Elevated Aspartate and Alanine Aminotransferase Levels and Natural Death among Patients with Methamphetamine Dependence

Background: Methamphetamine is one of the fastest growing illicit drugs worldwide, causing multiple organ damage and excessive natural deaths. The authors aimed to identify potential laboratory indices and clinical characteristics associated with natural death through a two-phase study. Methods: Methamphetamine-dependent patients (n = 1,254) admitted to a psychiatric center in Taiwan between 1990 and 2007 were linked with a national mortality database for causes of death. Forty-eight subjects died of natural causes, and were defined as the case subjects. A time-efficient sex-and age-matched nested case-control study derived from the cohort was conducted first to explore the potential factors associated with natural death through a time-consuming standardized review of medical records. Then the identified potential factors were evaluated in the whole cohort to validate the findings. Results: In phase I, several potential factors associated with natural death were identified, including aspartate aminotransferase (AST), alanine aminotransferase (ALT), comorbid alcohol use disorder, and the prescription of antipsychotic drugs. In phase II, these factors were confirmed in the whole cohort using survival analysis. For the characteristics at the latest hospital admission, Cox proportional hazards models showed that the adjusted hazard ratios for natural death were 6.75 (p<0.001) in the group with markedly elevated AST (>80 U/L) and 2.66 (p<0.05) in the group with mildly elevated AST (40-80 U/L), with reference to the control group (>40 U/L). As for ALT, the adjusted hazard ratios were 5.41 (p<0.001), and 1.44 (p>0.05). Comorbid alcohol use disorder was associated with an increased risk of natural death, whereas administration of antipsychotic drugs was not associated with lowered risk. Conclusions: This study highlights the necessity of intensive follow-up for those with elevated AST and ALT levels and comorbid alcohol use disorder for preventing excessive natural deaths

Perception of Shadows in Children with Autism Spectrum Disorders

Background: Cast shadows in visual scenes can have profound effects on visual perception. Much as they are informative, they also constitute noise as they are salient features of the visual scene potentially interfering with the processing of other features. Here we asked i) whether individuals with autism can exploit the information conveyed by cast shadows; ii) whether they are especially sensitive to noise aspects of shadows. Methodology/Principal Findings: Twenty high-functioning children with autism and twenty typically developing children were asked to recognize familiar objects while the presence, position, and shape of the cast shadow were systematically manipulated. Analysis of vocal reaction time revealed that whereas typically developing children used information from cast shadows to improve object recognition, in autistic children the presence of cast shadows—either congruent or incongruent—interfered with object recognition. Critically, vocal reaction times were faster when the object was presented without a cast shadow. Conclusions/Significance: We conclude that shadow-processing mechanisms are abnormal in autism. As a result, processing shadows becomes costly and cast shadows interfere rather than help object recognition

A model for describing and maximising Security Knowledge Sharing to enhance security awareness

Employees play a crucial role in enhancing information security in the workplace, and this requires everyone having the requisite security knowledge and know-how. To maximise knowledge levels, organisations should encourage and facilitate Security Knowledge Sharing (SKS) between employees. To maximise sharing, we need first to understand the mechanisms whereby such sharing takes place and then to encourage and engender such sharing. A study was carried out to test the applicability of Transactive Memory Systems Theory in describing knowledge sharing in this context, which confirmed its applicability in this domain. To encourage security knowledge sharing, the harnessing of Self-Determination Theory was proposed— satisfying employee autonomy, relatedness and competence needs to maximise sharing. Such sharing is required to improve and enhance employee security awareness across organisations. We propose a model to describe the mechanisms for such sharing as well as the means by which it can be encouraged

A genetically informed cross-lagged analysis of autistic-like traits and affective problems in early childhood

A genetically informed cross-lagged model was applied to twin data to explore etiological links between autistic-like traits and affective problems in early childhood. The sample comprised 310 same-sex twin pairs (143 monozygotic and 167 dizygotic; 53% male). Autistic-like traits and affective problems were assessed at ages 2 and 3 using parent ratings. Both constructs were related within and across age (r = .30-.53) and showed moderate stability (r = .45-.54). Autistic-like traits and affective problems showed genetic and environmental influences at both ages. Whereas at age 2, the covariance between autistic-like traits and affective problems was entirely due to environmental influences (shared and nonshared), at age 3, genetic factors also contributed to the covariance between constructs. The stability paths, but not the cross-lagged paths, were significant, indicating that there is stability in both autistic-like traits and affective problems but they do not mutually influence each other across age. Stability effects were due to genetic, shared, and nonshared environmental influences. Substantial novel genetic and nonshared environmental influences emerge at age 3 and suggest change in the etiology of these constructs over time. During early childhood, autistic-like traits tend to occur alongside affective problems and partly overlapping genetic and environmental influences explain this association

Evolution of the capsular gene locus of Streptococcus pneumoniae serogroup 6

Streptococcus pneumoniae expressing serogroup 6 capsules frequently causes pneumococcal infections and the evolutionary origins of the serogroup 6 strains have been extensively studied. However, these studies were performed when serogroup 6 had only two known members (serotypes 6A and 6B) and before the two new members (serotypes 6C and 6D) expressing wciNβ were found. We have therefore reinvestigated the evolutionary origins of serogroup 6 by examining the profiles of the capsule gene loci and the multilocus sequence types (MLSTs) of many serogroup 6 isolates from several continents. We confirmed that there are two classes of cps locus sequences for serogroup 6 isolates. In our study, class 2 cps sequences were limited to a few serotype 6B isolates. Neighbour-joining analysis of cps sequence profiles showed a distinct clade for 6C and moderately distinct clades for class 1 6A and 6B sequences. The serotype 6D cps profile was found within the class 1 6B clade, suggesting that it was created by recombination between 6C and 6B cps loci. Interestingly, all 6C isolates also had a unique wzy allele with a 6 bp deletion. This suggests that serotype switching to 6C involves the transfer of a large (>4 kb) gene segment that includes both the wciNβ allele and the ‘short’ wzy allele. The MLST studies of serotype 6C isolates suggest that the 6C cps locus is incorporated into many different pneumococcal genomic backgrounds but that, interestingly, 6C cps may have preferentially entered strains of the same genomic backgrounds as those of serotype 6A

Mucosal immunization with PspA (Pneumococcal surface protein A)-adsorbed nanoparticles targeting the lungs for protection against pneumococcal infection

Burden of pneumonia caused by Streptococcus pneumoniae remains high despite the availability of conjugate vaccines. Mucosal immunization targeting the lungs is an attractive alternative for the induction of local immune responses to improve protection against pneumonia. Our group had previously described the development of poly(glycerol adipate-co-ω-pentadecalactone) (PGA-co-PDL) polymeric nanoparticles (NPs) adsorbed with Pneumococcal surface protein A from clade 4 (PspA4Pro) within L-leucine microcarriers (nanocomposite microparticles-NCMPs) for mucosal delivery targeting the lungs (NP/NCMP PspA4Pro). NP/NCMP PspA4Pro was now used for immunization of mice. Inoculation of this formulation induced anti-PspA4Pro IgG antibodies in serum and lungs. Analysis of binding of serum IgG to intact bacteria showed efficient binding to bacteria expressing PspA from clades 3, 4 and 5 (family 2), but no binding to bacteria expressing PspA from clades 1 and 2 (family 1) was observed. Both mucosal immunization with NP/NCMP PspA4Pro and subcutaneous injection of the protein elicited partial protection against intranasal lethal pneumococcal challenge with a serotype 3 strain expressing PspA from clade 5 (PspA5). Although similar survival levels were observed for mucosal immunization with NP/NCMP PspA4Pro and subcutaneous immunization with purified protein, NP/NCMP PspA4Pro induced earlier control of the infection. Conversely, neither immunization with NP/NCMP PspA4Pro nor subcutaneous immunization with purified protein reduced bacterial burden in the lungs after challenge with a serotype 19F strain expressing PspA from clade 1 (PspA1). Mucosal immunization with NP/NCMP PspA4Pro targeting the lungs is thus able to induce local and systemic antibodies, conferring protection only against a strain expressing PspA from the homologous family 2