A Comprehensive Review: Pharmacogenomics and Personalized Medicine Customizing Drug Therapy Based on Individual Genetics Profiles.

Numerous factors, such as genetics, environmental factors, and illness determinants, might contribute to an unpleasant pharmaceutical response. In an effort to increase efficacy and safety, as well as to gain a better understanding of drug disposition and clinical consequences, researchers in the two quickly emerging fields of pharmacogenetics (which focuses on single genes) and pharmacogenomics (which focuses on many genes) have studied the genetic personalization of drug response. This is due to the fact that a large number of pharmacological responses seem to be genetically based, and the relationship between medication response and genotype may be important for diagnosis. We now have a better understanding of the genetic basis of individual medication responses because to research on pharmaceuticals and genes. Pharmacogenomics aims to improve patient outcomes by developing personalized medicine by using the diversity of the human genome and how it affects medication response. Translational in nature, pharmacogenomics research encompasses everything from the discovery of genotype-phenotype associations to clinical investigations that might show therapeutic relevance. Though the conversion of pharmacogenomics research findings into clinical practice has been sluggish, advances in the field offer considerable potential for future therapeutic applications in specific people.

Upper moiety vascular ureteropelvic junction obstruction in an incomplete duplex kidney: A variant of the Fraley's syndrome?

Although duplication of the collecting system is fairly common, ureteropelvic junction obstruction of the upper moiety in a patient with duplex system is rare, more so if the obstruction is extrinsic and vascular. Herein, we report a case of obstruction of the upper moiety infundibulum by a crossing vein, in a patient with partially duplex system who presented with flank pain and focal hydronephrosis of the superior calyx, a clinical presentation similar to that of Fraley's syndrome. The infundibulum was transected and transposed anterior to the crossing vessel.

Detection of human papillomavirus infection in oral cancers reported at dental facility: assessing the utility of FFPE tissues.

Incidence of human papillomavirus (HPV)-associated oral cancers is on the rise. However, epidemiological data of this subset of cancers are limited. Dental hospital poses a unique advantage in detection of HPV-positive oral malignancies. We assessed the utility of formalin-fixed paraffin-embedded (FFPE) tissues, which are readily available, for evaluation of high-risk HPV infection in oral cancer. For protocol standardization, we used 20 prospectively collected paired FFPE and fresh tissues of histopathologically confirmed oral cancer cases reported in Oral Medicine department of a dental hospital for comparative study. Only short PCRs (~ 200 bp) of DNA isolated using a modified xylene-free method displayed a concordant HPV result. For HPV analysis, we used additional 30 retrospectively collected FFPE tissues. DNA isolated from these specimens showed an overall 23.4% (11/47) HPV positivity with detection of HPV18. Comparison of HPV positivity from dental hospital FFPE specimens with overall HPV positivity of freshly collected oral cancer specimens (n = 55) from three cancer care hospitals of the same region showed notable difference (12.7%; 7/55). Further, cancer hospital specimens showed HPV16 positivity and displayed a characteristic difference in reported sub-sites and patient spectrum. Overall, using a xylene-free FFPE DNA isolation method clubbed with short amplicon PCR, we showed detection of HPV-positive oral cancer in dental hospitals.

Validation of hindi translation of DSM-5 level 1 cross-cutting symptom measure.

BACKGROUND: The DSM-5 Level 1 Cross-Cutting Symptom Measure is a self- or informant-rated measure that assesses mental health domains which are important across psychiatric diagnoses. The absence of this self- or informant-administered instrument in Hindi, which is a major language in India, is an important limitation in using this scale. AIM: To translate the English version of the DSM-5 Level 1 Cross-Cutting Symptom Measure to Hindi and evaluate its psychometric properties. MATERIALS AND METHODS: The study was conducted at a tertiary care hospital in Delhi. The DSM-5 Level 1 Cross-Cutting Symptom Measure was translated into Hindi using the World Health Organization's translation methodology. STATISTICAL ANALYSIS: Mean and standard deviation were evaluated for continuous variables while for categorical variables frequency and percentages were calculated. The translated version was evaluated for cross-language equivalence, test-retest reliability, internal consistency, and split half reliability. RESULTS: Hindi version was found to have good cross-language equivalence and test-retest reliability at the level of items and domains. Twenty two of the 23 items and all the 23 items had a significant correlation (ρ < 0.001) in cross language concordance and test-retest reliability data, respectively. The Cronbach's alpha was 0.95, and the Spearman-Brown Sphericity value was 0.79 for the Hindi version. CONCLUSION: The present study shows that cross-language concordance, internal consistency, split-half reliability, and test-retest reliability of the Hindi version of the measure are excellent. Thus, the Hindi version of DSM-5 Level 1 Cross-Cutting Symptom Measure as translated in this study is a valid instrument.

Characterization of key transcription factors as molecular signatures of HPV-positive and HPV-negative oral cancers.

Prior studies established constitutively active AP-1, NF-κB, and STAT3 signaling in oral cancer. Differential expression/activation of specific members of these transcription factors has been documented in HPV-positive oral lesions that respond better to therapy. We performed a comprehensive analysis of differentially expressed, transcriptionally active members of these pivotal signaling mediators to develop specific signatures of HPV-positive and HPV-negative oral lesions by immunohistochemical method that is applicable in low-resource settings. We examined a total of 31 prospective and 30 formalin-fixed, paraffin-embedded tissues from treatment-naïve, histopathologically and clinically confirmed cases diagnosed as oral or oropharyngeal squamous cell carcinoma (OSCC/OPSCC). Following determination of their HPV status by GP5 + /GP6 +  PCR, the sequential sections of the tissues were evaluated for expression of JunB, JunD, c-Fos, p50, p65, STAT3, and pSTAT3(Y705), along with two key regulatory proteins pEGFR and p16 by IHC. Independent analysis of JunB and p65 showed direct correlation with HPV positivity, whereas STAT3 and pSTAT3 were inversely correlated. A combined analysis of transcription factors revealed a more restrictive combination, characterized by the presence of AP-1 and NF-κB lacking involvement of STAT3 that strongly correlated with HPV-positive tumors. Presence of STAT3/pSTAT3 with NF-κB irrespective of the presence or absence of AP-1 members was present in HPV-negative lesions. Expression of pSTAT3 strongly correlated with all the AP-1/NF-κB members (except JunD), its upstream activator pEGFRY1092 , and HPV infection-related negative regulator p16. Overall, we show a simple combination of AP-1, NF-κB, and STAT3 members' expression that may serve as molecular signature of HPV-positive lesions or more broadly the tumors that show better prognosis.

Short-term acute effects of gutkha chewing on heart rate variability among young adults: A cross-sectional study.

BACKGROUND AND OBJECTIVES: An increase in the consumption of smokeless tobacco has been noticed among high school, college students, and adults. Despite the antiquity and popularity of chewing tobacco in India, its effects have not been investigated systematically in humans. The aim of this study was to investigate acute effects of gutkha chewing on heart rate variability (HRV) among healthy young adults. MATERIALS AND METHODS: A total of 60 young adult males were included in the study. Each individual was asked to chew tobacco and subjected to HRV analysis. HRV analysis using short-term electrocardiogram recording was used to measure HRV parameters before gutkha chewing and at 5, 15, and 30 min after chewing tobacco. One-way analysis of variance and paired t-test was used to assess changes over time. RESULTS: There was a significant increase in heart rate (HR) during tobacco chewing. Mean HR at baseline measured 73.0 ± 6.2 bpm. There was a rise in mean HR to 83.7 ± 9.1 bpm at 5 min during tobacco chewing and gradual reduction to baseline observed after 15 min followed by no significant change till 30 min. The normalized low-frequency power and LF/high-frequency (HF) power ratio were elevated after 5 min; however, normalized HF power was reduced after 5 min tobacco chewing. CONCLUSION: Gutkha is closely associated with traditional cardiovascular risk factors as detected by a transient enhancing sympathetic activity during tobacco chewing in the form of increased HRV parameters or an imbalance between sympathetic and parasympathetic neural activity among healthy young adults.

Bioactive Glass S53P4 versus Chlorhexidine Gluconate as Intracanal Medicament in Primary Teeth: An In-vivo Study Using Polymerase Chain Reaction Analysis.

BACKGROUND: Bacteria have long been recognized as the primary etiology for pulpal and periapical lesions, which necessitates the elimination of bacteria from the root canal system. In primary teeth, irrigation and debridement is the main protocol required to disinfect the canal. Biomechanical preparation cannot be vigorously done on the primary teeth due to anatomical barrier such as thin and flared roots. This calls for the use of an effective intracanal medication that will assist disinfection of root canal system. Aim of the study was to examine the in-vivo susceptibility of root canal bacteria to chlorhexidine (CHX) gluconate-1% gel and bioactive glass (BAG) S53P4 when used as intracanal medicaments using polymerase chain reaction (PCR). METHODOLOGY: PCR (analysis used oligonucleotide primers of Escherichia coli) was used to detect and compare the microbial load reduction after medication of 14 teeth for a week with either CHX gel - 1% or BAG S53P4. The pre and post microbial load was checked in the form of colony forming units. When analysis was done, a statistically significant difference was observed between the two groups. RESULTS: The study revealed that both medicaments caused a considerable amount of microbial load reduction. BAG S53P4 caused much more reduction than CHX 1% gel. Statistical analysis showed a significant difference between the two groups. CONCLUSION: BAG S53P4 has superior antibacterial property as compared to CHX 1% gel.

Rare association of dens invaginatus with impacted mesiodens - A case report.

Mesiodens is a supernumerary tooth occupying the position in the maxillary anterior region. This additional tooth structure may cause disturbance in eruption or position of the adjacent teeth. About 8-25% of supernumerary teeth in the anterior region erupt spontaneously. Un-erupted supernumerary teeth are incidentally identified on a routine radiographic examination. Dens invaginatus is a rare tooth malformation showing an in-folding of enamel and dentine of affected tooth sometimes extending deep into the pulp cavity and the root portion. We report a case of un-erupted mesiodens causing midline diastema of permanent teeth subsequently corrected following extraction of mesiodens. Dens invaginatus was identified affecting the un-erupted mesiodens. It is rare to find dens invaginatus associated with a supernumerary tooth and only 10 such instances of dens invaginatus affecting supernumerary teeth have been reported in the English literature.

Therapeutic drug monitoring by reverse iontophoresis.

Therapeutic molecules possessing distinct pharmacokinetic variation, narrow therapeutic index and concentration dependent therapeutic/adverse effects demand constant monitoring. The current methods for blood sampling are invasive and possess low patient compliance. Human skin, selective and effective membrane to chemical permeation, offers an alternative route for the extraction of endogenous molecules in the body. Significant attention has been received in the application of reverse iontophoresis in extracting drugs/biomaterials from the subdermal region. This technique involves transiting of a low electric current across the skin usually with couple of skin electrodes to extract charged as well as neutral molecules. Electromigration and electroosmosis are the two basic mechanisms involved in transport of molecules. Several in vitro and in vivo experiments demonstrated the potential of reverse iontophoresis as a noninvasive tool in clinical chemistry and therapeutic drug monitoring. This technology is currently being used in device such as Glucowatch Biogrpaher which allows blood glucose detection across skin layers. Advances in technology and rapid progress in research has widely improved the opportunity of this system, and the recent trend indicates that several products are likely to be developed very soon. This review provides an overview about the recent developments in reverse iontophoresis for therapeutic drug monitoring.