Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2923 plasma proteins assessed using the Olink Explore 3072 assay®. 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death of 70.1 years. The Spearman correlation between PAC proteomic age and chronological age was 0.77. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC proteomic age deviation were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that biological age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.

Perceptions and utilization of tele-orthodontics: a survey of the members of the American Association of Orthodontists.

OBJECTIVE: This study aimed to investigate orthodontists' utilization and perceptions of tele-orthodontics. MATERIALS AND METHODS: A 30-item online survey was distributed to members of the American Association of Orthodontists (AAO). The questionnaire encompassed topics concerning the orthodontists' utilization, perceptions, clinical applications, limitations, and concerns regarding tele-orthodontics. Descriptive statistics were employed, and comparisons between responses from users and non-users were conducted  using Wilcoxon rank-sum tests and Fisher's exact tests. RESULTS: 152 members completed the survey, (response rate: 2.4%). More than two third of respondents (69.74%) were users of tele-orthodontics. Users were more aligned with the belief that tele-orthodontics facilitates effective communication (mean ± standard deviation (SD) 4.06 ± 0.83 vs. 3.33 ± 0.94, p < 0.001). Both groups agreed on the requirement of patient fees for tele-orthodontic visits (mean ± SD: 3.62 ± 1.11 users vs. 3.74 ± 1.02 non-users, p = 0.659), and on the capability  of the system to reduce unwarranted referrals (p = 0.20). The majority of participants acknowledged  the utility of the system in monitoring aligners' patients (89% in users vs. 61% in non-users, p < 0.001). Non-users expressed greater concerns regarding privacy risks (mean ± SD: 3.06 ± 0.97 users vs. 3.57 ± 0.86 non-users, p = 0.002). Both groups stressed the significance of obtaining informed consent before utilizing tele-orthodontics. CONCLUSIONS: The widespread acceptance of tele-orthodontics among AAO members was apparent, as demonstrated by their recognition of its effectiveness. There was notable variation in how users and non-users perceived tele-orthodontics. The study's results offer valuable insights into both the potential benefits and drawbacks of incorporating this technology into clinical practice from the clincians' perspective.

Polygenic scores for cardiovascular risk factors improve estimation of clinical outcomes in CCB treatment compared to pharmacogenetic variants alone.

Pharmacogenetic variants are associated with clinical outcomes during Calcium Channel Blocker (CCB) treatment, yet whether the effects are modified by genetically predicted clinical risk factors is unknown. We analyzed 32,000 UK Biobank participants treated with dihydropiridine CCBs (mean 5.9 years), including 23 pharmacogenetic variants, and calculated polygenic scores for systolic and diastolic blood pressures, body fat mass, and other patient characteristics. Outcomes included treatment discontinuation and heart failure. Pharmacogenetic variant rs10898815-A (NUMA1) increased discontinuation rates, highest in those with high polygenic scores for fat mass. The RYR3 variant rs877087 T-allele alone modestly increased heart failure risks versus non-carriers (HR:1.13, p = 0.02); in patients with high polygenic scores for fat mass, lean mass, and lipoprotein A, risks were substantially elevated (HR:1.55, p = 4 × 10-5). Incorporating polygenic scores for adiposity and lipoprotein A may improve risk estimates of key clinical outcomes in CCB treatment such as treatment discontinuation and heart failure, compared to pharmacogenetic variants alone.

Retrospective evaluation of the success rate and factors associated with the stability of alveolar ridge orthodontic miniscrews: Pilot study.

BACKGROUND: An uncommon location for placing miniscrews, used to provide anchorage control in various tooth movements, is the alveolar ridge. This study aimed to provide an evaluation of the success rate of alveolar ridge miniscrews and examine variables that might impact their success. METHODS: Charts for 295 patients who had miniscrews were screened. Twenty patients (5 male and 15 female: average age = 38.15 ± 15.10 years) with a total of 50 alveolar ridge miniscrews were analyzed. A customized data form was used to collect patients' and miniscrews' related variables. Kaplan-Meier estimator was used for the survival function, whereas Cox proportional hazards regression models were used to associate collected variables with alveolar ridge miniscrew survival. RESULTS: In total, 31 (62.0%) miniscrews were stable and 19 (38.0%) failed. The survival time for those that failed was 6.03 ± 7.08 months. The follow-up period for those that survived was 35.84 ± 19.47 months. Male gender versus female (hazard ratio [HR] 2.46; 95% confidence interval [CI] 1.35-4.48; P = 0.003), and if the miniscrew was a replacement versus non-replacement (HR 0.27; 95% CI 0.07-0.99; P = 0.048) influenced the survival. Additionally, miniscrews that were used for both indirect and direct or indirect anchorage alone plus those with evidence of splinting showed a 100% survival rate, which led to an HR 0 (P < 0.001). When the previously mentioned variables were modeled, none seemed to have a significant effect on failure except for splinting and type of anchorage (P < 0.001), because none of the splinted miniscrews failed. CONCLUSIONS: The failure rate of alveolar ridge miniscrews was (38.0%) over 6.03 ± 7.08 months. The survival rate was (62.0%) over 35.84 ± 19.47 months. The evidence of splinting and the type of anchorage had a significant effect on survival probability.

Leukocyte telomere length is associated with MRI-thigh fat-free muscle volume: data from 16 356 UK Biobank adults.

BACKGROUND: Telomere attrition may share common biological mechanisms with bone and muscle loss with aging. Here, we investigated the association between these hallmarks of aging using data from UK Biobank, a large observational study. METHODS: Leukocyte telomere length (LTL as T/S ratio) was measured using a multiplex qPCR assay at baseline (2006-2010). Bone mineral density (whole body and regional; via dual-energy X-ray absorptiometry), trabecular bone score (via lumbar-spine dual-energy X-ray absorptiometry images), fat-free muscle volume (thighs; via magnetic resonance imaging), and muscle fat infiltration (thighs; via magnetic resonance imaging) were measured during the imaging visit (2014-2018). Regression models were used to model LTL against a muscle or bone outcome, unadjusted and adjusted for covariates. RESULTS: A total of 16 356 adults (mean age: 62.8 ± 7.5 years, 50.5% women) were included. In the fully adjusted model, thigh fat-free muscle volume was associated with LTL in the overall sample (adjusted standardized ß (aß) = 0.017, 95% CI 0.009 to 0.026, P < 0.001, per SD increase in LTL), with stronger associations in men (aß = 0.022, 95% CI 0.010 to 0.034, P < 0.001) than in women (aß = 0.013, 95% CI 0.000 to 0.025, P = 0.041) (sex-LTL P = 0.028). The adjusted odds ratio (aOR) for low thigh fat-free muscle volume (body mass index-adjusted, sex-specific bottom 20%) was 0.93 per SD increase in LTL (95% CI 0.89 to 0.96, P < 0.001) in the overall sample, with stronger associations in men (aOR = 0.92, 95% CI 0.87 to 0.99, P = 0.008) than women (aOR = 0.93, 95% CI 0.88 to 0.98, P = 0.009), although the sex difference was not statistically significant in this model (sex-LTL P = 0.37). LTL was not associated with bone mineral density, trabecular bone score, or muscle fat infiltration in the overall or subgroup analyses (P > 0.05). CONCLUSIONS: LTL was consistently associated with thigh fat-free muscle volume in men and women. Future research should investigate moderating effects of lifestyle factors (e.g., physical activity, nutrition, or chronic diseases) in the association between LTL and muscle volume.

Proteomic aging clock (PAC) predicts age-related outcomes in middle-aged and older adults.

Beyond mere prognostication, optimal biomarkers of aging provide insights into qualitative and quantitative features of biological aging and might, therefore, offer useful information for the testing and, ultimately, clinical use of gerotherapeutics. We aimed to develop a proteomic aging clock (PAC) for all-cause mortality risk as a proxy of biological age. Data were from the UK Biobank Pharma Proteomics Project, including 53,021 participants aged between 39 and 70 years and 2,923 plasma proteins assessed using the Olink Explore 3072 assay®. The Spearman correlation between PAC proteomic age and chronological age was 0.77. A total of 10.9% of the participants died during a mean follow-up of 13.3 years, with the mean age at death 70.1 years. We developed a proteomic aging clock (PAC) for all-cause mortality risk as a surrogate of BA using a combination of least absolute shrinkage and selection operator (LASSO) penalized Cox regression and Gompertz proportional hazards models. PAC showed robust age-adjusted associations and predictions for all-cause mortality and the onset of various diseases in general and disease-free participants. The proteins associated with PAC were enriched in several processes related to the hallmarks of biological aging. Our results expand previous findings by showing that age acceleration, based on PAC, strongly predicts all-cause mortality and several incident disease outcomes. Particularly, it facilitates the evaluation of risk for multiple conditions in a disease-free population, thereby, contributing to the prevention of initial diseases, which vary among individuals and may subsequently lead to additional comorbidities.

Accelerated aging mediates the associations of unhealthy lifestyles with cardiovascular disease, cancer, and mortality.

BACKGROUND: With two well-validated aging measures capturing mortality and morbidity risk, this study examined whether and to what extent aging mediates the associations of unhealthy lifestyles with adverse health outcomes. METHODS: Data were from 405,944 adults (40-69 years) from UK Biobank (UKB) and 9972 adults (20-84 years) from the US National Health and Nutrition Examination Survey (NHANES). An unhealthy lifestyles score (range: 0-5) was constructed based on five factors (smoking, drinking, physical inactivity, unhealthy body mass index, and unhealthy diet). Two aging measures, Phenotypic Age Acceleration (PhenoAgeAccel) and Biological Age Acceleration (BioAgeAccel) were calculated using nine and seven blood biomarkers, respectively, with a higher value indicating the acceleration of aging. The outcomes included incident cardiovascular disease (CVD), incident cancer, and all-cause mortality in UKB; CVD mortality, cancer mortality, and all-cause mortality in NHANES. A general linear regression model, Cox proportional hazards model, and formal mediation analysis were performed. RESULTS: The unhealthy lifestyles score was positively associated with PhenoAgeAccel (UKB: ß = 0.741; NHANES: ß = 0.874, all p < 0.001). We further confirmed the respective associations of PhenoAgeAccel and unhealthy lifestyles with the outcomes in UKB and NHANES. The mediation proportion of PhenoAgeAccel in associations of unhealthy lifestyles with incident CVD, incident cancer, and all-cause mortality were 20.0%, 17.8%, and 26.6% (all p < 0.001) in UKB, respectively. Similar results were found in NHANES. The findings were robust when using another aging measure-BioAgeAccel. CONCLUSIONS: Accelerated aging partially mediated the associations of lifestyles with CVD, cancer, and mortality in UK and US populations. The findings reveal a novel pathway and the potential of geroprotective programs in mitigating health inequality in late life beyond lifestyle interventions.

Does physical activity moderate the association between shorter leukocyte telomere length and incident coronary heart disease? Data from 54,180 UK Biobank participants.

Telomere shortening is a biological aging hallmark. The effect of short telomere length may be targeted by increased physical activity to reduce the risk of multiple aging-related diseases, including coronary heart disease (CHD). The objective was to assess the moderation effect of accelerometer-based physical activity (aPA) on the association between shorter leukocyte telomere length (LTL) relatively in the population sample and incident CHD. Data were from the UK Biobank participants with well-calibrated accelerometer data for at least 6.5 days (n = 54,180). Relative mean LTL at baseline (5-6 years prior to aPA assessment) was measured in T/S ratio, using a multiplex quantitative polymerase chain reaction (qPCR) technology, by comparing the amount of the telomere amplification product (T) to that of a single-copy gene (S). aPA measures included total number of events (at least 10-s continued physical activity > 32 milligravities [mg]), total volume, mean duration, mean intensity, and peak intensity of all events. LTL, aPA measures, and their interactions were associated with incident CHD (mean follow-up 6.8 years) using Cox proportional hazards models adjusting for covariates. Longer LTL (relative to the sample distribution) was associated with reduced incidence of CHD (adjusted hazard ratio [aHR] = 0.94 per standard deviation [SD] increase in LTL, [95% CI, 0.90 to 0.99], P = .010). Incidence of CHD was reduced by higher total volume of aPA (aHR = 0.82 per SD increase in LTL, [95% CI, 0.71 to 0.95], P = .010) but increased by higher total number of events (aHR = 1.11 per SD increase in LTL, [95% CI, 1.02 to 1.21], P = .020) after controlling for other aPA measures and covariates. However, none of the interactions between LTL and aPA measures was statistically significant (P = .171).

Prevalence of likely retro-odontoid pseudotumor in patients receiving dental CBCT examinations.

OBJECTIVES: We calculated the prevalence of unsuspected retro-odontoid pseudotumor (ROP) as detected in cone beam computed tomography (CBCT) examinations. Additionally, we examined patient age, sex, and presence and severity of cervical osteoarthritis (OA) as potential risk factors for ROP. STUDY DESIGN: We retrospectively analyzed de-identified CBCT scans of 455 patients from the Division of Oral and Maxillofacial Radiology at the University of Connecticut School of Dental Medicine. Identification of likely ROP was completed through a likelihood scoring scale (1-4) due to the lack of magnetic resonance images. Severity of cervical OA was determined using 5 osteoarthritic features. An ordinal logistic regression model was used to link potential risk factors to ROP. RESULTS: In total, 18 patients (3.9%) were classified with probable (11 patients [2.4%]) or definite (7 patients [1.5%]) likely ROP. Older age and the presence and severity of OA were significantly associated with higher ROP scores (P < .001). There was no significant association of ROP likelihood and patient sex (P = .637). An increase of 1 year of age increased the chance of a patient having a higher ROP likelihood score (P < .001). The age-adjusted chance of having a more severe ROP increased with moderate to severe OA (P ≤ .017). CONCLUSIONS: Prevalence of likely ROP increases with age and OA but is not associated with sex. Individuals with moderate or severe OA are more likely to have ROP.

Relationship between baseline plasma p-tau181 and longitudinal changes in cognition and structural brain measures in a cohort of cognitively unimpaired older adults.

INTRODUCTION: Preclinical Alzheimer's disease (AD) affects a significant proportion of cognitively unimpaired (CU) older adults. Currently, blood-based biomarkers detect very early changes in the AD continuum with great accuracy. METHODS: We measured baseline plasma phosphorylated tau (p-tau)181 using electrochemiluminescence (ECL)-based assay (MesoScale Discovery) in 533 CU older adults. Follow-up lasted up to 18 months. Cognitive performance assessment included memory and cognitive control. Structural brain measures included cortical thickness, which includes the AD magnetic resonance imaging (AD MRI) signature, and hippocampal volume. RESULTS: In this cohort of CU older adults, baseline plasma p-tau181 levels were not associated with short-term changes in cognition and structural brain measures. Also, baseline plasma p-tau levels did not influence the effects of behavioral interventions (exercise or mindfulness) on cognitive and structural brain changes. DISCUSSION: The short follow-up and healthy status of this CU cohort might have limited the sensitivity of plasma p-tau181 in detecting changes associated with AD pathology.

Characterizing orthodontic tooth movement in real time using dental monitoring scans: A pilot study.

OBJECTIVES: This pilot study aimed to quantify the magnitude and type of tooth movement occurring in short time intervals within the regular monthly orthodontic visits for patients with fixed appliances and undergoing maxillary canine retraction. Additionally, this pilot study aimed to provide a descriptive evaluation for the accuracy and reliability of the Dental Monitoring (DM)-captured scans to those of an iTero digital scans in an extraction space closure model. SETTINGS AND SAMPLE POPULATION: 3D intraoral photographic scans (DM) for 12 patients with maxillary first premolar extractions in a single-centre academic institution. MATERIALS AND METHODS: Twelve patients treated with fixed appliances and undergoing space closure for maxillary premolar extraction(s) were included. Nickel-titanium (200 g) closing coil springs were used for canine retraction. At initiation of space closure (T1), iTero scans were acquired, and patients were instructed to take DM scans every 4-5 days until their next visit in 4-5 weeks (T2). At T2, a final iTero scan in addition to a DM scan was taken. The number of patients who did the scans regularly as instructed declined as time elapsed. Stereolithography (STL) files generated from the DM scans were superimposed with the STL files from the iTero scans using GOM Inspect software to determine the accuracy of the DM 3D models. To assess rate, type and direction of tooth movement, each of the 3D image STL files generated from the DM scans, taken every 4-5 days by each patient, was superimposed on the previously captured scan. The rate of tooth movement for the maxillary molars and canines was calculated in the 3 planes of space (X, Y, Z) at each time point, until the end of the experiment. RESULTS: Preliminary results indicated that the maxillary canines appeared to be displaced the greatest amount in the first 4-5 days with initial distolateral movement. As time elapsed, the rate of tooth movement decreased, and the tooth started moving distolingually. CONCLUSIONS: Dental monitoring software provides a high-tech platform to monitor tooth movement in a 'real-time' approach. Accuracy of the photographic scans in relationship to the intraoral scans appears promising. There seems to be some evidence that the greatest amount of movement occurs initially in the first few days after activation, dropping thereafter to become a slower constant rate of tooth movement.

A Survey on Cone-beam Computed Tomography Usage Among Endodontists in the United States.

INTRODUCTION: The aim of the study was to investigate the accessibility and frequency of cone-beam computed tomography (CBCT) usage and to assess the economic and logistical factors involved with its usage among active American Association of Endodontists (AAE) members, utilizing a web-based survey. METHODS: A survey of 19 questions was sent to 3,071 AAE members addressing participant access to, along with financial and logistical aspects of CBCT imaging. Descriptive analysis was performed and Fisher exact test utilized to test associations between groups (P < .05). RESULTS: The overall response rate was 14.7% (n = 544). Ninety-five percent of respondents (n = 486) had an in-office CBCT unit, with those graduating after the year 2000 statistically more likely to have one (P < .05). Utilization of CBCT imaging for every case was reported by 40% of providers. Eighty-nine percent reported taking the scan at the consultation visit and 20% included this charge with the consultation fee. For those who charged for the scan separately, 85% charged more than $100. Providers who paid off their unit did so within 1-2 years (41%), 3-4 years (36%), 4-5 years (12%), and 5+ years (11%). Limited field of view was utilized by 95% of respondents. Fifty-eight percent reported interpreting the scans themselves, 38% send only if pathology is expected, and 3% always send their scans to a radiologist. CONCLUSIONS: In conclusion, accessibility and utilization of CBCT imaging among United States endodontists has increased and acquisition of this equipment has not made a long lasting financial burden on providers.

Ridge mini-implants, a versatile biomechanical anchorage device whose success is significantly enhanced by splinting: a clinical report.

OBJECTIVES: This clinical report aims to highlight the factors affecting the clinical success of alveolar ridge mini-implants used for orthodontic anchorage and provide an overview of the biomechanical versatility of this miniscrew and steps involving the proper technique of its placement. METHODS: For this clinical report, charts for 295 patients who had temporary anchorage devices (TADs) were screened. Twenty patients [15 females and 5 males: mean age = 38.15 ± 15.10 years] with 50 alveolar ridge mini-screws were assessed. A descriptive summary of the main factors affecting their clinical success and the technique employed for their placement was comprehensively discussed and illustrated, in addition to the presentation of some clinical cases illustrating their potential clinical uses. RESULTS: The survival duration (7.32 ± 9.01 months) and clinical success of the alveolar ridge mini-implants that failed (19/50) seem to be affected primarily by 2 factors: splinting; none of the splinted mini-implants failed (0/10) compared to (19/40) of the single mini-implants that failed, and the length of the used mini-implant; the average length of the mini-implants that did not fail was 9.23 mm. Additionally, it appears that these mini-implants are biomechanically robust and durable, those that did not fail had an average survival duration of 35.97 ± 19.79 months. CONCLUSION: Ridge mini-implants offer significant biomechanical versatility in patients with partially edentulous ridges needing complex pre-prosthetic orthodontic movements. The presence of splinting and the length of the used mini-implants are factors that might affect the clinical success of the alveolar ridge mini-implants.

Comparison of electronic versus mechanical torque-limiting devices for dental implants: An in vitro study.

PURPOSE: To determine the accuracy of new electronic torque-limiting devices (ET) when compared to new and used conventional-style beam-type (BT) mechanical torque-limiting devices and hand-piece style (HS) mechanical torque-limiting devices. The secondary purpose was to compare any difference in accuracy between new and used mechanical torque-limiting devices, and any difference in accuracy when used on a straight versus an angled screw channel abutment. MATERIALS AND METHODS: A total of five torque-limiting devices were used to obtain 2000 readings under standardized conditions. An implant analog was fastened into a digital torque meter, to which an abutment was connected. Pre-determined torque values of 15 Ncm and 35 Ncm were applied, and actual torque values were recorded. A straight and an angled abutment were used to record 1000 readings each using the five torque-limiting devices. An overall Kruskal-Wallis test was applied to compare the median deviation among devices followed by a pairwise comparison ( = 0.05). RESULTS: For a target torque value of 15 Ncm on a straight abutment, the electronic device (ET) was statistically more accurate than the beam type (BT) new (p < 0.001) and used (p < 0.048) devices but less accurate than the hand-piece style (HS) used device (p < 0.001). On an angled abutment for a target value of 15 Ncm, the electronic device (ET) was statistically more accurate than hand-piece style (HS) new and used devices (p < 0.001). For a target torque value of 35 Ncm on a straight abutment, the ET was statistically more accurate than the HS new device (p < 0.001) but less accurate than the BT new device (p < 0.001). On an angled abutment for a target value of 35 Ncm, the electronic device (ET) was statistically less accurate than the beam-type (BT) new device (p < 0.001), the beam-type (BT) used device (p = 0.001), and the hand-piece style (HS) used device (p < 0.001). The electronic device (ET) was the only device accurate within the ISO standard of accuracy of 6% for each of the target torque value/abutment design combinations. There was no statistically significant difference related to the type of abutment used (angled vs. straight). CONCLUSIONS: Electronic torque limiting devices (ET) are an acceptable method for delivering torque for implant restorations for straight and angled abutments at 15 Ncm and 35 Ncm torque values. Conventional style beam-type (BT) mechanical torque-limiting devices are a simple, predictable, validated, and inexpensive tool for delivering accurate torque at 15 Ncm and 35 Ncm torque values. The hand-piece style (HS) mechanical torque-limiting devices are predictable to deliver 15 Ncm torque values.

Assessment of clear aligner accuracy of 2 clear aligners systems.

INTRODUCTION: This study compared treatment efficacy for specific tooth movements between 2 clear aligner systems (Clarity [3M Oral Care Solutions, St Paul, Minn] and Invisalign [Align Technology, San Jose, Calif]). METHODS: The study sample included 47 patients (7 males, 40 females; mean age, 36.57 ± 15.97 years) treated with Invisalign and 37 (4 males, 33 females; mean age, 34.30 ± 16.35 years) treated with Clarity aligners who completed their first set of aligners and had an initial refinement scan. Initial and predicted models were obtained from the initial simulated treatment plan. The first model of the refinement scan was labeled as achieved. SlicerCMF software (version 3.1; http://www.slicer.org) was used to superimpose the achieved and predicted digital models over the initial ones with regional superimposition on the relatively stable first molars. Nine hundred forty teeth in the Invisalign system were measured for horizontal, vertical, and angular movements and transverse width and compared with similar measurements of 740 teeth for the Clarity aligners. The deviation from the predicted was calculated and compared between both systems. RESULTS: The deviation achieved from the predicted was significant between the groups for the mandibular interpremolar and intercanine widths (P <0.05). Clarity aligners significantly undercorrected rotations compared with Invisalign for the mandibular first premolars, mandibular canines, maxillary canines, and maxillary central incisors. There was no statistically significant difference between the groups for the achieved vs predicted movements in the horizontal and vertical planes (P >0.05). CONCLUSIONS: The efficacy of clear aligner therapy systems (Clarity and Invisalign) in treating mild and moderate malocclusions was comparable. Deviation of the achieved movements from the predicted was greatest for rotational and vertical movements.

Association between Residential Exposure to Air Pollution and Incident Coronary Heart Disease Is Not Mediated by Leukocyte Telomere Length: A UK Biobank Study.

Higher air pollution exposure and shorter leukocyte telomere length (LTL) are both associated with increased risk of coronary heart disease (CHD), and share plausible mechanisms, including inflammation. LTL may serve as a biomarker of air pollution exposure and may be intervened with to reduce the risk of CHD. To the best of our knowledge, we are the first to test the mediation effect of LTL in the relationship between air pollution exposure and incident CHD. Using the UK Biobank (UKB) data (n = 317,601), we conducted a prospective study linking residential air pollution exposure (PM2.5, PM10, NO2, NOx) and LTL to incident CHD during a mean follow-up of 12.6 years. Cox proportional hazards models and generalized additive models with penalized spline functions were used to model the associations of pollutant concentrations and LTL with incident CHD. We found non-linear associations of air pollution exposure with LTL and CHD. Pollutant concentrations in the lower range were decreasingly associated with longer LTL and reduced risk of CHD. The associations between lower pollutant concentrations and reduced risk of CHD, however, were minimally mediated by LTL (<3%). Our findings suggest that air pollution influences CHD through pathways that do not involve LTL. Replication is needed with improved measurements of air pollution that more accurately assesses personal exposure.

Rhinologist Use of Antibiotics With Nasal Packing for Epistaxis.

BACKGROUND: There is limited evidence supporting the usage of prophylactic antibiotics in the setting of nasal packing for epistaxis. It is unclear what current antiobiotic usage patterns are by otolaryngologists. OBJECTIVES: Characterize the antibiotic prescribing practices employed by otolaryngologists in the management of epistaxis patients treated with packing as well as the underlying rationale. Explore the impact of experience, geography, and academic affiliation on treatment decisions. METHODS: An anonymous survey of antibiotic prescribing patterns for patients with epistaxis requiring nasal packing was distributed to all physician members of the American Rhinologic Society. Responses to each question were descriptively summarized including 95% confidence intervals and were linked to demographics using Fisher's exact tests. RESULTS: One thousand one hundred and thirteen surveys were distributed with 307 responses (27.6%). Antibiotic prescription rates varied based on packing type, with 20.0% prescribing antibiotics for dissolvable packing compared to 84.2% to 84.6% for nondissolvable packing. The absorbance of nondissolvable packing does not impact the decision to prescribe antibiotics (P > .999). Precisely 69.7% (95% CI: 64.0%-74.8%) stop antibiotics immediately following packing removal. Precisely 85.6% (95% CI: 81.6%-89.9%) cite the risk of toxic shock syndrome (TSS) when prescribing antibiotics. Notable regional differences include greater utilization of amoxicillin-clavulanate in the Midwest (67.6%) and Northeast (61.4%) as compared with the South (42.1%) and West (45.1%) (P = .013). Further, years in practice were positively associated with several patterns including prescribing antibiotics for patients with dissolvable packing (P = .008), citing prevention of sinusitis as a rationale for antibiotic use (P < .001), and a higher likelihood of having treated a patient with TSS (P = .002). CONCLUSIONS: Antibiotic use in patients with epistaxis controlled with nondissolvable packing is common. Treatment patterns are influenced by geography, years in practice, and practice type. LEVEL OF EVIDENCE: 4.

Mid-life leukocyte telomere length and dementia risk: An observational and mendelian randomization study of 435,046 UK Biobank participants.

Telomere attrition is one of biological aging hallmarks and may be intervened to target multiple aging-related diseases, including Alzheimer's disease and Alzheimer's disease related dementias (AD/ADRD). The objective of this study was to assess associations of leukocyte telomere length (TL) with AD/ADRD and early markers of AD/ADRD, including cognitive performance and brain magnetic resonance imaging (MRI) phenotypes. Data from European-ancestry participants in the UK Biobank (n = 435,046) were used to evaluate whether mid-life leukocyte TL is associated with incident AD/ADRD over a mean follow-up of 12.2 years. In a subsample without AD/ADRD and with brain imaging data (n = 43,390), we associated TL with brain MRI phenotypes related to AD or vascular dementia pathology. Longer TL was associated with a lower risk of incident AD/ADRD (adjusted Hazard Ratio [aHR] per SD = 0.93, 95% CI 0.90-0.96, p = 3.37 × 10-7 ). Longer TL also was associated with better cognitive performance in specific cognitive domains, larger hippocampus volume, lower total volume of white matter hyperintensities, and higher fractional anisotropy and lower mean diffusivity in the fornix. In conclusion, longer TL is inversely associated with AD/ADRD, cognitive impairment, and brain structural lesions toward the development of AD/ADRD. However, the relationships between genetically determined TL and the outcomes above were not statistically significant based on the results from Mendelian randomization analysis results. Our findings add to the literature of prioritizing risk for AD/ADRD. The causality needs to be ascertained in mechanistic studies.

Effects of Panax notoginseng Water Extract on Immune Responses and Digestive Enzymes in White Shrimp Litopenaeus vannamei.

Panax notoginseng (Burk) F. H. Chen is a traditional Chinese herbal medicine commonly used in clinical applications. This study examined the effects of the Panax notoginseng water extract (PNWE) on the immune responses and digestive enzyme activity of Litopenaeus vannamei (L. vannamei). The PNWE (50, 100, and 200 µg (g shrimp)-1) was injected into L. vannamei to analyze the immune response parameters, including the total haemocyte count (THC), granular haemocytes (GC), semi-granular haemocytes (SGC), hialin haemocyte (HC), the respiratory burst (RB), the phagocytic ratio (PR), the phagocytic index (PI), and phenoloxidase (PO). We evaluated the activity of the intestinal digestive enzymes (trypsin, chymotrypsin, amylase, and lipase), the histopathology, and the intestine Vibrio numbers. The results showed that different concentrations of the PNWE significantly increased THC, GC, SGC, PO and RB activity, the PR, and the PI of L. vannamei while reducing the HC. In addition, the PNWE also significantly increased the chymotrypsin, trypsin, and amylase activity of L. vannamei. Furthermore, 50 µg (g shrimp)-1 of PNWE regulated the lipase activity. Additionally, different concentrations of the PNWE significantly reduced the Vibrio numbers in the intestine without damaging the hepatopancreas and intestine tissues. These results indicate that the PNWE improves the immune responses of L. vannamei by increasing the haemocyte count and regulating intestinal digestive enzymes.