Machine learning models reveal neurocognitive impairment type and prevalence are associated with distinct variables in HIV/AIDS.

Neurocognitive impairment (NCI) among HIV-infected patients is heterogeneous in its reported presentations and frequencies. To determine the prevalence of NCI and its associated subtypes as well as predictive variables, we investigated patients with HIV/AIDS receiving universal health care. Recruited adult HIV-infected subjects underwent a neuropsychological (NP) test battery with established normative (sex-, age-, and education-matched) values together with assessment of their demographic and clinical variables. Three patient groups were identified including neurocognitively normal (NN, n = 246), HIV-associated neurocognitive disorders (HAND, n = 78), and neurocognitively impaired-other disorders (NCI-OD, n = 46). Univariate, multiple logistic regression and machine learning analyses were applied. Univariate analyses showed variables differed significantly between groups including birth continent, quality of life, substance use, and PHQ-9. Multiple logistic regression models revealed groups again differed significantly for substance use, PHQ-9 score, VACS index, and head injury. Random forest (RF) models disclosed that classification algorithms distinguished HAND from NN and NCI-OD from NN with area under the curve (AUC) values of 0.87 and 0.77, respectively. Relative importance plots derived from the RF model exhibited distinct variable rankings that were predictive of NCI status for both NN versus HAND and NN versus NCI-OD comparisons. Thus, NCI was frequently detected (33.5%) although HAND prevalence (21%) was lower than in several earlier reports underscoring the potential contribution of other factors to NCI. Machine learning models uncovered variables related to individual NCI types that were not identified by univariate or multiple logistic regression analyses, highlighting the value of other approaches to understanding NCI in HIV/AIDS.

HIV-associated sensory polyneuropathy and neuronal injury are associated with miRNA-455-3p induction.

Symptomatic distal sensory polyneuropathy (sDSP) is common and debilitating in people with HIV/AIDS, leading to neuropathic pain, although the condition's cause is unknown. To investigate biomarkers and associated pathogenic mechanisms for sDSP, we examined plasma miRNA profiles in HIV/AIDS patients with sDSP or without sDSP in 2 independent cohorts together with assessing related pathogenic effects. Several miRNAs were found to be increased in the Discovery Cohort (sDSP, n = 29; non-DSP, n = 40) by array analyses and were increased in patients with sDSP compared with patients without sDSP. miR-455-3p displayed a 12-fold median increase in the sDSP group, which was confirmed by machine learning analyses and verified by reverse transcription PCR. In the Validation Cohort (sDSP n = 16, non-DSP n = 20, healthy controls n = 15), significant upregulation of miR-455-3p was also observed in the sDSP group. Bioinformatics revealed that miR-455-3p targeted multiple host genes implicated in peripheral nerve maintenance, including nerve growth factor (NGF) and related genes. Transfection of cultured human dorsal root ganglia with miR-455-3p showed a concentration-dependent reduction in neuronal ß-III tubulin expression. Human neurons transfected with miR-455-3p demonstrated reduced neurite outgrowth and NGF expression that was reversed by anti-miR-455-3p antagomir cotreatment. miR-455-3p represents a potential biomarker for HIV-associated sDSP and might also exert pathogenic effects leading to sDSP.

Measuring fecal testosterone in females and fecal estrogens in males: comparison of RIA and LC/MS/MS methods for wild baboons (Papio cynocephalus).

The development of non-invasive methods, particularly fecal determination, has made possible the assessment of hormone concentrations in wild animal populations. However, measuring fecal metabolites needs careful validation for each species and for each sex. We investigated whether radioimmunoassays (RIAs) previously used to measure fecal testosterone (fT) in male baboons and fecal estrogens (fE) in female baboons were well suited to measure these hormones in the opposite sex. We compared fE and fT concentrations determined by RIA to those measured by liquid chromatography combined with triple quadropole mass spectrometry (LC/MS/MS), a highly specific method. Additionally, we conducted a biological validation to assure that the measurements of fecal concentrations reflected physiological levels of the hormone of interest. Several tests produced expected results that led us to conclude that our RIAs can reliably measure fT and fE in both sexes, and that within-sex comparisons of these measures are valid: (i) fTRIA were significantly correlated to fTLC/MS/MS for both sexes; (ii) fTRIA were higher in adult than in immature males; (iii) fTRIA were higher in pregnant than non-pregnant females; (iv) fERIA were correlated with 17ß-estradiol (fE2) and with estrone (fE1) determined by LC/MS/MS in pregnant females; (v) fERIA were significantly correlated with fE2 in non-pregnant females and nearly significantly correlated in males; (vi) fERIA were higher in adult males than in immature males. fERIA were higher in females than in males, as predicted, but unexpectedly, fTRIA were higher in females than in males, suggesting a difference in steroid metabolism in the two sexes; consequently, we conclude that while within-sex comparisons are valid, fTRIA should not be used for intersexual comparisons. Our results should open the field to important additional studies, as to date the roles of testosterone in females and estrogens in males have been little investigated.