Menopause-Associated Changes in Mandibular Bone Microarchitecture Are Site-Specific.

BACKGROUND: There are conflicting reports on the effects of decreased estrogen levels on mandibular bone microarchitecture. Whether these effects are consistent throughout the mandible is unclear and may have important implications for treatment planning. PURPOSE: The goal of this study was to evaluate trabecular and cortical bone microstructure in the mandibular condyle and the mandibular basal bone and compare these sites between premenopausal and postmenopausal women. STUDY DESIGN, SETTING, SAMPLE: Participants were recruited for a cross-sectional cohort study at Columbia University Irving Medical Center. Each participant had cone-beam computed tomography taken of their mandibular condyles and the basal bone. Exclusion criteria for the population included a) current chemotherapy or immunotherapy; b) history of bisphosphonate or other osteoporosis therapy; and c) currently pregnant, nursing, or on hormonal birth control. INDEPENDENT VARIABLE: The predictor variables are menopausal status (before or after menopause) and mandibular region of interest (condyle/basal bone). MAIN OUTCOME VARIABLE: Parameters of interest included the following indicators of bone quality: trabecular bone volume fraction, trabecular thickness, trabecular number, trabecular separation, cortical bone volume fraction, cortical thickness, and cortical porosity. COVARIATES: Covariates included demographic variables such as age, estrogen levels, and ethnicity. ANALYSES: Quantitative microstructure analyses were conducted on cone-beam computed tomography images, and differences between groups for continuous measures (including age) were assessed with an unpaired t-test, and demographic variables were assessed by χ2. Statistical significance was recorded at P < .05. RESULTS: The premenopausal and postmenopausal groups each had 31 participants, with the following average age: premenopausal = 43.9 ± 6.9 versus postmenopausal = 57.5 ± 7.6 years old; P < .001, and estrogen levels: premenopausal = 91.77 ± 80.13 pg/ml versus postmenopausal = 41.44 ± 61.62 pg/ml; P < .01). Postmenopausal women had significantly greater condylar trabecular separation (0.61 ± 0.18 vs 0.47 ± 0.11 mm; P < .001) and lower trabecular number (1.03 ± 0.18 vs 1.21 ± 0.19 mm-1; P < .001) compared to premenopausal women. There were no significant differences in the basal bone microarchitectural parameters between the menopausal groups. CONCLUSION AND RELEVANCE: Menopause is associated with mandibular condylar trabecular bone loss but has minimal effects on the mandibular basal bone. This may have important ramifications for treatment planning in advanced-age individuals.

Postmenopausal women with HIV have increased tooth loss.

BACKGROUND: With effective antiretroviral therapy, people with HIV (PWH) are living longer and aging; the majority of PWH in the United States are now over the age of 50 and in women have gone through the menopause transition. Menopause potentiates skeletal bone loss at the spine, hip, and radius in PWH. The alveolar bone which surronds the teeth is different than long bones because it is derived from the neural crest. However, few studies have assessed the oral health and alveolar bone in middle aged and older women with HIV. Therefore, the objective of this study was to evaluate periodontal disease and alveolar bone microarchitecture in postmenopausal women with HIV. METHODS: 135 self-reported postmenopausal women were recruited (59 HIV-, 76 HIV + on combination antiretroviral therapy with virological suppression) from a single academic center. The following parameters were measured: cytokine levels (IFN-γ, TNF-α, IL-1ß, IL-2, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12p70, IL-13, IL-17 A, OPG, and RANKL) in gingival crevicular fluid, bleeding on probing, probing depth, clinical attachment loss, number of teeth present, alveolar crestal height, and alveolar bone microarchitecture. RESULTS: The mean age of participants was 57.04+/-6.25 years and a greater proportion of women with HIV were black/African American (HIV + 68.42%, HIV- 23.73%; p < 0.001). There was no significant difference in bleeding on probing (p = 0.17) and attachment loss (p = 0.39) between women who were HIV infected vs. HIV uninfected. Women with HIV had significantly higher RANKL expression in Gingival Crevicular Fluid (HIV + 3.80+/-3.19 pg/ul, HIV- 1.29+/-2.14 pg/ul ; p < 0.001), fewer teeth present (HIV + 17.75+/-7.62, HIV- 22.79+/-5.70; p < 0.001), ), lower trabecular number (HIV + 0.08+/-0.01, HIV- 0.09+/-0.02; p = 0.004) and greater trabecular separation (HIV + 9.23+/-3.11, HIV- 7.99+/-3.23; p = 0.04) compared to women without HIV that remained significant in multivariate logistic regression analysis in a sub-cohort after adjusting for age, race/ethnicity, smoking status, and diabetes. CONCLUSION: Postmenopausal women with HIV have deterioration of the alveolar trabecular bone microarchitecture that may contribute to greater tooth loss.

Evaluation of the mandibular condylar bone microarchitecture in people living with HIV.

OBJECTIVES: People living with HIV (PLWH) have been shown to have lower bone density at the spine, hip, and radius. However, whether a similar bone phenotype is seen in craniofacial bones is not known. The goal of this study was to evaluate the bone microarchitecture of the mandibular condyle in PLWH. METHODS: We recruited 212 participants, which included 88 HIV-negative participants and 124 PLWH on combination antiretroviral therapy with virological suppression from a single academic center. Each participant filled out a validated temporomandibular disorder (TMD) pain screening questionnaire and had cone beam computed tomography (CBCT) of their mandibular condyles. Qualitative radiographic evidence of temporomandibular joint disorders-osteoarthritis (TMJD-OA) assessment and quantitative microarchitecture analysis of their mandibular condylar bones were conducted. RESULTS: There was no statistically significant difference in either self-reported TMD or in radiographic evidence of TMJD-OA in PLWH compared with HIV-negative controls. Linear regression analysis revealed that positive HIV status remained significantly associated with increased trabecular thickness, decreased cortical porosity, and increased cortical bone volume fraction after adjusting for race, diabetes, sex, and age. CONCLUSION: PLWH have increased mandibular condylar trabecular bone thickness and cortical bone volume fraction compared with HIV-negative controls.

Challenges and opportunities of telehealth digital equity to manage HIV and comorbidities for older persons living with HIV in New York State.

BACKGROUND: Older persons living with HIV (PLWH) need routine healthcare to manage HIV and other comorbidities. This mixed methods study investigated digital equity, constituted as access, use and quality, of HIV and specialty telehealth services for PLWH > 50 years during the initial wave of the COVID-19 pandemic when services transitioned to remote care. METHODS: A survey of closed and open-ended questions was administered to 80 English (N = 63) and Spanish (N = 17) speaking PLWH receiving HIV care at an Academic Medical Center (N = 50) or a Federally Qualified Health Center (N = 30) in New York State. Quantitative analyses examined characteristics predicting telehealth use and visit quality. Qualitative analyses utilized thematic coding to reveal common experiences. Results were integrated to deepen the interpretation. RESULTS: Telehealth access and use were shaped by multiple related and unstable factors including devices and connectivity, technology literacy, and comfort including privacy concerns. Participants demonstrated their substantial effort to achieve the visit. The majority of patients with a telehealth visit perceived it as worse than an in-person visit by describing it as less interpersonal, and resulting in poorer outcomes, particularly participants with less formal education. Technology was not only a barrier to access, but also influenced perceptions of quality. CONCLUSIONS: In the COVID-19 pandemic initial wave, barriers to using telehealth were unequally distributed to those with more significant access and use challenges. Beyond these barriers, examining the components of equity indicate further challenges replicating in-person care using telehealth formats for older PLWH. Work remains to establish telehealth as both equitable and desirable for this population.

Development and performance of a point-of-care rapid antigen test for detection of SARS-COV-2 variants.

Background: SARS-CoV-2 antigen-based tests are well-calibrated to infectiousness and have a critical role to play in the COVID-19 public health response. We report the development and performance of a unique lateral flow immunoassay (LFA). Methods: Combinations of several monoclonal antibodies targeting multiple antigenic sites on the SARS-CoV-2 nucleocapsid protein (NP) were isolated, evaluated, and chosen for the development of a LFA termed CoV-SCAN (BioMedomics, Inc.). Clinical point-of-care studies in symptomatic and asymptomatic individuals were conducted to evaluate positive predictive agreement (PPA) and negative predictive agreement (NPA) with RT-PCR as comparator. Results: In laboratory testing, CoV-SCAN detected 14 recombinant N-proteins of SARS-CoV-2 variants with sensitivity in the range of 0.2-3.2 ng/mL, and 10 authentic SARS-CoV-2 variants with sensitivity in the range of 1.6-12.5 TCID50/swab. No cross reactivity was observed with other human coronaviruses or other respiratory pathogens. In clinical point-of-care testing on 148 individuals over age 2 with symptoms of ≤5 days, PPA was 87.2% (CI 95: 78.3-94.8%) and NPA was 100% (CI 95: 94.2-100%). In another 884 asymptomatic individuals, PPA was 85.7% (CI 95: 42.1-99.6%) and 99.7% (99.0-99.9%). Overall, CoV-SCAN detected over 97.2% of specimens with CT values <30 and 93.8% of nasal swab specimens with the Omicron variant, even within the first 2 days after symptom onset. Conclusions: The unique construction of CoV-SCAN using two pairs of monoclonal antibodies has resulted in a test with high performance that remains durable across multiple variants in both laboratory and clinical evaluations. CoV-SCAN should identify almost all individuals harboring infectious SARS-CoV-2. Summary: Unique construction of a point-of-care rapid antigen test using two pairs of monoclonal antibodies has led to good performance that remained durable across multiple variants in laboratory and clinical evaluations. Test should identify almost all individuals harboring infectious SARS-CoV-2.

Prolonged severe acute respiratory syndrome coronavirus 2 persistence, attenuated immunologic response, and viral evolution in a solid organ transplant patient.

Unlike immunocompetent hosts, the duration of viral persistence after infection with severe acute respiratory syndrome coronavirus 2 can be prolonged in immunosuppressed patients. Here, we present a case of viral persistence for over 19 weeks in a patient with a history of solid organ transplant and explore the clinical, virologic, and immunologic course. Our patient still demonstrated viral persistence at 138 days with low polymerase chain reaction cycle threshold values and evidence of continuing viral sequence evolution indicative of ongoing virus replication. These findings have important implications for infection prevention and control recommendations in immunosuppressed patients. Immune response, including neutralizing antibody titers, T cell activity, and cytokine levels, peaked around days 44-72 after diagnosis. Anti-S trimer antibodies were low at all time points, and T cell response was attenuated by day 119. As immune response waned and viral load increased, increased genetic diversity emerged, suggesting a mechanism for the development of viral variants.

SARS-CoV-2 RNA Shedding in Semen and Oligozoospermia of Patient with Severe Coronavirus Disease 11 Weeks after Infection.

We report severe acute respiratory syndrome coronavirus 2 in semen by using quantitative reverse transcription PCR during the late convalescent phase. Virus was associated with adequate humoral and cell-mediated responses, suggesting possible seeding of the immune-privileged testes. We provide longitudinal semen quality data for 6 other men, including 3 who had oligozoospermia.

Anxiety, depression, insomnia, and trauma-related symptoms following COVID-19 infection at long-term follow-up.

A developing finding from the novel coronavirus 2019 (COVID-19) pandemic is the burden of neuropsychiatric symptoms seen in COVID-19 survivors. While studies have shown clinically significant rates of depression, anxiety, insomnia, and trauma-related symptoms such as post-traumatic stress disorder (PTSD) after COVID-19, little is known about how these symptoms evolve over time. Here, we report findings from a cohort study of 52 participants recruited from the greater New York City area following acute COVID-19 infection. Participants completed the Patient Health Questionnaire-9 (PHQ-9) for depressive symptoms, the Generalized Anxiety Disorder-7 (GAD-7) for anxiety-related symptoms, the Insomnia Severity Scale (ISS) for sleep-related symptoms, and the PTSD Checklist-Civilian version (PCL-C) for trauma-related symptoms both at baseline and at long-term (24-60 weeks post-infection) follow-up. We found a high degree of correlation between psychiatric symptom scales within participants. More participants met established cutoffs for clinically significant insomnia and post-traumatic stress at follow-up compared to baseline. Symptom scales for depression, insomnia, and PTSD were increased at long-term follow-up, with only increased PCL-C scores surviving correction for multiple comparisons (Z â€‹= â€‹2.92, W â€‹= â€‹434, p â€‹= â€‹0.004). Our results present evidence from a small cohort that neuropsychiatric symptoms, particularly those related to PTSD, may worsen over time in COVID-19 survivors. Future studies should continue to investigate these questions in broader populations, while additionally exploring the potential biological and sociological mechanisms that may contribute to neuropsychiatric pathology after COVID-19 infection.

Epigenetic Aging Biomarkers Associated With Cognitive Impairment in Older African American Adults With Human Immunodeficiency Virus (HIV).

BACKGROUND: Accelerated epigenetic aging using DNA methylation (DNAm)-based biomarkers has been reported in people with human immunodeficiency virus (HIV, PWH), but limited data are available among African Americans (AA), women, and older PWH. METHODS: DNAm was measured using Illumina EPIC Arrays for 107 (69 PWH and 38 HIV-seronegative controls) AA adults ≥60 years in New York City. Six DNAm-based biomarkers of aging were estimated: (1) epigenetic age acceleration (EAA), (2) extrinsic epigenetic age acceleration (EEAA), (3) intrinsic epigenetic age acceleration (IEAA), (4) GrimAge, (5) PhenoAge, and (6) DNAm-estimated telomere length (DNAm-TL). The National Institutes of Health (NIH) Toolbox Cognition Battery (domains: executive function, attention, working memory, processing speed, and language) and Montreal Cognitive Assessment (MoCA) were administered. Participants were assessed for frailty by the Fried criteria. RESULTS: The PWH and control groups did not differ by sex, chronological age, or ethnicity. In total, 83% of PWH had a viral load <50 copies/mL, and 94% had a recent CD4 ≥200 cells/µL. The PWH group had a higher EAA, EEAA, GrimAge, and PhenoAge, and a lower DNAm-TL compared to the controls. IEAA was not different between groups. For PWH, there were significant negative correlations between IEAA and executive function, attention, and working memory and PhenoAge and attention. No associations between biomarkers and frailty were detected. CONCLUSIONS: Evidence of epigenetic age acceleration was observed in AA older PWH using DNAm-based biomarkers of aging. There was no evidence of age acceleration independent of cell type National Institutes of Health composition (IEAA) associated with HIV, but this measure was associated with decreased cognitive function among PWH.

Epigenetic Age in Young African American Adults With Perinatally Acquired HIV.

BACKGROUND: Prior studies have measured accelerated aging in people with HIV using a DNA methylation (DNAm)-based biomarker of aging, "epigenetic age," but data are limited in African American (AA) young adults with perinatally acquired HIV infection (PHIV). METHODS: We performed a cross-sectional study of AA young adults aged 20-35 years with PHIV (N = 31) and seronegative controls (N = 30) using DNAm measured in whole blood and cognitive function measured by the NIH Toolbox. Illumina EPIC array was used to measure DNAm age and accelerated aging markers including epigenetic age acceleration (EAA), as well as extrinsic (EEAA) and intrinsic (IEAA) EAA. RESULTS: PHIV and controls did not differ by sex (45 vs. 43% male), chronological age (26.2 vs. 28.0 years), or ethnicity. Chronological age and DNAm age were correlated (r = 0.56, P < 0.01). PHIV had a higher mean EAA (2.86 ± 6.5 vs. -2.96 ± 3.9, P < 0.01) and EEAA (4.57 ± 13.0 vs. -4.72 ± 6.0, P < 0.01) than controls; however, IEAA was not different between groups. Among PHIV, EAA and EEAA were higher in those with HIV viral load ≥50 copies/mL than <50 copies/mL (EEA: 8.1 ± 5.2 vs. 0.11 ± 5.5, P = 0 < 0.01 and EEAA: 16.1 ± 10.6 vs. -1.83 ± 9.7, P < 0.01). We observed negative correlations (r = -0.36 to -0.31) between EEAA and executive function, attention, and language scores. CONCLUSIONS: In conclusion, EAA in blood was observed in AA young adults with PHIV on ART using 2 measures, including EEAA which upweights the contribution of immunosenescent cell types. However, there was no evidence of age acceleration with a measure independent of cell type composition.