RESUMO
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.
Assuntos
Complexo AIDS Demência/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Síndrome da Imunodeficiência Adquirida/complicações , Adulto , Feminino , Infecções por HIV/complicações , Humanos , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de RiscoRESUMO
Niche partitioning facilitates species coexistence in a world of limited resources, thereby enriching biodiversity. For decades, biologists have sought to understand how diverse assemblages of large mammalian herbivores (LMH) partition food resources. Several complementary mechanisms have been identified, including differential consumption of grasses versus nongrasses and spatiotemporal stratification in use of different parts of the same plant. However, the extent to which LMH partition food-plant species is largely unknown because comprehensive species-level identification is prohibitively difficult with traditional methods. We used DNA metabarcoding to quantify diet breadth, composition, and overlap for seven abundant LMH species (six wild, one domestic) in semiarid African savanna. These species ranged from almost-exclusive grazers to almost-exclusive browsers: Grass consumption inferred from mean sequence relative read abundance (RRA) ranged from >99% (plains zebra) to <1% (dik-dik). Grass RRA was highly correlated with isotopic estimates of % grass consumption, indicating that RRA conveys reliable quantitative information about consumption. Dietary overlap was greatest between species that were similar in body size and proportional grass consumption. Nonetheless, diet composition differed between all species-even pairs of grazers matched in size, digestive physiology, and location-and dietary similarity was sometimes greater across grazing and browsing guilds than within them. Such taxonomically fine-grained diet partitioning suggests that coarse trophic categorizations may generate misleading conclusions about competition and coexistence in LMH assemblages, and that LMH diversity may be more tightly linked to plant diversity than is currently recognized.
Assuntos
Animais Selvagens/genética , Código de Barras de DNA Taxonômico , Herbivoria , África , Animais , Animais Selvagens/fisiologia , BiodiversidadeRESUMO
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.
Assuntos
Cromatografia Líquida/métodos , Estrogênios/análise , Fezes/química , Radioimunoensaio/métodos , Espectrometria de Massas em Tandem/métodos , Testosterona/análise , Animais , Feminino , Masculino , Papio cynocephalus , GravidezRESUMO
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.