Knowledge, attitude and practice on standard precautions for prevention of HIV infection among clinical year medical students.

BACKGROUND: Human Immunodeficiency Virus (HIV) can be transmitted through blood, vaginal secretion, infected semen, breast milk as well as blood containing saliva, vomitus and urine. Health care workers (HCWs) are at risk of HIV infection; and standard precautions is a guideline to be followed by HCWs to prevent it. OBJECTIVE: This study was aimed to evaluate the level of knowledge, attitude and practice on standard precautions for prevention of HIV infection; and its associated factors. MATERIALS AND METHODS: This cross-sectional study was conducted among 200 clinical year medical students from a public university in Malaysia. The clinical year medical students were arranged into strata according to year of study and were randomly selected via stratified random sampling. Each respondent were provided a selfadministered questionnaire. There were four sections in the questionnaire to obtain information on socio-demographic characteristics, knowledge, attitude and practice on standard precautions. Both descriptive and analytical analyses such as Chi-squared test were performed. RESULTS: A total of 162 respondents participated in this study, contributed to the response rate of 81%. The study demonstrated that there was no significant association between level of practice with socio-demographic characteristics such as gender, ethnicity, age, religion, year of study and total family income. However, there was a significant association between level of practice with level of knowledge and attitude (p<0.05). For every one year increase in age, the respondents were 1.7 times (p=0.001) and 1.5 times (p=0.012) more likely to have knowledge score between 50th and 75th percentile and above 75th percentile compared to below 50th percentile, respectively. CONCLUSION: It could be interpreted from the findings, that there is a need for further improvement in the knowledge and attitude level among the respondents; which will eventually improve their practice.

Sequence analysis of E/NS1 gene junction of Dengue Type-1 viruses isolated in Klang Valley 2010 to 2012.

Dengue is a mosquito-borne viral disease caused by four serotypes of dengue virus, affecting the human population for decades in many tropical and subtropical regions of the world. In Malaysia, all four dengue serotypes co-circulates in a dengue season even though any one of the serotypes can predominate. In this study, serum samples were collected from dengue fever and severe dengue fever patients within Klang Valley from 2010-2012 to determine the prevailing dengue serotypes. In addition, sequencing of the envelope/nonstructural 1 (E/NS1) gene junction of the virus isolated was performed to identify the presence of any mutations that are suggestive of increased virulence in the virus. The results showed that Dengue-1 (DEN-1) was the predominant circulating serotype. The E/NS1 gene sequences of the isolates were analysed to trace the evolutionary knowledge of the strains. All sequences of the isolates were compared with DEN-1 prototype Hawaii strain as the reference sequence. The E/NS1 sequences of other dengue strains from neighbouring regions as well as other parts of the world obtained from the GenBank database were also included in the phylogenetic tree analysis. Analyses showed that there was 97% to 100% similarity among the ten isolates at the nucleotide level. Similarly, the amino acid analogue also showed 98% to 100% homology. However, all five non-severe dengue isolates showed variation at position 780, resulting in an amino acid change from valine to alanine as compared to severe dengue isolates. A rooted phylogenetic tree was performed using neighbour-joining method with DEN-2 and DEN-3 as the outgroups. Results showed that all ten isolates were classified as genotype I. In addition, the five isolates from severe dengue patients were found to be clustered together with JN697057 and JN697058, Malaysian DEN-1 strains from the 2005 outbreak.

Androgen receptor mutations causing human androgen insensitivity syndromes show a key role of residue M807 in Helix 8-Helix 10 interactions and in receptor ligand-binding domain stability.

Transactivation activity of the androgen receptor (AR) is induced by the binding of an androgen to its ligand-binding domain (LBD). The tertiary architecture of the AR LBD, in common with other steroid/nuclear receptors, is a sandwich of 12 alpha-helices (H). We have encountered a missense substitution, M807T, which was associated with partially defective androgen binding in a 46,XY infant with ambiguous genitalia. In contrast, two other substitutions in the same residue 807 to valine and arginine, resulted in almost total abrogation of androgen-binding and complete androgen insensitivity syndrome in two unrelated individuals. We recreated these substitutions in residue 807 and observed that disruption of ligand-binding and transactivation activities was total for M807R and partial for M807V, while the least-affected was M807T. Modelling of the AR LBD indicate that van der Waal interactions between residue 807 (H8) to H9 and H10 were severely disrupted for the arginine mutant, but relatively preserved for the threonine and valine mutants. However, there was a subtle difference between these two variants in that M807T, but not M807V, improved van der Waal contacts with another residue L859 in H10, suggesting the importance of interactions between M807 and L859 for LBD stability. Atomic distances of M807 (H8) to L859 (H10) in corresponding residues of the distantly related ER alpha, RXR alpha, PPAR gamma and VDR LBD are highly conserved and almost invariant, suggesting that H8/H10 interactions are critical for LBD stability in other members of the steroid/nuclear receptor superfamily.

Androgen receptor polymorphisms and mutations in male infertility.

Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor (AR) gene was examined for mutations and polymorphisms in a large cohort of infertile men. Genetic screening of over 400 patients and controls showed that defects in the AR gene lead to the production of dysfunctional receptor protein in up to 10% of males with abnormally low sperm production and male infertility. The dozens of mutations and polymorphisms uncovered were associated with subtly reduced intrinsic AR activity, and are of two main categories: polymorphic changes in length of a trinucleotide CAG tract in the N-terminal transactivation domain, and missense mutations in the C-terminal ligand-binding domain. These polymorphisms and mutations are associated with reduced AR function due to defective intermolecular protein-protein interactions with coactivator molecules. Genetic screening for AR mutations and polymorphism should be offered to severely oligospermic and azoospermic patients. These traits can be transmitted to progeny, and counseling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.

Genetics of male infertility: role of androgen receptor mutations and Y-microdeletions.

INTRODUCTION: Although infertility affects about 5% of the male population, its cause in most cases is uncertain. Normal spermatogenesis depends on a sequential cascade of genetic events triggered by factors encoded by the sex chromosomes. To determine the contribution of genetic aberrations to male infertility, the X-linked androgen receptor gene and the Y-chromosome were examined for mutations in a large cohort of infertile men. METHODS: Screening of the androgen receptor (AR) gene for single-stranded conformation polymorphisms, confirmation by DNA sequencing, structure-function studies with androgen-responsive reporter genes and chimeric-protein constructs were performed. Y-chromosome microdeletions screening was done with multiplex polymerase chain reaction (PCR) analyses. RESULTS: Genetic screening of over 400 patients and controls showed that defects in the androgen receptor gene lead to the production of dysfunctional receptor protein in 15% of males with abnormally low sperm production. The dozens of mutations and polymorphisms uncovered were associated with reduced intrinsic androgen receptor activity and involve principally two regions of the androgen receptor. Gene-transfer experiments implicated defective intermolecular protein-protein interactions with coactivator molecules as the cause of reduced receptor function. Submicroscopic deletions of the Y-chromosome were also been detected in about 6% of patients with severely reduced spermatogenesis. The deleted segments encoded RNA-binding proteins of unknown function and are not linked to defects in the androgen receptor. CONCLUSIONS: Mutations and polymorphisms of the AR, and Y-microdeletions cause defective sperm production and male infertility in about 20% of subfertile men. These traits can be transmitted to progeny, and counselling can be offered to affected families. Clarification of the molecular mechanisms of pathogenesis has led to rational hormonal therapy.

Panax (ginseng)--panacea or placebo? Molecular and cellular basis of its pharmacological activity.

INTRODUCTION: The use of ethnobotanical drugs amongst Asians as complementary medicine is prevalent and is also gaining increasing popularity in the West. The most well-known herb traditionally used as a drug is the root of the ginseng species. There are many traditional and anecdotal claims to the therapeutic properties of ginseng. In recent years, there have been systematic efforts to analyse the bioactivities of ginseng saponins. METHODS: A comprehensive review of published literature covering molecular and cellular research as well as animal and human studies on ginseng and its derivatives. RESULTS AND CONCLUSION: Current published data would serve as a framework to understand the pharmacology of ginseng in its entirety, from its molecular action to actual therapeutic effects observed in human use. A new paradigm is emerging whereby the pharmacological effects of traditional herbs such as ginseng can be understood in the light of their polyvalent actions as demonstrated by ginseng saponins with their positive anti-mutagenic, anti-cancer, anti-inflammatory, anti-diabetes and neurovascular effects. With increasing understanding, evidence-based incorporation of traditional herbs as complementary medicine into mainstream medical science can be achieved in the near future.

Directed pharmacological therapy of ambiguous genitalia due to an androgen receptor gene mutation.

We report a 46,XY infant with an M807T mutation in his androgen receptor that abrogated cellular responses to testosterone, but not to dihydrotestosterone (DHT), resulting in ambiguous genitalia. Treatment with a topical DHT gel restored male genital development allowing the infant to be reared in accordance with his chromosomal sex.