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Introduction: Considering the growing interest in matched cancer treatment, our aim was to evaluate the ability of a comprehensive genomic profiling (CGP) assay to propose at least one targeted therapy given an identified genomic alteration or signature (actionability), and to collect the treatment modifications based on the CGP test results in clinical practise for solid tumors., Methods: This retrospective, multicentre French study was conducted among 25 centres that participated in a free of charge program between 2017 and 2019 for a tissue CGP test. Data were collected on the patient, disease, tumor genomic profile, treatment suggested in the report (related to the genomic profile results) and subsequent therapeutic decisions according to the physician's declaration., Results: Among the 416 patients, most had lung cancer (35.6%), followed by biliary tract cancer (11.5%) or rare cancers (11.1%); 75% had a metastatic disease. The actionability was 75.0% (95% CI [70.6%-78.9%]) for all patients, 85.1% and 78.4%, respectively in lung cancer and metastatic patients. After exclusion of clinical trial suggestions, the actionability decreased to 62.3% (95% CI [57.5%-66.8%]). Treatment modification based on the test results was observed in 17.3% of the patients and was more frequent in metastatic disease (OR = 2.73, 95% CI [1.31-5.71], p = 0.007). The main reasons for no treatment modification were poor general condition (33.2%) and stable disease or remission (30.2%). The genomic-directed treatment changes were performed mostly during the first six months after the CGP test, and interestingly a substantial part was observed from six to 24 months after the genomic profiling., Conclusion: This French study provides information on the real-life actionability of a CGP test based on tissue samples, and trends to confirm its utility in clinical practice across the course of the disease, in particularly for patients with lung cancer and/or advanced disease., Competing Interests: “I have read the journal’s policy and the authors of this manuscript have the following competing interests: Karen Leroy: Roche- board, conference fees, scientific collaboration, scientific meeting fees; AstraZeneca, BMS- board, conference fees, scientific meeting fees; Lilly, Janssen- board; Amgen, MSD, GSK- scientific meeting fees; Nanostring- conference fees, scientific collaboration. Clarisse Audigier Valette: AstraZeneca, Boehringer Ingelheim- Financial Interests, Personal, Principal Investigator, Advisory Role; BMS, Lilly, Novartis, Pfizer-Financial Interests, Personal, Invited Speaker, Advisory Role; Abb Vie, GlaxoSmithKline, Janssen, MSD, Roche, Sanofi, Takeda-Financial Interests, Personal, Advisory Role. Antoine Italiano: Roche- Financial Interests, Personal, Advisory Board, Research Grant Roche. This does not alter our adherence to PLOS ONE policies on sharing data and materials.”, (Copyright: © 2023 Leroy et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Skin-restricted lupus is a chronic inflammatory disease associated with high rates of depression and anxiety disorders. Patients without psychiatric disorders can experience anxiety and depressive symptoms at a subclinical level, which could be risk factors for progression towards psychiatric disorders. It was decided, therefore, to investigate the presence of specific symptoms in skin-restricted lupus patients without axis I psychiatric disorders and their impact on the occurrence of axis I psychiatric disorders during the study follow-up., Methods: Longitudinal data of 38 patients and 76 matched controls without active axis I psychiatric disorders from the LuPsy cohort were used. Depressive, neurovegetative, psychic and somatic anxiety symptom scores were established from the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating scale (HAMA)., Results: None of the participants had any current active axis I psychiatric disorders but the patients had personality disorders more frequently and had received more past psychotropic treatments than the controls. They also had higher MADRS and HAMA scores than the controls, in particular neurovegetative, psychic anxiety and somatic symptoms scores. No dermatological factor tested was associated with these scores, whereas being a lupus patient was associated with higher neurovegetative and somatic symptoms scores, having a current personality disorder with higher depressive and neurovegetative scores and receiving more past psychotropic treatments with psychic anxiety and somatic symptoms scores. The occurrence of psychiatric disorders during the study follow-up was associated with an elevated psychic anxiety score at baseline and past psychotropic treatment but not with history of psychiatric disorder., Limitations: The LuPsy cohort included a large number of patients with axis I psychiatric disorders, the sample without axis I psychiatric disorders is therefore limited., Conclusions: We observed numerous psychiatric symptoms among the skin-restricted lupus patients. They should therefore receive special attention in the management of their subclinical symptoms before they progress towards full psychiatric disorders., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Rondepierre et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Torque Teno Virus (TTV) is a small, non-enveloped, single-stranded and circular DNA virus that infects the majority of the population worldwide. Increased levels of plasma TTV viral load have been observed in various situations of immune deficiency or dysregulation, and several studies have suggested that TTV levels may be inversely correlated with immune competence. The measurement of TTV viremia by qPCR has been proposed as a potential biomarker for the follow-up of functional immune competence in immunosuppressed individuals, particularly hematopoietic stem cell transplant recipients. We hypothesized that TTV viral load could be used as a prognostic marker of immune checkpoint inhibitor (ICI) efficacy, and therefore investigated the TTV viral load in melanoma patients treated with nivolumab or pembrolizumab before and after 6 months of treatment. In the present study, TTV viral load was not different in melanoma patients before anti-PD-1 introduction compared to healthy volunteers, was not modified by ICI treatment and did not allowed to distinguish patients with treatment-sensitive tumor from patients with treatment-resistant tumor., Competing Interests: The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The design, analysis, and writing of this report are entirely the work and responsibility of the authors as the final responsibility for the decision to submit this work for publication. There are no patent products in development or marketed associated with this research to declare. This does not alter our adherence to PLOS ONE policies on sharing data and materials. W.M., and K.B.-P., are employed in bioMérieux SA, an in vitro diagnostic company. The other authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Introduction: In the past decade, new diagnostic methods and strategies have appeared, HIV testing efforts and the generalization of antiretroviral therapy may have influenced the number of opportunistic diagnoses and mortality of HIV-infected patients. To test this hypothesis we compiled data on the top opportunistic infections and causes of early death in the HIV cohort of French Guiana., Methods: HIV-infected persons followed in Cayenne, Kourou, and Saint Laurent du Maroni hospitals from 2010 to 2019 were studied. Annual incidence of different opportunistic infections and annual deaths are compiled. For patients with opportunistic infections we calculated the proportion of early deaths., Results: At the time of analysis, among 2 459 patients, (treated and untreated) 90% had a viral load <400 copies, 91% of the patients in the cohort were on antiretroviral treatment, and 94.2% of patients on treatment for over 6 months had undetectable viral loads. Only 9% of patients had CD4 counts under 200 per mm3. Histoplasmosis clearly remained the most frequent (128 cases) opportunistic infection among HIV-infected persons followed by cerebral toxoplasmosis (63 cases) and esophageal candidiasis (41 cases). Cryptococcal meningitis was ranked 5th most frequent opportunistic infection as was tuberculosis (31 cases). The trend for a sharp decline in early deaths continued (3.9% of patients)., Conclusions: Despite the successes of antiretrovirals, patients presenting with advanced HIV are still common and they are still at risk of dying. Improved diagnosis, and notably systematic screening with appropriate tools are still important areas of potential progress., Competing Interests: The authors have declared that no competing interests exist.

Background: Access to antiretroviral treatment has improved the life expectancy of HIV-positive patients, most often associated with a desire to limit childbearing. Women living with HIV (WLHIV) commonly have unmet need for contraception and could be at risk of unintended pregnancy. Preventing unintended pregnancies among women living with HIV are effective strategies to eliminate mother-to-child transmission of HIV., Objective: The aim of this study was to assess unmet need for limiting childbirth and its associated factors among women living with HIV in Togo., Methods: This facility based cross-sectional study was conducted, between June and August 2016, among WLHIV in their reproductive age (15-49 years) in HIV-care settings in Centrale and Kara regions Data was collected using a structured and pretested questionnaire. WLHIV who desired to limit childbirth but not using contraception were considered to have unmet need of birth limitations. Univariate and multivariate Poisson regression models with robust variance were performed to identify associated factors with unmet needs. A multi-model averaging approach was used to estimate the degree of the association between these factors and the unmet need of birth limitations., Results: A total of 443 WLHIV were enrolled, with mean age of 34.5 years (standard deviation [SD] = 7.0). Among them 244 (55.1%) were in couple and 200 (45.1%) had at least the secondary level of education. 39.1% were followed-up in a private healthcare facility. At the time of the survey, 40.0% did not desire childbearing but only 9.0% (95% CI [6.7-12.1]) of them expressed unmet needs for limiting childbirth. In multivariable analysis, associated factors with unmet needs of birth limitations were: being aged 35 years or more (adjusted prevalence ratio (aPR) = 3.11, 95% confidence intervals (95% CI) [1.52-6.38]), living in couple (aPR = 2.32 [1.15-4.65]), living in Kara region (aPR = 0.10 [0.01-0.76]), being followed in a private healthcare facility (aPR = 0.08[0.01-0.53]) and having severe HIV symptoms (aPR = 3.50 [1.31-9.37])., Conclusion: Even though the unmet need for births limitation was relatively low among WLHIV in Togo, interventions to improve more access to contraceptive methods, and targeting 35 to 49 years old women, those in couple or followed in the public healthcare facilities would contribute to the eradication of mother-to-child transmission of HIV., Competing Interests: The authors have declared that no competing interests exist.

Mycetoma is a neglected tropical disease caused by various actinomycetes or fungi. The disease is characterized by the formation of tumor like-swellings and grains. Senegal is an endemic country where mycetoma cases are under-or misdiagnosed due to the lack of capacities and knowledge among health workers and the community; and where the management of eumycetoma, burdened by a high amputation rate, is currently inadequate. This study aimed to update data on the epidemiology of mycetoma cases diagnosed in three hospital centres in Senegal over a 10 years-period. A total of 193 patients, diagnosed from 2008 to 2018, were included in the study. The most frequent presentation was eumycetoma (47.2%); followed by actinomycetoma (36.8%); it remained undetermined in 16.1% of the patients. The mean age was 38.3 years (68.4% of the patients were between 15 and 45 years-old); the male: female ratio was a 2.94; and most were farmers. One hundred fifty-six (80.8%) patients had used phytotherapy before attending the hospital. Mycetoma was mainly located to the lower limbs (91.2%). Grains were observed in 85% of the patients; including white (25.6%) and yellow (4.3%) grains. The etiological diagnosis was complex, resulting in negative direct microscopy, culture and/or histopathology findings, which explains that 16.1% remained uncharacterized. In most of cases, actinomycetoma were treated with a combination of cotrimoxazole, amoxicillin/clavulanic acid, and streptomycin; whereas eumycetoma cases were treated with terbinafine. The surgery was done in 100 (51.8%) of the patients including 9 in actinomycetoma, 78 in eumycetoma and 13 in undetermined form. The high number of uncharacterized mycetoma in this study, the delay in attending a qualified health-care facility, and the lack of available adequate antifungal drug, point out the need to strengthen mycetoma management capacities in Senegal., Competing Interests: The authors have declared that no competing interests exist.

Treponema pallidum subsp. pallidum, the causative agent of sexually transmitted syphilis, detected in clinical samples from France, was subjected to molecular typing using the recently developed Multilocus Sequence Typing system. The samples (n = 133) used in this study were collected from 2010-2016 from patients with diagnosed primary or secondary syphilis attending outpatient centers or hospitals in several locations in France. Altogether, 18 different allelic profiles were found among the fully typed samples (n = 112). There were five allelic variants identified for TP0136, 12 for TP0548, and eight for TP0705. Out of the identified alleles, one, seven, and three novel alleles were identified in TP0136, TP0548, and TP0705, respectively. Partial allelic profiles were obtained from 6 samples. The majority of samples (n = 110) belonged to the SS14-like cluster of TPA isolates while 7 clustered with Nichols-like isolates. Patients infected with Nichols-like samples were more often older (p = 0.041) and more often diagnosed with secondary syphilis (p = 0.033) compared to patients infected with SS14-like samples. In addition, macrolide resistance caused by the A2058G mutation was found to be associated with allelic profile 1.3.1 or with strains belonging to the 1.3.1 lineage (p<0.001). The genetic diversity among TPA strains infecting the European population was surprisingly high, which suggests that additional studies are needed to reveal the full genetic diversity of TPA pathogens infecting humans., Competing Interests: The authors have declared that no competing interests exist.

Background: Given the great efforts put into the strategic objective of reducing the proportion of HIV-infected patients that are undiagnosed, the aim of the present study was to review the temporal trends between 1997 and 2016 for median estimates of infection duration and median CD4 count at diagnosis for the main patient origins in French Guiana., Methods: CD4 cell count at HIV sero-conversion and square root of CD4 cell decline were obtained using the CD4 decline in a cohort of HIV-infected persons in the UK, fitting random effect (slope and intercept) multilevel linear regression models. Multivariate analysis used robust regression for modeling the delay between estimated HIV seroconversion and diagnosis and quantile regression for CD4 at HIV diagnosis., Results: The median interval between the estimated HIV seroconversion and HIV diagnosis was 8 years for patients fromBrazil, 4.5 years for those from Haiti, 6.6 years for those from Suriname, 3.3 years for patients from Guyana, and 3.1 years for French patients. A simple robust regression model with French patients as reference group adjusting for sex and age at the time of diagnosis showed that the interval was significantly longer for Brazilian (β = +3.7 years, P = 0.001), Surinamese (β = +4.2 years, P<0.0001), Haitian origins (β = +1.5 years, P = 0.049) but not for those originating from Guyana (β = -0.03 years, P = 0.9); Men independently had a longer interval than women (β = +3.5 years, P<0.0001)., Conclusions: Despite great efforts in French Guiana regarding HIV testing both in terms of diversification and intensification we still need to tailor the offer to better reach the communities in need. These results should help authorities scale up and optimize initiatives to reduce the proportion of patients who are unaware of their infection. They also raise the question of the role of stigma and discrimination as a barrier to HIV testing in small communities, and further emphasize the importance of reducing it., Competing Interests: The authors have declared that no competing interests exist.

Background: Over 75% of patients in the HIV cohort in French Guiana are of foreign origin. Our objective was to estimate what proportion of the migrant population of HIV-infected patients in Cayenne had been infected in French Guiana., Methods: We included patients of known foreign origin who were followed in Cayenne, for whom the year of arrival in French Guiana was known and the initial CD4 count at the time of diagnosis was available. The time between seroconversion and time at diagnosis was estimated using the formula [square root (CD4 at seroconversion)-square root(CD4 at HIV diagnosis)] / slope of CD4 decline.CD4 counts at the time of infection and the slope were computed in an age and ethnicity-dependent variable., Results: The median estimated time between infection and diagnosis was 4.5 years (IQR = 0.2-9.2). Overall, using a median estimate of CD4 count at the time of infection, it was estimated that 53.2% (95% CI = 48.3-58%) of HIV infected foreign patients had acquired HIV after having arrived in French Guiana. Patients having arrived in French Guiana before and during the 1990s and those receiving their HIV diagnosis before 2010 were more likely to have been infected in French Guiana., Conclusions: Contrary to widespread belief suggesting that most migrants are already HIV-infected when they arrive in French Guiana, a large proportion of foreign HIV patients seem acquire the virus in French Guiana.There is still much to do in terms of primary prevention and testing among migrants.

Background: Acute-serum Amyloid A (A-SAA), one of the major acute-phase proteins, is mainly produced in the liver but extra-hepatic synthesis involving the skin has been reported. Its expression is regulated by the transcription factors NF-κB, C/EBPβ, STAT3 activated by proinflammatory cytokines., Objectives: We investigated A-SAA synthesis by resting and cytokine-activated Normal Human Epidermal Keratinocytes (NHEK), and their inflammatory response to A-SAA stimulation. A-SAA expression was also studied in mouse skin and liver in a model mimicking psoriasis and in the skin and sera of psoriatic and atopic dermatitis (AD) patients., Methods: NHEK were stimulated by A-SAA or the cytokines IL-1α, IL-17A, IL-22, OSM, TNF-α alone or in combination, previously reported to reproduce features of psoriasis. Murine skins were treated by imiquimod cream. Human skins and sera were obtained from patients with psoriasis and AD. A-SAA mRNA was quantified by RT qPCR. A-SAA proteins were dosed by ELISA or immunonephelemetry assay., Results: IL-1α, TNF-α and mainly IL-17A induced A-SAA expression by NHEK. A-SAA induced its own production and the synthesis of hBD2 and CCL20, both ligands for CCR6, a chemokine receptor involved in the trafficking of Th17 lymphocytes. A-SAA expression was increased in skins and livers from imiquimod-treated mice and in patient skins with psoriasis, but not significantly in those with AD. Correlations between A-SAA and psoriasis severity and duration were observed., Conclusion: Keratinocytes could contribute to psoriasis pathogenesis via A-SAA production, maintaining a cutaneous inflammatory environment, activating innate immunity and Th17 lymphocyte recruitment.

Background: Nontuberculous mycobacteria (NTM) are environmental organisms associated with a range of infections. Reports of NTM epidemiology are mainly focused on pulmonary infections and isolations, and extrapulmonary infections are less frequently described., Methods: We conducted a retrospective study of NTM infections at the Bordeaux University Hospital, France, between January 2002 and December 2013. We used the microbiologic component of the American Thoracic Society/Infectious Diseases Society of America's pulmonary NTM disease criteria to define cases of pulmonary NTM, and patients with isolates from a normally sterile site were classified as having extrapulmonary disease., Results: In our setting, 170 patients were included. Pulmonary cases predominated (54.1%), followed by skin and soft tissue infections (22.9%), disseminated cases (10.6%), lymphadenitis (7.7%), bone and joint infections (2.9%) and the remaining 1.8% catheter-related infections. Overall, 16 NTM species were isolated. Mycobacterium avium (31.8%) and M. intracellulare (20%) were the most common species identified, followed by M. marinum (13.5%), M. kansasii (10.6%), M. xenopi (9.4%), rapidly growing mycobacteria (9.4%) and other slowly growing mycobacteria (5.3%). In general, NTM isolates were largely prevalent in people older than 50 (62.4%); patients aged 1-10 year-old exclusively yielded M. avium from lymph nodes, almost cases having being diagnosed after 2007. Among the 121 patients with complete follow-up, 78 (64.5%), 24 (19.8%), and 19 (15.7%) were cured, experienced relapse, or died, respectively., Conclusion: In our study, extrapulmonary NTM infections represented almost half of cases, consisting mainly in skin and soft tissue infections. The increase lymphadenitis cases in children after 2007 could be linked to the cessation of mandatory BCG vaccination in France. We observed similar cure rates (64%) between pulmonary and extrapulmonary infections., Competing Interests: The authors have declared that no competing interests exist.

Background: Propionibacterium acnes (P. acnes) is an anaerobic, Gram-positive bacteria encountered in inflammatory acne lesions, particularly in the pilosebaceous follicle. P. acnes triggers a strong immune response involving keratinocytes, sebocytes and monocytes, the target cells during acne development. Lipoteicoic acid and peptidoglycan induce the inflammatory reaction, but no P. acnes surface protein interacting with Toll-like receptors has been identified. P. acnes surface proteins have been extracted by lithium stripping and shown to induce CXCL8 production by keratinocytes., Methodology and Principal Findings: Far-western blotting identified two surface proteins, of 24.5- and 27.5-kDa in size, specifically recognized by TLR2. These proteins were characterized, by LC-MS/MS, as CAMP factor 1 devoid of its signal peptide sequence, as shown by N-terminal sequencing. Purified CAMP factor 1 induces CXCL8 production by activating the CXCL8 gene promoter, triggering the synthesis of CXCL8 mRNA. Antibodies against TLR2 significantly decreased the CXCL8 response. For the 27 P. acnes strains used in this study, CAMP1-TLR2 binding intensity was modulated and appeared to be strong in type IB and II strains, which produced large amounts of CXCL8, whereas most of the type IA1 and IA2 strains presented little or no CAMP1-TLR2 binding and low levels of CXCL8 production. The nucleotide sequence of CAMP factor displays a major polymorphism, defining two distinct genetic groups corresponding to CAMP factor 1 with 14 amino-acid changes from strains phylotyped II with moderate and high levels of CAMP1-TLR2 binding activity, and CAMP factor 1 containing 0, 1 or 2 amino-acid changes from strains phylotyped IA1, IA2, or IB presenting no, weak or moderate CAMP1-TLR2 binding., Conclusions: Our findings indicate that CAMP factor 1 may contribute to P. acnes virulence, by amplifying the inflammation reaction through direct interaction with TLR2., Competing Interests: The authors have declared that no competing interests exist.

Harlequin Ichthyosis is a severe skin disease caused by mutations in the human gene encoding ABCA12. Here, we characterize a novel mutation in intron 29 of the mouse Abca12 gene that leads to the loss of a 5' splice donor site and truncation of the Abca12 RNA transcript. Homozygous mutants of this smooth skin or smsk allele die perinatally with shiny translucent skin, typical of animal models of Harlequin Ichthyosis. Characterization of smsk mutant skin showed that the delivery of glucosylceramides and CORNEODESMOSIN was defective, while ultrastructural analysis revealed abnormal lamellar bodies and the absence of lipid lamellae in smsk epidermis. Unexpectedly, mutant stratum corneum remained intact when subjected to harsh chemical dissociation procedures. Moreover, both KALLIKREIN 5 and -7 were drastically decreased, with retention of desmoplakin in mutant SC. In cultured wild type keratinocytes, both KALLIKREIN 5 and -7 colocalized with ceramide metabolites following calcium-induced differentiation. Reducing the intracellular levels of glucosylceramide with a glucosylceramide synthase inhibitor resulted in decreased secretion of KALLIKREIN proteases by wild type keratinocytes, but not by smsk mutant keratinocytes. Together, these findings suggest an essential role for ABCA12 in transferring not only lipids, which are required for the formation of multilamellar structures in the stratum corneum, but also proteolytic enzymes that are required for normal desquamation. Smsk mutant mice recapitulate many of the pathological features of HI and can be used to explore novel topical therapies against a potentially lethal and debilitating neonatal disease., Competing Interests: The authors have declared that no competing interests exist.

In the present study, we examined the potential symptomatic and/or disease-modifying effects of monthly bee venom injections compared to placebo in moderatly affected Parkinson disease patients. We conducted a prospective, randomized double-blind study in 40 Parkinson disease patients at Hoehn & Yahr stages 1.5 to 3 who were either assigned to monthly bee venom injections or equivalent volumes of saline (treatment/placebo group: n = 20/20). The primary objective of this study was to assess a potential symptomatic effect of s.c. bee venom injections (100 μg) compared to placebo 11 months after initiation of therapy on United Parkinson’s Disease Rating Scale (UPDRS) III scores in the « off » condition pre-and post-injection at a 60 minute interval. Secondary objectives included the evolution of UPDRS III scores over the study period and [123I]-FP-CIT scans to evaluate disease progression. Finally, safety was assessed by monitoring specific IgE against bee venom and skin tests when necessary. After an 11 month period of monthly administration, bee venom did not significantly decrease UPDRS III scores in the « off » condition. Also, UPDRS III scores over the study course, and nuclear imaging, did not differ significantly between treatment groups. Four patients were excluded during the trial due to positive skin tests but no systemic allergic reaction was recorded. After an initial increase, specific IgE against bee venom decreased in all patients completing the trial. This study did not evidence any clear symptomatic or disease-modifying effects of monthly bee venom injections over an 11 month period compared to placebo using a standard bee venom allergy desensitization protocol in Parkinson disease patients. However, bee venom administration appeared safe in non-allergic subjects. Thus, we suggest that higher administration frequency and possibly higher individual doses of bee venom may reveal its potency in treating Parkinson disease., Trial Registration: ClinicalTrials.gov NCT01341431.

Background: In 2008, the proportion of truck drivers who were not systematically protected during sex was 63% with casual partners and 60% with sex workers. Despite the high level of knowledge on HIV/AIDS and the growing awareness of the existence of the risk of HIV infection, condom use always encounters resistance among truck drivers in Togo. We sought to document the factors associated with condom use during casual sex among trucks' drivers in Togo., Methods: This was an analytical cross-sectional study conducted in 2010 and targeted truckers at truck station on the two main roads of Togo, Lomé-Cinkassé and Kodjoviakopé-Sanvee Condji., Results: In this study, 1,782 trucks' drivers and their helpers were interviewed. All were men, and their mean age was 28.8 ± 8.8 years. Trucks' drivers were doing an average of 3 stops on their journeys and 1,229 (69%) of them had at least two years of experience in the work. Of the 1,782 trucks' drivers, only 620 (34.8%) had consistently used condoms during casual sex in the last three months. In multivariate analysis, predictors were: education level (primary schooling: OR = 1.54; p = 0.002; Secondary schooling and higher OR = 1.38; p = 0.036), good knowledge of ways of HIV transmission (OR = 1.53; p = 0.000), tested for HIV (OR = 1.67, p = 0.000), duration in the profession (2-5 years: OR = 1.43, p = 0.008; more than 5 years: OR = 1.38, p = 0.027), and HIV risk's perception (OR = 1.44, p = 0.000)., Conclusion: These results highlight factors associated with consistent condom use during casual sex by truck drivers in Togo. This is a key population group at high risk of HIV transmission toward which the national HIV/AIDS control program should strengthen the HIV prevention strategies.

Basal cell carcinoma (BCC) is the commonest tumor in human. About 70% sporadic BCCs bear somatic mutations in the PATCHED1 tumor suppressor gene which encodes the receptor for the Sonic Hedgehog morphogen (SHH). PATCHED1 germinal mutations are associated with the dominant Nevoid Basal Cell Carcinoma Syndrome (NBCCS), a major hallmark of which is a high susceptibility to BCCs. Although the vast majority of sporadic BCCs arises exclusively in sun exposed skin areas, 40 to 50% BCCs from NBCCS patients develop in non photo-exposed skin. Since overwhelming evidences indicate that microenvironment may both be modified by- and influence the- epithelial tumor, we hypothesized that NBCCS fibroblasts could contribute to BCCs in NBCCS patients, notably those developing in non photo-exposed skin areas. The functional impact of NBCCS fibroblasts was then assessed in organotypic skin cultures with control keratinocytes. Onset of epidermal differentiation was delayed in the presence of primary NBCCS fibroblasts. Unexpectedly, keratinocyte proliferation was severely reduced and showed high levels of nuclear P53 in both organotypic skin cultures and in fibroblast-led conditioning experiments. However, in spite of increased levels of senescence associated β-galactosidase activity in keratinocytes cultured in the presence of medium conditioned by NBCCS fibroblasts, we failed to observe activation of P16 and P21 and then of bona fide features of senescence. Constitutive extinction of P53 in WT keratinocytes resulted in an invasive phenotype in the presence of NBCCS fibroblasts. Finally, we found that expression of SHH was limited to fibroblasts but was dependent on the presence of keratinocytes. Inhibition of SHH binding resulted in improved epidermal morphogenesis. Altogether, these data suggest that the repertoire of diffusible factors (including SHH) expressed by primary NBCCS fibroblasts generate a stress affecting keratinocytes behavior and epidermal homeostasis. Our findings suggest that defects in dermo/epidermal interactions could contribute to BCC susceptibility in NBCCS patients.

Merkel cell polyomavirus (MCPyV) is the first polyomavirus clearly associated with a human cancer, i.e. the Merkel cell carcinoma (MCC). Polyomaviruses are small naked DNA viruses that induce a robust polyclonal antibody response against the major capsid protein (VP1). However, the polyomavirus VP1 capsid protein epitopes have not been identified to date. The aim of this study was to identify the neutralizing epitopes of the MCPyV capsid. For this goal, four VP1 mutants were generated by insertional mutagenesis in the BC, DE, EF and HI loops between amino acids 88-89, 150-151, 189-190, and 296-297, respectively. The reactivity of these mutants and wild-type VLPs was then investigated with anti-VP1 monoclonal antibodies and anti-MCPyV positive human sera. The findings together suggest that immunodominant conformational neutralizing epitopes are present at the surface of the MCPyV VLPs and are clustered within BC and EF loops.

Background: Many studies have reported factors associated with HIV status disclosure among People Living With HIV and AIDS (PLWHA) but very few were conducted among PLWHA receiving ART. In Togo, no study on HIV status disclosure to sexual partners has been conducted among PLWHA on ART yet. We sought to document factors associated with HIV status disclosure among PLWHA receiving ART at Sokodé regional hospital in Togo., Method: This was a cross-sectional study conducted from May to July 2013 at the regional hospital of Sokodé among 291 PLWHA who had been on ART for at least three months., Results: A total of 291 PLWHA on ART were enrolled in this study. Their mean age (± SD) was 37.3 ± 9.3 years and the sex ratio (Male/Female) was 0.4. Among them, 215 (74.6%) completed the questionnaire on HIV sero-status disclosure. We found that 131 PLWHA (60.9%) had disclosed their HIV sero-status to their sexual partners; 130 (60.5%) were aware of the HIV status of their sexual partners. In the multivariate analysis, the factors associated with HIV status disclosure to sexual partners were: adherence to ART (aOR = 4.89; 95%CI = [1.52; 15.78]), sexual partner awareness of HIV sero-status (aOR = 52.73; 95%CI = [14.76; 188.36]) and marital status of PLWHA (aOR = 6.10; 95%CI = [1.74; 21.37])., Conclusion: This study allowed us to note that the disclosure of HIV status to sexual partners is relatively low and to document the associated factors such as adherence to ART, sexual partner awareness of HIV sero-status and marital status.

Background: The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans., Methods: In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests., Results: We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control., Conclusion: Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.

Keratinocyte differentiation program leading to an organized epidermis plays a key role in maintaining the first line of defense of the skin. Epidermal integrity is regulated by a tight communication between keratinocytes and leucocytes, particularly under cytokine control. Imbalance of the cytokine network leads to inflammatory diseases such as psoriasis. Our attempt to model skin inflammation showed that the combination of IL-17A, IL-22, IL-1α, OSM and TNFα (Mix M5) synergistically increases chemokine and antimicrobial-peptide expression, recapitulating some features of psoriasis. Other characteristics of psoriasis are acanthosis and down-regulation of keratinocyte differentiation markers. Our aim was to characterize the specific roles of these cytokines on keratinocyte differentiation, and to compare with psoriatic lesion features. All cytokines decrease keratinocyte differentiation markers, but IL-22 and OSM were the most powerful, and the M5 strongly synergized the effects. In addition, IL-22 and OSM induced epidermal hyperplasia in vitro and M5 induced epidermal thickening and decreased differentiation marker expression in a mouse model, as observed in human psoriatic skin lesions. This study highlights the precise role of cytokines in the skin inflammatory response. IL-22 and OSM more specifically drive epidermal hyperplasia and differentiation loss while IL-1α, IL-17A and TNFα were more involved in the activation of innate immunity.

Background: The recommended first-line therapy of chronic urticaria is second-generation antihistamines, but the modalities of treatment remains unclear. Numerous recommendations with heterogeneous conclusions have been published. We wondered whether such heterogeneous conclusions were linked to the quality of published studies and their reporting., Objective: To review the study design and quality of reporting of randomized control trials investigating pharmacological treatment of autoimmune or idiopathic chronic urticaria., Methodology/principal Findings: MEDLINE and EMBASE were searched for pharmacological randomized controlled trials involving patients with chronic autoimmune or idiopathic urticaria, with the main outcome being treatment efficacy. Data were collected on general characteristics of the studies, internal validity, studied treatments, design of the trial, outcome measures and "spin" strategy in interpreting results. Spin was defined as use of specific reporting strategies to highlight that the experimental treatment is beneficial, despite statistically nonsignificant results. We evaluated 52 articles that met our criteria. Patients were reported as blinded in 42 articles (81%) and the outcome assessor was blinded in 37 (71%). A placebo was the only comparator in 13 (25%) studies. The study duration was <8 weeks in 39 articles (75%), with no follow-up after discontinuation of treatment in 37 (71%). In 4 articles (8%), blinding was clear because they described blinding of the outcome assessor, the treatment was not recognizable (identical or double-dummy) or had no major secondary effects, and computed randomization was centralized. The primary outcome was specified in 33 articles (63%) and was a score in 31. In total, 15 different scores were used. A spin strategy was used for 10 of 12 studies with a nonsignificant primary outcome., Conclusion: For establishing guidelines in treatment of chronic urticaria, studies should focus on choosing clinically relevant and reproducible primary outcomes, long-term follow-up, limited use of placebo and avoiding spin strategies.

Background: Although Dengue virus (DENV) circulation had been documented in neighbouring South-western Indian Ocean Islands, its presence in Mayotte is poorly characterised. To address this issue, we aimed to assess the seroprevalence of dengue IgG antibodies (DENV-IgG Ab) among the population and to investigate potential associations with individual and household characteristics., Methods/principal Findings: In November-December 2006 we conducted a cross-sectional serologic survey in Mayotte among 1,154 inhabitants aged≥2 years by using a multistage cluster random sampling method. The overall prevalence of DENV-specific IgG antibodies (ELISA) was 22.73% (95% CI, 18.16-27.31). The age-specific seroprevalence increased with age (χ2 for trend=11.86, P<0.0006), and was linked with previous known outbreaks in this region. In multivariate analysis, older age, being born in the Comoros and living in a household with a low socioeconomic index were positively associated with DENV IgG antibody positivity., Conclusions: These findings document substantial prior exposure of the population of Mayotte to DENV and highlight the risk of severe illness due to the possibility of sequential DENV infections. Further investigations characterizing current DENV circulation patterns and associated serotypes are needed.

Background: Indolent forms of mastocytosis account for more than 90% of all cases, but the types and type and severity of symptoms and their impact on the quality of life have not been well studied. We therefore performed a case-control cohort study to examine self-reported disability and impact of symptoms on the quality of life in patients with mastocytosis., Methodology/principal Findings: In 2004, 363 mastocytosis patients and 90 controls in France were asked to rate to their overall disability (OPA score) and the severity of 38 individual symptoms. The latter was used to calculate a composite score (AFIRMM score). Of the 363 respondents, 262 were part of an ongoing pathophysiological study so that the following data were available: World Health Organization classification, standard measures of physical and psychological disability, existence of the D816V KIT mutation, and serum tryptase level. The mean OPA and AFIRMM scores and the standard measures of disability indicated that most mastocytosis patients suffer from disabilities due to the disease. Surprisingly, the patient's measurable and perceived disabilities did not differ according to disease classification or presence or absence of the D816V KIT mutation or an elevated (> or = 20 ng/mL) serum tryptase level. Also, 32 of the 38 AFIRMM symptoms were more common in patients than controls, but there were not substantial differences according to disease classification, presence of the D816V mutation, or the serum tryptase level., Conclusions: On the basis of these results and for the purposes of treatment, we propose that mastocytosis be first classified as aggressive or indolent and that indolent mastocytosis then be categorized according to the severity of patients' perceived symptoms and their impact on the quality of life. In addition, it appears that mastocytosis patients suffer from more symptoms and greater disability than previously thought, that mastocytosis may therefore be under-diagnosed, and that the symptoms of the indolent forms of mastocytosis might be due more to systemic release of mediators than mast cell burden.