Distal leg epidermal nerve fiber density as a surrogate marker of HIV-associated sensory neuropathy risk: risk factors and change following initial antiretroviral therapy.

Distal leg epidermal nerve fiber density (ENFD) is a validated predictor of HIV sensory neuropathy (SN) risk. We assessed how ENFD is impacted by initiation of first-time antiretroviral therapy (ART) in subjects free of neuropathy and how it is altered when mitochondrial toxic nucleoside medications are used as part of ART. Serial changes in proximal thigh and distal leg ENFD were examined over 72 weeks in 150 Thai subjects randomized to a regimen of stavudine (d4T) switching to zidovudine (ZDV) at 24 weeks vs ZDV vs tenofovir (TDF) for the entire duration of study, all given in combination with nevirapine. We found individual variations in ENFD change, with almost equal number of subjects who decreased or increased their distal leg ENFD over 72 weeks and no relationship to nucleoside backbone or to development of neuropathic signs or symptoms. Lower baseline distal leg ENFD and greater increases in mitochondrial oxidative phosphorylation complex I (CI) activity were associated with larger increases in distal leg ENFD over 72 weeks. Distal leg ENFD correlated with body composition parameters (body surface area, body mass index, height) as well as with blood pressure measurements. Assessed together with a companion cross-sectional study, we found that mean distal leg ENFD in all HIV+ subjects was lower than in HIV- subjects but similar among HIV+ groups whether ART-naïve or on d4T with/without neuropathy/neuropathic symptoms. The utility of ENFD as a useful predictor of small unmyelinated nerve fiber damage and neuropathy risk in HIV may be limited in certain populations.

RNA-mediated degradation of microRNAs: A widespread viral strategy?

Regulation of small RNAs by other non-coding RNAs is a ubiquitous feature of gene regulatory systems that can be exploited by viruses. Examples of this have been described in 3 different herpesviruses, where viral non-coding RNAs bind to highly abundant cellular (miRNAs), mediating their degradation: miR-27 is targeted by both murine cytomegalovirus and herpesvirus saimiri, while the miR-17 family is targeted by human cytomegalovirus. We review what is known about RNA-mediated regulation of miRNA stability and propose 3 potential roles that viral non-coding RNAs might assume to initiate the destruction of a miRNA, acting as "recruiters," "localizers" or "exposers." Whereas the miRNAs (miR-17 and miR-27) appear to be ancient and pre-date the common ancestor of all mammalian herpesviruses, comparative analyses of herpesvirus genomes indicate that the 3 known viral regulators of miRNA each evolved independently, and much more recently. Noting that the anti-viral activity of miRNAs might be countered by a variety of mechanisms, we propose that (i) there has been continual turnover of these mechanisms during herpesvirus evolution, and (ii) there may be many other, as yet undescribed, anti-miRNA activities encoded by other herpesviruses and indeed by viruses from other families.

Sexual dimorphism of the twelfth thoracic vertebra for sex determination in the Central Thai population.

Analyzing skeletal remains is crucial for identifying individuals, and forensic anthropologists use this analysis to determine biological characteristics, particularly sex, aiding criminal investigations. Among thoracic vertebrae, the twelfth thoracic vertebra (T12) is highly sexually dimorphic in various populations. This study aims to establish a discriminant function equation (DFE) for sex determination based on T12 in the Central Thai population. A total of 15 parameters of T12 were examined in 69 bone samples (43 males and 26 females). Among the 15 parameters, 14 were significantly different between males and females. The discriminant function equation (DFE) was generated as DFE = -19.578 + 0.376(i) BDsm + 0.254(l) PW + 0.081TDm, with a cutoff value of -0.296 for males and females, showing 92.8 % accuracy. The evaluation of the DFE using 10 blind samples showed 90 % accuracy. These findings may offer an additional method for sex determination through T12, complementing the examination of other skeletal elements.

Sacral morphometrics for sex estimation of dead cases in Central Thailand.

Sex estimation by various forensic anthropology approaches is a crucial factor for identification of human skeletal remains. However, inexpensive, uncomplicated and reliable methods are still required, especially in a remote crime scene and a high crime incidence area. Here, we examined 13 sacral parameters from 78 independent skeletons derived from deceases found in Central Thailand (male, n = 46; female, n = 32) using simple standard anthropometric techniques for sex allocation. Discriminant analysis exhibited that anterior-posterior diameter of S1 vertebra corpus (APS) is the most accurate sacral parameter for sex determination in our study with 82.1% of correct discrimination rate. The accuracy could be improved up to 97.4% when additional three sacral variables including the length of sacrum measured from the medial anterior-superior sacral promontory to the medial anterior-inferior S5 vertebra (ASL), alar index (ALI), and the maximum anterior breadth of sacrum measured across sacral alar (ABS) were computed together with APS. These encourage the use of sacral morphometrics for sex assessment of human sacrum remains in Central Thailand. However, further investigation with broadening sacral morphometric data across the country might provide a promising sex determination equation from a sacral skeleton for Thai population.