Roles of lymphoid cells in the differentiation of Langerhans dendritic cells in mice

Langerhans dendritic cells are antigen presenting cells (APC) that reside within the epidermis and are capable of stimulating naive T cells. Reciprocally, lymphocytes may play a role in Langerhans cells (LC) differentiation. Our results show that the differentiation of skin LC is unaffected in the absence of lymphocytes and/or signaling through the common cytokine receptor gamma chain (gammac) required for IL-2, IL-4, IL-7, IL-9, IL-15 and IL-21 signaling. Migration of LC and other dendritic cells (DC) from the skin to the draining lymph nodes (LNs) after FITC skin sensitization, is unaffected in the absence of lymphocytes or CD40. FITC+ LC/DC sorted from the LNs of lymphoid deficient or control mice stimulated naive T cells with similar efficiency. However, while the absence of lymphocytes did not appear to affect the phenotype or number of emigrating LN DC/LC, their persistence in the LN appears to depend on alphabeta T cells. Thus, DC are strikingly reduced in numbers in the peripheral LNs of T-cell deficient mice. Finally, CD8alpha expression on skin emigrants was low and dependent on the presence of CD8+ lymphocytes, while spleen CD8+ DC were present in the absence of lymphocytes. We conclude that the presence of T cells is not required for the differentiation and migration of resident skin DC but is critical for the maintenance of DC and LC migrating into the LNs.     

Ambient air pollution and emergency department visits among children and adults in Casablanca,Morocco

This study presents the relationships between ambient air pollutants and morbidity and emergency department visits among children and adults performed in Great Casablanca, the most populated and economic region in Morocco. This research was analyzed using conditional Poisson model for the period 2011–2013. In the period of study, the daily average concentrations of SO₂, NO₂, O₃ and PM₁₀ in Casablanca were 209.4 µg/m³, 61 µg/m³, 113.2 µg/m³ and 75.1 µg/m³, respectively. In children less than 5 years old, risk of asthma could be increased until 12% per 10 µg/m³ increase in NO₂, PM10, SO₂ and O₃. In children over 5 years and adults, an increase of 10 µg/m³ air pollutant can cause an increase until 3% and 4% in respiratory consultations and acute respiratory infection, respectively. Similarly, impact on emergency department visits due to respiratory and cardiac illness was established. Our results suggest a not negligible impact on morbidity of outdoor air pollution by NO₂, SO₂, O₃, and PM₁₀.     

Novel Mutations in the Amyloid Precursor Protein Gene within Moroccan Patients with Alzheimer's Disease

In Morocco, Alzheimer's disease (AD) affects almost 30,000 individuals, and this number could increase to 75,000 by 2020. To our knowledge, the genes predisposing individuals to AD and predicting disease incidence remain elusive. In this study, we aimed to evaluate the genetic contribution of mutations in the amyloid precursor protein (APP) gene exons 16 and 17 to familial and sporadic AD cases. Seventeen sporadic cases and eight family cases were seen at the memory clinic of the University of Casablanca Neurology Department. These patients underwent standard somatic neurological examination, cognitive function assessment, brain imaging, and laboratory tests. Direct sequencing of exons 16 and 17 of the APP gene was performed on genomic DNA of AD patients. In this original Moroccan study, we identified seven novel frameshift mutations in exons 16 and 17 of the APP gene. Interestingly, only one novel splice mutation was detected in a family case. There is a strong correlation between clinical symptoms and genetic factors in Moroccan patients with a family history of AD. Therefore, mutations in APP gene exons 16 and 17 may eventually become genetic markers for AD predisposition.     

Functional Electrical Stimulation—A New Therapeutic Approach to Enhance Exercise Intensity in Chronic Obstructive Pulmonary Disease Patients: A Randomized,Controlled Crossover Trial

Objective

To evaluate the effect of quadriceps functional electrical stimulation (FES)-cycling on exertional oxygen uptake ($\dot{\text{V}}$o₂) compared with placebo FES-cycling in patients with chronic obstructive pulmonary disease (COPD).

Circulating markers of oxidative stress and liver fibrosis in Sudanese subjects at risk of schistosomiasis and hepatitis

Epidemiological studies in the developing world are frequently biased by the simultaneous presence of several infectious pathogens. In the present study, we examined the usefulness of circulating markers of oxidative stress and liver fibrosis to investigate the distinct forms of chronic liver inflammations associated with schistosomiasis and viral hepatitis, respectively. The study was performed in a Sudanese population exposed to Schistosoma. Circulating hyaluronic acid (HA) was used as a marker of liver fibrosis; the severity of schistosomiasis was determined by ultrasonic examination; viral hepatitis infection was ascertained by circulating anti-hepatitis antibodies. Serum markers were examined also in Sudanese subjects not exposed to Schistosoma infection and in French control subjects. We found a drastic decrease of lycopene levels in the subjects exposed to schistosomiasis in comparison with non-exposed Sudanese and French control subjects. Retinol, alpha-tocopherol and five carotenoids were unchanged. Lycopene depletion was unlikely to be due to variations of nutritional origin, since the lycopene/beta-carotene ratio was five-fold lower in the population at risk of schistosomiasis than in the other groups. We found that high HA serum levels were associated with severe periportal fibrosis but not with viral infection. Conversely, levels of the oxidized lipid malondialdehyde (MDA) were associated with viral infection but not with the severity of schistosomiasis, even though the two infections had additive effects. We concluded that serum markers are valuable tools for investigating the complex effects of co-existing factors of chronic liver inflammation.     

Clinical Prediction and Diagnosis of Neurosyphilis in HIV-Infected Patients with Early Syphilis

The diagnosis of neurosyphilis (NS) is a challenge, especially in HIV-infected patients, and the criteria for deciding when to perform a lumbar puncture (LP) in HIV-infected patients with syphilis are controversial. We retrospectively reviewed demographic, clinical, and laboratory data from 122 cases of HIV-infected patients with documented early syphilis who underwent an LP to rule out NS, and we evaluated 3 laboratory-developed validated real-time PCR assays, the Treponema pallidum particle agglutination (TPPA) assay, the fluorescent treponemal antibody absorption (FTA-ABS) assay, and the line immunoassay INNO-LIA Syphilis, for the diagnosis of NS from cerebrospinal fluid (CSF) samples of these patients. NS was defined by a reactive CSF-VDRL test result and/or a CSF white blood cell (WBC) count of >20 cells/μl. Thirty of the 122 patients (24.6%) had early NS. Headache, visual symptoms, a CD4 cell count of <500 cells/μl, and viremia, as defined by an HIV-1 RNA count of ≥50 copies/ml, were associated with NS in multivariate analysis (P = <0.001 for each factor). Blood serum rapid plasma reagin (RPR) titers were not associated with early NS (P = 0.575). For the diagnosis of NS, the PCR, FTA-ABS, TPPA, and INNO-LIA assays had sensitivities of 58%, 100%, 68%, and 100%, specificities of 67%, 12%, 49%, and 13%, and negative predictive values of 85%, 100%, 84%, and 100%, respectively. Visual disturbances, headache, uncontrolled HIV-1 viremia, and a CD4 cell count of <500 cells/μl were predictors of NS in HIV-infected patients with early syphilis, while blood serum RPR titers were not; therefore, RPR titers should not be used as the sole criterion for deciding whether to perform an LP in early syphilis. When applied to CSF samples, the INNO-LIA Syphilis assay easily helped rule out NS.     

Detection and genotyping of human papillomavirus by real-time PCR assay

BackgroundDiagnosis of human papillomavirus (HPV) disease remains a challenge due to several factors related to the cost, the workload of available commercial assays to detect and genotype HPV, and to the low prevalence of infected patients.ObjectiveOur study aimed to develop a real-time PCR, based on SPF10 primers, in order to combine HPV-DNA detection and genotype identification avoiding the negative samples.Study designValidation of SYBR-green based SPF10 real-time PCR on HPV-DNA plasmids followed by the investigation of the viral status in 92 samples from oropharyngeal (94%) cutaneous biopsies (3%) and anal smears (3%) which had previously been HPV-genotyped by LiPA hybridization. In-house HPV viral loads were performed to evaluate the SPF10 real-time PCR sensitivity.ResultsData showed that 100% of HPV plasmids, assessable by LiPA hybridization, were detected and genotyped appropriately after SPF10 real-time PCR assays. These results defined a range of melting temperature peaks for HPV positivity by real-time PCR. The efficient determination of the presence of HPV-DNA by SPF10 real-time PCR was validated for 98% of clinical samples compared to commercial method. Discordant results were due to a low HPV-DNA amount and to a supplementary HPV genotype identified. The SPF10 real-time PCR sensitivity was evaluated between 1 and 10 copies/10³ cells using in-house HPV (6, 11 and 16) viral load assays.ConclusionThe real-time PCR method was efficient in combining screening and genotyping of HPV-DNA. Cost and workload reduction by SPF10 real-time PCR approach may facilitate earlier diagnosis and clinical management of HPV infected patients.     

Hepatitis C virus infection and primary hepatic large B-cell lymphoma: a non-fortuitous association. Case report and review of literature

We report a case of hepatitis C virus infection in association with primary hepatic large B-cell non-Hodgkin's lymphoma. Primary hepatic non-Hodgkin's lymphoma is a rare disease. Association of hepatitis C virus infection with primary hepatic B-cell non-hodgkin's lymphoma is probably not fortuitous. Indeed, in case of primary hepatic non-hodgkin's lymphoma' patients are often hepatitis C virus positive. Moreover, several studies have reported a high prevalence of chronic hepatitis C virus infection among patients with B-cell non-Hodgkin's lymphoma whatever the localization of the lymphoma. A recent study found a high rate of remission of a splenic form of lymphoma after treatment of hepatitis C virus infection. Our case report confirms the hypothesis of a key role of hepatitis C virus in the pathogenesis of various forms of B-cell lymphoproliferative disorders and in particular in primary hepatic lymphoma.