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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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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: β = 0.741; NHANES: β = 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: This retrospective two‐centre study aimed to evaluate the occlusal outcomes in patients undergoing orthognathic surgery with clear aligners. Methods: A retrospective chart review and occlusal outcomes for 15 patients (10 females and five males) with different types of dentofacial deformities in the anteroposterior, vertical and transverse dimensions, who underwent orthognathic surgery in conjunction with clear aligners were evaluated. Weighed Peer Assessment Rating (PAR) index scores of the pre‐treatment and post‐treatment digital models were used to assess initial complexity, final occlusal outcomes and degree of improvement with surgery and clear aligners. Results: The mean post‐treatment PAR score was 3.5 ± 2.54, which was a statistically significant improvement from the pre‐treatment PAR score of 27.63 ± 12.09, an 87% improvement was achieved. All subcategories of the PAR index showed statistically significant improvement except for midline assessment component. Conclusions: Occlusal outcomes with aligners showed great improvement as indicated with the PAR index scores. Orthognathic surgical cases can be treated efficiently with aligners and future studies should compare occlusal outcomes between orthognathic surgical patients treated with clear aligners and those treated with fixed appliances. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

In order to implement successful and widespread administration of PVP-I prophylactic measures in clinical settings, patients must be willing to undergo the treatment. Our study surveys patients regarding their subjective experience and ability to tolerate the nasal and/or oral application of PVP-I. METHODS Ethical considerations This study was approved by the University's Institutional Review Board. Keywords: bacteriology; dental; endoscopy; epidemiology; infectious conditions; public health EN bacteriology dental endoscopy epidemiology infectious conditions public health 696 699 4 06/14/23 20230701 NES 230701 Key Points 0.5% povidone-iodine dilution is well tolerated within the nasal cavity for single use prior to in-office procedures. DISCUSSION PVP-I has proven in vitro antiseptic properties against a variety of bacterial and viral pathogens, including SARS-CoV-2 with in vivo studies ongoing. [Extracted from the article]

Objective: The objectives of the study were to evaluate the survival rates for lower lingual retainers (LLRs) and to establish a correlation between patients' treatment‐related factors (age, sex, malocclusion, appliance used for treatment, teeth bonded, retention protocols) to the survival of LLRs. Materials and Methods: A total of 765 subjects [474 females and 291 males: mean age = 24.29 ± 10.67 years] between 2013 and 2022 were included. A customized data collection form was utilized to gather the data from the electronic health record (EHR) of subjects. Patient‐related factors, crowding or spacing, deep bite or open bite and duration of treatment were extracted from patients' files. Kaplan–Meier estimator was used for the survival function, whereas Cox proportional hazards regression models were used to associate risk factors with retainer survival. Results: 328 (42.9%) subjects had their LLRs failed, and the survival period was on average 17.37 ± 22.85 months. On the other hand, the follow‐up period for the retainers that did not fail was on average 47.19 ± 23.66 months. 192 (28.3%) subjects had segment failure (retainer detached from 3 teeth or less), while 51 (7.5%) subjects had failures in more than 3 teeth (complete). None of the evaluated clinical variables were significantly associated with LLRs failure except for the bite category (P =.013) and the appliance used for treatment (P <.001). Conclusion: Success rate for LLRs was 57.1% over 47.19 months, failure rate was 42.9% over 17.37 months. The presence of deep bite and treatment with aligners were significantly associated with increased failure rate. [ABSTRACT FROM AUTHOR]

Aims: Pharmacogenetic variants impact dihydropyridine calcium‐channel blockers (dCCBs; e.g., amlodipine) treatment efficacy, yet evidence on clinical outcomes in routine primary care is limited. Reported associations in pharmacogenomics knowledge base PharmGKB have weak supporting evidence. We aimed to estimate associations between reported pharmacogenetic variants and incident adverse events in a community‐based cohort prescribed dCCB. Methods: We analysed up to 32 360 UK Biobank participants prescribed dCCB in primary care (from UK general practices, 1990–2017). We investigated 23 genetic variants. Outcomes were incident diagnosis of coronary heart disease, heart failure (HF), chronic kidney disease, oedema and switching antihypertensive medication. Results: Participants were aged 40–79 years at first dCCB prescription. Carriers of rs877087 T allele in RYR3 had increased risk of hazard ratio (HF 1.13: 95% confidence interval 1.02 to 1.25, P =.02). Although nonsignificant after multiple testing correction, the association is consistent with prior evidence. We estimated that if rs877087 T allele could experience the same treatment effect as noncarriers, the incidence of HF in patients prescribed dCCB would reduce by 9.2% (95% confidence interval 3.1 to 15.4). In patients with a history of heart disease prior to dCCB (n = 2296), rs877087 homozygotes had increased risk of new coronary heart disease or HF compared to CC variant. rs10898815 in NUMA1 and rs776746 in CYP3A5 increased likelihood of switching to an alternative antihypertensive. The remaining variants were not strongly or consistently associated with studied outcomes. Conclusion: Patients with common genetic variants in NUMA1, CYP3A5 and RYR3 had increased adverse clinical outcomes. Work is needed to establish whether outcomes of dCCB prescribing could be improved by prior knowledge of pharmacogenetics variants supported by clinical evidence of association with adverse events. [ABSTRACT FROM AUTHOR]

The complex relationship between life course traumas and cardiovascular disease (CVD) and the underpinning pathways are poorly understood. We aimed to (1) examine the associations of three separate assessments including childhood, adulthood (after 16 years of age), and lifetime traumas (childhood or adulthood) with CVD; (2) examine the associations between diverse life course traumatic profiles and CVD; and (3) examine the extent to which PhenoAge, a well‐developed phenotypic aging measure, mediated these associations. Using data from 104,939 participants from the UK Biobank, we demonstrate that subgroups of childhood, adulthood, and lifetime traumas were associated with CVD. Furthermore, life course traumatic profiles were significantly associated with CVD. For instance, compared with the subgroup experiencing nonsevere traumas across life course, those who experienced nonsevere childhood and severe adulthood traumas, severe childhood and nonsevere adulthood traumas, or severe traumas across life course had significantly higher odds of CVD (odds ratios: 1.07–1.33). Formal mediation analyses suggested that phenotypic aging partially mediated the above associations. These findings suggest a potential pathway from life course traumas to CVD through phenotypic aging, and underscore the importance of policy programs targeting traumas over the life course in ameliorating inequalities in cardiovascular health. [ABSTRACT FROM AUTHOR]

Objective: To estimate the effect of rs4149056 (SLCO1B1*5) genotype (decreases statin transport) on cholesterol control and treatment duration in male and female primary care patients prescribed common statin medications. Methods and Analysis: This study comprised 69 185 European‐ancestry UK Biobank cohort participants prescribed simvastatin or atorvastatin (aged 40‐79 years at first prescription, treatment duration 1 month to 29 years, mean 5.7 years). Principal outcomes were clinically high total cholesterol (>5 mmol/L) at baseline, plus treatment discontinuation. Results: A total of 48.4% of 591 females homozygous for SLCO1B1*5 decreased function genotype had raised cholesterol vs 41.7% of those with functioning SLCO1B1 (odds ratio 1.31, 95% confidence interval [CI] 1.1‐1.55, P =.001). Fewer males had high cholesterol and the genotype effect was attenuated. In primary care prescribing, females homozygous for SLCO1B1*5 were more likely to stop receiving these statins (29.5%) than women with normal SLCO1B1 (25.7%) (hazard ratio [HR] 1.19, 95% CI 1.03‐1.37, P =.01), amounting to five discontinuations per 100 statin‐years in the SLCO1B1*5 group vs four in the normal SLCO1B1 function group. This remained significant after the first year of treatment (HR for discontinuing >1 year after first prescription 1.3, 95% CI 1.08‐1.56, P =.006). In men SLCO1B1*5 was only associated with treatment discontinuation in the first year. Conclusions: In this large community sample of patients on commonly prescribed statins, the SLCO1B1*5 decreased function variant had much larger effects on cholesterol control and treatment duration in women than in men. Efforts to improve the effectiveness of statin therapy in women may need to include SLCO1B1*5 genotype‐guided statin selection. [ABSTRACT FROM AUTHOR]

Objectives: Quantify the effects of cochlear implants (CI) on tinnitus suppression in patients with previous cochlear implantation using a novel audiologic sequence: Tinnitus Interval Limited Tracking (TILT).Study Design: Prospective cohort study.Methods: Consecutive patients with tinnitus and previous cochlear implantation for profound hearing loss underwent an audiologic testing sequence called TILT. Patients rated tinnitus severity using the validated Tinnitus Handicap Inventory (THI) as well as a visual analog scale at baseline and in a variety of audiologic scenarios. Changes in tinnitus severity between scenarios allow for the isolation of the effects of masking and electrical stimulation on the reduction of tinnitus.Results: Twenty patients were enrolled, 10 of whom have tinnitus with average THI 30.2 (standard deviation 22.6). Patients had an acute decrease in tinnitus severity when their CIs were turned on, even in the absence of noise in a soundproof booth. This effect reversed once the CIs were turned off. This effect was greater in magnitude than with masking that occurred with the presentation of soft speech. Acute tinnitus severity trended toward improvement with increased level of presented speech. Degree of improvement was not correlated with THI.Conclusion: Acute tinnitus suppression in patients using CIs is multifactorial. Masking plays a role; however, it cannot sufficiently account for the totality of symptom improvement experienced by CI patients. Quantifiable tinnitus suppression observed when a CI is turned on, even in the absence of audiologic stimulation, suggests that electrical stimulation is involved in the mechanism of symptom improvement in these patients.Level Of Evidence: 4 Laryngoscope, 130: 2047-2052, 2020. [ABSTRACT FROM AUTHOR]

Purpose: To assess if there are any differences in maxillary dentogingival exposure between different facial expressions (maximum smile with eyes open and eyes closed), age groups and both sexes. Material and Methods: Digital photographs of the lower third of the face of 120 subjects, belonging to 6 different age groups were taken. There were 20 subjects in each of the 6 age groups (20‐30, 30‐40, 40‐50, 50‐60, 60‐70, and 70‐80) which were comprised of 80 women and 40 men. Two standardized images of each subject were taken, one of maximum smile with eyes open, and the second of maximum smile with eyes closed. These 240 images were used to quantify a dentogingival exposure ratio (DER) for each tooth spanning the second bicuspids on either side, using standardized measurement techniques. Additionally, incidence of interdental papilla visibility was studied in a binary manner, and all data were studied with respect to various covariables of age, sex and type of facial expression using a generalized linear mixed effects model. A p‐value < 0.05 was determined to be statistically significant. Results: There was a statistically significant difference between the dentogingival exposure ratio (DER) for all images with eyes open and eyes closed per tooth location studied, across all age groups (p ≤ 0.001) and both sexes, suggesting that subject images of smiles with eyes closed had significantly higher dentogingival exposure. There was a decreasing trend of DER with increasing age groups when eyes were open (p = 0.005) and when eyes were closed (p = 0.042), suggesting that older subjects had lower dentogingival exposure. With respect to sex, there was no statistically significant difference in mean DER between males and females, when eyes were open (p = 0.430) and closed (p = 0.351). The incidence of interdental papilla exposure also differed significantly between images with eyes open and eyes closed across all age groups (p ≤ 0.001). However, the incidence of interdental papilla exposure decreased with age, only in images with eyes open (p < 0.001) but was not statistically significant among images with eyes closed (p = 0.127). With respect to sex, there was a significant difference in incidence of interdental papilla exposure in images with eyes open (p = 0.029) but no significant difference when eyes were closed (p = 0.782). Conclusions: Maxillary dentogingival exposure decreases with increasing age and is significantly higher when recording maximum smile with eyes closed, for all age groups and both sexes. As this is a simple and clinically reproducible facial expression, incorporating patient's maximum smiling images with eyes closed may be routinely necessary for complete and accurate data collection for prosthodontic treatment planning purposes. [ABSTRACT FROM AUTHOR]

Biological age measures outperform chronological age in predicting various aging outcomes, yet little is known regarding genetic predisposition. We performed genome‐wide association scans of two age‐adjusted biological age measures (PhenoAgeAcceleration and BioAgeAcceleration), estimated from clinical biochemistry markers (Levine et al., 2018; Levine, 2013) in European‐descent participants from UK Biobank. The strongest signals were found in the APOE gene, tagged by the two major protein‐coding SNPs, PhenoAgeAccel—rs429358 (APOE e4 determinant) (p = 1.50 × 10−72); BioAgeAccel—rs7412 (APOE e2 determinant) (p = 3.16 × 10−60). Interestingly, we observed inverse APOE e2 and e4 associations and unique pathway enrichments when comparing the two biological age measures. Genes associated with BioAgeAccel were enriched in lipid related pathways, while genes associated with PhenoAgeAccel showed enrichment for immune system, cell function, and carbohydrate homeostasis pathways, suggesting the two measures capture different aging domains. Our study reaffirms that aging patterns are heterogeneous across individuals, and the manner in which a person ages may be partly attributed to genetic predisposition. [ABSTRACT FROM AUTHOR]

Traumatic operative injury of the optic nerve in an endoscopic sinus surgery may cause immediate or delayed blindness. It should be cautioned when operating in a sphenoethmoidal cell, or known as Onodi cell, with contact or bulge of the optic canal. It remains unclear how frequent progression to visual loss occurs and how long it progresses to visual loss because of a diseased sphenoethmoidal cell. Research to discuss these questions is expected to help decision making to treat diseased sphenoethmoidal cells. From July 2001 to June 2017, 216 patients received conservative endoscopic sinus surgery without opening a diseased sphenoethmoidal cell. We used their computed tomography images of paranasal sinuses to identify diseased sphenoethmoidal cells that could be associated with progression to visual loss. Among the 216 patients, 52.3% had at least one sphenoethmoidal cell, and 14.8% developed at least one diseased sphenoethmoidal cell. One patient developed acute visual loss 4412 days after the first computed tomography. Our results show that over half of the patients have a sphenoethmoidal cell but suggest a rare incidence of a diseased sphenoethmoidal cell progressing to visual loss during the follow-up period. [ABSTRACT FROM AUTHOR]

Cornstarch has been the primary treatment for glycogen storage disease type Ia (GSD Ia) for over 35 years. When cornstarch was first described as a treatment, few people survived beyond early childhood. As the prognosis for this population has improved, the need to ensure appropriate cornstarch dosing for different age groups has become imperative. Records from 115 patients (10‐62 years of age) with GSD Ia evaluated at our center between 2015 and 2017 were reviewed. Data collected included weight, age, genetic mutation, amount and frequency of cornstarch doses, body mass index, gender, 24‐hour glucose and lactate concentrations, and biochemical markers of metabolic control. The data demonstrate that adult treatment needs vary greatly from younger age groups, and the required cornstarch support decreases with age (P <.001). The required number of doses, however, did not change with a mean of six doses (range 4‐8) daily in all age groups. General laboratory findings across time demonstrate that significantly reducing the amount of starch required to maintain euglycemia with aging can be done without sacrificing metabolic control. Carbohydrate requirements decrease with aging, and older patients were found to require less cornstarch. Failure to lower the cornstarch doses contributes to over‐treatment in adults with GSD Ia. Not only does this lead to worsening hepatomegaly and excessive weight gain, but over‐treatment contributes to relative hyperinsulinism and rebound hypoglycemia. This knowledge is essential in designing nutritional therapies for the aging GSD population. [ABSTRACT FROM AUTHOR]

Purpose: To examine if an uncorrected radiographically detected immediate postoperative misfit (implant level or abutment level) in immediately loaded conversion prosthesis plays a significant role in early implant or prosthesis failure. In addition, clinical characteristics related to type of arch, implant position, type of implant, implant orientation, type of connection, and type of surgery were analyzed relative to their relationship to early implant or prosthesis failure. Materials and Methods: Immediate postoperative and subsequent follow‐up panoramic radiographs of 425 arches with immediately loaded complete‐arch fixed implant‐supported prostheses were screened in a retrospective analysis. Implants with misfit and nonmisfit within a given arch were summarized separately with respect to each clinical characteristic and the difference between misfit and nonmisfit groups was tested using a mixed‐effects logistic regression model with a patient‐specific random intercept. A p‐value <0.05 was determined to be statistically significant. Results: A total of 2025 implants from 311 patients were identified in the 425 arches that were screened for radiographic misfit. A total of 48 implants with misfit were found within 33 arches (23 patients) for a 2.4% prevalence rate. Among the misfit implants, two failures were documented during the healing phase for an early implant survival rate of 95.8%. Five conversion prostheses with misfit fractured during the healing phase for early prosthesis survival rate of 84.8%. None of the clinical variables analyzed were significantly associated with the misfit status (p < 0.05). Conclusions: The results from this retrospective study showed that misfit in immediately loaded complete‐arch fixed implant‐supported prostheses may not play a detrimental role in the implant survival but may affect survival of the conversion prostheses. [ABSTRACT FROM AUTHOR]

Objectives To evaluate national trends in opioid prescribing patterns by otolaryngologists for postoperative pain control after common otolaryngologic procedures. Study Design Cross-sectional; survey. Subjects and Methods A survey to determine opioid prescribing patterns for the treatment of postoperative pain following common otolaryngologic procedures was distributed to all members of the American Academy of Otolaryngology-Head and Neck Surgery. Results The most common pain medication prescribed for adults postoperatively was hydrocodone-acetaminophen (73%), followed by oxycodone-acetaminophen (39%). The most common pain medication prescribed postoperatively for children was acetaminophen (67%), followed by nonsteroidal anti-inflammatory drugs (65%). Overall, there was a wide variation in quantity of opioids prescribed for each surgery, ranging from 0 to more than 60 doses. Mean opioid prescriptions were greatest for tonsillectomy (37 tablets) and least for direct laryngoscopy (5.3 tablets). Conclusion This study identifies nationwide variations in opioid prescribing patterns among otolaryngologists. While otolaryngology is a relatively small specialty, we still have an obligation to work with all physicians to help combat the current opioid epidemic. By evaluating nationwide postoperative pain regimens, we are moving closer toward understanding how to reduce the opioid burden. [ABSTRACT FROM AUTHOR]

Abstract: Purpose: To study the subjective differences in direct lip support assessments and to determine if dentists and laypeople are able to discern and correctly identify direct changes in lip support between flange and flangeless dentures. Materials and Methods: A random sample of 20 maxillary edentulous patients described in part 2 of the study was used for analysis. A total of 60 judges comprising 15 general dentists, 15 prosthodontists, and 30 laypeople, the majority of who were distinct from part 2 of the study, were recruited. All images used in this study were cropped at the infraorbital level and converted to black and white tone, to encourage the judges to focus on lip support. The judges were un‐blinded to the study objectives and told what to look for, and were asked to rate the lip support of each of the 80 images on a 100 mm visual analog scale (VAS). The judges then took a discriminatory sensory analysis test (triangle test) where they were required to correctly identify the image with a flangeless denture out of a set of 3 images. Both the VAS and triangle test ratings were conducted twice in a random order, and mean ratings were used for all analyses. Results: The overall VAS ratings of lip support for images with flangeless dentures were slightly lower compared to images with labial flanges, and this difference was statistically significant (p < 0.0001). This was true for both profile and frontal images. However, the magnitude of these differences was too small (no greater than 5 mm on a 100‐mm scale) to be clinically significant or meaningful. The differences in VAS ratings were not significant between the judges. For the triangle test, judges overall correctly identified the flangeless denture image in 55% of frontal image sets and 60% of profile image sets. The difference in correct identification rate between frontal and profile images was statistically significant (p < 0.0001). For frontal and profile images, prosthodontists had the highest correct identification rate (61% and 69%), followed by general dentists (53% and 68%) and by laypeople (53% and 50%). The difference in correct identification rate was statistically significant between various judges (p = 0.012). For all judges, the likelihood of correctly identifying images with flangeless dentures was significantly greater than 1/3, which was the minimum chance for correct identification (p < 0.0001). Conclusions: Removal of a labial flange in a maxillary denture resulted in slightly lower ratings of lip support compared to images with a labial flange, but the differences were clinically insignificant. When judges were forced to look for differences, flangeless dentures were detected more often in profile images. Prosthodontists detected the flangeless dentures more often than general dentists and laypeople. [ABSTRACT FROM AUTHOR]

Objectives/hypothesis: To review the literature on neck recurrence in esthesioneuroblastoma.Study Design: PubMed database.Methods: A PubMed database search was performed using keywords "esthesioneuroblastoma," "olfactory neuroblastoma," and "esthesioneuroblastoma neck metastasis." Articles written in English with greater than 10 subjects that had data regarding the association of neck recurrence and mortality and/or the association of neck recurrence with Kadish stage were included for analysis.Results: Thirteen studies met inclusion criteria with information regarding the association of neck recurrence and mortality, and 15 studies had data associating neck recurrence and Kadish stage. The neck recurrence rate was 14.1% in studies analyzing mortality. Among those patients who developed regional metastases, mortality was 60%. Of patients without regional recurrence, the mortality rate from disease was 26% (P < 0.0001) and overall mortality was 32% (P < 0.0001). The rate of neck recurrence within each Kadish stage was 0%, 11%, 21%, and 18% for Kadish stages A, B, C, and D, respectively. The trend toward an increased incidence of neck recurrence from stage A to stage D is statistically significant, with P value 0.003.Conclusion: The rate of neck recurrence in esthesioneuroblastoma is close to 15%. There is a strong association of recurrence with Kadish stage B and C. Mortality from disease in patients with recurrence in cervical lymph nodes is significant when compared to those who never develop neck disease. Prospective studies are needed to evaluate a potential role for elective neck dissection versus elective neck radiation for patients with esthesioneuroblastoma.Level Of Evidence: N/A. Laryngoscope, 126:1373-1379, 2016. [ABSTRACT FROM AUTHOR]

Our current understanding regarding the contribution of donor cells in growth factor and cell based tissue regeneration strategies is limited. The present study attempts to utilize fluorescent protein reporter mice [Col3.6Topaz (enhanced yellow fluorescent protein, EYFP) as host and Col3.6Cyan (enhanced cyan fluorescent protein, ECFP) as donor] to determine donor cell contribution in bone regeneration using a bilateral calvarial defect model. Thermogelling chitosan hydrogels (Chi-AHP) were used as bone marrow stromal cell (BMSC) delivery vehicle in the presence and absence of recombinant human bone morphogenetic protein-2 (rhBMP-2). Co-delivery of rhBMP-2 and donor BMSCs led to a significant increase in bone formation indicating the potential of using the combination approach for improved regeneration. On a cellular level, presence of rhBMP-2 resulted in an increased host cell derived osteoblast infiltration at 8 weeks. However, the new mineralized tissue presented two distinct morphological features based on its cellular origin. Regenerated tissue associated with ECFP positive donor cells showed a woven bone-like structure with diffuse alizarin complexone (AC) label and minimal tartrate resistant acid phosphatase (TRAP) activity, indicating the presence of immature early osteoblast cells depositing mineralized tissue without progressing to a mature lamellar bone. Host derived bone showed sharp mineralization line (AC), strong alkaline phosphatase (ALP) and TRAP activity, indicating the presence of actively mineralizing and remodeling, mature lamellar bone matrix. The study demonstrated the remarkable potential of transgenic reporters to improve our understanding of donor cell contribution during bone formation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 928-941, 2016. [ABSTRACT FROM AUTHOR]

Lower urinary tract dysfunction (LUTD) increases with aging. Ensuing symptoms including incontinence greatly impact quality of life, isolation, depression, and nursing home admission. The aging bladder is hypothesized to be central to this decline, however, it remains difficult to pinpoint a singular strong driver of aging‐related bladder dysfunction. Many molecular and cellular changes occur with aging, contributing to decreased resilience to internal and external stressors, affecting urinary control and exacerbating LUTD. In this study, we examined whether cellular senescence, a cell fate involved in the etiology of most aging diseases, contributes to LUTD. We found that umbrella cells (UCs), luminal barrier uroepithelial cells in the bladder, show senescence features over the mouse lifespan. These polyploid UCs exhibit high cyclin D1 staining, previously reported to mediate tetraploidy‐induced senescence in vitro. These senescent UCs were not eliminated by the senolytic combination of Dasatinib and Quercetin. We also tested the effect of a high‐fat diet (HFD) and senescent cell transplantation on bladder function and showed that both models induce cystometric changes similar to natural aging in mice, with no effect of senolytics on HFD‐induced changes. These findings illustrate the heterogeneity of cellular senescence in varied tissues, while also providing potential insights into the origin of urothelial cancer. We conclude that senescence of bladder uroepithelial cells plays a role in normal physiology, namely in their role as barrier cells, helping promote uroepithelial integrity and impermeability and maintaining the urine‐blood barrier. [ABSTRACT FROM AUTHOR]

Inherited genetic variation influencing leukocyte telomere length provides a natural experiment for testing associations with health outcomes, more robust to confounding and reverse causation than observational studies. We tested associations between genetically determined telomere length and aging‐related health outcomes in a large European ancestry older cohort. Data were from n = 379,758 UK Biobank participants aged 40–70, followed up for mean of 7.5 years (n = 261,837 participants aged 60 and older by end of follow‐up). Thirteen variants strongly associated with longer telomere length in peripheral white blood cells were analyzed using Mendelian randomization methods with Egger plots to assess pleiotropy. Variants in TERC, TERT, NAF1, OBFC1, and RTEL1 were included, and estimates were per 250 base pairs increase in telomere length, approximately equivalent to the average change over a decade in the general white population. We highlighted associations with false discovery rate‐adjusted p‐values smaller than .05. Genetically determined longer telomere length was associated with lowered risk of coronary heart disease (CHD; OR = 0.95, 95% CI: 0.92–0.98) but raised risk of cancer (OR = 1.11, 95% CI: 1.06–1.16). Little evidence for associations were found with parental lifespan, centenarian status of parents, cognitive function, grip strength, sarcopenia, or falls. The results for those aged 60 and older were similar in younger or all participants. Genetically determined telomere length was associated with increased risk of cancer and reduced risk of CHD but little change in other age‐related health outcomes. Telomere lengthening may offer little gain in later‐life health status and face increasing cancer risks. [ABSTRACT FROM AUTHOR]