C1D is a major autoantibody target in patients with the polymyositis-scleroderma overlap syndrome

OBJECTIVE: To assess whether the recently discovered exosome-associated proteins MPP6, C1D, KIAA0052/hMtr4, hSki2, and hSki8 are targeted by autoantibodies, and to determine whether these autoantibodies are accompanied by antibodies directed to the established exosome-associated autoantigens PM-Scl-75 and PM-Scl-100. METHODS: Complementary DNAs encoding the recently identified human exosome-associated proteins were expressed as His-tagged fusion proteins in Escherichia coli cells. Sera obtained from patients with several different autoimmune diseases were analyzed for the presence of autoantibodies directed to these proteins, in an enzyme-linked immunosorbent assay (ELISA). The ELISA data obtained for C1D were confirmed by Western blot analysis, using recombinant C1D. RESULTS: All exosome-associated proteins were found to be targeted by autoantibodies, although the frequency with which such antibodies occurred in patient sera was relatively low, with the exception of anti-C1D antibodies. Autoantibodies recognizing C1D were detected in 7 of 30 patients (23%) with the polymyositis (PM)-scleroderma overlap syndrome; this frequency was similar to the frequencies for the established autoantigens PM-Scl-75c (27%) and PM-Scl-100 (23%). Importantly, several patients with the PM-scleroderma overlap syndrome had anti-C1D antibodies but no anti-PM-Scl antibodies. Anti-C1D autoantibodies were observed in only 2 of 204 patients with other diseases, including PM, dermatomyositis, and scleroderma. CONCLUSION: Our results demonstrate that the recently identified exosome-associated protein C1D is a major autoantigen in patients with the PM-scleroderma overlap syndrome and suggest that the use of recombinant C1D as an autoantibody target may aid in diagnosis of the PM-scleroderma overlap syndrome.     

Adherence to HAART therapy measured by electronic monitoring in newly diagnosed HIV patients in Botswana

Aims

This pilot study was designed to evaluate the feasibility and benefits of electronic adherence monitoring of antiretroviral medications in HIV patients who recently started Highly Active Anti Retroviral Therapy (HAART) in Francistown, Botswana and to compare this with self-reporting.

Methods

Dosing histories were compiled electronically using Micro Electro Mechanical Systems (MEMS) monitors to evaluate adherence to prescribed therapies. Thirty patients enrolled in the antiretroviral treatment program were monitored over 6 weeks. These patients were all antiretroviral (ARV) naïve. After each visit (mean three times) to the pharmacy, the data compiled by the monitors were downloaded. Electronic monitoring of adherence was compared to patient self-reports of adherence.

Results

The mean individual medication adherence level measured with the electronic device was 85% (range 21–100%). The mean adherence level measured by means of self-reporting was 98% (range 70–100%). Medication prescribed on a once-a-day dose base was associated with a higher adherence level (97.9% for efavirenz) compared with a twice-a-day regimen (88.4% for Lamivudine/Zidovudine).

Conclusions

It is feasible to assess treatment adherence of patients living in a low resource setting on HAART by using electronic monitors. Adherence, even in the early stages of treatment, appears to be insufficient in some patients and may be below the level required for continuous inhibition of viral replication. This approach may lead to improved targeting of counselling about their medication intake of such patients in order to prevent occurrence of resistant viral strains due to inadequate inhibition of viral replication. In this pilot study a significant difference between the data recorded through the electronic monitors and those provided by self-reporting was observed.

     

Automatic and controlled processes and the development of addictive behaviors in adolescents: a review and a model

This paper presents a review and a model of the development of addictive behaviors in (human) adolescents, with a focus on alcohol. The model proposes that addictive behaviors develop as the result of an imbalance between two systems: an appetitive, approach-oriented system that becomes sensitized with repeated alcohol use and a regulatory executive system that is not fully developed and that is compromised by exposure to alcohol. Self-regulation critically depends on two factors: ability and motivation to regulate the appetitive response tendency. The motivational aspect is often still weak in heavy drinking adolescents, who typically do not recognize their drinking as problematic. Motivation to regulate use often develops only years later, after the individual has encountered serious alcohol-related problems. Unfortunately, at that point behavioral change becomes harder due to several neurocognitive adaptations that result from heavy drinking. As we document, there is preliminary support for the central elements of the model (appetitive motivation vs. self-regulation), but there is a paucity of research directly addressing these mechanisms in human adolescents. Further, we emphasize that adolescent alcohol use primarily takes place in a social context, and that therefore studies should not solely focus on intra-individual factors predicting substance use and misuse but also on interpersonal social factors. Finally, we discuss implications of the model for interventions.     

Interference by new-generation mobile phones on critical care medical equipment

Introduction  

The aim of the study was to assess and classify incidents of electromagnetic interference (EMI) by second-generation and third-generation mobile phones on critical care medical equipment.     

Iron deficiency and NRAMP1 polymorphisms (INT4, D543N and 3'UTR) do not contribute to severity of anaemia in tuberculosis in the Indonesian population

Fe-deficiency anaemia is the most common cause of anaemia in developing countries. In these settings, many chronic infections, including tuberculosis (TB), are highly prevalent. Fe is an essential nutrient for both host and mycobacteria that play a pivotal role in host immunity and mycobacterial growth. A case-control study was performed in a TB-endemic region in Jakarta, Indonesia, among 378 pulmonary TB patients and 436 healthy controls from the same neighbourhood with the same socio-economic status. In a number of these subjects the Fe status could be explored. The distribution of three polymorphisms in the natural resistance-associated macrophage protein gene (NRAMP1) including INT4, D543N and 3'UTR was examined for a possible association with susceptibility to TB. Anaemia (corrected for sex) was present in 63.2 % of active TB compared with 6.8 % of controls, with female patients more often affected. Anaemia was more pronounced in advanced TB as diagnosed by chest radiography. Lower Hb concentrations in TB patients were accompanied by lower plasma Fe concentrations, lower Fe-binding capacity and higher plasma ferritin. After successful TB therapy, Fe parameters improved towards control values and Hb levels normalised, even without Fe supplementation. NRAMP1 gene polymorphisms were not associated with TB susceptibility, TB severity or anaemia. In conclusion, most active TB patients had anaemia, which was probably due to inflammation and not to Fe deficiency since TB treatment without Fe supplementation was sufficient to restore Hb concentration.     

Do Young Children of Alcoholics Hold More Positive or Negative Alcohol-Related Expectancies Than Controls?

Alcohol-related expectancies and alcohol use were examined in 185 children of alcoholics (COAs) and controls, aged 7 to 18 years. Concerning the expectancies of young COAs, two contrasting hypotheses have been proposed: COAs should hold more negative expectancies than controls due to aversive learning, or hold more positive expectancies due to either social learning or a more favorable response to alcohol. We propose that COAs of elementary school age hold more negative expectancies due to aversive learning, whereas older COAs hold more positive expectancies due to a more favorable response to alcohol. The critical variable with respect to the change from more negative to more positive expectancies is proposed to be the child's own initiation of alcohol use. The results of the present cross-sectional study provide suggestive evidence in favor of this hypothesis. First, elementary school-aged COAs had stronger negative expectancies than controls. Second, the hypothesized interaction between family history and own experience with alcohol was confirmed in the adolescent subsample. The proposed model should be critically tested with longitudinal data. If confirmed, the model may be of importance for prevention of alcohol-related problems in high-risk populations.