Hypertension-induced posterior reversible encephalopathy syndrome as the presentation of progressive bilateral renal artery stenosis

SummaryPosterior reversible encephalopathy syndrome (PRES) is characterized clinically by headache, altered mental status, visual loss, and seizures. PRES is associated with neuroradiological findings characterized by white matter abnormalities, predominantly in the parieto-occipital regions of the brain. PRES is most often described in cases of hypertensive encephalopathy, eclampsia, renal failure, and immunosuppressive or anticancer therapy. We report a case of PRES associated with severe hypertension in the setting of a progressive renovascular hypertension from bilateral atherosclerotic renal artery stenosis. The pathogenesis of PRES is discussed and the importance of a prompt diagnosis and treatment is emphasized

Identification of MiR-21-5p as a functional regulator of mesothelin expression using microRNA capture affinity coupled with next generation sequencing

MicroRNAs (miRNAs) are small non-coding RNAs that regulate mRNA expression mainly by silencing target transcripts via binding to miRNA recognition elements (MREs) in the 3′untranslated region (3′UTR). The identification of bona fide targets is challenging for researchers working on the functional aspect of miRNAs. Recently, we developed a method (miR-CATCH) based on biotinylated DNA antisense oligonucleotides that capture the mRNA of interest and facilitates the characterisation of miRNAs::mRNA interactions in a physiological cellular context. Here, the miR-CATCH technique was applied to the mesothelin (MSLN) gene and coupled with next generation sequencing (NGS), to identify miRNAs that regulate MSLN mRNA and that may be responsible for its increased protein levels found in malignant pleural mesothelioma (MPM). Biotinylated MSLN oligos were employed to isolate miRNA::MSLN mRNA complexes from a normal cell line (Met-5A) which expresses low levels of MSLN. MiRNAs targeting the MSLN mRNA were identified by NGS and miR-21-5p and miR-100-5p were selected for further validation analyses. MiR-21-5p was shown to be able to modulate MSLN expression in miRNA mimic experiments in a panel of malignant and non-malignant cell lines. Further miRNA inhibitor experiments and luciferase assays in Mero-14 cells validated miR-21-5p as a true regulator of MSLN. Moreover, in vitro experiments showed that treatment with miR-21-5p mimic reduced proliferation of MPM cell lines. Altogether, this work shows that the miR-CATCH technique, coupled with NGS and in vitro validation, represents a reliable method to identify native miRNA::mRNA interactions. MiR-21-5p is suggested as novel regulator of MSLN with a possible functional role in cellular growth

Effects of treatment for acromegaly on Bone Mineral Density (BMD): is Pegvisomant protective on lumbar BMD?

The abstract deals with the different effects of treatments for acromegaly on bon

Psychological, rather than organic and/or relational components are involved in sexual dysfunction in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men.

BACKGROUND: HIV-infection is associated to an increased prevalence of erectile dysfunction (ED)1,2. In HIV- infected men ED seems to be less related to serum Testosterone (T)2-4, ED and sexual dysfunction mainly depending from other factors1,2. However, data on other components of sexual dysfunction in HIV are scanty2. AIM: To investigate the role of different components (organic, relational, psychological) of erectile function by using different validate questionnaire in HIV-infected men with normal serum T who are mainly homosexual (70%). METHODOLOGY: Prospective, cross-sectional, observational study on 225 eugonadal, HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART) attending the Clinic of Infectious Diseases. The International Index of Erectile Function (IIEF)-15, IIEF-5 and Structured Interview for Erectile Dysfunction (SIEDY) were used for the evaluation of sexual function. Moreover, the sexual desire was further evaluated using a direct question during the visit. Statistical analysis: comparison of continue variables among groups was performed using Kruskal-Wallis test and Dunnet test for post-hoc analyses. RESULTS: 225 HIV-infected patients were enrolled (mean age 45.19±5.36 years) with average duration of HIV- infection and of HAART treatment of 187.62±101.71 and 156.38+89.81 months, respectively. Table 1 summarizes the score obtained in each item evaluated by questionnaires.The SIEDY scores obtained at appendix and scale 3 were significantly higher in patients with ED at IIEF-15 (n=136, 60.4%) compared with those without ED (appendix: 7.64+4.39 vs 4.35+3-14, p<0.001) (scale 3: 2.72+4.39 vs 2.07+1.86, p=0.015). Conversely, scale 1 (2.76+2.16 vs 2.46+2.10, p=0.448) and 2 (0.53+1.02 vs 0.61+1.47, p=0.503) of SIEDY did not differ between patients with or without ED. This suggests that the psychological basis of ED was predominant in HIV-infected men. However, when patients were grouped according to the severity of ED at IIEF-15 all SIEDY items did not differ among the 3 groups (p>0.05). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001). Similarly, the score at SIEDY appendix was significantly different among the ED degree found at IIEF-15 (p<0.001). In particular, lower score was found in HIV-infected men without ED compared to those with mild, moderate and severe ED (p<0.001, p=0.001, and p<0.001, respectively), confirming the reliability of these tools. Sexual desire was evaluated using IIEF-15 appropriate domain and during the interview through direct question performed by the clinician. Sexual desire was impaired in 73 patients (31.33%) at interview with a good correlation with the item of IIEF-15 on sexual desire (p<0.001). CONCLUSIONS: The psychological component of ED impacts in a significant manner on ED in men with HIV. Despite the high prevalence of comorbidities in these patients the organic component does not affect erectile function. Similarly, the relational component seems to play a not significant role probably because of the high percentage of men not in a stable relationship. All the three validated questionnaires well describe the degree of erectile dysfunction, with a good correlation index, suggesting that they are all reliable and accurate for the diagnosis of ED in this peculiar population. REFERENCES 1Zona S et al. Erectile dysfunction is more common in young to middle-aged HIV-infected men than in HIV-uninfected men. J Sex Med. 2012 Jul;9(7):1923-30. 2Santi D et al. Male sexual dysfunction and HIV--a clinical perspective. Nat Rev Urol. 2014 Feb;11(2):99-109. 3Rochira V et al. Premature decline of serum total testosterone in HIV-infected men in the HAART-era. PLoS One. 2011;6(12):e28512. 4Rochira V & Guaraldi G. Hypogonadism in the HIV-infected man. Endocrinol Metab Clin North Am. 2014 Sep;43(3):709-30

COMT but not 5HTTLPR Gene is associated with depression in First-Episode Psychosis: the role of stressful life events

Serotonergic and dopaminergic systems are involved in the regulation of mood and reactivity to psychological stress. This study explores, in a sample of first episode psychosis (FEP) patients, whether more severe depressive symptoms were found in those who: (1) experienced a major stressful event in the 6 months preceding illness onset; and (2) were homozygous for the COMT Val158 allele or carrying the S allele of 5-HTTLPR. A total of 186 FEP patients recruited were assessed using the Hamilton Rating Scale for Depression (HAMD) for depressive symptoms. Stressful life events (SLEs) were collected by the List of Events Scale. The genotypes of 5-HTTLPR, rs25531, and COMT Val158 Met were performed. It has been found that higher levels of depression is associated with the presence of SLEs (p = 0.019) and with COMT Val158 allele homozygosity (p = 0.029), but not with carrying the S allele of 5-HTTLPR. The COMT gene moderates the association between depression and SLEs as Val158 allele homozygote patients experiencing SLEs had the highest level of depressive symptoms compared to the others (p = 0.002). The present study provides initial evidence for an effect of the COMT Val158 homozygosity and severe stressful life events on the severity of depressive symptoms in first episode psychosis

Building capacity to provide innovative interventions for early psychosis in mental health professionals

Abstract Despite international guidelines, cognitive behavioural therapy for early psychosis (CBTep) is still under-used in daily clinical practice, mainly due to the lack of specific skills among mental health professionals. The aim of the study was to evaluate the feasibility and efficacy of a CBTep training course and to investigate the impact of trainees' variables on the level of skills acquisition. An intensive and graded CBTep training programme consisting of 112 hours of plenary lectures, 30 hours of group supervision and 3 months of practical training was offered to mental health professionals of 65 Italian community Mental Health Centers (CMHCs). CBT expert psychologists were used as the comparison group. Participants underwent pre-planned exams to test the level of skills acquisition and were requested to complete a satisfaction survey. The vast majority of participants (93%) completed the training with medium–high evaluation scores and reported to be highly satisfied with the course. CMHCs staff members achieved high scores in the examinations and no major differences between them and CBT expert psychologists were found in most of the final exam scores. Our results support the feasibility and the efficacy of the training to build specific CBTep capacity in a large cohort of professionals working in Italian Generalist Mental Health Services. Key learning aims (1) To understand the capacity building of a short training programme in CBT for early psychosis dedicated to community mental health professionals. (2) To consider the optimal characteristics of a CBT training programme for early psychosis. (3) To reflect on the feasibility of a CBT training programme for early psychosis in the context of Italian Community Mental Health Services

Association between CYP2E1 polymorphisms and risk of differentiated thyroid carcinoma

Differentiated thyroid carcinoma (DTC) results from complex interactions between genetic and environmental factors. Known etiological factors include exposure to ionizing radiations, previous thyroid diseases, and hormone factors. It has been speculated that dietary acrylamide (AA) formed in diverse foods following the Maillard's reaction could be a contributing factor for DTC in humans. Upon absorption, AA is biotransformed mainly by cytochrome P450 2E1 (CYP2E1) to glycidamide (GA). Considering that polymorphisms within CYP2E1 were found associated with endogenous levels of AA-Valine and GA-Valine hemoglobin adducts in humans, we raised the hypothesis that specific CYP2E1 genotypes could be associated with the risk of DTC. Analysis of four haplotype tagging SNPs (ht-SNPs) within the locus in a discovery case-control study (N = 350/350) indicated an association between rs2480258 and DTC risk. This ht-SNP resides within a linkage disequilibrium block spanning intron VIII and the 3'-untranslated region. Extended analysis in a large replication set (2429 controls and 767 cases) confirmed the association, with odds ratios for GA and AA genotypes of 1.24 (95 % confidence interval (CI) 1.03-1.48) and 1.56 (95 % CI, 1.06-2.30), respectively. Functionally, the minor allele was associated with low levels of CYP2E1 mRNA and protein expression as well as lower enzymatic activity in a series of 149 human liver samples. Our data support the hypothesis that inter-individual differences in CYP2E1 activity could modulate the risk of developing DTC suggesting that the exposure to specific xenobiotics, such as AA, could play a role in this process

Variation rs2235503 C > A Within the Promoter of MSLN Affects Transcriptional Rate of Mesothelin and Plasmatic Levels of the Soluble Mesothelin-Related Peptide.

Soluble mesothelin-related peptide (SMRP) is a promising biomarker for malignant pleural mesothelioma (MPM), but several confounding factors can reduce SMRP-based test's accuracy. The identification of these confounders could improve the diagnostic performance of SMRP. In this study, we evaluated the sequence of 1,000 base pairs encompassing the minimal promoter region of the MSLN gene to identify expression quantitative trait loci (eQTL) that can affect SMRP. We assessed the association between four MSLN promoter variants and SMRP levels in a cohort of 72 MPM and 677 non-MPM subjects, and we carried out in vitro assays to investigate their functional role. Our results show that rs2235503 is an eQTL for MSLN associated with increased levels of SMRP in non-MPM subjects. Furthermore, we show that this polymorphic site affects the accuracy of SMRP, highlighting the importance of evaluating the individual's genetic background and giving novel insights to refine SMRP specificity as a diagnostic biomarker

Testosterone (T) is poorly related to Erectile Dysfunction (ED) in Young/Middle Aged Human immunodeficiency virus (HIV)-Infected Men.

BACKGROUND: HIV infection is strongly associated to ED in men1,2. Preliminary data suggests that ED is poorly associated with serum T in HIV+ men1,3-4. AIM: To investigate the relationship between sexual function as assessed by the validated International Index of Erectile Function (IIEF-15) and T deficiency in HIV-infected men by assessing circulating T by Liquid Chromatography tandem Mass Spectrometry (LC-MS/MS). METHODOLOGY: Prospective, cross-sectional, observational study on 233 consecutive HIV-infected male patients with ongoing Highly Active Antiretroviral Therapy (HAART), attending the Clinic of Infectious Diseases. IIEF-15 questionnaire was used to define patients having ED (score <25), IIEF-5 was performed to check if it is reliable as IIEF-15 in this setting, while LC-MS/MS was used for hormonal assays. Statistical analysis: Continuous and categorical variables were compared using ANOVA univariate and Chi-Square test, respectively. Correlations were performed using Spearman\u2019s Rho coefficient. RESULTS: 233 HIV-infected patients were enrolled (mean age 45.29\ub15.33 years) with average duration of HIV-infection of 195.98\ub1129.54 months. Eight patients (3.4%) had hypogonadism, defined as total T serum levels below 300 ng/dL. 142 patients (61.5%) had ED (EF score 6425) (Table 1). Age, hormonal data and duration of HIV infection and HAART did not differ among groups of patients according to the degree of ED (Table 1). Although no differences were seen among categories, the direct comparison of each ED cluster showed that months of infection were significantly higher in men with severe ED compared to mild ED (p=0.037); moreover, men with severe ED had lower T levels than men with mild form (p=0.029). All hypogonadal men had erectile dysfunction (p=0.020). However, no differences were found among ED degree for hypogonadal men (p=0.151). The erectile function domain at IIEF-15 was directly correlated with IIEF-5 score (0.778, p<0.001), as expected. Moreover, the IIEF-15 score was inversely related to months of infection (-0.147, p=0.026) (Figure 1), but not to months of HAART therapy (-0.121, p=0.071). Total T showed an inverse relation with months of infection (-0.172, p=0.009) (Figure 1) and months of HAART (-0.173, p=0.010), but not with IIEF-15 score (0.039; p=0.559). CONCLUSIONS: To the best of our knowledge, this is the first, properly-designed prospective study aiming to investigate the relationship between erectile function and serum T, assessed using the LC-MS/MS in HIV-infected men. Similarly to the IIEF-15, the IIEF-5 recognize ED patients and the scores of both correlates each other. In our cohort, the prevalence of ED and hypogonadism was 61% and 3.4%, respectively. Thus, ED evaluated by IIEF-15 seems to be not directly related to serum total T, but it correlates with age and months of infection. In conclusion, in HIV-infected patients a) IIEF-5 is reliable as IIEF- 15 for ED diagnosis, b) ED is not associated with serum T, c) erectile function is not influenced by T and HAART, but only by HIV-infection duration. In conclusion, several specific factors, such as the duration of HIV infection, are involved in erectile function in HIV-infected men and should be carefully considered in this setting, while hormonal status seems to be less important