Human papillomavirus genotypes among women with or without HIV infection: an epidemiological study of Moroccan women from the Souss area

Background

Data on Human PapillomaVirus (HPV) infection are scarce in Morocco. The objective of the study was to determine the prevalence of HPV and cervical cytology abnormalities in women from the Souss area, Morocco.

Methods

Two hundred and thirty two women who attended the Hassan II hospital (Agadir, Morocco) were recruited in this study. Socio-economic data, sexual activity, reproductive life, history of Pap smear, smoking and HIV status were recorded. Cervical samples were taken using an Ayre spatula. Cytology was reported using the Bethesda system. HPVs were first detected by MY09/11 consensus PCR and then genotyped with INNO-LiPA^® assay. Data were analyzed using the logistic regression model.

Results

The median age of women was 42 years (18–76 years). HIV prevalence was 36.2 %. Any HPV type prevalence was 23.7 % in the study population, lower in HIV-negative women (13.3 %) than in HIV-positive women (39.3 %). HPV16 was the most prevalent type (6.5 %), followed by HPV53 and HPV74 (3.4 % each). Most women had normal cervical smears (82 %), the remaining were diagnosed with LGSIL (13 %) and HGSIL (5 %). HPV was detected in 17.4 % of normal smears, 43.4 % of LGSIL and 75 % of HGSIL. HIV status was the most powerful predictor of high risk (hr) and probable hr (phr) HPV infection (odds ratio 4.16, 95 % confidence interval 1.87–9.24, p?=?0.0005) followed by abnormal cytology (OR 3.98, 95 % CI 1.39–11.40, p?=?0.01), independently of socio-demographic and behavioral risk factors.

Conclusions

In a Moroccan hospital based-population of the Souss area, HPV infections are frequently detected. In addition, high prevalence of hr and phrHPVs and precancerous lesions among HIV-positive women is likely associated with an increased risk of cervical cancer. This highlights the need for HPV and cervical cancer prevention campaigns in Morocco.

     

Monitoring of Cornea Elastic Properties Changes during UV-A/Riboflavin-Induced Corneal Collagen Cross-Linking using Supersonic Shear Wave Imaging: A Pilot Study

Purpose. Keratoconus disease or post-LASIK corneal ectasia are increasingly treated using UV-A/riboflavin-induced corneal collagen cross-linking (CXL). However, this treatment suffers from a lack of techniques to provide an assessment in real-time of the CXL effects. Here, we investigated the potential interest of corneal elasticity as a biomarker of the efficacy of this treatment. Methods. For this purpose, supersonic shear wave imaging (SSI) was performed both ex vivo and in vivo on porcine eyes before and after CXL. Based on ultrasonic scanners providing ultrafast frame rates (～30 kHz), the SSI technique generates and tracks the propagation of shear waves in tissues. It provides two- and three-dimensional (2-D and 3-D) quantitative maps of the corneal elasticity. Results. After CXL, quantitative maps of corneal stiffness clearly depicted the cross-linked area with a typical 200-μm lateral resolution. The CXL resulted in a 56% ± 15% increase of the shear wave speed for corneas treated in vivo (n = 4). Conclusions. The in vivo CXL experiments performed on pigs demonstrated that the quantitative estimation of local stiffness and the 2-D elastic maps of the corneal surface provide an efficient way to monitor the local efficacy of corneal cross-linking.     

From the Cover: Targeting and in vivo imaging of non-small–cell lung cancer using nebulized multimodal contrast agents

One of the main reasons for the dismal prognosis of lung cancer is related to the late diagnosis of this pathology. In this work, we evaluated the potential of optimized lung MRI techniques and nebulized ultrasmall multimodal gadolinium-based contrast agents [ultrasmall rigid platforms (USRPs)] as a completely noninvasive approach for non-small–cell lung cancer (NSCLC) in vivo detection. A mouse model of NSCLC expressing the luciferase gene was developed. Ultrashort echo-time free-breathing MRI acquisitions were performed before and after i.v. or intrapulmonary administration of the nanoparticles to identify and segment the tumor. After orotracheal or i.v. administration of USRPs, an excellent colocalization of the position the tumor with MRI, bioluminescence and fluorescence reflectance imaging, and histology was observed in all mice. Significantly higher signal enhancements and contrast-to-noise ratios were observed with orotracheal administration using lower doses, reducing the toxicity issues and the interobserver variability in tumor detection. The observations suggested the existence of an unknown original mechanism (different from the enhanced permeability and retention effect) responsible for this phenomenon. MRI and USRPs were shown to be powerful imaging tools able to detect, quantify, and longitudinally monitor the development of submillimetric NSCLCs. The absence of ionizing radiation and high resolution MRI, along with the complete noninvasiveness and good reproducibility of the proposed protocol, make this technique potentially translatable to humans. To our knowledge this is the first time that the advantages of an orotracheal administration route are demonstrated for the investigation of the pathomorphological changes due to NSCLCs.Lung cancer is the leading cause of cancer deaths worldwide and the third cancer for occurrence in both sexes, after breast and prostate (1, 2). The burden of this disease is impressive because it is estimated that lung cancer is responsible for more than 1.3 million deaths per year (1, 2). Among the histological variants of this pathology, the non-small–cell lung cancer (NSCLC) known as adenocarcinoma has been increasing in many countries in the past few decades, becoming the most common type of lung cancer in smokers but also in lifelong nonsmokers (1, 3–5).Despite the advances in medical treatments and radiation-based therapies (5), the 5-y survival rate for lung cancer is still under 15% (1, 3). One of the main reasons for this discouraging prognosis is related to late diagnosis of this pathology. Indeed, close to 70% of patients with lung cancer present with locally advanced or metastatic disease at the time of diagnosis (3).In the race to improve global health through early detection of diseases, imaging techniques play a major role because they can provide early diagnostics of pathologies, noninvasive longitudinal patient follow-ups, and help prepare and guide radiotherapy or surgery. MRI has been shown to be especially promising because of high soft tissue contrast, good spatial resolution, and absence of ionizing radiation (6, 7). The latter, in particular, represents a strong advantage over nuclear medicine imaging techniques and computed tomography because it enables repeated acquisitions in patients and screening in old and young patients, without introducing a consistent risk of developing radiation-induced secondary pathologies (8).MRI was proven to be the most adequate imaging technique for the screening and diagnostics of a number of pathologies in brain, heart, or liver (9). Nevertheless, this consideration cannot yet be applied to the lung, which remains one of the most difficult organs to image with MRI because of its intrinsic properties (motion artifacts, low proton density, numerous susceptibility gradients) (6, 7, 10–12).Recently, optimized proton MRI sequences for lung tissue have been reported (10) both for preclinical and clinical lung imaging. Briefly, these sequences are based on ultrashort echo time (UTE) and radial sampling of the k-space (10, 13). UTE proton MRI sequences have been demonstrated to be extremely efficient for limiting motion and susceptibility artifacts and for enhancing MRI signal intensity of the lung tissue (14–19).At the same time in the last two decades, the design of new contrast agents has been actively pursued to improve the potential of MRI in early detection of pathologies. Multimodality, multivalency, combined therapeutic and imaging properties, or active targeting are indeed only some of the advantages that contrast media can provide (20–25).In this work we implement and validate a noninvasive protocol which employs UTE MRI and multimodal contrast agents to detect in vivo lung parenchyma tumor pathological changes at submillimetric spatial resolution in an orthotopic mouse model of bioluminescent lung adenocarcinoma. The contrast agents, hereafter referred as ultrasmall rigid platforms (USRPs), were administered orotracheally to the animals. These nanoparticles are made of a polysiloxane matrix and are surrounded by gadolinium chelates covalently grafted to the inorganic matrix. A near-infrared fluorophore [cyanine (Cy) 5.5] is grafted onto some of the nanoparticles to permit fluorescence imaging. The hydrodynamic diameter of the nanoparticles is entirely under 5 nm and the mass around 8.5 kDa (24).The sensitivity, specificity, contrast enhancement, and pharmacokinetics of this intrapulmonary [or intratracheal (i.t.)] administration route were evaluated against standard i.v. administration of contrast agents. The high-precision identification of tumor contours was validated with bioluminescence imaging (BLI) and conventional histological analysis. The accumulation of the USRPs in the tumor site was confirmed by 2D fluorescence reflectance imaging (FRI) exploiting the multimodal potential of these nanoassemblies.     

Assessing urine human papillomavirus polymerase chain reaction testing as a tool for screening anal HPV infection in HIV-positive MSM

Multiple types of human papillomavirus (HPV) are responsible for most cervical cancers but also cause anal cancers-especially in HIV-positive patients. Furthermore, men who have sex with men (MSM) are twice as likely to develop anal cancers as non-MSM. A simple screening test for HPV infection would be useful in these patients. The aim of our study was to evaluate the detection of HPV by real-time polymerase chain reaction (PCR) in urine as a marker of anal infection in MSM. The study included 52 HIV-positive MSM treated at Amiens University Hospital (Amiens, France). After obtaining informed consent, we performed an anal swab and gathered 10 mL of first-void urine. Samples were extracted and amplified in a real-time PCR. Genotypes were determined with a PapilloCheck(?) system (Greiner Bio-One, Frickenhausen, Germany). The anal test was the gold standard for calculating the characteristics of the urine test. The sensitivity of the urine test for diagnosing anal HPV infection was 15%, the specificity was 66%, the positive predictive value was 87.5%, and negative predictive value was 4.5%. The prevalence of anal HPV infection in the study population was 94%. Genotype 42 was the most common. The anal HPV viral load was significantly lower in men in a stable relationship than in single men. However, there was no statistically significant relationship between anal viral load and anal intraepithelial lesions. We conclude that urine-based HPV is a poor predictor of anal HPV infection in HIV-positive MSM.     

Microbiologic characteristics and in vitro susceptibility to antimicrobials in a large population of patients with cardiovascular implantable electronic device infection

Microbiologic Characteristics and In Vitro Susceptibility to Antimicrobials. Introduction: The incidence of cardiovascular implantable electronic device (CIED) infection is steadily increasing. However, no consensus has been reached with respect to the type and duration of antimicrobial therapy in this specific population of patients. The role played by new anti‐Staphylococcus agents has not been defined. The aims of this study were to describe the microbiological characteristics of a large population of patients with CIED infections and to test the in vitro susceptibility of the various strains to different antimicrobials. Methods: Two hundred eighty‐six patients with CIED infection were included. The minimal inhibitory concentrations of 9 antimicrobials, including linezolid, tigecycline, and daptomycin were measured against all strains of staphylococci isolated. Results: Microbiologic confirmation was obtained in 252 (88%) patients, the vast majority were from Staphylococcus species (86%), 90% of these were coagulase negative strains and 10% were Staphylococcus aureus; 30.5% were methicillin‐resistant. All strains were susceptible to vancomycin, nearly 15% of coagulase negative strains were nonsusceptible to teicoplanin, and nearly 100% of the strains were susceptible to the 3 new antimicrobials. Conclusions: In this large contemporary study, we show that Staphylococcus is by far the most common cause of CIED infections, with the majority due to coagulase negative strains. Methicillin‐resistance is common in this population. Currently, we would recommend vancomycin as first‐line empirical therapy. However, given that not all patients tolerate vancomycin, we believe that newer antimicrobial therapies should now be tested in clinical trials to establish their clinical effectiveness in treating patients with device infections.     

Coronary Microvascular Function in Patients With Isolated Systolic and Combined Systolic/Diastolic Hypertension

J Clin Hypertens (Greenwich). 2012;14:871–876. ©2012 Wiley Periodicals, Inc.Isolated systolic hypertension (ISH) is a common condition in the elderly that is associated with endothelial dysfunction. Concerning the effect of type of hypertension on coronary microvascular function, coronary flow reserve (CFR) in patients with ISH was evaluated and the results were compared with patients with combined systolic/diastolic hypertension (SDH). Seventy‐six elderly patients (older than 60 years) who were free of coronary artery disease and diabetes mellitus were enrolled in the study (38 with ISH and 38 with combined SDH). Using transthoracic Doppler echocardiography, CFR was calculated as the ratio of hyperemic to baseline diastolic peak flow velocities. A CFR value of >2 was accepted as normal. The mean age was 68.6±6.3 years and the groups had similar features with regard to demographic and clinical characteristics. Patients with ISH had significantly lower CFR values compared with those with combined SDH (2.22±0.51 vs 2.49±0.56, respectively; P=.03). On multivariate regression analysis, ISH (β=−0.40, P=.004) and dyslipidemia (β=−0.29, P=.04) were the independent predictors of CFR. These findings indicate that CFR, an indicator of coronary microvascular/endothelial function, is impaired more profoundly in patients with ISH than in patients with combined SDH.

Hypertension, which is a common condition in the population, is one of the major and modifiable risk factors for atherosclerosis. Around 50% of people older than 60 years have been demonstrated to have hypertension and in around half of these cases, hypertension was reported to be in the form of isolated systolic hypertension (ISH). ¹ , ² In contrast, in younger patients (younger than 50 years), combined systolic/diastolic hypertension (SDH) is the predominant form of hypertension characterized by increased systolic and diastolic blood pressure (BP) or diastolic BP alone.Endothelial dysfunction, characterized by decreased nitric oxide bioavailability, is a key event in the progression of atherosclerosis, and when detected in the systemic or coronary circulation, it is an independent predictor of cardiovascular mortality. ³ , ⁴ Atherosclerotic risk factors, including hypertension, are associated with systemic endothelial dysfunction and increased arterial stiffness.Determining coronary flow reserve (CFR) by transthoracic Doppler echocardiography (TTDE) has been introduced as a reliable and reproducible indicator of coronary microvascular‐endothelial function. Demonstrating CFR noninvasively by TTDE has been shown to have a strong correlation with CFR obtained invasively by intracoronary Doppler wire and positron emission tomography. ⁵ , ⁶ Coronary endothelial dysfunction has been reported to be of prognostic significance and an early manifestation of atherosclerosis and CAD. ⁴ , ⁷ Previously, Erdogan and colleagues ⁸ reported that coronary microvascular function is impaired in patients with hypertension. In that study, patients with prehypertension, compared with controls, were also found to have decreased CFR. However, there are no data describing the impact of ISH on coronary microvascular function.Keeping these data in mind, and concerning the effect of type of hypertension on coronary microvascular function, we aimed to evaluate CFR in patients with ISH and compare the results with that obtained from patients with SDH.     

Early life oxytocin treatment improves thermo-sensory reactivity and maternal behavior in neonates lacking the autism-associated gene Magel2

Atypical responses to sensory stimuli are considered as a core aspect and early life marker of autism spectrum disorders (ASD). Although recent findings performed in mouse ASD genetic models report sensory deficits, these were explored exclusively during juvenile or adult period. Whether sensory dysfunctions might be present at the early life stage and rescued by therapeutic strategy are fairly uninvestigated. Here we found that under cool environment neonatal mice lacking the autism-associated gene Magel2 present pup calls hypo-reactivity and are retrieved with delay by their wild-type dam. This neonatal atypical sensory reactivity to cool stimuli was not associated with autonomic thermoregulatory alteration but with a deficit of the oxytocinergic system. Indeed, we show in control neonates that pharmacogenetic inactivation of hypothalamic oxytocin neurons mimicked atypical thermosensory reactivity found in Magel2 mutants. Furthermore, pharmacological intranasal administration of oxytocin to Magel2 neonates was able to rescue both the atypical thermosensory response and the maternal pup retrieval. This preclinical study establishes for the first-time early life impairments in thermosensory integration and suggest a therapeutic potential benefit of intranasal oxytocin treatment on neonatal atypical sensory reactivity for autism.Subject terms: Autism spectrum disorders, Perception     

Prenatal cardiovascular manifestations in the twin-to-twin transfusion syndrome recipients and the impact of therapeutic amnioreduction

OBJECTIVE: We evaluated the cardiovascular pathologic condition in the recipient twin in twin-to-twin transfusion syndrome and the influence of amnioreduction. STUDY DESIGN: Fetal echocardiograms and medical records of 54 pregnancies that were complicated by twin-to-twin transfusion syndrome were reviewed. Recipient twin right and left ventricular wall thickness, diameters, systolic and diastolic function, valve regurgitation, and structural cardiac defects were assessed at examination and after amnioreduction. RESULTS: At examination (n = 28 pregnancies), cardiomegaly because of right ventricular and/or left ventricular hypertrophy was observed in 58% of recipient twins, and biventricular hypertrophy was observed in 33% of recipient twins, without ventricular dilation. Biventricular diastolic dysfunction was present in two thirds of recipient twins, and right ventricular systolic dysfunction and significant atrioventricular valve regurgitation was observed in one third of recipient twins. Serial assessment (n = 21 pregnancies) revealed progressive biventricular hypertrophy and right ventricular systolic and biventricular diastolic dysfunction in most recipient twins. Steeper progression of hypertrophy, diastolic dysfunction, and structural or functional right ventricular outflow disease (20% incidence) were associated with an increased perinatal mortality rate. CONCLUSION: In twin-to-twin transfusion syndrome, the recipient twin has progressive biventricular hypertrophy with predominant right ventricular systolic and biventricular diastolic dysfunction. Despite amnioreduction, the cardiovascular disease persists and even progresses in many recipient twins.