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OBJECTIVE: We prospectively examined whether subjective intoxication serves as a risk factor for experiencing alcohol-induced blackouts. We then examined whether subjective intoxication and/or blackouts predicted motivation to decrease their drinking, and whether this motivation to change would promote future changes in drinking behavior. METHOD: Participants (N = 1,854, 62.1% female, 53.2% Caucasian, M(age) = 21.8) were recruited the summer prior to matriculating into a large, public university to complete a 6-year longitudinal study. Self-reported motivation to decrease their drinking behavior, their frequency of blackouts, quantity of alcohol consumption, and subjective intoxication (i.e., feeling drunk) were assessed annually during the transition out of college (Years 4–6). RESULTS: In a cross-lagged model, subjective intoxication (i.e., feeling drunk) prospectively predicted experiencing blackouts (p < .001). Controlling for both objective (e.g., quantity) and subjective intoxication, blackouts at Year 4 predicted greater motivation to decrease drinking behavior at Year 5 (p < .01), but this motivation did not predict less quantity of alcohol use by Year 6 (p = .076). CONCLUSIONS: Subjective intoxication is a robust predictor of blackouts across time. Additionally, blackouts are modest, developmentally-limited predictors of motivation to change drinking behavior, but blackouts do not predict future behavior change.

OBJECTIVE: This study examined how freshman year substance use prospectively predicted time to college graduation, and whether delayed graduation predicted postponed adoption of adult roles and future substance use. PARTICIPANTS: Participants were part of a longitudinal study that began in 2004. The first analyses focused on freshman year (N=2,050). The second analyses corresponded to a subset of participants at age 27 (N=575). METHODS: Measures included self-reported substance use, adult role adoption, and university reported graduation dates. RESULTS: Results indicated that frequent binge drinking and marijuana use during freshman year predicted delayed college graduation. Those who took longer to graduate were more likely to have lower incomes and were less likely to obtain a graduate degree. Taking 5–6 years to graduate was associated with greater likelihood of alcohol-related problems. CONCLUSIONS: Findings support the importance of interventions during freshman year of college to decrease substance use and promote timely graduation.

Introduction: Robotic-assisted surgery (RAS) is increasingly used in adulthood but its application in pediatric population is limited. We report our initial experience in pediatric RAS, focusing on...

Gastric duplication cysts (GDCs) represent 4-9% of alimentary tract duplications. Early diagnosis and surgical excision are essential to avoid morbidity or neoplastic degeneration. Roboticassisted excision of GDCs has never been described in childhood. We report an asymptomatic male patient with 2 gastric cystic masses at ultrasonography (US)-study (diameter 25mm and 8mm), increasing in size at follow-up. At 20 months of age, magnetic- resonance-imaging-scan confirmed 2 round gastric masses (44×35mm and 16×12mm, respectively). Two months later, an elective robotic-assisted excision of GDCs was completed without complications. The patient was discharged at day 6 after procedure. Histology confirmed the diagnosis of GDCs. At a 2-year follow- up, US-study did not evidence any issue. In this first reported case of robotic-assisted cystectomy for CGD in childhood, the procedure seems safe, effective, and feasible. This approach improves the movements of the surgical instruments with better 3- D visualization in comparison with the laparoscopic approach.

Background Consequences of heavy drinking include alcohol-induced blackouts, which are periods of amnesia for all or part of a drinking event. One risk factor for blackouts is family history of problematic alcohol use (FH +); however, research rarely distinguishes maternal from paternal FH +. The objective of this study was to examine whether maternal or paternal FH + better predicts likelihood of experiencing blackouts than a general measure of overall FH +, and whether gender moderates this association. Method Participants (N = 1164; 65.4% are female) were first-time college freshmen (age range = 17–19) who participated in a 6-year, 10-assessment, longitudinal study in the United States. Alcohol-induced blackouts, the dependent measure, were dichotomized (yes/no) based on endorsement of memory problems after drinking using a single item during Years 4–6. FH +, captured at baseline, was coded if participants self-reported that their mother, father, or any of their four grandparents were a possible or definite problem drinker. Results Overall, 773 (66.4%) participants reported experiencing blackouts during Years 4–6. Women were more likely to report blackouts than men; however, compared with women with a maternal FH +, men with a maternal FH + were more than twice as likely to report blackouts. Discussion Men appear to be more susceptible than women to the effects of a maternal FH +. Genetic and environmental explanations for this finding are discussed. In sum, these findings are an important step toward understanding a significant yet understudied negative consequence of heavy alcohol use.

Despite the high prevalence of prescription opioid dependence in the U.S., little is known about the course of this disorder and long-term response to treatment. We therefore examined 18-month post-randomization outcomes of participants in the Prescription Opioid Addiction Treatment Study, a multi-site, randomized controlled trial examining varying durations of buprenorphine-naloxone treatment and different intensities of counseling for prescription opioid dependence. Thus the current follow-up study provides a unique contribution to the field by reporting longer-term outcomes of a well-characterized population of treatment-seeking prescription opioid dependent patients. Participants from the treatment trial (N=252/653) completed an 18-month follow-up telephone assessment. Multivariable analyses examined associations between participant characteristics and key indicators of month-18 status: opioid abstinence, DSM-IV opioid dependence, and opioid agonist treatment. Overall, participants showed improvement from baseline to month 18: 49.6% were abstinent in the previous 30 days, with only 16.3% opioid-dependent. Some participants, however, had initiated past-year heroin use (n=9) or opioid injection (n=17). Most participants (65.9%) engaged in substance use disorder treatment during the past year, most commonly opioid agonist therapy (48.8%). Of particular interest in this population, multivariable analysis showed that greater pain severity at baseline was associated with opioid dependence at 18 months. In conclusion, although opioid use outcomes during the treatment trial were poor immediately following a buprenorphine-naloxone taper compared to those during 12 weeks of buprenorphine-naloxone stabilization, opioid use outcomes at 18-month follow-up showed substantial improvement over baseline and were comparable to the rate of successful outcomes during buprenorphine-naloxone stabilization in the treatment trial.

Opioid analgesics misuse is a significant military health concern recognized as a priority issue by military leadership. Opioids are among those most commonly prescribed medications in the military for pain management. The military has implemented opioid risk mitigation strategies, including the Sole Provider Program and the Controlled Drug Management Analysis and Reporting Tool, which are used to identify and monitor for risk and misuse. However, there are substantial opportunities to build on these existing systems to better ensure safer opioid prescribing and monitor for misuse. Opioid risk mitigation strategies implemented by the civilian sector include establishing clinical guidelines for opioid prescribing and prescription monitoring programs. These strategies may help to inform opioid risk mitigation in the military health system. Reducing the risk of opioid misuse and improving quality of care for our Warfighters is necessary. This must be done through evidence-based approaches with an investment in research to improve patient care and prevent opioid misuse as well as its sequelae.

Summary. A multicentre cross-sectional survey was performed to provide an accurate picture of patients with chronic hepatitis B (CHB) cared for by Italian Infectious Diseases Centers (IDCs). This analysis describes factors associated with access to the treatment of CHB in a country where barriers to treatment are not expected to exist because of comprehensive coverage under the National Health System (NHS). The study was performed in 74 IDCs. The analysis focused on 3305 patients with CHB of 3760 HBsAg-positive patients enrolled from March to September, 2008. To account for missing values, a Multiple Imputation method was used. Treatment was reported in 2091 (63.3%) patients. In the multivariate analysis, an increased chance of getting treatment was independently associated with 10 years increase of age at diagnosis (adjusted odds ratio [aOR] 1.2, 95% confidence interval [CI] 1.1–1.3, P

Neuroticism is associated with greater susceptibility to the adverse effects of stress and greater exposure to the stressors associated with acculturation in U.S. born Mexican Americans. Neuroticism and acculturation have been associated with injury to crucial stress response systems and are known risk factors for certain mood and anxiety disorders. The purpose of the current study was to examine the effects of neuroticism, and acculturation on the cortisol awakening response (CAR) in healthy Mexican-American adults. Salivary cortisol samples were collected at awakening and 30, 45, and 60 min thereafter, on two consecutive weekdays from 59 healthy Mexican American adult males (26) and females (33), ages 18 to 38 years. Participants were assessed for level of neuroticism and acculturation. Data were analyzed using a mixed effects regression model with repeated measures at four time points. Results showed a significant Neuroticism × Acculturation × Time interaction. The CAR was virtually eliminated in highly acculturated Mexican Americans with greater Anglo orientation and high neuroticism compared with less acculturated Mexican Americans with greater Mexican orientation and lower neuroticism. Findings suggest that some Mexican Americans with high levels of neuroticism may be particularly susceptible to certain challenges and stressors associated with acculturation leading over time to the development of allostatic load, desensitization of the Hypothalamic CRF system and attenuation of the CAR.

BACKGROUND: Early onset drinking is associated with later heavy drinking and related consequences. Early drinking onset and binge drinking are also independently associated with blackouts, which are periods of amnesia for events during a drinking episode. The objective of this study was to examine how early onset drinking relates to changes in the frequency of experiencing blackouts across 3 years controlling for year-specific binge drinking. METHODS: Participants (N = 1,145; 67.9% female) from a 6-year, longitudinal study are included in these analyses. Measures of self-reported age at drinking onset included ages at first drink, first high, and first drunk, which were used to create a latent early onset drinking factor. Frequency of binge drinking and blackouts were assessed annually during Years 4 to 6. RESULTS: Overall, 69.2% of participants reported experiencing blackouts. After controlling for year-specific binge drinking, a growth curve model indicated that early onset drinkers reported more frequent blackouts at Year 4. There were, however, no significant effects of acceleration or deceleration in the frequency of blackouts across the 3 years. Early onset drinkers continued to experience more frequent blackouts compared with those who initiated alcohol use later, despite decreases in binge drinking over time. CONCLUSIONS: Early onset drinkers reported more frequent blackouts across all 3 years, indicating that early alcohol initiation predisposes those individuals to continue to experience more frequent blackouts, despite a decrease in their binge drinking. This may be due to various factors, such as altered hippocampal development and functioning resulting from early alcohol exposure. Language: en

Chronic inflammation contributes to tumorigenesis. The retinoblastoma protein (pRb), in its hyperphosphorylated form, releases E2 promoter binding factor-1 (E2F1), which drives cell proliferation. Here, we show that pRb is hyperphosphorylated in both mouse and human colitis. In turn, pRb hyperphosphorylation is associated with release of E2F1 from pRb, resulting in the activation of E2F1 target molecules involved in proliferation and apoptosis. These observations provide insight into the in vivo mechanisms associated with chronic colon inflammation and increased colon cancer risk.

But: Comparer l'appendicectomie trans-ombilicale (TULAA) et l'appendicectomie conventionnelle (OA) dans les formes non-compliquees d'appendicite aigue. Methodes: 58 TULAA et 65 OA avec un diagnostic pre-operatoire d'appendicite aigue non compliquee sont comparees. Le pneumoperitoine etait obtenu avec un trocart trans-ombilical de 10 mm et un trocart de 5 mm etait introduit dans la fosse iliaque gauche. L'appendicectomie etait realisee en dehors de l'abdomen apres l'exteriorisation de l'appendice a travers l'incision ombilicale. Resultats: Dans le groupe TULAA, le temps operatoire et le sejour hospitalier etaient reduits. La conversion n'a ete necessaire que dans 1 cas (1,7%) et dans 1 cas (1,7%), un trocart supplementaire de 5 mm a ete introduit. Aucune complication per et post-operatoire n'est survenue dans le groupe TULAA avec un excellent resultat cosmetique. Dans le groupe OA, nous avons une infection parietale (1,5%) et dans 8 cas (12,3%) un elargissement de l'incision etait necessaire. Conclusion: TULAA est la meilleure approche de l'appendicite non compliquee, est moins agressif et traumatique. Elle permet une evaluation complete de la cavite peritoneale avec des resultats cosmetiques superieures, particulierement chez les patients obeses et en cas d'appendice ectopique.

But: Decrire un cas pediatrique de syndrome de «Blue Rubber Bleb Nevus» (BRBNS) ou syndrome de Bean, un desordre systemique rare caracterise par des malformations vasculaires, cutanees et gastro-intestinales qui aboutissent souvent a des hemorragies gastro-intestinales majeures ou a des pertes occultes avec anemie et deficit en fer. Observation: Une fille de 6 ans avec de multiples lesions vasculaires, cutanees caracteristiques etait admise pour une hemorragie rectale massive. Quelques mois auparavant, elle avait ete traitee endoscopiquement pour des angiomes gastriques qui entrainaient un melaena. Les investigations pre-operatoires revelent la recidive des lesions gastriques. A la laparotomie, plus de 25 angiomes du tractus gastro-intestinal ont ete trouves, de multiples resections intestinales etaient realisees. Resultats: Aucun probleme per- ou post-operatoire n'est observe et l'enfant est completement saine, sans recidive d'hemorragie apres un suivi de 3 annees. Conclusions: BRBNS appartient au groupe des malformations vasculaires veineuses. Dans la majorite des cas, il survient sporadiquement mais il peut-etre la consequence d'une transmission autosomale dominante. Des analyses recentes ont localise un locus sur le chromosome 9 responsable des malformations veineuses. Les patients avec BRBNS presentent des lesions cutanees typiques avec quelques lesions mamelonnees caoutchouteuses; le nombre de lesions cutanees et du tractus gastro-intestinal et la severite de l'anemie sont en rapport. Le traitement est dependant de l'extension sur le tube digestif et la severite de la presentation clinique. En l'absence d'hemorragie massive, un traitement conservateur peut etre suffisant, autrement, des resections sont necessaires, mais des lesions supplementaires peuvent secondairement se developper. Le management avec electrocoterisation ou photocoagulation par laser est generalement inefficace meme si quelques publications le recommandent. Le traitement pharmacologique est inutile. Le pronostic de BRBNS est inconnu.

Introduction Most patients relapse to opioids within one month of opioid agonist detoxification, making the antecedents and parallel processes of first use critical for investigation. Craving and withdrawal are often studied in relationship to opioid outcomes, and a novel analytic strategy applied to these two phenomena may indicate targeted intervention strategies. Methods Specifically, this secondary data analysis of the Prescription Opioid Addiction Treatment Study used a discrete-time mixture analysis with time-to-first opioid use (survival) simultaneously predicted by craving and withdrawal growth trajectories. This analysis characterized heterogeneity among prescription opioid-dependent individuals (N = 653) into latent classes (i.e., latent class analysis [LCA]) during and after buprenorphine/naloxone stabilization and taper. Results A 4-latent class solution was selected for overall model fit and clinical parsimony. In order of shortest to longest time-to-first use, the 4 classes were characterized as 1) high craving and withdrawal, 2) intermediate craving and withdrawal, 3) high initial craving with low craving and withdrawal trajectories and 4) a low initial craving with low craving and withdrawal trajectories. Odds ratio calculations showed statistically significant differences in time-to-first use across classes. Conclusions Generally, participants with lower baseline levels and greater decreases in craving and withdrawal during stabilization combined with slower craving and withdrawal rebound during buprenorphine taper remained opioid-free longer. This exploratory work expanded on the importance of monitoring craving and withdrawal during buprenorphine induction, stabilization, and taper. Future research may allow individually tailored and timely interventions to be developed to extend time-to-first opioid use.

Generally laser ablation of materials is performed at laser fluences above a definite threshold for which a dense plume of energetic particles is ejected from the irradiated target and considerably high ablation rate is achieved. No particular effort has been devoted to correlate the film quality to the employed laser fluence, also in correlation with different possible ablation mechanisms of ablation. We have performed measurements of ablation rate on silicon carbide single crystal targets by XeCl laser pulses as function of the laser fluence and we have investigated the angular distribution of the emitted material through the measurements of the thickness of the deposited films as well as the morphology of the craters in the irradiated targets as a function of the laser fluence. We have also modelled the melting dynamics and calculated the surface temperature and the consequent ‘pure thermal’ evaporation following each laser pulse by using the well known ‘thermal model’ often used for the laser annealing. In the presented paper we show that SiC ablation behaviour depends on the laser fluence so that three phenomenologically different energy density ranges may be defined.

Background The continuing migration of individuals from geographic areas with high/medium endemicity has determined the arrival of new chronic hepatitis B virus (HBV) carriers in Italy. The magnitude of this phenomenon and clinical/virological features of HBsAg-positive migrants remain not very well defined. Aims To evaluate the proportion of HBsAg-positive immigrants enrolled in this multicenter Societa` Italiana di Malattie Infettive e Tropicali (SIMIT) cross-sectional study and to compare the characteristics of chronic hepatitis B infection in migrants to those of Italian carriers. Methods From February 1 to July 31 2008, anonymous data were obtained from all HBsAg-positive patients aged C18 years observed at 74 Italian centers of infectious diseases. Results Of the 3,760 HBsAg-positive subjects enrolled, 932 (24.8 %) were immigrants, with a prevalent distribution in central to northern Italy. The areas of origin were: Far East (37.1 %), Eastern Europe (35.4 %), Sub- Saharan Africa (17.5 %), North Africa (5.5 %), and 4.5 % from various other sites. Compared to Italian carriers, migrants were significantly younger (median age 34 vs. 52 years), predominantly female (57.5 vs. 31 %), and most often at first observation (incident cases 34.2 vs. 13.3 %). HBeAg-positives were more frequent among migrants (27.5 vs. 14 %). Genotype D, found in 87.8 % of Italian carriers, was present in only 40 % of migrants, who were more frequently inactive HBV carriers, with a lower prevalence of chronic hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). Only 27.1 % of migrants received antiviral treatment compared to 50.3 % of Italians. Conclusions Twenty-five percent of all HBV carriers examined at Italian centers was composed of immigrants with demographic, serological, and virological characteristics that differed from those of natives and appeared to have an inferior access to treatment

Positron emission tomography (PET) is a clinical and research tool for in vivo metabolic imaging. The demand for better image quality entails continuous research to improve PET instrumentation. In clinical applications, PET image quality benefits from the time of flight (TOF) feature. Indeed, by measuring the photons arrival time on the detectors with a resolution less than 100 ps, the annihilation point can be estimated with centimeter resolution. This leads to better noise level, contrast and clarity of detail in the images either using analytical or iterative reconstruction algorithms. This work discusses a silicon photomultiplier (SiPM)-based magnetic-field compatible TOF-PET module with depth of interaction (DOI) correction. The detector features a 3D architecture with two tiles of SiPMs coupled to a single LYSO scintillator on both its faces. The real-time front-end electronics is based on a current-mode ASIC where a low input impedance, fast current buffer allows achieving the required time resolution. A pipelined time to digital converter (TDC) measures and digitizes the arrival time and the energy of the events with a timestamp of 100 ps and 400 ps, respectively. An FPGA clusters the data and evaluates the DOI, with a simulated z resolution of the PET image of 1.4 mm FWHM.

Summary Introduction The identification of novel reverse-transcriptase (RT) drug-resistance mutations is critical in predicting the probability of success to anti-HBV treatment. Furthermore, due to HBV-RT/HBsAg gene-overlap, they can have an impact on HBsAg-detection and quantification. Methods 356 full-length HBV-RT sequences from 197 drug-naive patients and 159 patients experiencing virological-breakthrough to nucleoside/nucleotide-analogs (NUCs) were analyzed. Mutants and wild-type HBs-antigens were expressed in HuH7-hepatocytes and quantified in cell-supernatants and cell-lysates by Architect HBsAg-assay. Results Ten novel RT-mutations (rtN53T-rtS78T-rtS85F-rtS135T-rtA181I-rtA200V-rtK212Q-rtL229V/F-rtM309K) correlated with specific NUC-treatments and classical drug-resistance mutations on divergent evolutionary pathways. Some of them reduced RT-binding affinity for anti-HBV drugs and altered S-antigen structure. Indeed, rtS78T (prevalence: 1.1% in drug-naive and 12.2% in adefovir-failing patients) decreased the RT-affinity for adefovir more than the classical adefovir-resistance mutations rtA181 T/V (WT:−9.63 kcal/mol, rtA181T:−9.30 kcal/mol, rtA181V:−7.96 kcal/mol, rtS78T:−7.37 kcal/mol). Moreover, rtS78T introduced a stop-codon at HBsAg-position 69, and completely abrogated HBsAg-quantification in both supernatants and cell-lysates, indicating an impaired HBsAg-secretion/production. Furthermore, the HBsAg-mutation sP217L, silent in RT, significantly correlated with M204V/I-related virological-breakthrough and increased HBsAg-quantification in cell-lysate. Conclusions Mutations beyond those classically known can affect drug-binding affinity of mutated HBV-RT, and may have potential effects on HBsAg. Their cumulative effect on resistance and HBV-pathogenicity indicates the importance of preventing therapeutic failures.

Ion beam therapy is a valuable method for the treatment of deep-seated and radio-resistant tumors thanks to the favorable depth-dose distribution characterized by the Bragg peak. Hadrontherapy facilities take advantage of the specific ion range, resulting in a highly conformal dose in the target volume, while the dose in critical organs is reduced as compared to photon therapy. The necessity to monitor the delivery precision, i.e. the ion range, is unquestionable, thus different approaches have been investigated, such as the detection of prompt photons or annihilation photons of positron emitter nuclei created during the therapeutic treatment. Based on the measurement of the induced β+ activity, our group has developed various in-beam PET prototypes: the one under test is composed by two planar detector heads, each one consisting of four modules with a total active area of 10 × 10 cm2. A single detector module is made of a LYSO crystal matrix coupled to a position sensitive photomultiplier and is read-out by dedicated frontend electronics. A preliminary data taking was performed at the Italian National Centre for Oncological Hadron Therapy (CNAO, Pavia), using proton beams in the energy range of 93–112 MeV impinging on a plastic phantom. The measured activity profiles are presented and compared with the simulated ones based on the Monte Carlo FLUKA package.

Some interesting features of laser ablation of fused silica at 308 nm wavelength are reported. In particular it is shown that the major ablation mechanism does not involve a phase transition of the irradiated target but leads to the emission of fragments instead of vapour. Only a few percent of the amount of ablated material is in the gaseous or plasma phase. We present the features (thickness, morphology, particle density, composition) of the film produced for different laser fluences and as a function of the angle subtended by the substrate and the normal to the target. Also we provide evidence that an electrical field does affect the spatial distribution of the emitted material.

Impulsivity and sensation seeking have been associated with substance use disorders, including opioid use disorders. This pilot study sought to examine whether impulsivity and sensation seeking, as measured by the Barratt Impulsiveness Scale (BIS) and Sensation Seeking Scale (SSS), were associated with opioid analgesic misuse risk in chronic, low-back pain patients prescribed opioid analgesics. Participants were 42 chronic, low-back pain patients enrolled in a larger study examining problematic opioid analgesic use. Impulsivity was assessed using the BIS, sensation seeking was measured using the SSS, and opioid analgesic misuse risk was assessed using the Current Opioid Misuse Measure (COMM). Significant bivariate associations were found between the COMM and the following predictor variables: age and the three BIS subscales: Attentional Impulsiveness, Non-planning Impulsiveness, and Motor Impulsiveness. Using a multivariate linear regression, after controlling for age, the BIS subscales accounted for 29.0% of the variance in the COMM. Attentional Impulsiveness was the only significant BIS subscale. These results suggest a potential relationship between impulsivity, but not sensation seeking, and risk for opioid analgesic misuse. Impulsivity is not a prominent trait observed in chronic pain patients; however, it may be an important risk factor for opioid analgesic misuse for a subset of individuals with chronic pain. As such, these findings suggest that additional exploration of this potential risk factor is warranted.

The design of a Positron Emission Tomography detection module capable of working inside a Magnetic Resonant Imaging system is the main objective of the 4D-MPET project. Combining the two imaging technologies offers better soft tissue contrast and lower radiation doses by providing both functional and morphological information at the same time. The proposed detector will feature a three-dimensional architecture based on two tiles of Silicon Photomultipliers coupled to a single LYSO scintillator on both its faces. Silicon Photomultipliers are magnetic-field compatible photo-detectors with a very small size enabling novel detector geometries that allow the measurement of the Depth of Interaction as well as a high detector packing fraction to maximize system sensitivity. Furthermore they can be fabricated using standard silicon technology, have a large gain in the order of 106 and are very fast thus allowing evaluating the Time of Flight. Among the other features of the proposed detection system, the architecture of the innovative readout electronics will be also described which plays a relevant role for the achievement of the desired performance and is based on custom integrated circuits. Simulation results of the whole system show good performance in terms of time and spatial resolution: a timestamp of 100 ps is the ultimate performance achievable with the use of a double threshold technique along with fast electronics. Time over threshold is exploited to provide the energy information with a bin size of 400 ps. Moreover, a z resolution of 1.4 mm Full Width at Half Maximum can be achieved. The proposed detector can also be exploited in other tracking applications, such as High Energy Physics and Astrophysics.

While childhood trauma appears to be a risk factor for the onset of depression and subclinical depressive symptomatology in Mexican Americans, the specific physiological mechanisms contributing to this relationship remain to be clarified. Stress-induced dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis is associated with depressive symptomatology in non-Hispanics. The current study assessed the extent to which the cortisol awakening response (CAR) predicts subclinical depressive symptomatology beyond the influence of childhood trauma in a sample of 55 Mexican American males and females ages 18–38 years, without a diagnosis of clinical depression. Participants were assessed for exposure to early trauma and current depressive symptomatology. Salivary cortisol samples were collected on two consecutive days at awakening, 30, 45, and 60 minutes thereafter, and again at 3pm, 6pm and 9pm. Data were analyzed using general linear models with repeated measures at four morning time points, and again, at three afternoon and evening time points. Results indicated a significant Symptoms × Time interaction for the CAR (p

Results Three out of four HBV patients with occult infection, showed reactivation phases of HBV viremia. Different mutations were observed, with differences between preand post-reactivation sera. HBV-DNA remained at low levels during the entire study period also in absence of specific anti-HBV therapy. The phylogenetic analysis showed that, for each patient with HBV reactivation, all the isolates were originated from a unique parental virus. Specific mutations of PreS/S, Core and X regions were observed. Discussion Mutations in the “a” determinant of the S protein could be responsible for the absence of HBsAg detection. The presence of stop codon in the pre-core region and of mutations in the X region could, in part, explain the reactivation of HBV viremia.

We have undertaken a series of structure observations of hydroxyapatite (HA) films obtained by pulsed laser deposition (PLD) using a pulsed ruby laser as well as of “in situ” mass spectrometry measurements, in order to elucidate the mechanism of target ablation and film deposition. In the present paper we report Rutherford backscattering analysis (RBS), Auger electron spectroscopy (AES) and scanning electron microscopy (SEM) observations of HA films. Moreover, through the analysis of the angular distribution of the film thickness and the quadrupole mass analysis obtained during the irradiation, we also give evidence of two different mechanisms leading to material removal from the irradiated target.

Infarct expansion can be defined pathologically as a distortion of ventricular topography produced by thinning and disproportionate dilation of the infarct segment. Large transmural infarcts tend to be associated with greater propensity for infarct expansion. Two-dimensional echocardiography has made it feasible to detect these acute alterations in cardiac topography by serial examination of patients with acute myocardial infarction. A practical approach to the echocardiographic quantification of expansion involves analysis of end-diastolic cross-sectional echo views at the papillary muscle level, which can be used as fixed internal landmarks to divide the left ventricle into 2 segments, anterior and posterior. An off-line computer system can be used to track relative lengths of these segments as well as their thicknesses over time. In the initial clinical study, one third of patients with acute anterior transmural infarcts showed an average 50% increase in the infarct segment length beginning within the first 3 days of infarction, characterized by disproportionate progressive dilation and transmural thinning of this zone. These patients demonstrated a significantly higher mortality than those without expansion. Later studies demonstrated not only continuing dilation of the infarcted anterior wall, but also progressive dilation of the noninfarcted posterior wall, underscoring the importance of continuing long-term noninvasive follow-up. Not only is expansion associated with a poor clinical outcome; it has also been shown experimentally and clinically to be modifiable or even preventable by various therapeutic maneuvers, which may well improve survival. Because of the limitations of the echocardiographic window, it is often possible to obtain only a single cross-sectional view of high quality, and even then technical quality may not be sufficiently high to enable detailed quantitative analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Identifying molecular changes that predict the risk for developing colon cancer is critical for designing effective prevention strategies. In the present study, we determined early-stage molecular alterations within the colonic epithelium of A/J and AKR/J mice that are sensitive and resistant to Azoxymethane (AOM)-initiated tumor development, respectively. Six week-old male mice were injected intraperitoneally with AOM (10 mg/kg body weight) once a week for six weeks. One week after the last injection, distal colons from both strains were analyzed for cell proliferation using a proliferating cell nuclear antigen (PCNA) assay. Unlike AKR/J, a significant increase (2.5-fold, p

The azoxymethane (AOM)-induced mouse colon tumor model recapitulates many of the histopathological features associated with the multistage progression of human sporadic colorectal cancers (CRCs). To better define the genetic events associated with tumorigenesis in this murine model, we analysed tumors from A/J mice for chromosomal (CIN) and microsatellite (MSI) instabilities, two fundamental pathways of genomic instability that play a critical role in the pathogenesis of human CRCs. Male A/J mice, 6-week old, were injected with either AOM (n=5) (10 mg/kg b.w., i.p.) or vehicle (n=5) (0.9% NaCl solution) once a week for 6 weeks. At 32 weeks after the last dose, comparative genomic hybridization (CGH) was performed on 16 tumors harvested from five animals. Although 25% of the tumors displayed either a gain of chromosome 2 or loss of Y, the majority (75%) showed no genomic imbalances. Further analysis of chromosomal aberrations, using CGH and spectral karyotyping (SKY) was performed in our recently established A/J colon tumor-derived cell line, AJ02-NM0. Results showed a pseudotetraploid karyotype with loss of only the Y chromosome in these cultured cells, thereby providing additional evidence for the minimal role of CIN in the primary AOM-induced tumors. Interestingly, the majority (81%) of A/J tumors displayed low-level microsatellite instability (MSI-L) when analysed using mono- and dinucleotide repeat markers, and showed a significant expansion to high-level instability (MSI-H) in the AJ02-NM0 cells. This finding in cultured cells additionally provides evidence that a mild mutator pathway may contribute to the development of behaviorally benign carcinomas in situ in A/J mice. To better understand the tumorigenic process in the A/J colons, we screened for mutational alterations in key regions of the K-ras and Apc genes. Results showed a very low frequency (6%) of K-ras activating mutations, together with the absence of Apc truncation mutations in primary tumors and AJ02-NM0 cells. However, these tumors displayed intense nuclear accumulation of beta-catenin protein, indicating activation of the Wnt signaling pathway. Based on our molecular and cytogenetic findings, we propose that carcinogen-induced tumors may develop via mechanisms independent of the 'classical' CIN or MSI pathways.

whereas tramadol produced positive and negative subject-rated effects. These data suggest that tapentadol has significant abuse potential, at least on the level of hydromorphone. The mixed subject-rated profile of tramadol is consistent with previous findings indicating reduced abuse potential relative to the prototypic opioids. Financial support: Grant R01 DA 025649 (PI: WWS) and Departmental Startup Funds awarded to WWS.

Background Knee osteoarthritis (OA) is the most common form of joint disease and the major cause of pain and physical disability among elderly people. To relieve pain, many patients, in order to avoid long-term complications of conventional therapy, turn toward non-pharmacologic therapies. Among these, pulsed electromagnetic fields (PEMF) therapy, although it has shown promising in vivo results, has controversial clinical benefits in human studies [1]. Objectives The aim of the study is therefore to evaluate the efficacy of a wearable PEMF device on pain intensity reduction in patients affected by knee osteoarthritis. Secondary aim is to evaluate the effect on stiffness, function, quality of life and pressure pain threshold. Methods Randomized, double-blind, placebo-controlled clinical trial, with equal randomization (1:1) and parallel group study. Knee OA patients, enrolled according to the ACR criteria, with age >40 years, persistent pain, defined as a minimum mean score of 40 on a 100 mm visual analog scales (VAS), symptomatic disease for at least 6 months prior to enrollment have been recruited to be randomly assigned to wear active (n=20) or placebo (n=20) device for 12 hours daily for 4 weeks. Patients affected by secondary causes of OA or by diabetes mellitus have been excluded. The primary outcome measure was score improvement from baseline to 1 months posttreatment in VAS and in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), as recommended by the Outcome Measures in Rheumatology Clinical Trials group [2]. In addition, quality of life, evaluated through the 36-item Medical Outcomes Study Short-Form 36 version 2 (SF-36 v.2) and pressure pain threshold measured through a pressure algometer applied on the anterior part of the thigh (PPT-THI) and on the distal interphalangeal joint (PPT-DIPJ) have been measured. Trial registration number: NCT01877278 Results Baseline data of placebo and active groups were not significantly different. In the active group, after 4 weeks of treatment, T-test results showed a significant improvement of VAS pain (p Conclusions Wearable PEMF therapy, given the low risk of adverse events, appears to be a promising and effective therapy in reducing pain intensity, modulating pain threshold and increasing quality of life in OA patients. Larger human studies are needed to confirm the long-term effect on pain intensity and on the modulation of pain threshold. References Ryang We S et al. Effects of pulsed electromagnetic field on knee osteoarthritis: a systematic review. Rheumatology (Oxford). 2013 May;52(5):815-24 Bellamy N et al. Recommendations for a core set of outcome measures for future phase III clinical trials in knee, hip and hand osteoarthritis. Consensus development at OMERACT III J Rheumatol 1997;24: 799–802 Disclosure of Interest None declared DOI 10.1136/annrheumdis-2014-eular.6015

Background Individuals suffering from chronic pain are frequently affected by depression, which in turn increases the risk of development of chronic pain complaints over time. Objectives This study aims to investigate the relationship between depression and pain intensity and threshold in a cohort of rheumatic patients compared to healthy subjects. Methods 124 individuals of whom 50 affected by rheumatoid arthritis (RA), 23 by psoriatic arthritis (PsA), 23 by ankylosing spondylitis (AS) and 28 age-matched controls without chronic pain underwent quantitative sensory testing (QST) to assess pressure pain threshold with an algometer. Pain intensity was evaluated through the Visual Analogue Scale (VAS) and depression through the Hamilton Depression rating Scale (HAMD). Results A significant reverse correlation between HAMD values and algometer scores was found in the entire cohort of patients (p Conclusions The evaluation of chronic pain in patients affected by rheumatoid arthritis, psoriatic arthritis and ankylosing spondylitis that display comorbid depression seems more reproducible and reliable with the use of an algometer which, therefore, could be considered an useful instrument in pain/depression overlap management. Disclosure of Interest None Declared

Using bDNA, the plasma viral load trend of HCV-infected patients undergoing IFN therapy was analyzed. Nine patients were enrolled, each assigned to one of three groups, based on IFN response as determined by ALT and AST level trend. HCV was genotyped using DEIA. Each patient's clinical stage was determined by liver biopsy analysis. In nonresponding patients elevated viral loads and biochemical parameters were observed. These values were not influenced by IFN treatment. In relapsed patients the cessation of IFN treatment increased viral load; this was associated with a rise in ALT and AST values. In responders ALT and AST levels remained normal; viral load was low. Patients with elevated HCV viral load showed a worsening in their liver histology during the follow-up period. These results confirm that plasma viral load is a good marker of biochemical change and disease progression.

s of the A.I.S.F. – Italian Association for the Study of the Liver – Monothematic Conference 2011 “Hepatic diseases related to migratory flows” Milan, 13–14 October 2011

was higher in the NRG (p 0.70 was the more accurate RT-MCE value to predict LV regional recovery with positive predictive value of 70% and negative predictive value of 56% (p

Background and Aim: Measuring serum HBVDNA levels after diagnosing acute hepatitis B is not a routine procedure. Its kinetics, however, could have a significant prognostic importance for the future development of the infection. The aim of our study is to detrmine whether HBVDNA levels could have prognostic value as far as the outcome of the infection is concerned: self-limited disease, fulminant or self-limited infection Material and methods: Our study included a dynamic examination of HBVDNA in 45 patients with acute HBV infection with different outcome – recovery, protrached course and fulminant hepatitis as two forms that differ from the self-limited HBV infection. HBVDNA was measured on the 1, 2, 7, 30, 60, 90, 180 day after admission to the hospital using Taq Man HBVDNA Real-time PCR. Results: HBVDNA was found in all patients. In fulminant cases relatively high levels of HBVDNA were found from the very beginning (above 10,000,000 IU/ml) and they were HBeAg(−). In patients who recovered and became HBsAg(−) replication reached maximal levels in the beginning of the symptomatic phase. With the recovery form the symptoms it fell and its disappearance marked the fall of the ALT levels and negativation of the HBsAg. The fall of HBVDNA on the 7 day from the admission to the hospital and the following disappearance in the range of the 60 day proved to be predictive for the self-limited course. In patients with protrached hepatitis HBVDNA proved to be with relatively higher levels drom the beginning (p < 0.016, F = 6.196) especially in the HBeAg(+) cases. These levels persisted at the time of 90 and 180 day with following chronification. Conclusion: The follow-up of the replication showed, that in the majority of cases the elimination of the virus becomes in the first 2 months. The persistence of the viremia on the 60 day necessitates its further examination due to the risk of chronification. High risk for protrached course is observed in the anicteric HBeAg(+) cases with relatively high replication (above 100,000,000 IU/ml).

Introduction and objectives. The duodenum is the second most comon site of intestinal diverticula, after the large bowel. Duodenal lesions re usually occasionally evidenced in adults during barium swallow (2–6%) r upper tract endoscopy (9–23% of ERCP) performed for other reasons. earby 10% of cases present with flogistic onset (diverticulitis, diverticular bscess, depending on the diverticulum localization), duodenal perforation r bilio-pancreatic complications (in case of juxta-papillaric diverticula). In hildhood, symptomatic duodenal diverticola are extremely rare and, to the est of our knowledge, no cases of paediatric laparoscopic diverticulectomy as been described in the literature. Materials and methods. The authors describe the case of a 13-year-old dolescent girl presenting recurrent epigastric pain and significant weight oss (10 kg in 2 months), with endoscopic and radiologic evidence of a large xtraluminal duodenal diverticulum, localized along the antero-lateral wall f the second duodenal portion, lined with inflamed mucosa; two smaller iverticula were immediately adjacent the previous lesion. A cycle of PPI herapy was performed, with symptoms recurrence after a short period of pain elief. Considering the relevant clinical history and the antero-lateral position f the larger diverticulum, a laparoscopic diverticulectomy (linear 30 mm ndoGia stapler), without any intraoperative complication. The remaining wo smaller diverticula, not evidenced during the laparoscopic exploration of he duodenal wall, were left in site; the postoperative period was uneventful nd the patient was discharged home at the 5th p.o. day. In the follow-up 6 months) the girl is symptom-free while an endoscopic control has been lanned in the future. Summary. Extraluminal duodenal diverticula are rare lesions in childood; when evidenced in asymptomatic patients they do not require a surgical reatment. In symptomatic case, the more adequate surgical solution depends n their localization. Conclusions. When evidenced along the anterior duodenal wall, far rom the papilla, laparoscopic diverticulectomy represents a simple and safe ption; diverticula localized posteriorly or juxtapapillary, are best treated ith an open approach with duodenal mobilization, particularly when comlicated with inflammation or perforation.

Introduction Major known risk factors for stroke in nonvalvular atrial fibrillation (NVAF) identified by transesophageal echocardiography (TEE) are left atrial thrombus (LAT), spontaneous echocardiographic contrast (dense smoke), left atrial appendage emptying velocity (LAAEV) less than or equal to 0.2 m/sec, and complex aortic plaque (CAP). Study Hypothesis Transthoracic echocardiography (TTE) variables may predict the presence of LAT. Methods Of 183 consecutive patients (median age 73, range 35 to 103 years) who underwent TEE prior to cardioversion for NVAF and who had a TTE within 3 months of the index TEE, 20 were excluded because of mitral valve disease (any mitral stenosis, moderate-severe mitral reurgitation, or mitral prosthesis). The following variables were entered as potential predictors of TEE risk factors for stroke in logistic regression analyses: age $ 70 years, left ventricular hypertrophy (LVH, septum in diastole > 1.2 cm), left ventricular systolic dysfunction (LVSD, LVEF 4.0 cm). Results The following table presents the results of the logistic regression analyses (n = 163): Conclusion LVH and LVSD were identified as independent predictors of LAT, dense smoke, and low LAAEV. RV pacing lead was found to be an additional predictor of dense smoke, whereas age $ 70 years was the only predictor of complex aortic plaque.

Background Transesophageal echocardiography (TEE) is used prior to cardioversion of atrial fibrillation to assess for the presence of left atrial thrombus (LAT). Study Hypothesis Transthoracic echocardiography (TTE) variables can identify a subgroup of patients with nonvalvular atrial fibrillation (NVAF) who are at low risk for LAT. Methods Of 183 consecutive patients who underwent TEE prior to cardioversion and who had a TTE within 3 months of the index TEE, 20 were excluded because of mitral valve disease. A low risk cohort for LAT or dense smoke was defined by normal left ventricular systolic function (LVEF $ 50%), normal left ventricular wall thickness (septum in diastole ≤ 1.2 cm), and absence of right ventricular (RV) pacing lead. Results On TEE, 11 (6.7%) patients had LAT. The combination of left ventricular systolic dysfunction (LVSD), left ventricular hypertrophy (LVH), and RV pacing lead gave a sensitivity of 100%, a specificity of 34%, and a negative predictive value (NPV) of 100% for LAT. Hence, the probability of finding LAT on TEE given the absence of LVSD, LVH, and RV lead was 0%. Further, if the more stringent criteria of LAT or dense smoke was used, the same combination had a sensitivity of 98% and a NPV of 98%. Conclusion A combination of variables obtained from TTE (absence of LVH, LVEF $ 50%, absence of RV pacing lead) can identify a subgroup of patients with NVAF, in whom LAT or dense smoke is unlikely to be present on TEE.

Cystatin C has been suggested as a simple method of estimating GFR more accurately than creatinine in children. We compared the diagnostic accuracy of cystatin C with serum creatinine and the Schwartz formula for estimating GFR in patients with UTMs.We prospectively compared 72 patients with UTMs (20 days to 36 months old, 58 males and 14 females) with a group of 72 healthy controls (10 days to 48 months old, 53 males and 19 females). All patients underwent nuclear medicine clearance investigations with (99m)Tc DTPA.Serum concentration of cystatin C revealed a higher correlation with (99m)Tc DTPA (r = 0.62, p0.001) than serum concentration of creatinine (r = 0.30, p0.01) or Schwartz formula (r = 0.51, p0.001). These results were more evident in patients with uropathy (19) with mild renal impairment. Agreement between methods was assessed using Bland Altman analysis. Mean differences between GFR calculated with (99m)Tc DTPA and cystatin C based GFR estimation or Schwartz formula were -2.6% +/- 46.7% and -73.4% +/- 53.6%, respectively. Diagnostic accuracy in identifying decreased GFR measured as AUC was always highest for cystatin C but hardly sufficient for the 3 variables. Cystatin C performed better in the 0 to 6-month-olds (0.70 +/- 0.08 for cystatin C, 0.58 +/- 0.07 for Schwartz estimate) and patients older than 12 months (0.82 +/- 0.09 for cystatin C, 0.65 +/- 0.11 for Schwartz estimate).Cystatin C proved to be a superior marker rate over serum creatinine in estimating glomerular filtration in children younger than 3 years with UTMs and mild renal impairment, thus, offering a more specific and practical measure for monitoring GFR.