Cognitive functioning, clinical profile and life events in young adults addicted to drugs. Does being a girl make a difference?

Objective: Gender features play a fundamental role as risk factors in drug addiction, entailing differences in vulnerability, onset, drug use and clinical trajectories. Even if increasing empirical evidence has attested that drug abuse in emerging adulthood is associated with cognitive impairments, personality disorders and psychological distress, limited research has analyzed these aspects from a gender perspective. The present research focuses on gender differences in youths (18–24 years of age) diagnosed with substance use disorders (SUDs), in order to detect possible differences between females and males as regards their neuropsychological functioning, clinical profiles and past life experiences. Method: Neuropsychological functioning (neuropsychological battery Esame Neuropsicologico Breve-2), the severity of the symptomatology (Symptom Checklist-90-Revised), personality profile and disorders (Shedler Westen Assessment Procedure-200) and life history were assessed in two groups of young adults with SUDs, 20 males and 20 females (mean age = 21 years, SD = 2.2). Participants were recruited in a therapeutic community in Venice, Italy. Results: Girls showed less cognitive impairment but higher psychological distress with respect to boys; between the two groups, no differences emerged regarding the personality profiles. The girls’ life histories presented more experiences of abuse and maltreatment; they also moved more quickly from substance use to dependence. Boys, instead, were more involved in criminal activity. Conclusions: Given our results, it seems that gender differences manifest early, at emerging adulthood. Consequently, a gender-oriented treatment for drug addiction should be offered even at an early age, focusing on early adverse experiences and their potential traumatic effect on girls. By contrast, young men seem to rely on compromised cognitive functions, which require a specific treatment approach, since they constitute a crucial factor for individual adjustment and treatment outcomes. Results should be interpreted relative to some limitations (such as the small sample size and the preliminary and cross-sectional nature of the research), and future studies are require

miR-214 coordinates melanoma progression by upregulating ALCAM through TFAP2 and miR-148b downmodulation

Malignant melanoma is one of the most aggressive human cancers, but the mechanisms governing its metastatic dissemination are not fully understood. Upregulation of miR-214 and ALCAM and the loss of TFAP2 expression have been implicated in this process, with TFAP2 a direct target of miR-214. Here, we link miR-214 and ALCAM as well as identify a core role for miR-214 in organizing melanoma metastasis. miR- 214 upregulated ALCAM, acting transcriptionally through TFAP2 and also posttranscriptionally through miR-148b (itself controlled by TFAP2), both negative regulators of ALCAM. We also identified several miR-214–mediated prometastatic functions directly promoted by ALCAM. Silencing ALCAM in miR-214–overexpressing melanoma cells reduced cell migration and invasion without affecting growth or anoikisin vitro, and it also impaired extravasation and metastasis formation in vivo. Conversely, cell migration and extravasation was reduced in miR-214–overexpressing cells by upregulation of either miR 148b or TFAP2. These findings were consistent with patterns of expression of miR-214, ALCAM, and miR-148b in human melanoma specimens. Overall, our results define a pathway involving miR-214, miR-148b, TFAP2, and ALCAM that is critical for establishing distant metastases in melanoma

Sustained molecular remission after low dose gemtuzumab-ozogamicin in elderly patients with advanced acute promyelocytic leukemia.

We report here a preliminary experience with gemtuzumab ozogamicin (GO) used at low dosage (3 mg/m2) in 3 elderly patients with acute promyelocytic leukaemia (APL) who presented molecular relapse and were unfit for intensive chemotherapy

Effect of Poor Access to Water and Sanitation As Risk Factors for Soil-Transmitted Helminth Infection: Selectiveness by the Infective Route

Background: Soil-transmitted helminth (STH) infections are a public health problem in resource-limited settings worldwide. Chronic STH infection impairs optimum learning and productivity, contributing to the perpetuation of the poverty-disease cycle. Regular massive drug administration (MDA) is the cardinal recommendation for its control; along with water, sanitation and hygiene (WASH) interventions. The impact of joint WASH interventions on STH infections has been reported; studies on the independent effect of WASH components are needed to contribute with the improvement of current recommendations for the control of STH. The aim of this study is to assess the association of lacking access to water and sanitation with STH infections, taking into account the differences in route of infection among species and the availability of adequate water and sanitation at home. Methods and Findings: Cross-sectional study, conducted in Salta province, Argentina. During a deworming program that enrolled 6957 individuals; 771 were randomly selected for stool/serum sampling for parasitological and serological diagnosis of STH. Bivariate stratified analysis was performed to explore significant correlations between risk factors and STH infections grouped by mechanism of entry as skin-penetrators (hookworms and Strongyloides stercoralis) vs. orally-ingested (Ascaris lumbricoides and Trichuris trichiura). After controlling for potential confounders, unimproved sanitation was significantly associated with increased odds of infection of skin-penetrators (adjusted odds ratio [aOR] = 3.9; 95% CI: 2.6–5.9). Unimproved drinking water was significantly associated with increased odds of infection of orally-ingested (aOR = 2.2; 95% CI: 1.3–3.7). Conclusions: Lack of safe water and proper sanitation pose a risk of STH infections that is distinct according to the route of entry to the human host used by each of the STH species. Interventions aimed to improve water and sanitation access should be highlighted in the recommendations for the control of STH.Fil: Echazú, Adriana. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Bonanno, Daniela. Ministerio de Salud de la Nación. Dirección Nacional de Prevención de Enfermedades y Riesgos; ArgentinaFil: Juarez, Marisa. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Fundación Mundo Sano; ArgentinaFil: Cajal, Silvana P.. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Heredia, Viviana. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Caropresi, Silvia. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Cimino, Rubén Oscar. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caro, Nicolas. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; ArgentinaFil: Vargas Flores, Paola Andrea. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Paredes, Gladys. Provincia de Salta. Hospital Zonal Juan Domingo Perón ; ArgentinaFil: Krolewiecki, Alejandro Javier. Universidad Nacional del Litoral. Facultad de Ciencias Económicas. Instituto de Investigación Estado, Territorio y Economía; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

A New Transgenic Mouse Model of Heart Failure and Cardiac Cachexia Raised by Sustained Activation of Met Tyrosine Kinase in the Heart

Among other diseases characterized by the onset of cachexia, congestive heart failure takes a place of relevance, considering the high prevalence of this pathology in most European countries and in the United States, and is undergoing a rapid increase in developing countries. Actually, only few models of cardiac cachexia exist. Difficulties in the recruitment and follow-up of clinical trials implicate that new reproducible and well-characterized animal models are pivotal in developing therapeutic strategies for cachexia. We generated a new model of cardiac cachexia: a transgenic mouse expressing Tpr-Met receptor, the activated form of c-Met receptor of hepatocyte growth factor, specifically in the heart. We showed that the cardiac-specific induction of Tpr-Met raises a cardiac hypertrophic remodelling, which progresses into concentric hypertrophy with concomitant increase in Gdf15 mRNA levels. Hypertrophy progresses to congestive heart failure with preserved ejection fraction, characterized by reduced body weight gain and food intake and skeletal muscle wasting. Prevention trial by suppressing Tpr-Met showed that loss of body weight could be prevented. Skeletal muscle wasting was also associated with altered gene expression profiling. We propose transgenic Tpr-Met mice as a new model of cardiac cachexia, which will constitute a powerful tool to understand such complex pathology and test new drugs/approaches at the preclinical level

Assessment of severity in aortic stenosis – Incremental value of endocardial function parameters compared to standard indexes

Several studies have reported that patients (pts) with severe aortic stenosis and similar pressure gradients or even similar aortic valve areas may have quite different symptomatic status and clinical outcomes suggesting that other factors might have a significant impact on the pathophysiology of this disease. Our purpose was to assess the severity of subendocardial wall dysfunction in symptomatic and asymptomatic pts with aortic stenosis using tissue Doppler imaging (TDI), strain rate imaging (SRI) and cyclic variation of integrated backscatter (IB). We studied 68 pts with aortic valvar stenosis and 46 subjects with no signs of heart disease. SRI/IB indexes were calculated in the apical four chambers views at endocardial level. Early diastolic endocardial strain rate showed the best correlation with transvalvar pressure gradients and valve areas. Compared with controls, symptomatic pts showed a more marked decrease in endocardial strain, strain rate and cyclic variation of IB. Receiver operating characteristic (ROC) curves suggested that the thresholds offering an adequate compromise between sensitivity and specificity for the prediction of symptoms were >/=60 mm Hg for the pressure gradient, less than 0.60 cm(2)/m(2) for aortic valve area, less than 20% for strain, less than 2.0 s(-1) for strain rate and less than 3.0 dB for cyclic variation. The combination of pressure gradient, aortic valve area and SRI/IB parameters resulted in an improvement of the overall performance for predicting the symptomatic state. Thus, SRI/IB parameters have an incremental value in differentiating symptomatic and asymptomatic pts with aortic stenosis compared with conventional hemodynamic parameters

Neuropsychological deficits in young drug addicts

Background: Adolescence is a highly vulnerable age for experimenting with drugs; increasing evidence attests that several substances might have detrimental effects on cognitive functioning in this developmental phase, when prefrontal brain areas are still immature and may actually be the main target of the neurotoxic effects of drugs. There are still, in any case, too few studies that specifically address early adulthood. Aim: The present study aims to investigate neuropsychological performance in young drug addicts in residential treatment (aged 18-24). Methods: 41 young drug addicts, after admission to residential treatment, were compared with 27 subjects in the control group. A battery of neuropsychological tests (Brief Neuropsychological Exam-2) was administered to detect possible cognitive impairments. Descriptive and non-parametric statistics (Pearson’s chi square test) were performed. Results and conclusions: Findings suggest that drug dependence in youth is distinguished by neuropsychological deficits, in particular, attention and executive function impairments – issues that now call for tailored and innovative treatment approaches

Assessment of ascending aorta distensibility after successful coarctation repair by strain Doppler echocardiography

BACKGROUND: Increased arterial stiffness may participate in the genesis of hypertension and increase of left ventricular (LV) mass after surgical correction of coarctation of the aorta. The purpose of the current study was to assess the aortic elastic properties using Doppler tissue imaging and strain rate imaging in patients after coarctoplasty. METHODS: Echocardiography with Doppler tissue/strain rate imaging capabilities was performed in 26 adult normotensive patients who had successful repair of coarctation of the aorta in infancy and in 24 control subjects. Transesophageal aortic transverse sections were imaged at the level of the proximal and distal segments to the repair site. Doppler tissue imaging wall velocities during systole (S(w)), early relaxation (E(w)), and atrial systole (A(w)) and peak systolic strain (ps epsilon) were measured in both groups. Transthoracic ascending aorta (AAo) measurements were also obtained. RESULTS: In the patients with coarctoplasty, S(w) velocities and ps epsilon were significantly decreased in the proximal segments compared with control subjects. Both peak systolic blood pressure after exercise (P < .001) and pulse pressure after exercise (P < .001) were directly related to AAo wall strain. LV annular early diastolic velocity was significantly reduced compared with control subjects in patients with decreased AAo wall strain and exercise-induced hypertension (P < .001) and related to AAo wall velocity (P < .005) and strain (P < .001). In multiple linear regression analysis, only weight, study group, and AAo wall strain were correlated to LV mass index. CONCLUSIONS: Patients with coarctation of the aorta have reduced proximal aortic wall velocities and strain and increased stiffness even after successful repair. This amplifies stress-induced hypertension and increases LV burden

Prognostic accuracy of Prostate Health Index and urinary Prostate Cancer Antigen 3 in predicting pathologic features after radical prostatectomy

Objective: To compare the prognostic accuracy of Prostate Health Index (PHI) and Prostate Cancer Antigen 3 in predicting pathologic features in a cohort of patients who underwent radical prostatectomy (RP) for prostate cancer (PCa). Methods and materials: We evaluated 156 patients with biopsy-proven, clinically localized PCa who underwent RP between January 2013 and December 2013 at 2 tertiary care institutions. Blood and urinary specimens were collected before initial prostate biopsy for [-2] pro-prostate-specific antigen (PSA), its derivates, and PCA3 measurements. Univariate and multivariate logistic regression analyses were carried out to determine the variables that were potentially predictive of tumor volume >0.5. ml, pathologic Gleason sum 657, pathologically confirmed significant PCa, extracapsular extension, and seminal vesicles invasions. Results: On multivariate analyses and after bootstrapping with 1,000 resampled data, the inclusion of PHI significantly increased the accuracy of a baseline multivariate model, which included patient age, total PSA, free PSA, rate of positive cores, clinical stage, prostate volume, body mass index, and biopsy Gleason score (GS), in predicting the study outcomes. Particularly, to predict tumor volume>0.5, the addition of PHI to the baseline model significantly increased predictive accuracy by 7.9% (area under the receiver operating characteristics curve [AUC] = 89.3 vs. 97.2, P>0.05), whereas PCA3 did not lead to a significant increase.Although both PHI and PCA3 significantly improved predictive accuracy to predict extracapsular extension compared with the baseline model, achieving independent predictor status (all P's<0.01), only PHI led to a significant improvement in the prediction of seminal vesicles invasions (AUC = 92.2, P<0.05 with a gain of 3.6%).In the subset of patients with GS 646, PHI significantly improved predictive accuracy by 7.6% compared with the baseline model (AUC = 89.7 vs. 97.3) to predict pathologically confirmed significant PCa and by 5.9% compared with the baseline model (AUC = 83.1 vs. 89.0) to predict pathologic GS 657. For these outcomes, PCA3 did not add incremental predictive value. Conclusions: In a cohort of patients who underwent RP, PHI is significantly better than PCA3 in the ability to predict the presence of both more aggressive and extended PCa

Quantitative expression profiling of highly degraded RNA from formalin-fixed, paraffin-embedded breast tumor biopsies by oligonucleotide microarrays

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