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1.
AIDS ; 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33587445

RESUMO

OBJECTIVE: Nearly half of individuals living with HIV in the USA are now 50 or older. This rapidly aging populace may be at an increasingly greater risk of Alzheimer's disease (AD). However, the potential interaction between HIV-disease and AD pathogenesis (i.e., AD genetic risk factors) on brain function remains an open question. The present study aimed to investigate the impact of APOE ε4 on brain function in middle-aged to older PWH, as well as the putative interaction between ε4 and HIV disease severity. METHODS: Ninety-nine PWH participated in a cross-sectional study (56.3 ±â€Š6.5yrs, range 41-70yrs, 27 females, 26 ε4 carriers and 73 noncarriers). Structural MRI and resting-state functional MRI were collected to assess alterations in brain structure and functional connectivity (FC), respectively. RESULTS: APOE ε4 was associated with worse memory performance and reduced FC in the memory network. The FC reduction was centered at the caudate nucleus rather than hippocampus and correlated with worse memory performance. In ε4 carriers, low CD4 nadir was associated with reduced FC in the memory network, but this association was absent in noncarriers. Furthermore, there was an indirect detrimental impact of ε4 on memory performance through memory network FC. However, this indirect effect was contingent on CD4 nadir - that is, the indirect effect of ε4 on memory was only significant when CD4 nadir was low. INTERPRETATION: APOE ε4 is associated with reduced memory and reduced FC within the memory network, and low CD4 nadir-indicating a history of severe immunosuppression-may exacerbate the effects of ε4.

2.
Glob Chang Biol ; 2021 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-33464665

RESUMO

Increasing water-use efficiency (WUE), the ratio of carbon gain to water loss, is a key mechanism that enhances carbon uptake by terrestrial vegetation under rising atmospheric CO2 (ca ). Existing theory and empirical evidence suggest a proportional WUE increase in response to rising ca as plants maintain a relatively constant ratio between the leaf intercellular (ci ) and ambient (ca ) partial CO2 pressure (ci /ca ). This has been hypothesized as the main driver of the strengthening of the terrestrial carbon sink over the recent decades. However, proportionality may not characterize CO2 effects on WUE on longer time-scales and the role of climate in modulating these effects is uncertain. Here, we evaluate long-term WUE responses to ca and climate from 1901 to 2012 CE by reconstructing intrinsic WUE (iWUE, the ratio of photosynthesis to stomatal conductance) using carbon isotopes in tree rings across temperate forests in the northeastern USA. We show that iWUE increased steadily from 1901 to 1975 CE but remained constant thereafter despite continuously rising ca . This finding is consistent with a passive physiological response to ca and coincides with a shift to significantly wetter conditions across the region. Tree physiology was driven by summer moisture at multi-decadal time-scales and did not maintain a constant ci /ca in response to rising ca indicating that a point was reached where rising CO2 had a diminishing effect on tree iWUE. Our results challenge the mechanism, magnitude, and persistence of CO2 's effect on iWUE with significant implications for projections of terrestrial productivity under a changing climate.

3.
J Neurovirol ; 27(1): 160-167, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33405198

RESUMO

We examined the joint effects of depressive symptoms (Beck Depression Inventory-II (BDI-II)) and systemic inflammation (plasma C-reactive protein (CRP)) on longitudinal profiles of neurocognition in a cohort of 143 people with HIV (PWH) on antiretroviral therapy. Global neurocognition, processing speed, motor skills, and attention/working memory all worsened as CRP increased but only among PWH who, on average, exhibited moderate to severe depressive symptoms (BDI-II > 22). Findings suggest that some PWH with chronically elevated depressive symptoms may have an inflammatory subtype of depression and a particular vulnerability to neurocognitive changes that may respond to drugs targeting inflammation or its neural sequelae.

4.
Ophthalmology ; 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33515595

RESUMO

PURPOSE: To develop an agreed set of outcomes known as a core outcome set (COS) for Non-Infectious Uveitis of the Posterior Segment (NIU-PS) clinical trials. DESIGN: Mixed-methods study design comprising a systematic review and qualitative study followed by a two round Delphi exercise and face-to-face consensus meeting. PARTICIPANTS: Key stakeholders including: patients diagnosed with NIU-PS; their caregivers; healthcare professionals involved in decision-making for patients with NIU-PS including ophthalmologists, nurse practitioners and policymakers/commissioners. METHODS: A long list of outcomes was developed based on the results of (1) a systematic review of clinical trials of NIU-PS and (2) a qualitative study of key stakeholders including focus groups and interviews. The long list was used to generate a two-round Delphi exercise of stakeholders rating the importance of outcomes on a nine-point Likert scale. The proportion of respondents rating each item was calculated, leading to recommendations of 'include', 'exclude' or 'for discussion' that were taken forward to a face-to-face consensus meeting of key stakeholders at which the final COS was agreed. MAIN OUTCOME MEASURE: Items recommended for inclusion in the COS for NIU-PS RESULTS: A total of 57 outcomes grouped in 11 outcome domains were presented for evaluation in the Delphi exercise, resulting in 9 outcomes directly qualifying for inclusion and 15 outcomes being carried forward to the consensus meeting of which 7/15 were agreed for inclusion. The final COS contained 16 outcomes organized into 4 outcome domains comprising visual function, Health Related Quality of Life (HRQoL), treatment side effects and disease control. CONCLUSION: This study builds on international work across the clinical trials community and our qualitative research to construct the world's first COS for NIU-PS. The COS provide a list of outcomes that represent the priorities of key stakeholders and provides a minimum set of outcomes for use in all future NIU-PS clinical trials. Adoption of this COS can improve the value of future uveitis clinical trials and reduce non-informative research. Some of the outcomes identified do not yet have internationally agreed methods for measurement and should be the subject of future international consensus development. TRIAL REGISTRATION: The study was registered with COMET (http://comet-initiative.org/studies/details/640).

5.
Syst Rev ; 10(1): 33, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33472668

RESUMO

BACKGROUND: A variety of public health interventions have been undertaken in low- and middle-income countries (LMICs) to prevent morbidity and mortality associated with household air pollution (HAP) due to cooking, heating and lighting with solid biomass fuels. Pregnant women and children under five are particularly vulnerable to the effects of HAP, due to biological susceptibility and typically higher exposure levels. However, the relative health benefits of interventions to reduce HAP exposure among these groups remain unclear. This systematic review aims to assess, among pregnant women, infants and children (under 5 years) in LMIC settings, the effectiveness of interventions which aim to reduce household air pollutant emissions due to household solid biomass fuel combustion, compared to usual cooking practices, in terms of health outcomes associated with HAP exposure. METHODS: This protocol follows standard systematic review processes and abides by the PRISMA-P reporting guidelines. Searches will be undertaken in MEDLINE, EMBASE, CENTRAL, WHO International Clinical Trials Registry Platform (ICTRP), The Global Index Medicus (GIM), ClinicalTrials.gov and Greenfile, combining terms for pregnant women and children with interventions or policy approaches to reduce HAP from biomass fuels or HAP terms and LMIC countries. Included studies will be those reporting (i) pregnant women and children under 5 years; (ii) fuel transition, structural, educational or policy interventions; and (iii) health events associated with HAP exposure which occur among pregnant women or among children within the perinatal period, infancy and up to 5 years of age. A narrative synthesis will be undertaken for each population-intervention-outcome triad stratified by study design. Clinical and methodological homogeneity within each triad will be used to determine the feasibility for undertaking meta-analyses to give a summary estimate of the effect for each outcome. DISCUSSION: This systematic review will identify the effectiveness of existing HAP intervention measures in LMIC contexts, with discussion on the context of implementation and adoption, and summarise current literature of relevance to maternal and child health. This assessment reflects the need for HAP interventions which achieve measurable health benefits, which would need to be supported by policies that are socially and economically acceptable in LMIC settings worldwide. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020164998.

7.
Ecology ; 102(3): e03264, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33325555

RESUMO

The response of understory trees to climate variability is key to understanding current and future forest dynamics. However, analyses of climatic effects on tree growth have primarily focused on the upper canopy, leaving understory dynamics unresolved. We analyzed differences in climate sensitivity based on canopy position of four common tree species (Acer rubrum, Fagus grandifolia, Quercus rubra, and Tsuga canadensis) using growth information from 1,084 trees across eight sites in the northeastern United States. Effects of canopy position on climate response varied, but were significant and often nonlinear, for all four species. Compared to overstory trees, understory trees showed stronger reductions in growth at high temperatures and varied shifts in precipitation response. This contradicts the prevailing assumption that climate responses, particularly to temperature, of understory trees are buffered by the overstory. Forest growth trajectories are uncertain in compositionally and structurally complex forests, and future demography and regeneration dynamics may be misinferred if not all canopy levels are represented in future forecasts.

8.
Polymers (Basel) ; 12(12)2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33291576

RESUMO

Polyethylene glycols (PEGs) and PEG derivatives are used in a range of cosmetic and pharmaceutical products. However, few studies have investigated the influence of PEGs and their related derivatives on skin permeation, especially when combined with other solvents. Previously, we reported niacinamide (NIA) skin permeation from a range of neat solvents including propylene glycol (PG), Transcutol® P (TC), dimethyl isosorbide (DMI), PEG 400 and PEG 600. In the present work, binary and ternary systems composed of PEGs or PEG derivatives combined with other solvents were investigated for skin delivery of NIA. In vitro finite dose studies were conducted (5 µL/cm2) in porcine skin over 24 h. Higher skin permeation of NIA was observed for all vehicles compared to PEG 400. However, overall permeation for the binary and ternary systems was comparatively low compared with results for PG, TC and DMI. Interestingly, values for percentage skin retention of NIA for PEG 400:DMI and PEG 400:TC were significantly higher than values for DMI, TC and PG (p < 0.05). The findings suggest that PEG 400 may be a useful component of formulations for the delivery of actives to the skin rather than through the skin. Future studies will expand the range of vehicles investigated and also look at skin absorption and residence time of PEG 400 compared to other solvents.

9.
JMIR Res Protoc ; 9(12): e21592, 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33300885

RESUMO

BACKGROUND: African Americans are disproportionally affected by HIV and have poorer rates of antiretroviral therapy (ART) adherence compared to other racial or ethnic groups in the United States. Factors associated with poor HIV disease outcomes are commonly associated with sociostructural barriers that prevent engagement with and retention in HIV care. SMS text messaging interventions to promote ART adherence among predominantly non-Hispanic White persons with HIV (PWH) have been shown to be efficacious; however, limited research has been devoted to culturally tailoring interventions for underrepresented racial/ethnic groups. Considering African Americans show poorer engagement along the HIV care continuum, we developed an individualized and culturally tailored two-way SMS text messaging intervention to improve ART adherence and associated virologic suppression among African American PWH. OBJECTIVE: In this paper we describe the protocol of a culturally tailored individualized Texting for Adherence Building (iTAB) intervention in a 24- to 48-week, single-arm study. METHODS: We developed a culturally tailored iTAB intervention, which we are implementing in a 24- to 48-week, single-arm study. Participants were recruited from the Family Health Centers of San Diego (FHCSD), a federally qualified health center. Patient inclusion criteria were (1) receiving care at the FHCSD, (2) living with HIV, (3) self-identification as Black, African American, or of African ancestry, (4) English speaking, (5) age 18 or older, (6) currently on ART, and (7) able to provide informed consent. Study enrollment began in November 2017 and closed in July 2019. A total of 90 participants from the FHCSD enrolled in the iTAB intervention, and we anticipate completing data collection in July 2020. Participants were assisted in individualizing and customizing their SMS text message preferences at the baseline study visit. Self-assessment measures are collected at baseline, interim, and final study visits. Problems related to sending/receiving SMS text messages and barriers to ART adherence are assessed at each interim study visit. The FHCSD staff monitors and tracks participants' daily SMS text message responses to ART adherence reminders using a clinical dashboard. RESULTS: We hypothesize that the proportion of individuals achieving HIV virologic suppression (viral load <40 copies/mL) will be greater at the end of the intervention period compared to the proportion prior to study implementation. Additionally, we anticipate that rates of virologic suppression at the end of the intervention among participants receiving iTAB will be comparable to those among the general FHCSD non-African American population who did not receive iTAB. Finally, we anticipate a high response rate to iTAB SMS text messages as well as positive participant feedback at the end of the intervention with regard to the acceptability of, satisfaction with, and perceived efficacy of iTAB. CONCLUSIONS: The iTAB intervention is a novel individualized two-way SMS text messaging intervention that has been culturally tailored for use among African Americans with HIV. We anticipate that iTAB will demonstrate efficacy in future randomized control trials and will be supportive of medication adherence among other populations facing health disparities. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/21592.

10.
J Infect Dis ; 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33319235

RESUMO

BACKGROUND: Memory impairment occurs in both HIV-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment (aMCI), the precursor to Alzheimer's disease (AD). Methods are needed to distinguish aMCI-associated from HAND-associated impairment in people with HIV (PWH). We developed a neuropsychological method of identifying aMCI in PWH and tested this method by relating AD neuropathology (ß-amyloid, phospho-Tau) to aMCI versus HAND classification. METHODS: Seventy-four HIV+ cases (age: 50-68) from the National NeuroAIDS Tissue Consortium had neurocognitive data within one-year of death and had data on ß-amyloid and phospho-Tau pathology in frontal brain tissue. High aMCI risk was defined as impairment (<1.0 SD below normative mean) on two of four delayed recall or recognition outcomes from a verbal and non-verbal memory test (at-least one recognition impairment required). Differences in ß-amyloid and phospho-Tau by aMCI and HAND classification were examined. RESULTS: High aMCI risk classification was more common in the HAND (69.0%) versus no HAND (37.5%) group. ß-amyloid pathology was 4.75 times more likely in the high versus low aMCI risk group. Phospho-Tau pathology did not differ between aMCI groups. Neither neuropathological feature differed by HAND status. CONCLUSIONS: amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.

11.
AIDS ; 2020 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-33252483

RESUMO

OBJECTIVES: Given the rising number of older people with HIV (PWH) and the overlap in cognitive dysfunction profiles in HIV-associated Neurocognitive Disorders (HAND) and Alzheimer's disease (AD) and its precursor, amnestic mild cognitive impairment (aMCI), methods are needed to distinguish aMCI/AD from HAND. As an early indicator of AD, we examined whether olfactory dysfunction could help to distinguish between aMCI/AD and HAND among PWH. DESIGN: Observational cohort study METHODS:: Eighty-one older (≥50 years) PWH (83% male, 65% Caucasian) from the California NeuroAIDS Tissue Consortium completed the University of Pennsylvania Smell Identification Test (UPSIT; higher scores = better smell identification) and a comprehensive seven-domain neuropsychological test battery and neuromedical evaluation. HAND was classified via Frascati criteria. High aMCI risk was defined as impairment (>1.0 SD below normative mean) on two of four delayed recall or recognition outcomes (at-least one recognition impairment required) from the Hopkins Verbal Learning Test-Revised and the Brief Visuospatial Memory Test-Revised. We examined UPSIT scores in relation to: 1) aMCI risk and HAND status, and 2) continuous memory scores considering adjustments for demographics and relevant clinical or HIV disease characteristics. RESULTS: Fifty-seven participants were classified with HAND (70%) and 35 participants were classified as high aMCI risk (43%). UPSIT scores were lower (worse) in the high versus low aMCI risk group (F (1,76) = 10.04, p = .002), but did not differ by HAND status (F (1,76) = 0.62, p = .43). UPSIT scores positively correlated with all memory outcomes (ps < .05). CONCLUSIONS: Olfactory assessments may help in detecting early aMCI/AD among PWH and allow for appropriate and early disease intervention.

12.
Pain Rep ; 5(6): e861, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33235944

RESUMO

Introduction: Individuals with autism spectrum disorder (ASD) often exhibit differences in pain responsivity. This altered responsivity could be related to ASD-related social communication difficulties, sensory differences, or altered processing of pain stimuli. Previous neuroimaging work suggests altered pain evaluation could contribute to pain-related anxiety in ASD. Objectives: We hypothesized that individuals with ASD would report increased pain sensitivity and endorse more pain-related anxiety, compared to typically developing controls. Methods: We recruited 43 adults (ASD, n = 24; typically developing, n = 19) for 3 heat pain tasks (applied to the calf). We measured heat pain thresholds using a method of limits approach, a pain-rating curve (7 temperatures between 40 and 48°C, 5 seconds, 5 trials each), and a sustained heat pain task with alternating low (42°C) and high (46°C) temperatures (21 seconds, 6 trials each). Individual differences in pain-related anxiety, fear of pain, situational pain catastrophizing, depressive symptoms, and autism-related social communication were assessed by self-report. Results: There were no group differences in pain thresholds. For suprathreshold tasks, mean pain ratings were higher in ASD across both the pain-rating curve and the sustained heat pain tasks, but responses in the ASD group were more varied. Pain anxiety (PASS-Total) and pain-related fear (FOP-III-Total) were higher in the ASD group and were positively associated with pain ratings. Conclusions: Our results suggest that both sensory and cognitive experiences of pain are heightened and interact reciprocally in adults with ASD. Future studies are needed to evaluate the impact of pain-related anxiety on treatment-seeking and pain behaviors, given higher levels of pain-related anxiety in ASD.

13.
Artigo em Inglês | MEDLINE | ID: mdl-33055205

RESUMO

OBJECTIVE: To determine whether oxidative stress in virologically suppressed people with HIV (PWH) may contribute to or result from neurodegeneration, we measured 7,8-dihydro-8-oxoguanine (8-oxo-dG), a marker of DNA damage due to oxidative stress, and markers of age-related neurodegeneration, specifically, reduced levels of CSF Aß-42, and elevated CSF total tau and neurofilament light (NFL). METHODS: This cross-sectional study prospectively enrolled participants at 6 US centers in the CNS HIV Antiretroviral Effects Research study. Inclusion criteria included HIV+ with a plasma level of HIV RNA ≤50 copies/mL. Exclusions included significant CNS confounding conditions. Measurements of total tau and Aß-42 were performed by bead suspension array. NFL and 8-oxo-dG were measured using ELISA. RESULTS: Participants were 53 PWH, mean age 55 (±9.3) years, 19% women, and 48% non-Hispanic White. Higher 8-oxo-dG correlated with markers of AD-related neurodegeneration including lower CSF Aß-42 (r = -0.34; p = 0.012) and higher CSF NFL (r = 0.39; p = 0.0091) and total tau (r = 0.6696; p < 0.0001). Relationships remained after adjusting for demographic variables. Levels of protein carbonyls, a marker of protein oxidation, were not related to neurodegeneration markers. CONCLUSIONS: Among virologically suppressed PWH, nucleic acid oxidation was associated with standard CSF biomarkers of neurodegeneration. Potential sources of oxidative stress in PWH include low-level HIV replication, inflammation, mitochondrial dysfunction, and specific antiretroviral drugs. Results suggest that the higher levels of oxidative stress among PWH may play a role in neurodegeneration. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among virologically suppressed PWH, nucleic acid oxidation is associated with standard CSF biomarkers of neurodegeneration.

14.
Psychiatry Res ; 294: 113510, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33096437

RESUMO

Wisdom is a unique human personality trait with cognitive, affective or compassionate, and reflective dimensions. We evaluated relationships of three specific dimensions of wisdom with cognitive function and physical and mental well-being in people with HIV (PWH) and HIV-negative (HIV-) participants. Subjects included 138 adults (61 PWH, 77 HIV-) from the San Diego community. Validated measures were used to assess wisdom and well-being. Cognitive function was assessed via the Montreal Cognitive Assessment. We conducted multivariate linear regressions to evaluate the associations of wisdom dimensions with cognitive function and physical and mental well-being. Compared to the HIV- group, PWH had lower mean scores on cognitive function, and physical and mental well-being, and cognitive and reflective dimensions of wisdom, but similar scores on affective or compassionate wisdom. Among PWH, higher total wisdom scores were associated with older age, lower likelihood of substance dependence, greater mental well-being, better cognitive function, higher resilience, social support, and optimism scores, as well as lower levels of perceived stress and nadir CD4 count. Our findings of an association of different dimensions of wisdom with physical and/or mental well-being in PWH would point to a possibility that enhancing these dimensions of wisdom might improve health outcomes in PWH.

15.
BMJ Open Ophthalmol ; 5(1): e000579, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083555

RESUMO

Objectives: Risk stratification is needed for patients referred to hospital eye services by Diabetic Eye Screening Programme UK. This requires a set of candidate predictors. The literature contains a large number of predictors. The objective of this research was to arrive at a small set of clinically important predictors for the outcome of the progression of diabetic retinopathy (DR). They need to be evidence based and readily available during the clinical consultation. Methods and analysis: Initial list of predictors was obtained from a systematic review of prediction models. We sought the clinical expert opinion using a formal qualitative study design. A series of nominal group technique meetings to shorten the list and to rank the predictors for importance by voting were held with National Health Service hospital-based clinicians involved in caring for patients with DR in the UK. We then evaluated the evidence base for the selected predictors by critically appraising the evidence. Results: The source list was presented at nominal group meetings (n=4), attended by 44 clinicians. Twenty-five predictors from the original list were ranked as important predictors and eight new predictors were proposed. Two additional predictors were retained after evidence check. Of these 35, 21 had robust supporting evidence in the literature condensed into a set of 19 predictors by categorising DR. Conclusion: We identified a set of 19 clinically meaningful predictors of DR progression that can help stratify higher-risk patients referred to hospital eye services and should be considered in the development of an individual risk stratification model. Study design: A qualitative study and evidence review. Setting: Secondary eye care centres in North East, Midlands and South of England.

16.
Ocul Immunol Inflamm ; : 1-12, 2020 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-33021418

RESUMO

PURPOSE: This systematic review aims to identify instrument-based tests for quantifying vitreous inflammation in uveitis, report the test reliability and the level of correlation with clinician grading. METHODS: Studies describing instrument-based tests for detecting vitreous inflammation were identified by searching bibliographic databases and trials registers. Test reliability measures and level of correlation with clinician vitreous haze grading are extracted. RESULTS: Twelve studies describing ultrasound, optical coherence tomography (OCT), and retinal photography for detecting vitreous inflammation were included: Ultrasound was used for detection of disease features, whereas OCT and retinal photography provided quantifiable measurements. Correlation with clinician grading for OCT was 0.53-0.60 (three studies) and for retinal photography was 0.51 (1 study). Both instruments showed high inter- and intra-observer reliability (>0.70 intraclass correlation and Cohen's kappa), where reported in four studies. CONCLUSION: Retinal photography and OCT are able to detect and measure vitreous inflammation. Both techniques are reliable, automatable, and warrant further evaluation.

17.
Neurourol Urodyn ; 39(5): 1494-1504, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32893408

RESUMO

BACKGROUND: To investigate whether meteorological factors (temperature, barometric pressure, relative humidity, ultraviolet index [UVI], and seasons) trigger flares in male and female urologic chronic pelvic pain patients. METHODS: We assessed flare status every 2 weeks in our case-crossover study of flare triggers in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain 1-year longitudinal study. Flare symptoms, flare start date, and exposures in the 3 days preceding a flare or the date of questionnaire completion were assessed for the first three flares and at three randomly selected nonflare times. We linked these data to daily temperature, barometric pressure, relative humidity, and UVI values by participants' first 3 zip code digits. Values in the 3 days before and the day of a flare, as well as changes in these values, were compared to nonflare values by conditional logistic regression. Differences in flare rates by astronomical and growing seasons were investigated by Poisson regression in the full study population. RESULTS: A total of 574 flare and 792 nonflare assessments (290 participants) were included in the case-crossover analysis, and 966 flare and 5389 nonflare (409 participants) were included in the full study analysis. Overall, no statistically significant associations were observed for daily weather, no patterns of associations were observed for weather changes, and no differences in flare rates were observed by season. CONCLUSIONS: We found minimal evidence to suggest that weather triggers flares, although we cannot rule out the possibility that a small subset of patients is susceptible.

18.
Clin Neuropsychol ; : 1-20, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-32993422

RESUMO

OBJECTIVE: Poor sleep quality is related to worse neurocognition in older adults and in people with HIV (PWH); however, many previous studies have relied only on self-report sleep questionnaires, which are inconsistently correlated with objective sleep measures. We examined relationships between objective and subjective sleep quality and neurocognition in persons with and without HIV, aged 50 and older. Method: Eighty-five adults (PWH n = 52, HIV-negative n = 32) completed comprehensive neuropsychological testing to assess global and domain-specific neurocognition. Objective sleep quality was assessed with wrist actigraphy (total sleep time, efficiency, sleep fragmentation) for five to 14 nights. Subjective sleep quality was assessed with the Pittsburgh Sleep Quality Index. Results: Objective and subjective sleep measures were unrelated (p's > 0.30). Compared to HIV-negative participants, PWH had greater sleep efficiency (80% vs. 75%, p = 0.05) and were more likely to be using prescription and/or over the counter sleep medication (p = 0.04). In the whole sample, better sleep efficiency (p < 0.01) and greater total sleep time (p = 0.05) were associated with better learning. Less sleep fragmentation was associated with better learning (p < 0.01) and recall (p = 0.04). While PWH had slightly stronger relationships between total sleep time and sleep fragmentation, it is not clear if these differences are clinically meaningful. Better subjective sleep quality was associated with better executive function (p < 0.01) and working memory (p = 0.05); this relationship was primarily driven by the HIV-negative group. Conclusions: Objective sleep quality was associated with learning and recall whereas subjective sleep quality was associated with executive function and working memory. Therefore, assessing objective and subjective sleep quality could be clinically useful, as they are both related to important domains of cognition frequently impacted in HIV-associated neurocognitive disorders as well as neurodegenerative disorders associated with aging. Future studies should evaluate if behavioral sleep interventions can improve neurocognition.

19.
JMIR Mhealth Uhealth ; 8(9): e19579, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-32969829

RESUMO

BACKGROUND: Daily activities have been associated with neurocognitive performance. However, much of this research has used in-person neuropsychological testing that requires participants to travel to a laboratory or clinic, which may not always be feasible and does not allow for the examination of real-time relationships between cognition and behavior. Thus, there is a need to understand the real-time relationship between activities in the real world and neurocognitive functioning to improve tracking of symptoms or disease states and aid in the early identification of neurocognitive deficits among at-risk individuals. OBJECTIVE: We used a smartphone-based ecological momentary cognitive assessment (EMCA) platform to examine real-time relationships between daily activities and neurocognitive performance (executive functioning and verbal learning) in the everyday environment of middle-aged and older adults with and without HIV. METHODS: A total of 103 adults aged 50-74 years (67 persons with HIV; mean age 59 years, SD 6.4) were recruited from the University of California, San Diego HIV Neurobehavioral Research Program and the San Diego community. Participants completed our EMCA protocol for 14 days. Participants reported their current daily activities 4 times per day; following 2 of the 4 daily ecological momentary assessment (EMA) surveys, participants were administered the mobile Color-Word Interference Test (mCWIT) and mobile Verbal Learning Test (mVLT), each once per day. Activities were categorized into cognitively stimulating activities, passive leisure activities, and instrumental activities of daily living (IADLs). We used multilevel modeling to examine the same-survey and lagged within-person and between-person effects of each activity type on mobile cognitive performance. RESULTS: On average, participants completed 91% of the EMA surveys, 85% of the mCWIT trials, and 80% of the mVLT trials, and they reported engaging in cognitively stimulating activities on 17% of surveys, passive leisure activities on 33% of surveys, and IADLs on 20% of surveys. Adherence and activity percentages did not differ by HIV status. Within-persons, engagement in cognitively stimulating activities was associated with better mCWIT performance (ß=-1.12; P=.007), whereas engagement in passive leisure activities was associated with worse mCWIT performance (ß=.94; P=.005). There were no lagged associations. At the aggregate between-person level, a greater percentage of time spent in cognitively stimulating activities was associated with better mean mVLT performance (ß=.07; P=.02), whereas a greater percentage of time spent in passive leisure activities was associated with worse mean mVLT performance (ß=-.07; P=.01). IADLs were not associated with mCWIT or mVLT performance. CONCLUSIONS: Smartphones present unique opportunities for assessing neurocognitive performance and behavior in middle-aged and older adults' own environment. Measurement of cognition and daily functioning outside of clinical settings may generate novel insights on the dynamic association of daily behaviors and neurocognitive performance and may add new dimensions to understanding the complexity of human behavior.

20.
Brain Behav Immun ; 90: 353-363, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32966871

RESUMO

BACKGROUND: HIV-related neuroinflammation has been proposed as a catalyst for dopaminergic dysregulation in mesocortical pathways, which may contribute to the pathogenesis of depression. Abnormalities in dopaminergic neurotransmission and depression are common in people with HIV (PWH), however the link between dopamine (DA) and depression in PWH is poorly characterized. This study investigated CSF dopaminergic biomarkers, specifically DA and its metabolite, homovanillic acid (HVA), and examined their relationship with depressive symptoms and CSF neuroinflammatory markers in PWH and HIV-seronegative (HIV-) individuals. METHODS: Participants were 102 HIV- individuals and 123 PWH (mean age = 42) who underwent neuropsychiatric evaluations and lumbar puncture. Current depression severity was classified using the Beck Depression Inventory-II (BDI-II). CSF was assayed for DA and HVA using high performance liquid chromatography and neuroinflammatory markers using immunoassays. Linear regressions modelled BDI-II scores as a function of HIV, dopaminergic biomarker z-scores, and their interaction, controlling for psychosocial factors. Correlational analyses examined dopaminergic and neuroinflammatory relationships. RESULTS: PWH had significantly higher BDI-II scores than HIV- participants. DA and HVA were not associated with HIV status but both significantly moderated the effect of HIV on BDI-II scores, such that PWH exhibited higher depressive symptoms than HIV- participants only at lower concentrations of HVA (z ≤ 0.06) and DA (z ≤ 0.11). In PWH only, lower HVA significantly correlated with higher BDI-II scores and higher neuroinflammation, including higher MCP-1 and IP-10. CONCLUSIONS: Results suggest that the pathophysiology of depression in PWH differs from that in HIV- individuals. Specifically, lower central dopaminergic activity was selectively associated with greater depressive symptoms and neuroinflammation in PWH. With the rise in consideration of DA agonists for the treatment of depression, these results suggest that PWH may show a greater response to these agents than their HIV- peers.

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