Synovial Fluid Regulates the Gene Expression of a Pattern of microRNA via the NF-κB Pathway: An In Vitro Study on Human Osteoarthritic Chondrocytes.

Synovial fluid (SF) represents the primary source of nutrients of articular cartilage and is implicated in maintaining cartilage metabolism. We investigated the effects of SF, from patients with osteoarthritis (OA), rheumatoid arthritis (RA), and controls, on a pattern of microRNA (miRNA) in human OA chondrocytes. Cells were stimulated with 50% or 100% SF for 24 h and 48 h. Apoptosis and superoxide anion production were detected by cytometry; miRNA (34a, 146a, 155, 181a), cytokines, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, B-cell lymphoma (BCL)2, and nuclear factor (NF)-κB by real-time PCR. The implication of the NF-κB pathway was assessed by the use of NF-κB inhibitor (BAY-11-7082). RA and OA SF up-regulated miR-34a, -146a, -155, -181a, interleukin (IL)-1ß, IL-6, tumor necrosis factor (TNF)-α, MMP-1, MMP-13, and ADAMTs-5 gene expression, while it down-regulated Col2a1. Pathological SF also induced apoptosis, reduced viability, and decreased BCL2 mRNA, whereas it increased superoxide anions, the expression of antioxidant enzymes, p65 and p50 NF-κB. Opposite and positive results were obtained with 100% control SF. Pre-incubation with BAY-11-7082 counteracted SF effects on miRNA. We highlight the role of the SF microenvironment in regulating some miRNA involved in inflammation and cartilage degradation during OA and RA, via the NF-κB pathway.

Exploring the Crosstalk between Hydrostatic Pressure and Adipokines: An In Vitro Study on Human Osteoarthritic Chondrocytes.

Obesity is a risk factor for osteoarthritis (OA) development and progression due to an altered biomechanical stress on cartilage and an increased release of inflammatory adipokines from adipose tissue. Evidence suggests an interplay between loading and adipokines in chondrocytes metabolism modulation. We investigated the role of loading, as hydrostatic pressure (HP), in regulating visfatin-induced effects in human OA chondrocytes. Chondrocytes were stimulated with visfatin (24 h) and exposed to high continuous HP (24 MPa, 3 h) in the presence of visfatin inhibitor (FK866, 4 h pre-incubation). Apoptosis and oxidative stress were detected by cytometry, B-cell lymphoma (BCL)2, metalloproteinases (MMPs), type II collagen (Col2a1), antioxidant enzymes, miRNA, cyclin D1 expressions by real-time PCR, and ß-catenin protein by western blot. HP exposure or visfatin stimulus significantly induced apoptosis, superoxide anion production, and MMP-3, -13, antioxidant enzymes, and miRNA gene expression, while reducing Col2a1 and BCL2 mRNA. Both stimuli significantly reduced ß-catenin protein and increased cyclin D1 gene expression. HP exposure exacerbated visfatin-induced effects, which were counteracted by FK866 pre-treatment. Our data underline the complex interplay between loading and visfatin in controlling chondrocytes' metabolism, contributing to explaining the role of obesity in OA etiopathogenesis, and confirming the importance of controlling body weight for disease treatment.

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes.

Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1-5 MPa) and continuous static HP (10 MPa) for 3 hrs. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and ß-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. ß-catenin protein expression was reduced in cells exposed to HP 1-5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/ß-catenin pathway.

Genetic characterization of variants of HPV­16, HPV­18 and HPV­52 circulating in Italy among general and high­risk populations.

Viral factors, such as high­risk human papillomavirus variants, can increase the risk of viral persistence and influence the progression to cancer. In the present study, the long control region (LCR) of human papillomavirus (HPV)­16 and HPV­52, and the L1 region of HPV­16 and HPV­18, identified from subjects belonging to both general and high­risk populations (migrants, HIV+ subjects and adolescent/young people) residing in Italy, were characterized using molecular and phylogenetic techniques. To the best of our knowledge, this is the first Italian study to analyze a large number of sequences (n=458) and report phylogenetic data on the HPV­52 variants. The phylogenetic analysis showed that 90% of the LCR variants of HPV­16 and HPV­52 clustered within lineage A (European lineage) and only sequences identified from subjects belonging to high­risk populations fell into the non­European lineages. Analysis of the LCRs revealed a high genomic diversity with a large number of changes. Several mutations in the binding sites for viral and cellular transcription factors characterized the HPV­16 LCR variants belonging to the African lineages B and C, were observed in subjects with cytological abnormalities (high squamous intraepithelial lesions). The HPV­16 and HPV­18 L1 molecular characterization identified 30% of changes in the immune­dominant epitope loops. These data give a clear picture of the situation in Italy, and a starting point for understanding the molecular pathogenesis and developing molecular diagnostics for HPV, vaccines and other therapeutic approaches in order to control and/or eliminate virus­induced diseases.

Exploring the Involvement of NLRP3 and IL-1ß in Osteoarthritis of the Hand: Results from a Pilot Study.

Hand osteoarthritis (HOA) includes different subsets; a particular and uncommon form is erosive HOA (EHOA). Interleukin- (IL-) 1ß plays a crucial role in the pathogenesis of osteoarthritis (OA); it is synthesized as an inactive precursor which requires the intervention of a cytosolic multiprotein complex, named inflammasome, for its activation. The aim of this study was to investigate the involvement of IL-1ß and the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome in patients with EHOA and nonerosive HOA (NEHOA) compared to healthy controls. In particular, we evaluated the gene expression of IL-1ß and NLRP3, the serum levels of IL-1ß, IL-6, IL-17, and tumor necrosis factor- (TNF-) α, and the protein levels of IL-1ß and NLRP3. We also assessed the relationships between IL-1ß and NLRP3 and clinical, laboratory, and radiological findings. Fifty-four patients with HOA (25 EHOA and 29 NEHOA) and 20 healthy subjects were included in the study. Peripheral blood mononuclear cell (PBMC) gene and protein expressions of IL-1ß and NLRP3 were quantified by quantitative real-time PCR and western blot. IL-1ß, IL-6, IL-17, and TNF-α serum levels were determined by ELISA. IL-1ß gene expression was significantly reduced (p = 0.0208) in EHOA compared to healthy controls. NLRP3 protein levels were significantly increased in the NEHOA group versus the control (p = 0.0063) and EHOA groups (p = 0.0038). IL-1ß serum levels were not significantly different across the groups; IL-6, IL-17, and TNF-α were not detectable in any sample. IL-1ß concentrations were negatively correlated with the Kellgren-Lawrence score in the whole population (r = -0.446; p = 0.0008) and in NEHOA (r = -0.608; p = 0.004), while IL-1ß gene expression was positively correlated with the number of joint swellings in the EHOA group (r = 0.512; p = 0.011). Taken together, our results, showing poorly detectable IL-1ß concentrations and minimal inflammasome activity in the PBMCs of HOA patients, suggest a low grade of systemic inflammation in HOA. This evidence does not preclude a possible involvement of these factors at the local level.

Time-scaled phylogeography of complete Zika virus genomes using discrete and continuous space diffusion models.

Zika virus (ZIKV), a vector-borne infectious agent that has recently been associated with neurological diseases and congenital microcephaly, was first reported in the Western hemisphere in early 2015. A number of authors have reconstructed its epidemiological history using advanced phylogenetic approaches, and the majority of Zika phylogeography studies have used discrete diffusion models. Continuous space diffusion models make it possible to infer the possible origin of the virus in real space by reconstructing its ancestral location on the basis of geographical coordinates deduced from the latitude and longitude of the sampling locations. We analysed all the ZIKV complete genome isolates whose sampling times and localities were available in public databases at the time the study began, using a Bayesian approach for discrete and continuous phylogeographic reconstruction. The discrete phylogeographic analysis suggested that ZIKV emerged to become endemic/epidemic in the first decade of the 1900s in the Ugandan rainforests, and then reached Western Africa and Asia between the 1930s and 1950s. After a long period of about 40 years, it spread to the Pacific islands and reached Brazil from French Polynesia. Continuous phylogeography of the American epidemic showed that the virus entered in north-eastern Brazil in late 2012 and started to spread in early 2013 from two high probability regions: one corresponding to the entire north-east Brazil and the second surrounding the city of Rio de Janeiro, in a mainly northwesterly direction to Central America, the north-western countries of south America and the Caribbean islands. Our data suggest its cryptic circulation in both French Polynesia and Brazil, thus raising questions about the mechanisms underlying its undetected persistence in the absence of a known animal reservoir, and underline the importance of continuous diffusion models in making more reliable phylogeographic reconstructions of emerging viruses.

Incident genital HPV infections and potential impact of HPV vaccines in adult women living with HIV/AIDS.

This study aims to describe and characterize incident HR-HPV infections and associated diseases in HIV-infected women. 805 HIV-infected women enrolled in the VALHIDATE Study were screened and followed-up for HPV by co-testing. Social, behavioral and health data were collected. HPV-DNA positive samples were typed using a commercial kit or RFLP analysis. Conventional Pap-smears were evaluated using the 2001 Bethesda System. The participants with abnormal cytological results were referred for colposcopy. 565 HIV-infected women (median age: 43 years) were analysed, 40.9% had >5 lifetime sexual partners, 77.2% contracted HIV through sexual intercourse, 93% were receiving antiretroviral treatment and 77.3% had undetectable HIV-RNA. The women underwent 1254 follow-ups (median follow-up: 33 months) for 1430.6 PersonYear-Follow-Up. 37.4% of baseline HPV-negative women acquired incident HPV-infections, 69.6% of which were HR-HPVs. HPV-53 was the most common HPV type detected (9.3%). 18.2% of women showed incident or progressive cytological abnormalities (7.8% ASC-US, 9.7% LSIL and 0.6% HSIL) and colposcopy revealed CIN2 (N = 2), CIN1 (N = 2) and VIN3 (N = 1). The preventable fraction of incident infections was 11.3%, 16.7%, and 35.2% for the 2v-4v-9v-HPV vaccines respectively (χ2 p < 0.0001). The overall burden of incident lesions attributable to the vaccine types were 9.1% for 2v-, 14.5% for 4v- and 30.9% for 9v-vaccine. High HPV incidence rates and high percentages of multiple HR-HPV infections were observed in a cohort of HIV-infected women receiving effective antiretroviral treatment. Primary prevention strategies based on the new 9v-HPV vaccine may help to prevent incident infections and disease progression in this cohort of women.

Low Doses of Etanercept Can Be Effective to Maintain Remission in Psoriatic Arthritis Patients.

OBJECTIVES: We realized a longitudinal open-label study to determine if increasing intervals between etanercept (ETN) administration could be effective in maintaining remission with a stable dose in a patient population affected by psoriatic arthritis (PsA) who had achieved sustained remission with ETN 25 mg biweekly. METHODS: Fifty-four PsA patients were recruited at the Rheumatology Unit of Azienda Ospedaliera Universitaria Senese. Patients, who were in clinical sustained remission with biweekly ETN 25 mg at weeks 12 and 16, and were switched to a weekly regimen. If clinical remission persists at weeks 24 and 28, patients were switched to an every-other-week regimen, continuing with this administration schedule for the entire duration of the study if at weeks 36 and 40 clinical remission was maintained. If, on the contrary, in one of the check there was an increase in disease activity, the therapeutic scheme returned to the previous one. RESULTS: The results of our study indicate that a consistent percentage (72%) of subjects with PsA, achieving a sustained remission with ETN 25 mg biweekly, maintains a remission, after a year of starting therapy, despite a progressive dose reduction by an increase in the dosing interval, 21% with a weekly regimen and 51% with an every-other-week regimen. CONCLUSIONS: Our results show that the main reasons that hinder the dosing interval increase in ETN in PsA patients in sustained clinical remission at standard doses are peripheral polyarthritis pattern and exacerbation of cutaneous manifestations.

Ongoing large measles outbreak with nosocomial transmission in Milan, northern Italy, March-August 2017.

A large measles outbreak has been ongoing in Milan and surrounding areas. From 1 March to 30 June 2017, 203 measles cases were laboratory-confirmed (108 sporadic cases and 95 related to 47 clusters). Phylogenetic analysis revealed the co-circulation of two different genotypes, D8 and B3. Both genotypes caused nosocomial clusters in two hospitals. The rapid analysis of epidemiological and phylogenetic data allowed effective surveillance and tracking of transmission pathways.

Sexually Transmitted Infections: A Novel Screening Strategy for Improving Women's Health in Vulnerable Populations.

BACKGROUND: Migrant women are one of the most vulnerable population to health problems and well-being. This study aimed at implementing a counseling and preventive strategy for sexually transmitted infections (STIs) in undocumented migrant women in Milan, Italy. METHODS: Women (ages 18-65) were enrolled at the NAGA Centre (2012-2013) and asked for a urine sample in order to carry out molecular detection of Human papillomavirus (HPV), Chlamydia trachomatis (Ct), Trichomonas vaginalis (Tv), Neisseria gonorrhoeae (Ng)-DNA. Socio-demographic and sexual behavior information were collected. All HPV/Ct+ women were offered Pap tests and/or were prescribed antibiotic treatment. RESULTS: 537/757 women participated in the study (acceptability rate: 70.9%). Most of the women were from Latin America (45.6%) and Eastern Europe (30.7%); >60% of them had stable partners, did not use contraception and had had at least one pregnancy. The prevalence rates of HPV, Ct, Tv and Ng infections were 24.2%, 7.8%, 4.8% and 0%, respectively. In all, 43.2% of the positive women agreed to undergo a gynecological examination and accepted suitable treatment. CONCLUSIONS: This study shows an overall high prevalence of STIs in undocumented migrant women in Milan. The screening strategy based on counseling and urine testing contributed to the successfully high acceptability rate. More appropriate health services that adequately address all aspects of women's health are required.

Chlamydia trachomatis infection and HPV/Chlamydia trachomatis co-infection among HPV-vaccinated young women at the beginning of their sexual activity.

PURPOSE: This study investigated the prevalence of Chlamydia trachomatis infection, co-infection with Human Papillomavirus (HPV) and associated risk factors in a cohort of sexually active young women enrolled in an ongoing trial on HPV vaccination at the European Institute of Oncology (IEO, Milan, Italy). METHODS: Cervical samples were collected from 591 girls (median age 18.8 years) at the beginning of their sexual activity. At the time of sample collection, 354 women had not yet been vaccinated, and 237 women had been vaccinated for at least 12 months. All samples were analyzed through a molecular assay for the detection of C. trachomatis infection. Demographic, behavioral risk factors and high-risk HPV (HR-HPV) status were investigated. RESULTS: The prevalence of C. trachomatis infection was 4.9 % and HPV/C. trachomatis co-infection rate was 1.5 %. The exact analysis has not underlined statistical significance for the variables considered, except for the infection with HR-HPV (p < 0.001). The prevalence of C. trachomatis infection among women who had not been immunized and those already vaccinated was similar (5.6 vs 3.8 %). However, the rate of HPV/C. trachomatis co-infection was twice as high in unvaccinated women (2 %) compared to vaccinated women (0.8 %). CONCLUSIONS: Over 16 % of young women had at least one of the two STIs investigated. The risk of C. trachomatis infection was higher in HR-HPV infected compared to HR-HPV uninfected young women. The rate of co-infection was halved in HPV-vaccinated compared to unvaccinated women. This study underlines that HPV vaccination can confer benefits also in terms of co-infections prevention, leading to a decreased risk of developing cervical malignancies.

Mechanical Ventilation and Diaphragmatic Atrophy in Critically Ill Patients: An Ultrasound Study.

OBJECTIVE: Mechanical ventilation contributes to diaphragmatic atrophy and dysfunction, and few techniques exist to assess diaphragmatic function: the purpose of this study was to quantify diaphragm atrophy in a population of critically ill mechanically ventilated patients with ultrasound and to identify risk factors that can worsen diaphragmatic activity. DESIGN: Prospective observational study. SETTING: ICU of a 1,200-bed university hospital. PATIENTS: Newly intubated adult critically ill patients. INTERVENTIONS: Diaphragm thickness in the zone of apposition was measured daily with ultrasound, from the first day of mechanical ventilation till discharge to the main ward. MEASUREMENTS AND MAIN RESULTS: Daily atrophy rate (ΔTdi/d) was calculated as the reduction in percentage from the previous measurement. To analyze the difference in atrophy rate (ΔTdi/d), ventilation was categorized into four classes: spontaneous breathing or continuous positive airway pressure; pressure support ventilation 5-12 cm H2O (low pressure support ventilation); pressure support ventilation greater than 12 cm H2O (high pressure support ventilation); and controlled mechanical ventilation. Multivariate analysis with ventilation support and other clinical variables was performed to identify risk factors for atrophy. Forty patients underwent a total of 153 ultrasonographic evaluations. Mean (SD) ΔTdi/d was -7.5% (12.3) during controlled mechanical ventilation, -5.3% (12.9) at high pressure support ventilation, -1.5% (10.9) at low pressure support ventilation, +2.3% (9.5) during spontaneous breathing or continuous positive airway pressure. At multivariate analysis, only the ventilation support was predictive of diaphragm atrophy rate. Pressure support predicted diaphragm thickness with coefficient -0.006 (95% CI, -0.010 to -0.002; p = 0.006). CONCLUSIONS: In critically ill mechanically ventilated patients, there is a linear relationship between ventilator support and diaphragmatic atrophy rate.

Dating the origin and dispersal of Human Papillomavirus type 16 on the basis of ancestral human migrations.

A major limitation when reconstructing the origin and evolution of HPV-16 is the lack of reliable substitution rate estimates for the viral genes. On the basis of the hypothesis of human HPV-16 co-divergence, we estimated a mean evolutionary rate of 1.47×10(-7) (95% HPD=0.64-2.47×10(-7)) subs/site/year for the viral LCR region. The results of a Bayesian phylogeographical analysis suggest that the currently circulating HPV-16 most probably originated in Africa about 110 thousand years ago (Kya), before giving rise to four known geographical lineages: the Asian/European lineage, which most probably originated in Asia a mean 38 Kya, and the Asian/American and two African lineages, which probably respectively originated about 33 and 27 Kya. These data closely reflect current hypotheses concerning modern human expansion based on studies of mitochondrial DNA phylogeny. The correlation between ancient human migration and the present HPV phylogeny may be explained by the co-existence of modes of transmission other than sexual transmission.

Clinical practice in perioperative monitoring in adult cardiac surgery: is there a standard of care? Results from an national survey.

This study was to investigate and define what is considered as a current clinical practice in hemodynamic monitoring and vasoactive medication use after cardiac surgery in Italy. A 33-item questionnaire was sent to all intensive care units (ICUs) admitting patients after cardiac surgery. 71 out of 92 identified centers (77.2 %) returned a completed questionnaire. Electrocardiogram, invasive blood pressure, central venous pressure, pulse oximetry, diuresis, body temperature and blood gas analysis were identified as routinely used hemodynamic monitoring, whereas advanced monitoring was performed with pulmonary artery catheter or echocardiography. Crystalloids were the fluids of choice for volume replacement (86.8 % of Centers). To guide volume management, central venous pressure (26.7 %) and invasive blood pressure (19.7 %) were the most frequently used parameters. Dobutamine was the first choice for treatment of left heart dysfunction (40 %) and epinephrine was the first choice for right heart dysfunction (26.8 %). Half of the Centers had an internal protocol for vasoactive drugs administration. Intra-aortic balloon pump and extra-corporeal membrane oxygenation were widely available among Cardiothoracic ICUs. Angiotensin-converting enzyme inhibitors were suspended in 28 % of the Centers. The survey shows what is considered as standard monitoring in Italian Cardiac ICUs. Standard, routinely used monitoring consists of ECG, SpO2, etCO2, invasive BP, CVP, diuresis, body temperature, and BGA. It also shows that there is large variability among the various Centers regarding hemodynamic monitoring of fluid therapy and inotropes administration. Further research is required to better standardize and define the indicators to improve the standards of intensive care after cardiac surgery among Italian cardiac ICUs.

Endogenous Ouabain: An Old Cardiotonic Steroid as a New Biomarker of Heart Failure and a Predictor of Mortality after Cardiac Surgery.

Cardiovascular diseases remain the main cause of mortality and morbidity worldwide; primary prevention is a priority for physicians. Biomarkers are useful tools able to identify high-risk individuals, guide treatments, and determine prognosis. Our aim is to investigate Endogenous Ouabain (EO), an adrenal stress hormone with hemodynamic effects, as a valuable biomarker of heart failure. In a population of 845 patients undergoing elective cardiac surgery, we have investigated the relationships between EO and echocardiography parameters/plasmatic biomarker of cardiac function. EO was found to be correlated negatively with left ventricular EF (p = 0.001), positively with Cardiac End-Diastolic Diameter (p = 0.047), and positively with plasmatic NT-proBNP level (p = 0.02). Moreover, a different plasmatic EO level (both preoperative and postoperative) was found according to NYHA class (p = 0.013). All these results have been replicated on an independent cohort of patients (147 subjects from US). Finally, a higher EO level in the immediate postoperative time was indicative of a more severe cardiological condition and it was associated with increased perioperative mortality risk (p = 0.023 for 30-day morality). Our data suggest that preoperative and postoperative plasmatic EO level identifies patients with a more severe cardiovascular presentation at baseline. These patients have a higher risk of morbidity and mortality after cardiac surgery.

Percutaneous tracheostomy in patients on anticoagulants.

AIMS: To determine if percutaneous tracheostomy is safe in critically ill patients treated with anticoagulant therapies. SETTINGS AND DESIGN: Single-center retrospective study including all the patients who underwent percutaneous dilatational tracheostomy (PDT) placement over a 1-year period in a 14-bed, cardiothoracic and vascular Intensive Care Unit (ICU). MATERIALS AND METHODS: Patients demographics and characteristics, anticoagulant and antiplatelet therapies, coagulation profile, performed technique and use of bronchoscopic guidance were retrieved. RESULTS: Thirty-six patients (2.7% of the overall ICU population) underwent PDT over the study period. Twenty-six (72%) patients were on anticoagulation therapy, 1 patient was on antiplatelet therapy and 2 further patients received prophylactic doses of low molecular weight heparin. Only 4 patients had normal coagulation profile and were not receiving anticoagulant or antiplatelet therapies. Overall, bleeding of any severity complicated 19% of PDT. No procedure-related deaths occurred. CONCLUSIONS: PDT was proved to be safe even in critically ill-patients treated with anticoagulant therapies. Larger prospective studies are needed to confirm our findings.

HPV Testing from Dried Urine Spots as a Tool for Cervical Cancer Screening in Low-Income Countries.

Nowadays, several screening strategies are available to prevent cervical cancer, but inadequate resources, sociocultural barriers, and sampling issues impede their success in low-income countries. To overcome these issues, this study aimed to evaluate the performance of human papillomavirus (HPV) testing from dried urine spots (DUS). Eighty-eight urine samples (including 56 HPV DNA positive specimens) were spotted on filter paper, dried, and stored in paper-bags. HPV DNA was detected from the DUS after 1 week and 4 weeks of storage using a polymerase chain reaction (PCR) assay. The sensitivity, specificity, and concordance of the DUS-based HPV test were evaluated by comparing the results with those of HPV testing on fresh urine samples as the gold standard. The sensitivity of the test was 98.21% (95% CI: 90.56-99.68) for DUS stored for 1 week and 96.42% (95% CI: 87.88-99.01) for DUS stored for 4 weeks. The specificity was 100% (95% CI: 89.28-100) at both time points. The concordance between DUS and fresh urine HPV testing was "almost perfect" using the κ statistic. These preliminary data suggest that a DUS-based assay could bypass sociocultural barriers and sampling issues and therefore could be a suitable, effective tool for epidemiological surveillance and screening programs, especially in low-income countries.

Dexmedetomidine vs midazolam as preanesthetic medication in children: a meta-analysis of randomized controlled trials.

INTRODUCTION: The preoperative period is a stressing occurrence for most people undergoing surgery, in particular children. Approximately 50-75% of children undergoing surgery develop anxiety which is associated with distress on emergence from anesthesia and with later postoperative behavioral problems. Premedication, commonly performed with benzodiazepines, reduces preoperative anxiety, facilitates separation from parents, and promotes acceptance of mask induction. Dexmedetomidine is a highly selective α2 -agonist with sedative and analgesic properties. A meta-analysis of all randomized controlled trials (RCTs) on dexmedetomidine versus midazolam was performed to evaluate its efficacy in improving perioperative sedation and analgesia, and in reducing postoperative agitation when used as a preanesthetic medication in children. METHODS: Studies were independently searched in PubMed, BioMedCentral, Embase, and the Cochrane Central Register of clinical trials and updated on August 15th, 2014. Primary outcomes were represented by improved sedation at separation from parents, at induction of anesthesia, and reduction in postoperative agitation. Secondary outcomes were reduction in rescue analgesic drugs, and duration of surgery and anesthesia. Inclusion criteria were random allocation to treatment and comparison between dexmedetomidine and midazolam. Exclusion criteria were adult studies, duplicate publications, intravenous administration, and no data on main outcomes. RESULTS: Data from 1033 children in 13 randomized trials were analyzed. Overall, in the dexmedetomidine group there was a higher incidence of satisfactory sedation at separation from parents (314 of 424 [74%] in the dexmedetomidine group vs 196 of 391 [50%] in the midazolam group, RR = 1.30 [1.05-1.62], P = 0.02), a reduced incidence of postoperative agitation (14 of 140 [10%] vs 56 of 141 [40%], RR = 0.31 [0.13-0.73], P = 0.008), and a significant reduction in the rescue doses of analgesic drugs (49 of 241 [20%] vs 95 of 243 [39%], RR = 0.52 [0.39-0.70], P < 0.001). There was no evidence of a higher incidence of satisfactory sedation at anesthesia induction or any reduction of duration of surgery and anesthesia. CONCLUSIONS: Dexmedetomidine is effective in decreasing anxiety upon separation from parents, decreasing postoperative agitation, and providing more effective postoperative analgesia when compared with midazolam.