Neuroimaging and immunological features of neurocognitive function related to substance use in people with HIV.

This study sought to identify neuroimaging and immunological factors associated with substance use and that contribute to neurocognitive impairment (NCI) in people with HIV (PWH). We performed cross-sectional immunological phenotyping, neuroimaging, and neurocognitive testing on virally suppressed PWH in four substance groups: cocaine only users (COC), marijuana only users (MJ), dual users (Dual), and Non-users. Participants completed substance use assessments, multimodal MRI brain scan, neuropsychological testing, and blood and CSF sampling. We employed a two-stage analysis of 305 possible biomarkers of cognitive function associated with substance use. Feature reduction (Kruskal Wallis p-value < 0.05) identified 53 biomarkers associated with substance use (22 MRI and 31 immunological) for model inclusion along with clinical and demographic variables. We employed eXtreme Gradient Boosting (XGBoost) with these markers to predict cognitive function (global T-score). SHapley Additive exPlanations (SHAP) values were calculated to rank features for impact on model output and NCI. Participants were 110 PWH with sustained HIV viral suppression (33 MJ, 12 COC, 22 Dual, and 43 Non-users). The ten highest ranking biomarkers for predicting global T-score were 4 neuroimaging biomarkers including functional connectivity, gray matter volume, and white matter integrity; 5 soluble biomarkers (plasma glycine, alanine, lyso-phosphatidylcholine (lysoPC) aC17.0, hydroxy-sphingomyelin (SM.OH) C14.1, and phosphatidylcholinediacyl (PC aa) C28.1); and 1 clinical variable (nadir CD4 count). The results of our machine learning model suggest that substance use may indirectly contribute to NCI in PWH through both metabolomic and neuropathological mechanisms.

Correlation between intraocular pressure, central corneal thickness, stage of glaucoma, and demographic patient data: prospective analysis of biophysical parameters in tertiary glaucoma practice populations.

PURPOSE: To determine the correlation of central corneal thickness (CCT) to Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT, PASCAL), and to glaucoma stage as assessed by cup-to-disc ratio (CDR). DESIGN: Prospective, cross-sectional tricenter observation study. PATIENTS AND METHODS: From three glaucoma specialty practices a sample of 406 independent eyes was included. After ultrasound pachymetry, intraocular pressure was measured using PASCAL and Goldmann applanation tonometry and cup-to-disc ration was reassessed. Demographic data were included in the multivariate analysis. RESULTS: Mean corneal thickness was 540 microm. African Americans and normal-tension glaucoma patients showed the lowest values (518 microm and 522 microm, respectively). These values were significantly thinner than the central corneal thickness of Caucasians (549 microm) and ocular hypertensives (564 microm). Intraocular pressure assessed by Goldmann applanation tonometry shows a significant correlation with central corneal thickness (r = 0.068, P < 0.001), whereas PASCAL is not significantly associated with central corneal thickness (r < 0.001, P = 0.997). Increased IOP is significantly correlated with large ocular pulse amplitudes (r = 0.13, P < 0.001), which is predominantly seen in ocular hypertensives. A significant negative correlation was detected between cup-to-disc ratio and central corneal thickness (r = 0.102, P < 0.001). CONCLUSION: Glaucoma patients with thin central corneal thickness are more likely to be found at an advanced stage of the disease and among those with normal-tension glaucoma and black African ancestry. Underestimation of intraocular pressure by Goldmann applanation tonometry could be one causative factor.

Clinical comparison of contour and applanation tonometry and their relationship to pachymetry.

OBJECTIVES: To compare intraocular pressure readings of recently introduced dynamic contour tonometry (DCT) with pneumatonometry (PTG) and Goldmann applanation tonometry (GAT) and to correlate central corneal thickness (CCT) with these readings. DESIGN: Prospective, cross-sectional observation and instrument validation study. We included 258 independent eyes with normal anterior segment examinations results, irrespective of glaucoma diagnosis or glaucoma suspect. After pachymetry, DCT, PTG, and GAT were performed in a randomized order. Intraocular pressures as measured by DCT, PTG, and GAT were compared with each other and with CCT. RESULTS: Eyes with thinner CCTs tended to yield lower intraocular pressure measurements by GAT. A significant correlation (Pearson product moment correlation, P<.001) between CCT and GAT was found with a regression of 0.25 mm Hg per 10 microm (R2 = 0.060). Variation of CCT had no significant effect on intraocular pressure measurements by PTG (P = .10; R2 = 0.01) and DCT (P = .80; R2<0.01). A piecewise regression model showed that GAT readings are not linearly correlated with CCT. Comparison of the slopes below and above 535 microm showed the highest significance (P<.001). CONCLUSIONS: Goldmann applanation tonometry readings are potentially influenced by CCT, whereas PTG and DCT seem to be less dependent on CCT. Correlation between CCT and GAT is not linear. A simple correction formula suggesting a linear relationship might not be correct.

Central corneal thickness of Caucasians, Chinese, Hispanics, Filipinos, African Americans, and Japanese in a glaucoma clinic.

OBJECTIVE: To characterize the central corneal thickness (CCT) of Asian (Chinese, Japanese, and Filipino), Caucasian, Hispanic, and African American patients in a multiethnic glaucoma practice. DESIGN: Retrospective study (chart review). PARTICIPANTS: Glaucomatous (n = 600) and nonglaucomatous (n = 201) eyes of 801 patients examined in a San Francisco glaucoma clinic from June 2002 to April 2004 who met inclusion criteria were included in the study. The 6 racial (ethnic) groups represented in the study were Caucasian (n = 186, 23.2%), Chinese (n = 157, 19.6%), Japanese (n = 121, 15.1%), Hispanic (n = 116, 14.5%), Filipino (n = 114, 14.2%), and African American (n = 107, 13.4%). METHODS: Central corneal thickness was measured by means of ultrasound pachymetry in Asian (Chinese, Japanese, and Filipino), Caucasian, Hispanic, and African American participants with glaucomatous and normal eyes. The relationship between CCT and race was investigated using multivariate regression analyses, controlling for confounders. One eye of each of 801 participants was included for analysis. MAIN OUTCOME MEASURES: Correlation of mean CCT with race, glaucoma diagnosis, age, spherical equivalent, gender, and history of ocular surgery. RESULTS: The mean CCT of all participants was 542.9 mum. Central corneal thicknesses of Chinese (555.6 microm), Caucasian (550.4 microm), Filipino (550.6 microm), and Hispanic (548.1 microm) participants did not significantly differ. The CCT of Japanese participants (531.7 microm) was significantly less than that of Caucasians, Chinese, Filipinos, and Hispanics (all, P< or =0.001) and greater than that of African Americans (P = 0.03). African Americans had a CCT (521.0.0 microm) less than that of all races (P< or =0.05). Glaucoma suspects and patients with normal tension glaucoma (NTG), primary open-angle glaucoma (POAG), pseudoexfoliation glaucoma (PEX), and chronic angle-closure glaucoma (CACG) had corneas significantly thinner than those of normal participants (P< or =0.004), whereas ocular hypertensives had significantly thicker corneas (P<0.0001). Among all participants, decreasing values of CCT were significantly related to older age (P<0.01). Less negative or more positive refractive errors, gender, and history of ocular surgery were not associated with changes in CCT (P = 0.38, P = 0.50, and P = 0.97, respectively). CONCLUSIONS: Studies examining individual Asian subpopulations in isolation suggest that differences in CCT may exist among different Asian groups. The results of this study indicate that CCT does, in fact, vary among Asian subpopulations; Japanese have thinner corneas than Chinese and Filipinos. Caucasians, Chinese, Hispanics, and Filipinos have comparable CCT measurements, whereas the corneas of African Americans are significantly thinner. Additionally, older individuals; glaucoma suspects; and participants with NTG, POAG, PEX, and CACG have thinner corneas. Ocular hypertensives, however, have thicker corneas.

Culture plate temperature and delayed incubation effect on bacterial recovery.

PURPOSE: To discover if initial culturing conditions (plate temperature and time delay to incubation) adversely influence the recovery of organisms associated with bacterial keratitis. METHODS: The rate of temperature equilibration of culture plates taken from a refrigerator and placed in an incubator and left on the desk was evaluated with a digital thermometer. A standard inoculum for each of five organisms (S. aureus, S. pneumoniae, P. aeruginosa, E. aerogenes, K. oxytoca) isolated from human bacterial keratitis was spread evenly on blood agar plates at refrigerator (Tcold; 4 degrees C), room (Troom; 24 degrees C), and incubator (Twarm; 37 degrees C) temperatures. The plates were then kept at room temperature for 0, 1, 3, 5, and 8 hours before overnight incubation at 37 degrees C (S. pneumoniae under microaerophilic conditions), and the number of colony-forming units was counted. RESULTS: Cold plates took at least 15 minutes in an incubator to attain room temperature, and up to an hour when left on the desk. Increased organism recovery was found comparing both Twarm and Troom plates (6.2 to 24.8% and 7.0 to 14.7%, respectively, P<0.001) to Tcold plates for all organisms except S. pneumoniae (P=0.057). Comparing Twarm plates to Troom plates demonstrated an increased recovery (P<0.001) for S. aureus. Delayed incubation resulted in decreased recovery for S. pneumoniae (P<0.001). CONCLUSIONS: Culture plates should preferably be warmed at least to room temperature before inoculation, as well as promptly incubated to increase bacterial recovery from cases of septic keratitis.