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1.
MMWR Morb Mortal Wkly Rep ; 73(31): 677-681, 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39116025

ABSTRACT

Final annual mortality data from the National Vital Statistics System for a given year are typically released 11 months after the end of the calendar year. Provisional data, which are based on preliminary death certificate data, provide an early estimate of deaths before the release of final data. In 2023, a provisional total of 3,090,582 deaths occurred in the United States. The age-adjusted death rate per 100,000 population was 884.2 among males and 632.8 among females; the overall rate, 750.4, was 6.1% lower than in 2022 (798.8). The overall rate decreased for all age groups. Overall age-adjusted death rates in 2023 were lowest among non-Hispanic multiracial (352.1) and highest among non-Hispanic Black or African American persons (924.3). The leading causes of death were heart disease, cancer, and unintentional injury. The number of deaths from COVID-19 (76,446) was 68.9% lower than in 2022 (245,614). Provisional death estimates provide an early signal about shifts in mortality trends. Timely and actionable data can guide public health policies and interventions for populations experiencing higher mortality.


Subject(s)
COVID-19 , Cause of Death , Mortality , Humans , United States/epidemiology , Male , Female , Middle Aged , Adult , Adolescent , Young Adult , Aged , Infant , Child, Preschool , Child , Mortality/trends , COVID-19/mortality , COVID-19/ethnology , Infant, Newborn , Aged, 80 and over , Vital Statistics , Age Distribution , Sex Distribution
2.
J Glaucoma ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39133059

ABSTRACT

PRECIS: There were statistically significant differences across multiple socioeconomic characteristics and self-reported barriers to care among primary glaucoma patients with severity staging data versus those missing this data in the NIH All of Us database. PURPOSE: To characterize missing data among glaucoma patients within All of Us. PATIENTS AND METHODS: We used diagnosis codes to define cohorts of primary glaucoma patients with and without severity staging specified. Descriptive analyses were conducted by presence of disease severity stage. Analysis of missing data was conducted using a set intersection plot and Little's Test of Missing Completely at Random. T-tests were performed to evaluate differences. RESULTS: Of 2982 participants, 1714 (57%) did not have glaucoma severity stage specified, and 11 of 23 analyzed variables had missing data. Little's Test indicated data was not missing completely at random (P<0.001). Significant differences existed between the two cohorts with respect to age, age of first glaucoma diagnosis, gender, ethnicity, education, income, insurance, history of glaucoma surgery and medication use, and answers regarding ability to afford eyeglasses and having seen an eye care provider in the last 12 months (all P values≤0.01). CONCLUSION: There were significant differences between glaucoma participants with glaucoma severity stage specified versus those with unstaged disease across multiple socioeconomic characteristics and self-reported barriers to care. Glaucoma severity staging data was not missing completely at random. The unstaged cohort included higher rates of multiple underrepresented communities, which may potentially contribute to bias in ophthalmology research as participants from vulnerable populations may be disproportionately excluded from electronic health records or claims data studies where diagnosis codes with severity/staging levels are used to examine risk factors for disease, progression, and treatment efficacy.

3.
J Glaucoma ; 2024 Aug 13.
Article in English | MEDLINE | ID: mdl-39133058

ABSTRACT

PRCIS: Increased oxygen saturation was significantly associated with the severity of VF damage in glaucoma patients. PURPOSE: To investigate the association between retinal oxygen saturation (StO2) % and the severity of visual field (VF) loss in glaucoma. METHODS: A total of 198 eyes from 131 glaucoma patients were included in this cross-sectional study. Participants underwent imaging using ocular oximetry (Zilia; Quebec City, Canada) and 24-2 SITA standard VF (Carl Zeiss-Meditec, San Leandro). StO2 (%), was measured at 2 locations of the peripapillary optic nerve head (ONH) (superotemporal, and inferotemporal). Measurements were reported as the mean of at least 5 measurements in each location. Associations between the severity of VF loss, reported as mean deviation (MD), and StO2 (%) was calculated. RESULTS: 198 eyes of 131 patients (mean (95% CI) age, 71.1 (68.9,73.3) years, 68 females [51.9%], 63 males (48.1%)) were analyzed. In univariable analysis, higher StO2 -0.06 (-0.12, 0.00) was associated with severity in all hemifields (P=0.047). Multivariate regression analysis showed that each 1% increase in StO2 was associated with -0.06 (-0.12,-0.00) dB loss in MD in all hemifields (P=0.043). In multivariate regression analysis in the superior hemifields, higher StO2 -0.07 (-0.16, 0.01) tended to be associated with superior hemifield severity (P=0.09). CONCLUSIONS: Retinal oximetry enabled the continuous quantitative measurement of retinal StO2. Increased StO2 was significantly associated with the severity of VF damage in glaucoma patients.

5.
Adv Healthc Mater ; : e2400668, 2024 Aug 12.
Article in English | MEDLINE | ID: mdl-39135411

ABSTRACT

This review highlights the promise of fiber-reinforced hydrogel composites (FRHCs) for augmenting tendon and ligament repair and regeneration. Composed of reinforcing fibers embedded in a hydrogel, these scaffolds provide both mechanical strength and a conducive microenvironment for biological processes required for connective tissue regeneration. Typical properties of FRHCs are discussed, highlighting their ability to simultaneously fulfill essential mechanical and biological design criteria for a regenerative scaffold. Furthermore, features of FRHCs are described that improve specific biological aspects of tendon healing including mesenchymal progenitor cell recruitment, early polarization to a pro-regenerative immune response, tenogenic differentiation of recruited progenitor cells, and subsequent production of a mature, aligned collagenous matrix. Finally, the review offers a perspective on clinical translation of tendon FRHCs and outlines key directions for future work.

6.
J Gen Intern Med ; 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39095571

ABSTRACT

BACKGROUND: High prevalence of depression or anxiety with opioid use for chronic pain complicates co-management and may influence prescribing behaviors. OBJECTIVE: Compare clinical effectiveness of electronic medical record clinical decision support (EMR-CDS) versus additional behavioral health (BH) care management for reducing rates of high-dose opioid prescriptions. DESIGN: Type 2 effectiveness-implementation hybrid stepped-wedge cluster randomized trial in 35 primary care clinics within a health system in LA, USA. PARTICIPANTS: Patients aged 18+ receiving chronic opioid therapy for non-cancer pain with depression or anxiety and matched controls. INTERVENTION: EMR-CDS included opioid risk mitigation procedures. BH care included cognitive behavioral therapy; depression or anxiety medication adjustments; and case management. MAIN MEASURES: Outcomes of interest included difference-in-difference (DID) estimate of changes in probability for prescribing high-dose morphine equivalent daily dose (MEDD ≥50 mg/day and MEDD ≥90), average MEDD, and rates of hospitalization, emergency department use, and opioid risk mitigation. KEY RESULTS: Most participants were female with 3+ pain syndromes. Data analysis included 632 patients. Absolute risk differences for MEDD≥50 and ≥90 decreased post-index compared to pre-index (DID of absolute risk difference [95%CI]: -0.036 [-0.089, 0.016] and -0.029 [-0.060, 0.002], respectively). However, these differences were not statistically significant. The average MEDD decreased at a higher rate for the BH group compared to EMR-CDS only (DID rate ratio [95%CI]: 0.85 [0.77, 0.93]). There were no changes in hospitalization and emergency department utilization. The BH group had higher probabilities of new specialty referrals and prescriptions for naloxone and antidepressants. CONCLUSIONS: Incorporation of a multidisciplinary behavioral health care team into primary care did not decrease high-dose prescribing; however, it improved adherence to clinical guideline recommendations for managing chronic opioid therapy for non-cancer pain. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT03889418.

7.
bioRxiv ; 2024 Jul 24.
Article in English | MEDLINE | ID: mdl-39091740

ABSTRACT

Coronavirus relevancy for human health has surged over the past 20 years as they have a propensity for spillover into humans from animal reservoirs resulting in pandemics such as COVID-19. The diversity within the Coronavirinae subfamily and high infection frequency in animal species worldwide creates a looming threat that calls for research across all genera within the Coronavirinae subfamily. We sought to contribute to the limited structural knowledge within the Gammacoronavirus genera and determined the structure of the viral core replication-transcription complex (RTC) from Infectious Bronchitis Virus (IBV) using single-particle cryo-EM. Comparison between our IBV structure with published RTC structures from other Coronavirinae genera reveals structural differences across genera. Using in vitro biochemical assays, we characterized these differences and revealed their differing involvement in core RTC formation across different genera. Our findings highlight the value of cross-genera Coronavirinae studies, as they show genera specific features in coronavirus genome replication. A broader knowledge of coronavirus replication will better prepare us for future coronavirus spillovers.

8.
Kidney360 ; 2024 Aug 06.
Article in English | MEDLINE | ID: mdl-39115860

ABSTRACT

BACKGROUND: Depression and diminished health-related quality of life (HRQOL) are common in kidney failure. In this study we investigate whether kidney transplant (KT), the treatment of choice for kidney failure, improves depression and HRQOL across lifespan and whether this effect is sustained. METHODS: In this longitudinal observational cohort study, we assessed depression and HRQOL in patients on the KT waitlist and again at 3-months and 1-year after KT. We measured depression using the Beck Depression Inventory-II (BDI-II) and HRQOL using the Kidney Disease Quality of Life Short Form Version 1.3 (KDQOL-SF) physical health composite score (PCS) and mental health composite score (MCS). We used linear mixed effect models with random intercepts for patients to evaluate the effect of time, age, and KT status on BDI-II score, PCS, and MCS. For models with significant age interactions, we estimated this effect for baseline age groups. RESULTS: We analyzed 239 longitudinal BDI-II assessments completed by 99 patients and 143 KDQOL-SF assessments completed by 59 patients (16% Black, 79% White). The BDI-II scores improved pre- to post-KT (10 pre-KT vs 5 post-KT, p<0.001). PCS improved pre- to post-KT in younger patients, but the magnitude of change was lower with older age (p for interaction=0.01). In the sub-group analysis by age, there was improvement in PCS post-KT in patients <60 years (p=0.003 for 30-39, p=0.007 for 40-49, p=0.03 for 50-59). The MCS also improved from 47 pre-KT to 51 post-KT (p<0.001), and the magnitude of improvement was again lower with older age (p for interaction=0.03). CONCLUSIONS: Depression and HRQOL improve with KT. While depression improves in all ages, the improvement in HRQOL, especially PCS, is more evident in younger patients. This improvement in depression and HRQOL is sustained until at least 1-year post-KT. These data help frame expectations for patients and transplant teams.

9.
Am J Ophthalmol ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39094992

ABSTRACT

PURPOSE: To examine the time to glaucoma progression detection by retinal nerve fiber layer thickness (RNFLT) and visual field (VF) among African descent (AD) individuals. DESIGN: Retrospective cohort study. METHODS: Setting: Multi-center. STUDY POPULATION: We included AD glaucoma eyes from DIGS/ADAGES with ≥2-year/5-visits of optic nerve head RNFLT and 24-2 VF examinations. Intervention or Observation Procedure: Rates of VF mean deviation (MD) and RNFLT worsening were analyzed using linear mixed-effects models, and longitudinal data was simulated using the variability estimates. MAIN OUTCOME MEASURE: The simulated time to detect trend-based glaucoma progression was assessed with assumed rates of VF MD and RNFLT change derived from the cohort (25th, 50th, 75th percentile [p25, median, p75] slopes and mean slopes). Severity-stratified analyses were also performed. RESULTS: We included 184 eyes from 128 AD subjects (mean baseline age: 63.4 years; VF MD: -4.2 dB, RNFLT: 80.2 µm). The p25, median, mean and p75 rates of change were -0.43, -1.01, -1.15 and -1.64 µm/year for RNFLT, and 0.00, -0.21, -0.30 and -0.51 dB/year for VF MD, respectively. Compared to VF MD, RNFLT showed an overall shorter mean time to progression detection (time difference: 0.4-1.7 years), with the mean rates showing the largest difference (RNFLT: 5.2 years vs. VF MD: 6.9 years). Similarly, we found an overall shorter time to detect RNFLT progression, compared to that of VF MD progression, in mild glaucoma eyes (≥1 year earlier) and in moderate-advanced glaucoma eyes (∼0.5 year earlier). CONCLUSIONS: Computer simulation showed potentially shorter time to detect RNFLT progression than VF MD progression in AD eyes. Our findings support the importance of using RNFLT to detect progressive glaucoma in AD individuals.

10.
Plant Dis ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39115954

ABSTRACT

Eastern redbud (Cercis canadensis L.) is a popular and high-value woody ornamental plant native to the eastern and south-central United States of America (U.S.A.). In recent years, redbud production in the Southeastern U.S.A. has been greatly affected by a novel threat: vascular streak dieback (VSD). Infected plants exhibit a common set of symptoms, including leaf scorch, tip dieback, and vascular streaking that creates a marbled pattern in stem cross-section. Based on both conventional diagnosis and molecular identification, it has been found that the fungus Ceratobasidium sp. D.P. Rogers (Csp) is consistently associated with VSD-symptomatic eastern redbuds. However, the causal agent(s) of VSD has not yet been conclusively confirmed. Although eastern redbud has been the most frequently identified host tree, more than 25 other native plant genera have been confirmed to have VSD associated with Csp. The near-obligate nature of this fungus has made it challenging to culture, extract DNA, and conduct further studies to confirm its pathogenicity. This article highlights the emerging challenges of VSD, focusing on the following: 1) the recent history of VSD; 2) the increasing importance of VSD to woody ornamental nursery production in the U.S.A.; 3) the currently available protocols for isolating, culturing, storing, and maintaining the putative causal agent; 4) the rapid molecular detection of Csp; 5) phylogenetic findings on the origin and relatedness of Csp to previously recorded diseases, especially VSD in cacao (Theobroma cacao L.); and 6) preliminary results and observations from fungicide trials and cultivar screening in Tennessee. The article also outlines research needed to comprehensively understand VSD and accelerate the development of effective management strategies.

11.
JAMA ; 2024 Aug 08.
Article in English | MEDLINE | ID: mdl-39116093

ABSTRACT

This Viewpoint from the National Center for Health Statistics reports the leading causes of death in the US from 2019 to 2023, including the emergence of COVID-19 and shifts in other top causes as pandemic deaths decreased.

12.
Br J Ophthalmol ; 2024 Aug 07.
Article in English | MEDLINE | ID: mdl-39117359

ABSTRACT

BACKGROUND/AIMS: To design a deep learning (DL) model for the detection of glaucoma progression with a longitudinal series of macular optical coherence tomography angiography (OCTA) images. METHODS: 202 eyes of 134 patients with open-angle glaucoma with ≥4 OCTA visits were followed for an average of 3.5 years. Glaucoma progression was defined as having a statistically significant negative 24-2 visual field (VF) mean deviation (MD) rate. The baseline and final macular OCTA images were aligned according to centre of fovea avascular zone automatically, by checking the highest value of correlation between the two images. A customised convolutional neural network (CNN) was designed for classification. A comparison of the CNN to logistic regression model for whole image vessel density (wiVD) loss on detection of glaucoma progression was performed. The performance of the model was defined based on the confusion matrix of the validation dataset and the area under receiver operating characteristics (AUC). RESULTS: The average (95% CI) baseline VF MD was -3.4 (-4.1 to -2.7) dB. 28 (14%) eyes demonstrated glaucoma progression. The AUC (95% CI) of the DL model for the detection of glaucoma progression was 0.81 (0.59 to 0.93). The sensitivity, specificity and accuracy (95% CI) of DL model were 67% (34% to 78%), 83% (42% to 97%) and 80% (52% to 95%), respectively. The AUC (95% CI) for the detection of glaucoma progression based on the logistic regression model was lower than the DL model (0.69 (0.50 to 0.88)). CONCLUSION: The optimised DL model detected glaucoma progression based on longitudinal macular OCTA images showed good performance. With external validation, it could enhance detection of glaucoma progression. TRIAL REGISTRATION NUMBER: NCT00221897.

14.
J Innov Card Rhythm Manag ; 15(7): 5930-5934, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39011464

ABSTRACT

With the expanding use of cardiac implantable electronic device (CIED) therapy, intravascular device infections are becoming more common. In the case of transvenous implantable cardioverter-defibrillator (ICD) infections requiring extraction for bacterial clearance, there remains no standard method to deliver temporary ICD therapy following device removal. We present a case of persistent bacteremia complicated by monomorphic ventricular tachycardia (VT) electrical storm where biventricular ICD system extraction was performed and a temporary transvenous dual-coil lead with an externalized ICD generator was used to treat VT episodes prior to the re-implantation of a new permanent system. This case demonstrates the utility of a temporary externalized transvenous ICD system in the successful detection and pace-termination of VT, thereby reducing episodes of painful and potentially harmful external defibrillator shocks during the treatment of CIED infection.

15.
Invest Ophthalmol Vis Sci ; 65(8): 18, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38980269

ABSTRACT

Purpose: To compare rates of retinal nerve fiber layer change over time in healthy, eyes with nonprogressing glaucoma and eyes with progressing glaucoma using single wide-field (SWF) and optic nerve head (ONH) cube scan optical coherence tomography (OCT) images. Methods: Forty-five eyes of 25 healthy individuals and 263 eyes of 161 glaucoma patients from the Diagnostic Innovations in Glaucoma Study were included. All eyes underwent 24-2 visual field testing and OCT (Spectralis SD-OCT) ONH and macular imaging. SWF images (up to 43° × 28°) were created by stitching together ONH cube scans centered on the optic disc and macular cube scans centered on the fovea. Visual field progression was defined as guided progression analysis likely progression and/or a significant (P < 0.01) mean deviation slope of less than -1.0 dB/year. Mixed effects models were used to compare rates of change. Highly myopic eyes were included. Results: Thirty glaucomatous eyes were classified as progressing. In eyes with glaucoma, mean global rate of change was -1.22 µm/year (P < 0.001) using SWF images and -0.83 µm/year (P = 0.003) using ONH cube scans. Rate of change was significantly greater in eyes with progressing glaucoma compared with eyes with nonprogressing glaucoma (-1.51 µm/year vs. -1.24 µm/year; P = 0.002) using SWF images and was similar using ONH cube scans (P = 0.27). Conclusions: In this cohort that includes eyes with and without high axial myopia, the mean rate of retinal nerve fiber layer thinning measured using SWF images was faster in eyes with progressing glaucoma than in eyes with nonprogressing glaucoma. Wide-field OCT images including the ONH and macula can be effective for monitoring glaucomatous progression in patients with and without high myopia.


Subject(s)
Disease Progression , Glaucoma , Intraocular Pressure , Nerve Fibers , Optic Disk , Retinal Ganglion Cells , Tomography, Optical Coherence , Visual Fields , Humans , Tomography, Optical Coherence/methods , Female , Male , Visual Fields/physiology , Middle Aged , Retinal Ganglion Cells/pathology , Nerve Fibers/pathology , Optic Disk/pathology , Optic Disk/diagnostic imaging , Intraocular Pressure/physiology , Aged , Glaucoma/diagnosis , Glaucoma/diagnostic imaging , Visual Field Tests , Adult
16.
Eur J Heart Fail ; 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38980212

ABSTRACT

AIMS: Soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF), components of the vascular endothelial growth factor (VEGF) system, play key roles in angiogenesis. Reports of elevated plasma levels of sFlt-1 and PlGF in coronary heart disease and heart failure (HF) led us to investigate their utility, and VEGF system gene single nucleotide polymorphisms (SNPs), as prognostic biomarkers in HF. METHODS AND RESULTS: ELISA assays for sFlt-1, PlGF and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were performed on baseline plasma samples from the PEOPLE cohort (n = 890), a study of outcomes among patients after an episode of acute decompensated HF. Eight SNPs potentially associated with sFlt-1 or PlGF levels were genotyped. sFlt-1 and PlGF were assayed in 201 subjects from the Canterbury Healthy Volunteers Study (CHVS) matched to PEOPLE participants. All-cause death was the major endpoint for clinical outcome considered. In PEOPLE participants, mean plasma levels for both sFlt-1 (125 ± 2.01 pg/ml) and PlGF (17.5 ± 0.21 pg/ml) were higher (both p < 0.044) than in the CHVS cohort (81.2 ± 1.31 pg/ml and 15.5 ± 0.32 pg/ml, respectively). sFlt-1 was higher in HF with reduced ejection fraction compared to HF with preserved ejection fraction (p = 0.005). The PGF gene SNP rs2268616 was univariately associated with death (p = 0.016), and was also associated with PlGF levels, as was rs2268614 genotype. Cox proportional hazards modelling (n = 695, 246 deaths) showed plasma sFlt-1, but not PlGF, predicted survival (hazard ratio 6.44, 95% confidence interval 2.57-16.1; p < 0.001) in PEOPLE, independent of age, NT-proBNP, ischaemic aetiology, diabetic status and beta-blocker therapy. CONCLUSIONS: Plasma sFlt-1 concentrations have potential as an independent predictor of survival and may be complementary to established prognostic biomarkers in HF.

17.
Am J Ophthalmol ; 267: 257-270, 2024 Jul 08.
Article in English | MEDLINE | ID: mdl-38986858

ABSTRACT

PURPOSE: To evaluate the association between rates of juxtapapillary choriocapillaris microvasculature dropout (MvD) change and rates of ganglion cell inner plexiform layer (GCIPL) loss in primary open-angle glaucoma (POAG) and glaucoma suspect eyes with and without myopia. DESIGN: Cohort study from clinical trial data. METHODS: 238 eyes from 155 POAG and glaucoma suspect patients were stratified into no-myopia (axial length (AL) ≤ 24 mm; n = 78 eyes), mild myopia (24 mm < AL ≤ 26 mm; n = 114 eyes), and high myopia (AL > 26 mm; n = 46 eyes). Eyes with a minimum of 3 visits and 1.5 years of follow-up with both optical coherence tomography angiography (OCT-A) and OCT macula scans were included. Presence, area, and angular circumference of juxtapapillary MvD were evaluated on en face choroidal images and horizontal B-scans obtained from OCT-A imaging. RESULTS: Over the mean follow-up of 4.4 years, the mean MvD area rates of change (95% CI) were largest in high and mild myopia group (0.04 [0.03, 0.05] mm2/year in both groups), followed by the no-myopia group (0.03 [0.02, 0.04] mm2/year). The mean MvD angular circumference rates of change (95% CI) were highest in mild myopia group (8.7° [6.9°, 10.5°]/year) followed by the high myopia and no-myopia groups (8.1° [5.3°, 10.9°]/year, and 7.4° [5.3°, 9.6°]/year, respectively). While the mean global GCIPL thinning rates between eyes with MvD at baseline compared to eyes without were similar in all myopia groups, the rates of MvD area change were significantly faster in all myopia groups with baseline MvD (all p ≤ 0.004). Significant faster rates of MvD angular circumference change were found in the mild myopia group with baseline MvD (P < .001) only. In multivariable models, the rates of GCIPL thinning over time were significantly associated with rates of MvD angular circumference change and MvD area change (R2 = 0.33, P < .001 and R2 = 0.32, P = .006, respectively). CONCLUSIONS: Rates of GCIPL thinning were associated with rates of MvD area and angular circumference change over time in myopic POAG eyes. Utilizing OCT-A to detect MvD may provide an additional tool for monitoring macular structural changes in glaucomatous eyes with myopia.

18.
Proc Natl Acad Sci U S A ; 121(29): e2401420121, 2024 Jul 16.
Article in English | MEDLINE | ID: mdl-38995966

ABSTRACT

Cerebral (Aß) plaque and (pTau) tangle deposition are hallmarks of Alzheimer's disease (AD), yet are insufficient to confer complete AD-like neurodegeneration experimentally. Factors acting upstream of Aß/pTau in AD remain unknown, but their identification could enable earlier diagnosis and more effective treatments. T cell abnormalities are emerging AD hallmarks, and CD8 T cells were recently found to mediate neurodegeneration downstream of tangle deposition in hereditary neurodegeneration models. The precise impact of T cells downstream of Aß/pTau, however, appears to vary depending on the animal model. Our prior work suggested that antigen-specific memory CD8 T ("hiT") cells act upstream of Aß/pTau after brain injury. Here, we examine whether hiT cells influence sporadic AD-like pathophysiology upstream of Aß/pTau. Examining neuropathology, gene expression, and behavior in our hiT mouse model we show that CD8 T cells induce plaque and tangle-like deposition, modulate AD-related genes, and ultimately result in progressive neurodegeneration with both gross and fine features of sporadic human AD. T cells required Perforin to initiate this pathophysiology, and IFNγ for most gene expression changes and progression to more widespread neurodegenerative disease. Analogous antigen-specific memory CD8 T cells were significantly elevated in the brains of human AD patients, and their loss from blood corresponded to sporadic AD and related cognitive decline better than plasma pTau-217, a promising AD biomarker candidate. We identify an age-related factor acting upstream of Aß/pTau to initiate AD-like pathophysiology, the mechanisms promoting its pathogenicity, and its relevance to human sporadic AD.


Subject(s)
Alzheimer Disease , CD8-Positive T-Lymphocytes , Disease Models, Animal , Alzheimer Disease/immunology , Alzheimer Disease/pathology , Alzheimer Disease/genetics , Animals , CD8-Positive T-Lymphocytes/immunology , Mice , Humans , Plaque, Amyloid/pathology , Plaque, Amyloid/immunology , Amyloid beta-Peptides/metabolism , Mice, Transgenic , Brain/pathology , Brain/immunology , Male , Interferon-gamma/metabolism , Interferon-gamma/immunology , Aging/immunology , Immunologic Memory , Memory T Cells/immunology , Perforin/metabolism , Perforin/genetics , Female
19.
Ophthalmol Glaucoma ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38959998

ABSTRACT

PURPOSE: To examine social factors associated with the 5-year risk of glaucoma suspects (GS) converting to open-angle glaucoma (OAG). DESIGN: Retrospective cohort analysis. SUBJECTS: We screened for participants diagnosed with GS in the All of Us database. Cases that converted to OAG within 5 years of GS diagnosis (the "conversion group") were compared with control cases that did not convert. METHODS: Demographic, socioeconomic and healthcare utilization data of the cases were extracted and compared between the conversion group and the control group. Multivariable Cox proportional hazards modeling was used to identify potential factors associated with the risk of conversion. MAIN OUTCOME MEASURES: Hazard ratios (HRs) of significant factors associated with the risk of conversion. RESULTS: A total of 5274 GS participants were identified, and 786 (15%) cases converted to OAG within 5-year follow-up. The two groups showed significant differences in age, race, gender, employment status, income/education level, history of intra-ocular surgery, and healthcare utilization patterns. In the multivariable model, African American/Black race (HR [95% confidence interval] =1.70 [1.44-2.00]), older age at GS diagnosis (1.17 [1.09-1.25]), male gender (1.30 [1.13-1.50], no history of recreational drug use (1.23 [1.07-1.42]), history of intra-ocular surgery (1.60 [1.02-1.53]) and having more reasons for delayed healthcare access (2.27 [1.23-4.18]) were associated with a greater hazard of conversion, while being employed (0.71 [0.60-0.86]) was associated with a smaller hazard of conversion (P<0.05 for all). CONCLUSIONS: Several social factors were associated with the conversion from GS to OAG, which may help to identify patients at higher risk of disease progression. Future studies are needed to examine the basis for these findings and the potential interventions that could address them.

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