Introduction: Tacrolimus (Tac) is effective in preventing acute rejection but has considerable toxicity and inter-individual variability in pharmacokinetics and pharmacodynamics. Part of this is explained by polymorphisms in genes encoding Tac-metabolizing enzymes and transporters. A better understanding of Tac pharmacokinetics and pharmacodynamics may help to minimize different outcomes amongst transplant recipients by personalizing immunosuppression. Areas covered: The pharmacogenetic contribution of Tac metabolism will be examined, with a focus on recent discoveries, new developments and ethnic considerations. Expert opinion: The strongest and most consistent association in pharmacogenetics is between the CYP3A5 genotype and Tac dose requirement, with CYP3A5 expressers having a~40-50% higher dose requirement compared to non-expressers. Two recent randomized-controlled clinical trials using CYP3A5 genotype, however, did not show a decrease in acute rejections nor reduced toxicity. CYP3A4*22, CYP3A4*26, and POR*28 are also associated with Tac dose requirements and may be included to provide the expected improvement of Tac therapy. Studies focusing on the intracellular drug concentrations and on calcineurin inhibitor-induced nephrotoxicity also seem promising. For all studies, however, the ethnic prevalence of genotypes should be taken into account, as this may significantly impact the effect of pre-emptive genotyping.ARTICLE HISTORY

Small vessel disease, a disorder of cerebral microvessels, is an expanding epidemic and a common cause of stroke and dementia. Despite being almost ubiquitous in brain imaging, the clinicoradiologic association of small vessel disease is weak, and the underlying pathogenesis is poorly understood. The STandards for ReportIng Vascular changes on nEuroimaging (STRIVE) criteria have standardized the nomenclature. These include white matter hyperintensities of presumed vascular origin, recent small subcortical infarcts, lacunes of presumed vascular origin, prominent perivascular spaces, cerebral microbleeds, superficial siderosis, cortical microinfarcts, and brain atrophy. Recently, the rigid categories among cognitive impairment, vascular dementia, stroke, and small vessel disease have become outdated, with a greater emphasis on brain health. Conventional and advanced small vessel disease imaging markers allow a comprehensive assessment of global brain heath. In this review, we discuss the pathophysiology of small vessel disease neuroimaging nomenclature by means of the STRIVE criteria, clinical implications, the role of advanced imaging, and future directions.ABBREVIATIONS: BOLD ¼ blood oxygen level-dependent; CAA ¼ cerebral amyloid angiopathy (SVD type 2); CMB ¼ cerebral microbleeds; cSS ¼ cortical superficial siderosis; HA ¼ hypertensive arteriolosclerosis (SVD type 1); ICH ¼ intracerebral hemorrhage; PVS ¼ prominent perivascular spaces; STRIVE ¼ STandards for ReportIng Vascular changes on nEuroimaging; SVD ¼ small vessel disease; WMH ¼ white matter hyperintensities

OBJECTIVES:To evaluate Health Related Quality of Life (HRQoL) among general population of Quetta city, Pakistan. METHODS: The study was designed as a questionnaire-based cross sectional analysis. European Quality of Life scale (EQ-5D) was used for assessment of HRQoL. A total of 1500 healthy participants from March 2011 to July 2011, aging 18 years and above were approached. Descriptive statistics were used to describe demographic characteristics of the general population. Percentages and frequencies were used to categorize the categorical variables, while means and standard deviations were calculated for the continuous variables. Inferential statistics (Mann-Whitney and Kruskal Wallis tests) were used where appropriate. HRQoL was scored using values adapted from the UK general population survey. All analyses were performed using SPSS 16.0. RESULTS: One thousand five hundred questionnaires were distributed and 1255 were returned (with response rate of 83.67%). Six hundred and forty three (51.2%) were males. Majority (nϭ427, 34.0%) were categorized in age group of 28-37 years. Three hundred and thirty three (26.5%) had intermediate level of education. Two hundred and ninety one (23.2%) had monthly income of in between 10001-15000 Pakistan rupees with 828 (66.0%) having urban residency. HRQoL was measured as 0.64Ϯ0.21 and VAS score was 68.71Ϯ11.71. Only age and marital status, among all demographic characteristics had significant relation with HRQoL score (pϽ0.05). CONCLUSIONS: Results of the present study provide the general health status of healthy population of Quetta city, Pakistan, which could sever as baseline data for further investigations.