BackgroundBrief interventions via the internet have been shown to reduce university students’ alcohol intake. This study tested two smartphone applications (apps) targeting drinking choices on party occasions, with the goal of reducing problematic alcohol intake among Swedish university students.MethodsStudents were recruited via e-mails sent to student union members at two universities. Those who gave informed consent, had a smartphone, and showed risky alcohol consumption according to the Alcohol Use Disorders Identification Test (AUDIT) were randomized into three groups. Group 1 had access to the Swedish government alcohol monopoly’s app, Promillekoll, offering real-time estimated blood alcohol concentration (eBAC) calculation; Group 2 had access to a web-based app, PartyPlanner, developed by the research group, offering real-time eBAC calculation with planning and follow-up functions; and Group 3 participants were controls. Follow-up was conducted at 7 weeks.ResultsAmong 28574 students offered participation, 4823 agreed to join; 415 were excluded due to incomplete data, and 1932 fulfilled eligibility criteria for randomization. Attrition was 22.7–39.3 percent, higher among heavier drinkers and highest in Group 2. Self-reported app use was higher in Group 1 (74%) compared to Group 2 (41%). Per-protocol analyses revealed only one significant time-by-group interaction, where Group 1 participants increased the frequency of their drinking occasions compared to controls (p = 0.001). Secondary analyses by gender showed a significant difference among men in Group 1 for frequency of drinking occasions per week (p = 0.001), but not among women. Among all participants, 29 percent showed high-risk drinking, over the recommended weekly drinking levels of 9 (women) and 14 (men) standard glasses.ConclusionsSmartphone apps can make brief interventions available to large numbers of university students. The apps studied using eBAC calculation did not, however, seem to affect alcohol consumption among university students and one app may have led to a negative effect among men. Future research should: 1) explore ways to increase user retention, 2) include apps facilitating technical manipulation for evaluation of added components, 3) explore the effects of adapting app content to possible gender differences, and 4) offer additional interventions to high-risk users.Trial registrationclinicaltrials.gov: NCT01958398.

PurposeUniversity students in a study on estimated blood alcohol concentration (eBAC) feedback apps were offered participation in a second study, if reporting continued excessive consumption at 6-week follow-up. This study evaluated the effects on excessive alcohol consumption of offering access to an additional skills training app.MethodA total of 186 students with excessive alcohol consumption were randomized to an intervention group or a wait list group. Both groups completed online follow-ups regarding alcohol consumption after 6 and 12 weeks. Wait list participants were given access to the intervention at 6-week follow-up. Assessment-only controls (n = 144) with excessive alcohol consumption from the ongoing study were used for comparison.ResultsThe proportion of participants with excessive alcohol consumption declined in both intervention and wait list groups compared to controls at first (p < 0.001) and second follow-ups (p = 0.054). Secondary analyses showed reductions for the intervention group in quantity of drinking at first follow-up (−4.76, 95% CI [−6.67, −2.85], Z = −2.09, p = 0.037) and in frequency of drinking at both follow-ups (−0.83, 95% CI [−1.14, −0.52], Z = −2.04, p = 0.041; −0.89, 95% CI [−1.16, −0.62], Z = −2.12, p = 0.034). The odds ratio for not having excessive alcohol consumption among men in the intervention group compared to male controls was 2.68, 95% CI [1.37, 5.25] (Z = 2.88, p = 0.004); the figure for women was 1.71, 95% CI [1.11, 2.64] (Z = 2.41, p = 0.016).ConclusionSkills training apps have potential for reducing excessive alcohol use among university students. Future research is still needed to disentangle effects of app use from emailed feedback on excessive alcohol consumption and study participation.Trial RegistrationNCT02064998Electronic supplementary materialThe online version of this article (doi:10.1007/s12529-016-9629-9) contains supplementary material, which is available to authorized users.

A high throughput protein biomarker discovery tool has been developed based on multiplexed proximity ligation assays in a homogeneous format in the sense of no washing steps. The platform consists of four 24-plex panels profiling 74 putative biomarkers with sub-pM sensitivity each consuming only 1 l of human plasma sample. The system uses either matched monoclonal antibody pairs or the more readily available single batches of affinity purified polyclonal antibodies to generate the target specific reagents by covalently linking with unique nucleic acid sequences. These paired sequences are united by DNA ligation upon simultaneous target binding forming a PCR amplicon. Multiplex proximity ligation assays thereby converts multiple target analytes into real-time PCR amplicons that are individually quantified using microfluidic high capacity qPCR in nano liter volumes. The assay shows excellent specificity, even in multiplex, by its dual recognition feature, its proximity requirement, and most importantly by using unique sequence specific reporter fragments on both antibodybased probes. To illustrate the potential of this protein detection technology, a pilot biomarker research project was performed using biobanked plasma samples for the detection of colorectal cancer using a multivariate signature.

Despite the progress in the treatment of lysosomal storage disorders (LSDs) mainly by enzyme replacement therapy, only limited success was reported in targeting the appropriate lysosomal enzyme into the brain. This prevents efficient clearance of neuronal storage, which is present in many of these disorders including alpha-mannosidosis. Here we show that the neuropathology of a mouse model for alpha-mannosidosis can be efficiently treated using recombinant human alpha-mannosidase (rhLAMAN). After intravenous administration of different doses (25-500 U/kg), rhLAMAN was widely distributed among tissues, and immunohistochemistry revealed lysosomal delivery of the injected enzyme. Whereas low doses (25 U/kg) led to a significant clearance (<70%) in visceral tissues, higher doses were needed for a clear effect in central and peripheral nervous tissues. A distinct reduction (<50%) of brain storage required repeated high-dose injections (500 U/kg), whereas lower doses (250 U/kg) were sufficient for clearance of stored substrates in peripheral neurons of the trigeminal ganglion. Successful transfer across the blood-brain barrier was evident as the injected enzyme was found in hippocampal neurons, leading to a nearly complete disappearance of storage vacuoles. Importantly, the decrease in neuronal storage in the brain correlated with an improvement of the neuromotor disabilities found in untreated alpha-mannosidosis mice. Uptake of rhLAMAN seems to be independent of mannose-6-phosphate receptors, which is consistent with the low phosphorylation profile of the enzyme. These data suggest that high-dose injections of low phosphorylated enzymes might be an interesting option to efficiently treat LSDs with CNS involvement.

This study evaluated automated techniques including personalized normative feedback and protective behavioral strategies, for brief interventions intended to reduce peak alcohol concentrations in university students. After completing baseline assessment, a total of 1,678 hazardous-drinking consumers were randomized to a single or a repeated Internet (WEB) or Interactive Voice Response (IVR) intervention, or to a control group (Single WEB: 323; Single IVR: 329; Repeated WEB: 318; Repeated IVR: 334; Control group: 374). At follow-up, six weeks after baseline, questionnaires were returned by 1,422 participants (Single WEB: 277; Single IVR: 286; Repeated WEB: 259; Repeated IVR: 279; Control group: 321). It was found that peak estimated BAC was reduced in the total group (b -0.14, 95% confidence interval (CI) -0.023; -0.005), in the total (b -0.17, 95% CI -0.027; -0.007) and single (b -0.021, 95% CI -0.032; -0.011) WEB group, and in the total (b -0.011, 95% CI -0.021; -0.015) and repeated (b -0.012, 95% CI -0.023; -0.000) IVR groups, compared to controls. The reduction in peak estimated BAC was greater in the single WEB group compared to the single IVR group (b -0.011, 95% CI -0.022; -0.000). This study concluded that both WEB and IVR interventions have a small but significant effect in reducing heavy episodic drinking, which may be due to the relatively large sample size. Repeated intervention may be needed if delivered by IVR.

Background:The heme precursors porphobilinogen (PBG) and 5-aminolevulinic acid (ALA) accumulate during overt crises of acute intermittent porphyria (AIP), and high excretion of these metabolites often continues in the asymptomatic phase. Methods: We measured concentrations of PBG and ALA and investigated the correlation between these metabolites in plasma and urine in 10 asymptomatic AIP carriers with high excretion and in 5 healthy individuals. We quantified plasma concentrations with an HPLCmass spectrometric method and urine concentrations with ion-exchange chromatography. Results: The mean (SD) plasma concentrations of PBG and ALA in the AIP carriers were 3.1 (1.0) and 1.7 (0.7) mol/L, respectively. The mean 8-h urinary excretion amounts of PBG and ALA in the AIP carriers were 102 (25) and 56 (18) mol, respectively, whereas the corresponding values for healthy individuals were 2.9 (0.7) and 9.3 (1.2) mol. The correlations between PBG and ALA values in plasma and urine of the AIP carriers were 0.678 and 0.856, respectively. The mean PBG/ALA ratio was ϳ2.0 in both plasma and urine for the AIP carriers and 0.3 in urine for the healthy individ-

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