolines were explored. METHODS: The compounds were designed using Autodock Vina program, then synthesized and evaluated in vitro and in silico for their inhibitory activity against HDACs. The cytotoxicity was measured by SRB method. The enzyme inhibitory effects of the compounds were evaluated by the fluorescent assay. RESULTS: Biological evaluation showed that these hydroxamic acids were generally cytotoxic against four human cancer cell lines (SW620, colon; PC-3, prostate; AsPC-1, pancreas; NCI-H23, lung). Several compounds, e.g. 7g, 11c, and 11g, displayed up to 10-fold more potent than SAHA (suberoylanilide hydroxamic acid, vorinostat) in term of cytotoxicity. The synthesized compounds were also comparably potent to SAHA in inhibiting HDAC2. In particular, compound 11c displayed potential inhibitory effects against HDAC1, HDAC2, HDAC6, and HDAC8 with comparable or slightly higher potency than SAHA. Docking results on four class I and IIB isoenzymes indicated that these compounds tightly bound to HDACs at the active site with binding affinities much higher than that of SAHA. Finally, chemo-informatics approaches were employed to assess the pharmacokinetic and toxicity profiles of 7g and 11c. We identified degradation via phase II metabolism and toxicity two of the most serious problems that need further optimization. CONCLUSION: Taking altogether our findings are encouraging and current hydroxamate derivatives are worth being considered as potential HDAC inhibitors and could be useful for further research on the development of new anti-cancer agents.

New Record of the Scrub Typhus Vector, Leptotrombidium rubellum, in Southwest China.

There are several main vectors of scrub typhus in China, and Leptotrombidium rubellum Wang et Liao, 1984 is one of them, which was previously considered to be restricted to the coastal regions of Changle to Xiamen, Fujian province of east China. Ecological investigation of chigger mites in recent years demonstrated the presence of L. rubellum also in Yunnan province. Chigger mites were collected from 34 counties, in which 127,460 larval mites were collected from 14,381 small mammal hosts. A total of 277 species belonging to 26 genera and three subfamilies were identified. A total of 705/127,460 (0.55%) L. rubellum were collected from eight counties. Leptotrombidium rubellum was collected mainly at low elevations in southern Yunnan. A total of 663/705 (94.04%) of L. rubellum were collected from Rattus flavipectus (Milne-Edwards, 1871) found in outdoor habitats with relatively high infestation prevalence and mean intensity. Although it was collected from several hosts, the primary host was Rattus tanezumi. This represents a new distribution record of L. rubellum for Yunnan province.

[Placental malaria and pregnancy outcome in a peri urban area in Senegal]. / Infection palustre placentaire et issue de l'accouchement dans une zone péri-urbaine au Sénégal.

BACKGROUND: In areas of seasonal malaria transmission in Senegal, two previous studies have found that maternal direct obstetrics deaths and preeclampsia were more frequent during the rainy/malaria season. These observations suggest a possible link between malaria and maternal or fetal morbidity and mortality. In this study, we explore this link in a peri urban maternity in Senegal. METHODS: We carried out an exhaustive survey at "Maternité Roi-Baudouin" in Guédiawaye, which is the main maternity of the suburb of Dakar, Senegal. From August 1998 to December 1999, we included all women attending the maternity for delivery. Placental malaria was diagnosed by the presence of parasites or malarial pigment in placental apposition. Delivery diagnosis was assessed by obstetricians or midwives. Sociodemographic data and information about chloroquine intake were recorded. Multivariate analysis was performed to compare prevalence of placental malaria between normal and poor deliveries outcomes. RESULTS: Eight thousand two hundred and seventy three women were included. There were 5597 (67.7%) normal deliveries, 1214 (14.6%) low birth weight babies (<2500 g) and 1462 (17.7%) deliveries with a maternal or fetal poor outcome. Placental malaria prevalence was 9.5% (785/8273). Placental malaria was associated with low birth weight (adjusted OR=2.06 (1.72-2.57)), preterm birth (adjusted OR=3.51 (1.84-6.68)) and perinatal mortality (adjusted OR=2.56 (1.65-3.97)). We did not find an association between placental malaria and occurrence of a maternal pathology (dystocia, preeclampsia, eclampsia, retroplacental haematoma). CONCLUSION: Although malaria at delivery is not associated with occurrence of a maternal obstetric pathology, it has detrimental effects for the fetus and newborns. Effective antimalarial strategies during the antenatal period are urgently needed.

HLA-DM and the MHC class II antigen presentation pathway.

The MHC class II antigen processing pathway provides a mechanism to selectively present peptides generated in the endosomal compartments of antigen presenting cells to CD4+ T cells. Transport of newly synthesized class II molecules to the endosomal pathway requires the function of an accessory protein, invariant chain, which contains a region that interacts directly with the class II peptide binding site. Release of invariant chain and peptide loading by class II molecules are facilitated by a second accessory protein, HLA-DM. This MHC-encoded membrane protein catalyzes peptide exchange reactions, influencing the repertoire of peptides that are available for recognition by T cells.

Corneal eccentricity as a tool for the diagnosis of keratoconus.

Ninety-nine eyes with keratoconus of 64 patients were examined using the sagittal radii method to determine the corneal flattening and compared with 100 eyes of 50 healthy controls. To express the degree of this flattening, four numerical eccentricity (E) values for each eye were calculated. The highest E value of the four was chosen as a parameter for diagnosis of the disease. In keratoconus patients in whom the highest E values of keratoconus eyes were > or = 0.8, the specificity of the test was 98% and the sensitivity was 97%. This abnormal eccentricity was observed in keratoconus eyes with a visual acuity of 1.0, whereas slit-lamp examination showed no abnormalities. This study demonstrates that eccentricity can be helpful to diagnose keratoconus at an early stage.

PTHrP drives breast tumor initiation, progression, and metastasis in mice and is a potential therapy target.

Parathyroid hormone-related protein (PTHrP) is a secreted factor expressed in almost all normal fetal and adult tissues. It is involved in a wide range of developmental and physiological processes, including serum calcium regulation. PTHrP is also associated with the progression of skeletal metastases, and its dysregulated expression in advanced cancers causes malignancy-associated hypercalcemia. Although PTHrP is frequently expressed by breast tumors and other solid cancers, its effects on tumor progression are unclear. Here, we demonstrate in mice pleiotropic involvement of PTHrP in key steps of breast cancer - it influences the initiation and progression of primary tumors and metastases. Pthrp ablation in the mammary epithelium of the PyMT-MMTV breast cancer mouse model caused a delay in primary tumor initiation, inhibited tumor progression, and reduced metastasis to distal sites. Mechanistically, it reduced expression of molecular markers of cell proliferation (Ki67) and angiogenesis (factor VIII), antiapoptotic factor Bcl-2, cell-cycle progression regulator cyclin D1, and survival factor AKT1. PTHrP also influenced expression of the adhesion factor CXCR4, and coexpression of PTHrP and CXCR4 was crucial for metastatic spread. Importantly, PTHrP-specific neutralizing antibodies slowed the progression and metastasis of human breast cancer xenografts. Our data identify what we believe to be new functions for PTHrP in several key steps of breast cancer and suggest that PTHrP may constitute a novel target for therapeutic intervention.

Eosinophil and neutrophil colony-forming cells in culture.

Clusters of cells obtained from a short-term culture of human bone marrow cells in methylcellulose were transplanted in cell-free plates containing conditioned medium. Of 2559 transplants, 439 gave small clusters, 223 gave large clusters, and 70 gave colonies. A better cloning efficiency was achieved from 4-day-old clusters, from aggregates containing 3 cells or more, and from large cells rather than from small cells. Cytocentrifugation could be performed on 215 large clusters or colonies. The population consisted of pure neutrophils in 36.3% and of pure macrophages in 36.8%. A mixture of neutrophils and macrophages was found in 23.2%, thus indicating that these two cell lines originated from the same committed cell (G-CFC). Eosinophils were found in 8 (3.7%) clusters as a pure population, and were never mixed with either neutrophils or macrophages in the other 207 clusters. Despite the small number of eosinophil colonies, one could suggest that using the in vitro technique the committed eosinophil colony-forming cells could be distinguished from the G-CFC.

Normal human bone marrow cultures in vitro: cellular composition and maturation of the granulocytic colonies.

The analysis of single haemopoietic colonies grown in methylcellulose and in agar was performed at intervals by a cytocentrifugation method. Correlation was established between morphology of the whole colonies and their cellular content. Three main cell lines predominated: neutrophils, macrophages, eosinophils; a few colonies contained a pure population of basophil-like granulocytes. Development was followed from myeloblasts to polymorphs, both being present in most of the colonies. Cumulated results showed that (1) the proliferating compartment remained quite large till day 14, with 58% of cells in S phase, and rapidly decreased after day 16, and that (2) the polymorphs rapidly disappeared from the culture medium. Differentiation proceeded at different rates from one colony to the other, thus suggesting heterogeneity between colony forming cells (CFC). Neutrophil colonies appeared and lysed more rapidly than did eosinophil colonies. Macrophages arose from large immature cells with many promyelocyte features; such cells were present in mixed colonies, containing both neutrophils and macrophages. It is very likely that granulopoiesis results from the development of distinct committed CFC. This work was carried out using normal human bone marrow and may be a useful tool for studying pathological material in the future.

'Gd(-) Hôtel Dieu': a new G-6PD variant with chronic hemolysis in a Negro patient from Senegal.

A G-6PD deficiency was detected in a Negro patient from Senegal suffering from congenital nonspherocytic hemolytic anemia. The main characteristics of this variant were: profound defect of G-6PD activity in the red cells, decreased immunologic specific activity, fast electrophoretic mobility, decreased Km-G-6P and normal Km-NADP+, normal inhibition by ATP and NADPH, slightly increased utilization of the substrate analogues, slightly biphasic pH curve, high heat lability, subnormal activation energy. The characteristics of this variant being unique, it was called 'G-6PD Hôtel Dieu.'

[Hematological and clinical manifestations of bone marrow metastasis of carcinomas. Apropos of 36 cases verified by biopsy]. / Manifestations cliniques et hématologiques des métastases médullaires des carcinomes. A propos de 36 cas prouvés par biopsie.

A retrospective study of 36 cases of bone marrow metastases from carcinoma is reported. In all cases, the presence of tumour cells was confirmed by needle biopsy of the bone marrow. The clinical picture was fairly typical: decline in general health, fever, bony pain and skin and mucosal hemorrhages. Radiological lesions of the skeleton were present in 64% of cases. Sometimes the blood disorders were isolated. Anemia was almost constant (86), normochromic, normocytic, and may be associated with leukocytosis and thrombopenia. Pancytopenia is rarer as also is a rise in the number of platelets. Erythremia, very suggestive, is demonstrated in 73% of the blood smears. In 31% of the slides examined again, schizocytes were found among the normal red cells. Disorders of hemostasis were easily circumscribed. As fibrinolysis was sometime found, hemostasis was studied as a routine in all patients. The special recruitment of a hematology unit explains the high frequency of blood abnormalities in this series of bone metastases.

[Diffusion of cefotiam into ascitic fluid]. / Etude de la diffusion du céfotiam dans le liquide d'ascite.

The large apparent volume of distribution of cefotiam (reported by Fourtillan et al. [4]), prompted an investigation of cefotiam diffusion into ascitic fluid. Eight patients with non-infected ascites were each given a single intravenous bolus of 2 gr cefotiam. Samples of blood and ascitic fluid were collected 0.5, 1, 2, 3, 4, 6 and 8 hours after the injection. Plasma and ascitic fluid concentrations of unchanged cefotiam were determined using HPLC. Peak concentration in ascitic fluid averaged 18 micrograms/ml and was reached at two hours. Concentrations were still high (approximately 13 micrograms/ml) at 8 hours, leading to further assays 12 and 24 hours after the injection in three subjects. Cefotiam concentrations achieved in ascitic fluid seem adequate for the treatment of infected ascites, given the antibiotic's MICs for the organisms most commonly involved.

T-lymphocyte colonies in the lymphoproliferative disorders.

Human lymphocytes from peripheral blood, bone marrow spleen and lymph nodes were cultured. Continuous phytoheamagglutinin (PHA) stimulation was used, first during a 24 h liquid preincubation, then during a 5 day culture in methylcellulose. In normal donors a rapid colony formation took place, with a mean of 124+/-82 colonies per 1 times 10(5) preincubated lymphocytes. Cells from such colonies were studied by cytology, scanning electron microscopy and rosette formation techniques; arguments favour the hypothesis that these could be T lymphocytes. Neither granulocytes nor macrophages could be grown, and no lymphoid colony formation occurred without PHA stimulation. The same technique was applied to patients with various lymphoproliferative disorders. Significant colony suppression was observed in nearly every case of chronic lymphatic leukaemia; the number of colonies was reduced in some patients with acute lymphatic leukaemia, lymphosarcoma, dysglobulinaemia and Hodgkin's disease. This lymphoid culture method should be applied to a larger number of patients to determine whether it has a classification value and/or prognostic significance. When colonies were grown in pathological states, rosette formation was identical to that of normal donors; colony formation could be due to persisting normal lymphocytes.

[Culture of human bone marrow. Counts of colony forming granulocytes and macrophages in 100 patients without hematologic diseases]. / La culture de moelle osseuse chez l'homme. Numération des cellules donnant des colonies de granuleux et de macrophages chez 100 sujets exempts d'hémopathie

Bone marrow suspensions from non hematologic patients have been cultured in methyl cellulose, with conditioned medium prepared with normal peripheral blood cells. The granulocytic-monocytic colony forming cell (G-CFC) can give rise to colonies, which were counted on the 14th day. The mean G-CFC number is 38 +/- 26 when 2.10(5) cells are cultured. The striking disparity from one patient to an other cannot be explained by the culture conditions, nor by the clinical status. There is no sex difference; older patients have a significant reduction of the colony numbers compared to younger patients.

Transmembrane domain-mediated colocalization of HLA-DM and HLA-DR is required for optimal HLA-DM catalytic activity.

HLA-DM catalyzes peptide loading and exchange reactions by MHC class II molecules. Soluble recombinant DM, lacking transmembrane and cytoplasmic domains, was observed to have 200- to 400-fold less activity compared with the full-length protein in assays measuring DM-catalyzed peptide dissociation from purified HLA-DR1 in detergent solutions. Additional studies with truncated soluble DR1 demonstrated that transmembrane domains in DR1 molecules are also required for optimal activity. The potential requirement for specific interaction between the transmembrane domains of DM and DR was ruled out in experiments with chimeric DR1 molecules containing transmembrane domains from either DM or the unrelated protein CD80. These results suggested that the major role of the transmembrane domains is to facilitate colocalization of DM and DR in detergent micelles. The latter conclusion was further supported by the observation that HLA-DM-catalyzed peptide binding to certain murine class II proteins is increased by reducing the volume of detergent micelles. The importance of membrane colocalization was directly demonstrated in experiments in which DM and DR were reconstituted separately or together into membrane bilayers in unilamellar liposomes. Our findings demonstrate the importance of membrane anchoring in DM activity and underscore the potential importance of membrane localization in regulating peptide exchange by class II molecules.

[Erythrocytic and immunologic abnormalities in myeloid splenomegaly]. / Anomalies erythrocytaires et immunitaires dans la splénomégalie myéloide.

Screening for red cell defects, and exploration of cellular and humoral immunity has been performed in 33 patients : 31 had agnogenic myelosclerosis with myeloid metaplasia, 3 had polycythemia vera with secondary myelosclerosis. No patient had the biological abnormalities characteristical of paroxysmal nocturnal hemoglobinuria (Marchiafava-Micheli). In 19 out of 21 cases, red cells had antigen i on their membrane, thus suggesting that splenic erythropoiesis could give rise to immature erythrocytes. Two patients had a monoclonal dysglobulinemia, 5 a positive Coombs test, 6 a rhumatoid factor in the serum, 3 antitissue antibodies, 1 LE cells, 3 a positive Paul-Bunnel-Davidsohn test without mononucleosis, 11 a negative skin test. Implications of the uncommon occurrence of these dissorders are discussed.

[Hodgkin's disease: the value of prognostic criteria and of the combination of radiotherapy and chemotherapy in localised lymphoid stages (I and II). 94 patients undergoing laparotomy (author's transl)]. / Maladie de Hodgkin: valeur des critères dits de pronostic et de l'association radio-chimiothérapique dans les stabes lymphoïdes localisés (I et II). 94 malades laparotomisés.

Criteria reputed to be of grave prognostic significance were studied in 94 patients suffering from Hodgkin's disease at stages I and II, after laparotomy and splenectomy. The parameters studied (age, general signs, histological type, mediastinal involvement) are less prognostic factors than indications of unrecognised extension of the disease: almost 1/3 of unrecognised lesions in the presence of one of the criteria; almost 2/3 with two or more. Exploratory laparotomy revealed lesions unsuspected on the basis of clinical evaluation only in 10% of patients with no criteria of poor prognosis. The long term prognosis of the disease depends, in fact, not upon the existence of these criteria but upon the method used in initial treatment. Five year survival and cure rates are significantly better in patients treated with combined polychemotherapy (MOPP) and radiotherapy than in those treated with radiotherapy alone. These results would indicate that routine laparotomy should be abandoned in patients with a localised clinical staging if it is decided to begin treatment with a combination of radiotherapy and chemotherapy. So-called prognostic factors could then be used simply to vary the intensity of the treatment prescribed.

[Sarcomatous and leukemic forms of Waldenström's macroglobulinemia]. / Formes sarcomateuses et leucémiques de la macroglobulinémie de Waldenström

Four cases of sarcomatous or leukaemic types of Waldenström's macroglobulinemia are presented. They are characterized by tumoral and compressive localizations of lymph node or spleen, or by a hyper-leukocytosis with many circulating abnormal cells. These cells are different from the lympho-plasma cells regularly observed in Waldenström's macroglobulinemia, and can be assimilated to malignant immunoblasts. They have a proliferative aspect and seem to produce less macroglobulin and to recover some beta-glucuronidase activity. The sarcomatous and leukemic types of Waldenström's macroglobullinemia have a poor prognosis and may appear as terminal transformation of the disease.