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Journal of Neurovirology Jun 2024Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with...
Although previous studies have suggested that subtype B HIV-1 proviruses in the brain are associated with physiological changes and immune activation accompanied with microgliosis and astrogliosis, and indicated that both HIV-1 subtype variation and geographical location might influence the neuropathogenicity of HIV-1 in the brain. The natural course of neuropathogenesis of the most widespread subtype C HIV-1 has not been adequately investigated, especially for people living with HIV (PLWH) in sub-Saharan Africa. To characterize the natural neuropathology of subtype C HIV-1, postmortem frontal lobe and basal ganglia tissues were collected from nine ART-naïve individuals who died of late-stage AIDS with subtype C HIV-1 infection, and eight uninfected deceased individuals as controls. Histological staining was performed on all brain tissues to assess brain pathologies. Immunohistochemistry (IHC) against CD4, p24, Iba-1, GFAP, and CD8 in all brain tissues was conducted to evaluate potential viral production and immune activation. Histological results showed mild perivascular cuffs of lymphocytes only in a minority of the infected individuals. Viral capsid p24 protein was only detected in circulating immune cells of one infected individual, suggesting a lack of productive HIV-1 infection of the brain even at the late-stage of AIDS. Notably, similar levels of Iba-1 or GFAP between HIV + and HIV- brain tissues indicated a lack of microgliosis and astrogliosis, respectively. Similar levels of CD8 + cytotoxic T lymphocyte (CTL) infiltration between HIV + and HIV- brain tissues indicated CTL were not likely to be involved within subtype C HIV-1 infected participants of this cohort. Results from this subtype C HIV-1 study suggest that there is a lack of productive infection and limited neuropathogenesis by subtype C HIV-1 even at late-stage disease, which is in contrast to what was reported for subtype B HIV-1 by other investigators.
PubMed: 38943022
DOI: 10.1007/s13365-024-01219-6 -
Journal of General Internal Medicine Jun 2024Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs)....
BACKGROUND
Diabetes self-management education and support can be effectively and efficiently delivered in primary care in the form of shared medical appointments (SMAs). Comparative effectiveness of SMA delivery features such as topic choice, multi-disciplinary care teams, and peer mentor involvement is not known.
OBJECTIVE
To compare effects of standardized and patient-driven models of diabetes SMAs on patient-level diabetes outcomes.
DESIGN
Pragmatic cluster randomized trial.
PARTICIPANTS
A total of 1060 adults with type 2 diabetes in 22 primary care practices.
INTERVENTIONS
Practice personnel delivered the 6-session Targeted Training in Illness Management (TTIM) curriculum using either standardized (set content delivered by a health educator) or patient-driven SMAs (patient-selected topic order delivered by health educators, behavioral health providers [BHPs], and peer mentors).
MAIN MEASURES
Outcomes included self-reported diabetes distress and diabetes self-care behaviors from baseline and follow-up surveys (assessed at 1st and final SMA session), and HbA1c, BMI, and blood pressure from electronic health records. Analyses used descriptive statistics, linear regression, and linear mixed models.
KEY RESULTS
Both standardized and patient-driven SMAs effectively improved diabetes distress, self-care behaviors, BMI (- 0.29 on average), and HbA1c (- 0.45% (mmol/mol) on average, 8.3 to 7.8%). Controlling for covariates, there was a small, significant effect of condition on overall diabetes distress in favor of standardized SMAs (F(1,841) = 4.3, p = .04), attributable to significant effects of condition on emotion and regimen distress subscales. There was a small, significant effect of condition on diastolic blood pressure in favor of standardized SMAs (F(1,5199) = 4.50, p = .03). There were no other differences between conditions.
CONCLUSIONS
Both SMA models using the TTIM curriculum yielded significant improvement in diabetes distress, self-care, and HbA1c. Patient-driven diabetes SMAs involving BHPs and peer mentors and topic selection did not lead to better clinical or patient-reported outcomes than standardized diabetes SMAs facilitated by a health educator following a set topic order.
NIH TRIAL REGISTRY NUMBER
NCT03590041.
PubMed: 38943014
DOI: 10.1007/s11606-024-08868-7 -
Journal of General Internal Medicine Jun 2024Personal characteristics may be associated with believing misinformation and not believing in best practices to protect oneself from COVID-19.
BACKGROUND
Personal characteristics may be associated with believing misinformation and not believing in best practices to protect oneself from COVID-19.
OBJECTIVE
To examine the associations of a person's age, race/ethnicity, education, residence, health literacy, medical mistrust level, and sources of health-related information with their COVID-19 health and conspiracy myth beliefs.
DESIGN
We surveyed adults with hypertension in Maryland and Pennsylvania between August 2020 and March 2021. Incorrect responses were summed for eight health (mean = 0.68; range 0-5) and two conspiracy (mean = 0.92; range 0-2) COVID-19 questions. Higher scores indicated more incorrect responses. Statistical analyses included two-sample t-tests, Spearman's correlation, and log binomial regression.
PARTICIPANTS
In total, 561 primary care patients (mean age = 62.3 years, 60.2% female, 46.0% Black, 10.2% Hispanic, 28.2% with a Bachelor's degree or higher, 42.8% with annual household income less than $60,000) with a diagnosis of hypertension and at least one of five commonly associated conditions.
MAIN MEASURES
Sociodemographic characteristics, health literacy, medical mistrust level, source of health-related information, and COVID-19 conspiracy and health myth beliefs.
KEY RESULTS
In multivariable analyses, participants who did not get information from medical professional sources (prevalence ratio (PR) = 1.28; 95% CI = 1.06-1.55), had less than a bachelor's degree (PR = 1.49; 95% CI = 1.12-1.99), were less confident filling out medical forms (PR = 1.24; 95% CI = 1.02-1.50), and had higher medical mistrust (PR = 1.34; 95% CI = 1.05-1.69) were more likely to believe any health myths. Participants who had less than a bachelor's degree (PR = 1.22; 95% CI = 1.02-1.45), were less confident filling out medical forms (PR = 1.21; 95% CI = 1.09-1.34), and had higher medical mistrust (PR = 1.72; 95% CI = 1.43-2.06) were more likely to believe any conspiracy myths.
CONCLUSIONS
Lower educational attainment and health literacy, greater medical mistrust, and certain sources of health information are associated with misinformed COVID-19 beliefs. Programs addressing misinformation should focus on groups affected by these social determinants of health by encouraging reliance on scientific sources.
PubMed: 38943013
DOI: 10.1007/s11606-024-08867-8 -
Nature Medicine Jun 2024Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma...
Supplementation with CBM588, a bifidogenic live bacterial product, has been associated with improved clinical outcomes in persons with metastatic renal cell carcinoma (mRCC) receiving nivolumab and ipilimumab. However, its effect on those receiving tyrosine kinase inhibitor-based combinations is unknown. In this open-label, randomized, investigator-initiated, phase 1 study, 30 participants with locally advanced or mRCC with histological confirmation of clear cell, papillary or sarcomatoid component were randomized in a 2:1 fashion to receive cabozantinib (an inhibitor of vascular endothelial growth factor receptor, MET and AXL) and nivolumab (anti-programmed cell death protein 1) with or without CBM588 as first-line treatment. Metagenomic sequencing was performed on stool samples to characterize their gut microbiome at baseline and 13 weeks into treatment. The primary endpoint was a change in the relative abundance of Bifidobacterium spp.; secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and toxicity profile. The primary endpoint of the study was not met and the addition of CBM588 to cabozantinib and nivolumab did not result in a difference in the relative abundance of Bifidobacterium spp. or alpha diversity (as measured by the Shannon index). However, ORR was significantly higher in participants treated with CBM588 compared to those in the control arm (14 of 19, 74% versus 2 of 10, 20%; P = 0.01). PFS at 6 months was 84% (16 of 19) and 60% (6 of 10) in the experimental and control arms, respectively. No significant difference in toxicity profile was seen between the study arms. Our results provide a preliminary signal of improved clinical activity with CBM588 in treatment-naive participants with mRCC receiving cabozantinib and nivolumab. Further investigation is needed to confirm these findings and better characterize the underlying mechanism driving this effect.ClinicalTrials.gov identifier: NCT05122546.
PubMed: 38942995
DOI: 10.1038/s41591-024-03086-4 -
Nature Aging Jun 2024Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we...
Investigating the genetic underpinnings of human aging is essential for unraveling the etiology of and developing actionable therapies for chronic diseases. Here, we characterize the genetic architecture of the biological age gap (BAG; the difference between machine learning-predicted age and chronological age) across nine human organ systems in 377,028 participants of European ancestry from the UK Biobank. The BAGs were computed using cross-validated support vector machines, incorporating imaging, physical traits and physiological measures. We identify 393 genomic loci-BAG pairs (P < 5 × 10) linked to the brain, eye, cardiovascular, hepatic, immune, metabolic, musculoskeletal, pulmonary and renal systems. Genetic variants associated with the nine BAGs are predominantly specific to the respective organ system (organ specificity) while exerting pleiotropic links with other organ systems (interorgan cross-talk). We find that genetic correlation between the nine BAGs mirrors their phenotypic correlation. Further, a multiorgan causal network established from two-sample Mendelian randomization and latent causal variance models revealed potential causality between chronic diseases (for example, Alzheimer's disease and diabetes), modifiable lifestyle factors (for example, sleep duration and body weight) and multiple BAGs. Our results illustrate the potential for improving human organ health via a multiorgan network, including lifestyle interventions and drug repurposing strategies.
PubMed: 38942983
DOI: 10.1038/s43587-024-00662-8 -
International Journal of Behavioral... Jun 2024Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but...
BACKGROUND
Adolescents account for 15% of new HIV cases in Kenya. HIV pre-exposure prophylaxis (PrEP) and post-exposure prophylaxis (PEP) are highly effective prevention tools, but uptake is low among adolescents, particularly in resource-limited settings. We assessed awareness and acceptability of PrEP and PEP among Kenyan adolescents.
METHOD
Focus group discussions were conducted with 120 adolescent boys and girls ages 15 to 19 in Kisumu. Data were analyzed using the Framework Approach.
RESULTS
Adolescent participants often had not heard of or could not differentiate between PrEP and PEP. They also confused these HIV prevention tools with emergency contraceptives. Taking a daily pill to prevent HIV was perceived as analogous to taking a pill to treat HIV. Boys were aware of and willing to consider using PrEP and PEP due to their dislike for using condoms. Adolescents identified insufficient information, cost, and uncomfortableness speaking with healthcare workers about their HIV prevention needs due to sexuality stigma as barriers to using PrEP and PEP.
CONCLUSION
Low awareness and poor understanding of PrEP and PEP among adolescents reveal the need for increased education and sensitization about these HIV prevention options. Expanding access to sexual and reproductive health services that are tailored to the needs of adolescents and staffed with non-judgmental providers could help reduce sexuality stigma as a barrier to accessing care. New HIV prevention approaches such as long-acting injectables or implants, on-demand regimens, and multipurpose prevention technologies may encourage increased uptake of PrEP and PEP by adolescents.
PubMed: 38942977
DOI: 10.1007/s12529-024-10290-6 -
Clinical Oral Investigations Jun 2024Increasing evidence indicates that the thickness of periodontal soft tissues plays an important role in various clinical scenarios, thus pointing to the need of further...
OBJECTIVES
Increasing evidence indicates that the thickness of periodontal soft tissues plays an important role in various clinical scenarios, thus pointing to the need of further clinical research in this area. Aim of the present study was to assess gingival thickness at the mandibular incisors by translucency judgement with two different probes and to validate if these methods are comparable and applicable as diagnostic tools.
MATERIALS AND METHODS
A total of 200 participants were included; gingival tissue thickness was measured by judging probe translucency at both central mandibular incisors, mid-facially on the buccal aspect of each tooth using a standard periodontal probe and a set of color-coded probe, each with a different color at the tip, i.e. Colorvue Biotype Probe (CBP). Frequencies and relative frequencies were calculated for probe visibility. Agreement between the standard periodontal probe and the CBP was evaluated via the kappa statistic.
RESULTS
When the periodontal probe was visible, the frequency of CBP being visible was very high. Kappa statistic for the agreement between the standard periodontal probe and the CBP was 0.198 (71.5% agreement; p-value < 0.001) for tooth 41 and 0.311 (74.0% agreement; p-value < 0.001) for tooth 31, indicating a positive association of the two methods.
CONCLUSIONS
An agreement that reached 74% was estimated between the standard periodontal probe and the color-coded probe at central mandibular incisors. CLINICAL RELEVANCE: In the context of the present study, the two methods of evaluating gingival thickness seem to produce comparable measurements with a substantial agreement. However, in the 1/4 of the cases, the visibility of the color-coded probe could not assist in the categorization of the gingival phenotype.
Topics: Humans; Incisor; Cross-Sectional Studies; Female; Gingiva; Male; Mandible; Adult; Middle Aged
PubMed: 38942966
DOI: 10.1007/s00784-024-05672-9 -
Evidence-based Dentistry Jun 2024The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora...
DESIGN
The study was designed as a single-blinded, parallel, randomized controlled trial to compare the effectiveness of the Salvadora persica toothbrush (MTB), Salvadora persica chewing stick (MCS), and a standard toothbrush (STB) in controlling plaque and gingivitis. A total of 78 participants were randomly divided into three groups and instructed to use their assigned oral hygiene tool in a standardized manner for three.
CASE SELECTION
Participants were non-dental students and staff of Universiti Kebangsaan Malaysia, Kuala Lumpur Campus, selected through convenience sampling. They met specific inclusion criteria, such as being systemically healthy, having ≥20 teeth, and having a Basic Periodontal Examination score of 0, 1, or 2, with no periodontal pockets greater than 5.5 mm.
DATA ANALYSIS
Clinical outcomes were measured using the Plaque Index (PI) and Periodontal Inflamed Surface Area (PISA) at baseline, one-, and three-weeks post-intervention. Data analysis was performed using mixed-model analysis of variance for continuous variables and Fisher's exact test for categorical variables.
RESULTS
All three groups showed significant improvements in plaque levels and severity of gingivitis from baseline to three weeks post-intervention. The MCS group demonstrated a significant improvement in mean PISA values of the anterior teeth compared to the MTB and STB groups. However, there was no significant difference in plaque level reduction or overall gingivitis severity among the three groups. This indicates that when used correctly, Salvadora persica toothbrushes and chewing sticks are as effective as standard toothbrushes in plaque control and gingival health.
CONCLUSIONS
The study concludes that both Salvadora persica toothbrushes and chewing sticks can serve as effective alternatives to the standard toothbrush for plaque control and gingival health. This showcases the beneficial anti-plaque and anti-gingivitis properties of Salvadora persica. However, the effectiveness of these oral hygiene tools is contingent upon the correct usage techniques.
PubMed: 38942941
DOI: 10.1038/s41432-024-01030-6 -
Scientific Reports Jun 2024Tourism carbon offsetting is a crucial pathway to achieving peak carbon and carbon neutrality in the tourism industry. Accurately grasping the collaborative evolutionary...
Tourism carbon offsetting is a crucial pathway to achieving peak carbon and carbon neutrality in the tourism industry. Accurately grasping the collaborative evolutionary mechanisms among local governments, tourism enterprises, and tourists is key to promoting the implementation of tourism carbon offsetting. By constructing an evolutionary game model involving local governments, tourism enterprises, and tourists in carbon offsetting, this study uses MATLAB to simulate the evolutionary stable strategies under various conditions. Additionally, it dynamically simulates the collaborative strategies of the three parties under the influence of local government incentive and constraint mechanisms. The results indicate that under strong governmental constraint mechanisms, there is a promotion of active participation in carbon offsetting by local governments, tourism enterprises, and tourists. Incentive policies at certain levels also play a positive guiding role. As incentives increase, local subsidies and intervention costs also rise, leading to an evolution towards less enthusiastic participation among the three parties. Appropriately balanced government incentives and penalties are beneficial in achieving an equilibrium of benefits among multiple stakeholders involved in carbon offsetting, thus helping to attain carbon neutrality goals.
PubMed: 38942938
DOI: 10.1038/s41598-024-65964-8 -
Pharmaceutical Medicine Jun 2024To optimize cost effectiveness, engagement, reach, inclusivity, insight quality and quantity, and participant satisfaction of pharmaceutical meetings such as advisory...
BACKGROUND
To optimize cost effectiveness, engagement, reach, inclusivity, insight quality and quantity, and participant satisfaction of pharmaceutical meetings such as advisory boards, the organizers have to carefully weigh the pros and cons of the available meeting formats (in-person, synchronous virtual, asynchronous, hybrid). While budgets and organizer preferences are typically key considerations, participants' preferences are rarely factored into this decision. Hence, the objectives of this study were to gain a better understanding of participants' preferences for meeting format, frequency, and updates.
METHODS
Between September 1, 2022, and December 31, 2023, health care providers (HCPs) participating in asynchronous advisory board touchpoints on a proprietary virtual platform were asked to answer between 1-4 survey questions, selected at the pharmaceutical organizers' discretion.
RESULTS
A total of 443 HCPs answered the survey. Among respondents, 76.0% preferred meetings with a virtual component. Overall, the most popular meeting approach was a combination of synchronous and asynchronous virtual meetings over time (34.6%). The preference for hybrid meetings increased from 14.3 to 27.3% between 2022 and 2023. The preferred meeting frequency was 2-3 times a year (39.2%), followed by quarterly (33.2%). According to the respondents, the most important benefits of virtual over in-person meetings include: (i) superior convenience and flexibility (81.0%), (ii) avoidance of time off work and away from patients (62.3%), (iii) the low environmental impact and carbon footprint (32.5%).
CONCLUSIONS
Although these findings are preliminary and from a small dataset, they highlight the importance of customizing each pharmaceutical meeting or program with the target audience in mind.
PubMed: 38942923
DOI: 10.1007/s40290-024-00531-0