Psychometric evaluation of the Hospital Anxiety and Depression Scale in a large community sample of adolescents in Hong Kong

Purpose: The Hospital Anxiety and Depression Scale (HADS) is widely used in adult populations; however, its usefulness with adolescents has been explored less. This study sought to evaluate the reliability, validity, and factor structure of the Chinese version of HADS in a community sample of adolescents residing in Hong Kong. Methods: A prospective cohort of 5,857 students recruited from 17 secondary schools completed the HADS. Internal consistency and concurrent validity were examined. Confirmatory factor analysis was applied to test the relative fits of six factor structures of the HADS. The best fitting model was further cross-validated by male, female, splithalf samples, and age subgroups. Results: The HADS possessed adequate internal consistency, especially for the anxiety subscale. Significant concurrent intercorrelations with self-reported suicidal thoughts and the Youth Self Report Anxious/Depressed subscale were discovered and found to be stronger for females. The cross-validation supported a two-factor model, where anxiety item 7, "I can sit at ease and feel relaxed", was placed in the depression subscale. Conclusions: The HADS showed satisfactory psychometric properties as a screening instrument in assessing anxious and depressive states as two correlated but distinct factors in adolescents. Study implications and recommendations for future research were discussed.published_or_final_versionSpringer Open Choice, 21 Feb 201

Copper binding to the Alzheimer’s disease amyloid precursor protein

Alzheimer’s disease is the fourth biggest killer in developed countries. Amyloid precursor protein (APP) plays a central role in the development of the disease, through the generation of a peptide called Aβ by proteolysis of the precursor protein. APP can function as a metalloprotein and modulate copper transport via its extracellular copper binding domain (CuBD). Copper binding to this domain has been shown to reduce Aβ levels and hence a molecular understanding of the interaction between metal and protein could lead to the development of novel therapeutics to treat the disease. We have recently determined the three-dimensional structures of apo and copper bound forms of CuBD. The structures provide a mechanism by which CuBD could readily transfer copper ions to other proteins. Importantly, the lack of significant conformational changes to CuBD on copper binding suggests a model in which copper binding affects the dimerisation state of APP leading to reduction in Aβ production. We thus predict that disruption of APP dimers may be a novel therapeutic approach to treat Alzheimer’s disease

Molecular control of HIV-1 postintegration latency: implications for the development of new therapeutic strategies

The persistence of HIV-1 latent reservoirs represents a major barrier to virus eradication in infected patients under HAART since interruption of the treatment inevitably leads to a rebound of plasma viremia. Latency establishes early after infection notably (but not only) in resting memory CD4+ T cells and involves numerous host and viral trans-acting proteins, as well as processes such as transcriptional interference, RNA silencing, epigenetic modifications and chromatin organization. In order to eliminate latent reservoirs, new strategies are envisaged and consist of reactivating HIV-1 transcription in latently-infected cells, while maintaining HAART in order to prevent de novo infection. The difficulty lies in the fact that a single residual latently-infected cell can in theory rekindle the infection. Here, we review our current understanding of the molecular mechanisms involved in the establishment and maintenance of HIV-1 latency and in the transcriptional reactivation from latency. We highlight the potential of new therapeutic strategies based on this understanding of latency. Combinations of various compounds used simultaneously allow for the targeting of transcriptional repression at multiple levels and can facilitate the escape from latency and the clearance of viral reservoirs. We describe the current advantages and limitations of immune T-cell activators, inducers of the NF-κB signaling pathway, and inhibitors of deacetylases and histone- and DNA- methyltransferases, used alone or in combinations. While a solution will not be achieved by tomorrow, the battle against HIV-1 latent reservoirs is well- underway

Virus occurrence in private and public wells in a fractured dolostone aquifer in Canada

Groundwater samples from 22 wells completed in a regional fractured dolostone aquifer in the Guelph region of southern Ontario, Canada, were collected over an 8-month period and analyzed for viruses and Campylobacter jejuni. Only 8% of the 118 samples exhibited viruses at extremely low concentrations, but of the 22 wells sampled, 10 (45%) were positive for human enteric viruses (polyomavirus, adenovirus A, and GII norovirus) including 5 of the 8 public supply wells (62.5%) and 5 of the 11 private wells (45%). Each virus-positive well had only one virus occurrence with six sampling events during the 8-month sampling campaign and only one virus type was detected in each well. The probability of virus detection was positively associated with well open-interval length. Virus concentration (in the wells that were virus-positive) was negatively associated with well depth and open-interval length and positively associated with overburden thickness (ie, the thickness of unconsolidated materials overlying bedrock facies) and the amount of precipitation 8–14 and 15–21 days prior to the sampling date. The ephemeral nature of the virus detections and the low detection rate on a per sample basis were consistent with previous studies. The percentage of virus-positive wells, however, was much higher than previous studies, but consistent with the fact that the hydrogeologic conditions of fractured bedrock aquifers create wide capture zones and short groundwater travel times to wells making them more vulnerable to contamination occurrence but at very low concentrations