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Background JC polyomavirus (JCPyV) establishes a stable and successful interaction with the host, causing progressive multifocal leukoencephalopathy (PML) in immunocompromised subjects. Recently, it has been reported that JCPyV, like other viruses, may exploit extracellular vesicles (EV) in cell cultures. Objective To investigate the presence of JCPyV-DNA in EV circulating in human plasma obtained from patients at risk for PML. Study design JCPyV-DNA status was studied in EV obtained from 170 plasma samples collected from 120 HIV positive patients and 50 healthy donors. EV were extracted from plasma and characterized by Nanoparticle tracking analysis, by western blot for presence of tetraspanin CD63, CD81, annexin II, cythocrome C protein and, finally, by immunoelectron microscopy (IEM). Presence and quantitation of JCPyV-DNA were assessed with Multiplex real-time TaqMan PCR assay. Toyocamycin cell line Results The JCPyV-DNA plasma prevalence in 120 HIV positive patients and 50 healthy donors was 28% and 4%, respectively. The investigation performed on well-characterized plasma EV reported JCPyV-DNA detection in 15 out of 36 (42%) of the viremic samples (14 were from HIV patients and 1 from healthy people) at a mean level of 23.5 copies/mL. The examination of EV selected samples reported the percentage of JCPyV-DNA in EV of 5.4% of the total viral load. Moreover, IEM reported the presence of JCPyV Vp1 antigen in plasma-derived EV. Conclusion The potential role of EV-associated JCPyV-DNA open new avenues and mechanistic insights into the molecular strategies adopted by this polyomavirus to persist in the host and spread to the central nervous system.Background Despite the death rate of COVID-19 is less than 3%, the fatality rate of severe/critical cases is high, according to World Health Organization (WHO). Thus, screening the severe/critical cases before symptom occurs effectively saves medical resources. Methods and materials In this study, all 336 cases of patients infected COVID-19 in Shanghai to March 12th, were retrospectively enrolled, and divided in to training and test datasets. In addition, 220 clinical and laboratory observations/records were also collected. Clinical indicators were associated with severe/critical symptoms were identified and a model for severe/critical symptom prediction was developed. Results Totally, 36 clinical indicators significantly associated with severe/critical symptom were identified. The clinical indicators are mainly thyroxine, immune related cells and products. Support Vector Machine (SVM) and optimized combination of age, GSH, CD3 ratio and total protein has a good performance in discriminating the mild and severe/critical cases. The area under receiving operating curve (AUROC) reached 0.9996 and 0.9757 in the training and testing dataset, respectively. When the using cut-off value as 0.0667, the recall rate was 93.33 % and 100 % in the training and testing datasets, separately. Cox multivariate regression and survival analyses revealed that the model significantly discriminated the severe/critical cases and used the information of the selected clinical indicators. Conclusion The model was robust and effective in predicting the severe/critical COVID cases.Background Many people who need specialty treatment for substance use disorders (SUDs) do not receive it. Clinical interventions could increase treatment utilization but are not routinely used. This systematic review aimed to describe clinical interventions that may increase SUD specialty treatment utilization (i.e., treatment initiation, attendance, meaningful engagement) and to determine which intervention(s) most consistently increase treatment utilization. Methods We conducted a systematic review of clinical intervention studies (published in English between 2000 and 2017) reporting outcomes relevant to specialty SUD treatment utilization. Outcomes were treatment initiation, attendance, and meaningful engagement. Risk of bias was assessed using Cochrane guidelines and randomized controlled trials (RCTs) with bias scores less then 3 were included in a synthesis of results. Proportions of positive to negative utilization outcomes were calculated for each low-bias RCT; studies with 50% positive outcomes or more were considered "majority-positive". Studies were categorized by theory-based approach. Results Twenty-three RCTs had low risk of bias and were synthesized. Among intervention types with two or more studies, cognitive-behavioral (100% majority-positive) and coordinated care (67% majority-positive) interventions were most likely to increase treatment initiation, while 12-step promotion interventions were most likely to increase treatment attendance (50% majority-positive). One study (12-step promotion) measured meaningful engagement, with majority-positive outcomes. Conclusions A systematic review and narrative synthesis of clinical interventions promoting specialty SUD treatment utilization provided preliminary evidence that cognitive-behavioral and coordinated care interventions may increase treatment initiation, while 12-step promotion interventions may promote treatment attendance. More quality studies and greater consistency in treatment utilization measurement are needed.Historically, the roots of alcoholism have been linked to either environment or heredity. However, the interaction between these factors is still largely unexplored. The evidence supports a link between alcohol consumption and the endogenous opioid system. We here studied the opioid genes expression in male and female Wistar rats derived from a short-term breeding program which selected -- at adolescence -- for high (ADHI line) or low (ADLO line) ethanol drinking. Specifically, in this work we analyzed central opioid gene expression in the rats of the second filial generation (S2-ADLO and S2-ADHI). Selective downregulation of pronociceptin (Pnoc) and its receptor (Oprl1) mRNA levels were observed in the prefrontal cortex of male S2-ADHI rats when compared to S2-ADLO, and for Oprl1 also in the nucleus accumbens. An increase in gene expression was instead observed for pro-opiomelanocortin (Pomc) in the nucleus accumbens of S2-ADHI males when compared to S2-ADLO, as well as for mu opioid receptor (Oprm1) but in females.

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