Expression of TRIM22 mRNA in chronic hepatitis C patients treated with direct-acting antiviral drugs

Hepatitis C is a global public health problem, and Pakistan is the second largest country in the globe with highest prevalence rate of hepatitis C virus (HCV). Until 2014, pegylated interferon (PEG-IFN) plus ribavirin (RBV) has been the standard therapy for HCV, however, owing to its adverse side effects and very low sustained virologic response (SVR) rates therapeutics trend is shifted toward direct-acting antivirals. Tripartite motif containing 22 (TRIM22) is a dynamic antiviral protein that can inhibit multiple viruses in vivo. Expression of TRIM22 mRNA has been linked to outcome of PEG-IFN and ribavirin therapy, where its higher expression leads to rapid virus clearance. However, in terms of therapy with direct-acting antiviral (DAA) or double DAA, impact of TRIM22 expression is largely unknown. These new drugs show more than 90% of SVR rates and lesser side effects and have proven to be better than IFN therapy. Endogenous IFN system suppresses various pathogens through the induction of antiviral effectors termed as interferon-stimulating genes (ISGs). We have studied the expression levels of one of these antiviral effectors, TRIM22 in response to sofosbuvir (SOF) and daclatasvir (DAC) in combination with RBV, using quantitative PCR in the peripheral blood mononuclear cells (PBMCs) of HCV-infected patients. We have observed sustained virus clearance in more than 90% of patients treated with DAA and double DAA and have seen the expression of TRIM22 to be higher in patients who attained SVR as compared to the untreated patients. We have also observed downregulation of TRIM22 in patients who failed to attain rapid virus clearance, and upregulation in those who achieved rapid clearance of virus. Genetic factors that determine the lower TRIM22 expression in these patients are needed to be explored that may also play a role in lower response to anti-HCV therapy. Endogenous IFN system and effects of antiviral proteins in response to DAA therapy is needed to be studied in order to better understand the host response toward these drugs to make them more effective.     

Health-seeking behavior and the meaning of medications in Balochistan, Pakistan

A wide variety of health care options--home-based, indigenous, and cosmopolitan--exists in northern Balochistan, Pakistan. This paper examines health-seeking behavior in the area of mother and child health for villagers in this pluralistic medical setting. The analysis of a specific series of illness episodes shows that the majority of cases obtain treatment from different medical systems for a single episode. Interest in medications takes precedence over practitioners, and the meaning the villagers attach to such substances is explored. Long-established patterns of behavior relating to indigenous medicine continue to occur when cosmopolitan medicine is utilized. Information presented here helps to explain problems in utilization of cosmopolitan pharmaceuticals and delineates areas for future health programme activity.     

Training in clinical genetics and genetic counseling in Asia

The status of training in clinical genetics and genetic counseling in Asia is at diverse stages of development and maturity. Most of the training programs are in academic training centers where exposure to patients in the clinics or in the hospital is a major component. This setting provides trainees with knowledge and skills to be competent geneticists and genetic counselors in a variety of patient care interactions. Majority of the training programs combine clinical and research training which provide trainees a broad and integrated approach in the diagnosis and management of patients while providing opportunities for research discoveries that can be translated to better patient care. The background on how the training programs in clinical genetics and genetic counseling in Asia evolved to their current status are described. Each of these countries can learn from each other through sharing of best practices and resources.     

In situ hybridization analysis of the Y chromosome in gonadoblastoma

Gonadoblastoma is a rare tumor arising in the streak gonads of about 30% of 46, XY sex-reversed females. Because gonadoblastoma develops only in patients who have Y-chromosome material and dysgenetic gonads, it has been hypothesized that positive expression of a gene (or genes) on the Y chromosome (GBY) is involved in the etiology of the tumor. To examine the Y chromosome directly in tumors, we performed nonisotopic in situ hybridization of a biotin-labeled Y-specific probe for the DYZI locus on formalin-fixed, paraffin-embedded sections of tumor samples from four different patients. After hybridization to DYZI, the Y chromosome was found to be present in all gonadoblastoma foci in the four patients studied, and the gonadoblastoma foci showed an average of 85% cell nuclei positive for the Y chromosome on tissue sections. Normal male and female control tissues showed an average of 78% and 0% positive nuclei, respectively. One patient with bilateral gonadoblastoma had previously been shown to be mosaic, with a 45, X/46, XY karyotype in lymphocytes, skin fibroblasts, and cultures from both gonads. Examination of sections of this patient's gonads showed 79% positive nuclei within the gonadoblastoma foci, whereas the nontumor stromal tissue had 19% positive nuclei. These results indicate that, in this mosaic gonad, tumor foci developed only from cells that had a Y chromosome. Our results support the hypothesis that there is a GBY locus on the Y chromosome and that the Y chromosome is retained in the gonadoblastoma foci during the development of the tumor. © 1995 Wiley-Liss, Inc.     

Development of nested PCR based on the ViaB sequence to detect Salmonella typhi.

For a rapid diagnosis of typhoid fever, we developed a nested PCR based on the nucleotide sequence encoding the Vi antigen. All Salmonella typhi strains along with a Salmonella paratyphi C strain were PCR positive. This assay was able to detect S. typhi at the single-cell level.