Faculty Bibliography

Oral biofilm plays a central role in the development of periodontal and systemic diseases, with growing evidence highlighting significant gender-specific differences. Hormonal fluctuations in women, during puberty, menstruation, pregnancy, menopause, and with oral contraceptive use, may alter the composition and behavior of oral biofilm, increasing susceptibility to gingival inflammation and periodontal disease. Conditions such as polycystic ovary syndrome (PCOS), osteoporosis, and pregnancy-associated gingivitis further demonstrate the influence of endocrine factors on oral health. In men, higher rates of severe periodontitis are observed, potentially linked to testosterone-related immune responses and behavioral factors with associations to lower sperm counts, increased incidence of prostate cancer, and erectile dysfunction. These distinctions underscore the importance of considering sex-specific biology in both the prevention and management of oral and systemic diseases influenced by biofilm. This study reviews the connections between gender-specific health and oral biofilm.

BACKGROUND:Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of dying before age 70 years (70q0) and the mean age at death by cause and sex. This study enables comparisons of the impact of causes of death over time, offering a deeper understanding of how these causes affect global populations. METHODS:GBD 2023 produced estimates for 292 causes of death disaggregated by age-sex-location-year in 204 countries and territories and 660 subnational locations for each year from 1990 until 2023. We used a modelling tool developed for GBD, the Cause of Death Ensemble model (CODEm), to estimate cause-specific death rates for most causes. We computed YLLs as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. Probability of death was calculated as the chance of dying from a given cause in a specific age period, for a specific population. Mean age at death was calculated by first assigning the midpoint age of each age group for every death, followed by computing the mean of all midpoint ages across all deaths attributed to a given cause. We used GBD death estimates to calculate the observed mean age at death and to model the expected mean age across causes, sexes, years, and locations. The expected mean age reflects the expected mean age at death for individuals within a population, based on global mortality rates and the population's age structure. Comparatively, the observed mean age represents the actual mean age at death, influenced by all factors unique to a location-specific population, including its age structure. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 250-draw distribution for each metric. Findings are reported as counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2023 include a correction for the misclassification of deaths due to COVID-19, updates to the method used to estimate COVID-19, and updates to the CODEm modelling framework. This analysis used 55 761 data sources, including vital registration and verbal autopsy data as well as data from surveys, censuses, surveillance systems, and cancer registries, among others. For GBD 2023, there were 312 new country-years of vital registration cause-of-death data, 3 country-years of surveillance data, 51 country-years of verbal autopsy data, and 144 country-years of other data types that were added to those used in previous GBD rounds. FINDINGS/RESULTS:The initial years of the COVID-19 pandemic caused shifts in long-standing rankings of the leading causes of global deaths: it ranked as the number one age-standardised cause of death at Level 3 of the GBD cause classification hierarchy in 2021. By 2023, COVID-19 dropped to the 20th place among the leading global causes, returning the rankings of the leading two causes to those typical across the time series (ie, ischaemic heart disease and stroke). While ischaemic heart disease and stroke persist as leading causes of death, there has been progress in reducing their age-standardised mortality rates globally. Four other leading causes have also shown large declines in global age-standardised mortality rates across the study period: diarrhoeal diseases, tuberculosis, stomach cancer, and measles. Other causes of death showed disparate patterns between sexes, notably for deaths from conflict and terrorism in some locations. A large reduction in age-standardised rates of YLLs occurred for neonatal disorders. Despite this, neonatal disorders remained the leading cause of global YLLs over the period studied, except in 2021, when COVID-19 was temporarily the leading cause. Compared to 1990, there has been a considerable reduction in total YLLs in many vaccine-preventable diseases, most notably diphtheria, pertussis, tetanus, and measles. In addition, this study quantified the mean age at death for all-cause mortality and cause-specific mortality and found noticeable variation by sex and location. The global all-cause mean age at death increased from 46·8 years (95% UI 46·6-47·0) in 1990 to 63·4 years (63·1-63·7) in 2023. For males, mean age increased from 45·4 years (45·1-45·7) to 61·2 years (60·7-61·6), and for females it increased from 48·5 years (48·1-48·8) to 65·9 years (65·5-66·3), from 1990 to 2023. The highest all-cause mean age at death in 2023 was found in the high-income super-region, where the mean age for females reached 80·9 years (80·9-81·0) and for males 74·8 years (74·8-74·9). By comparison, the lowest all-cause mean age at death occurred in sub-Saharan Africa, where it was 38·0 years (37·5-38·4) for females and 35·6 years (35·2-35·9) for males in 2023. Lastly, our study found that all-cause 70q0 decreased across each GBD super-region and region from 2000 to 2023, although with large variability between them. For females, we found that 70q0 notably increased from drug use disorders and conflict and terrorism. Leading causes that increased 70q0 for males also included drug use disorders, as well as diabetes. In sub-Saharan Africa, there was an increase in 70q0 for many non-communicable diseases (NCDs). Additionally, the mean age at death from NCDs was lower than the expected mean age at death for this super-region. By comparison, there was an increase in 70q0 for drug use disorders in the high-income super-region, which also had an observed mean age at death lower than the expected value. INTERPRETATION/CONCLUSIONS:We examined global mortality patterns over the past three decades, highlighting-with enhanced estimation methods-the impacts of major events such as the COVID-19 pandemic, in addition to broader trends such as increasing NCDs in low-income regions that reflect ongoing shifts in the global epidemiological transition. This study also delves into premature mortality patterns, exploring the interplay between age and causes of death and deepening our understanding of where targeted resources could be applied to further reduce preventable sources of mortality. We provide essential insights into global and regional health disparities, identifying locations in need of targeted interventions to address both communicable and non-communicable diseases. There is an ever-present need for strengthened health-care systems that are resilient to future pandemics and the shifting burden of disease, particularly among ageing populations in regions with high mortality rates. Robust estimates of causes of death are increasingly essential to inform health priorities and guide efforts toward achieving global health equity. The need for global collaboration to reduce preventable mortality is more important than ever, as shifting burdens of disease are affecting all nations, albeit at different paces and scales. FUNDING/BACKGROUND:Gates Foundation.

BACKGROUND:Metabolic syndrome is a pressing public health issue and risk factor for the development of type 2 diabetes (T2D) and cardiovascular disease (CVD), yet clinical practice is lacking in biomarkers that represent pre-clinical perturbations of the heterogenous subtypes of risk. This study aimed to characterize the baseline metabolome in relation to known clinical characteristics of risk in a sample of obese adults. METHODS:Untargeted metabolome data from N = 126 plasma samples with baseline data from a previously completed study including obese adults with metabolic syndrome. Metabolites were acquired using validated liquid chromatography mass spectrometry methods with 15-25 internal standards quantified by peak heights. Pearson's correlations were used to determine relationships between baseline metabolites, sample characteristics (e.g., age, body mass index (BMI)), and atherosclerotic clinical characteristics (e.g., high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL), triglycerides), adjusting for multiple comparisons using the Benjamini-Hochberg False Discovery Rate (FDR) method. Differences in metabolite levels between clinical classifications of dysglycemia (e.g., normal, prediabetes, diabetes) at baseline were assessed using ANOVA and adjusted for multiple comparisons and adjusted for covariates. RESULTS:The sample consisted primarily of female (74%) participants, predominantly white (70%), with an average age of 56 years. After FDR adjustment, two baseline metabolites were significantly associated with age (xylose, threitol), two with BMI (shikimic acid, propane-1,3-diol), one with LDL (tocopherol-alpha), and 42 with HDL cholesterol. Three metabolites were significantly associated with fasting blood glucose (FBG) levels at baseline (glucose, gluconic acid lactone, pelargonic acid). CONCLUSIONS:This study identified novel metabolite associations with known markers of T2D and CVD risk. Specific metabolites, such as alpha-tocopherol, branched-chain amino acids (BCAAs), and sugar-derived metabolites like mannose and xylose, were significantly associated with age, BMI, lipid profiles, and glucose measures. Although most sample participants had normal HDL cholesterol at baseline, 42 metabolites including branched chain amino acids were significantly associated with HDL, suggesting pre-clinical perturbations in biological pathways associated with both diabetes and cardiovascular comorbidities. Metabolomic signatures specific to prediabetes and metabolic syndrome can enhance risk stratification and enable targeted prevention strategies for T2D. Longitudinal studies are needed to understand how these associations change over time in at-risk individuals compared with controls.

BACKGROUND:The purpose of this pilot study was to determine if recombinant human platelet-derived growth factor-ßß (rhPDGF-ßß) and recombinant human bone morphogenetic protein-2 (rhBMP-2) can be released over an extended timeframe from a biologic fibrin membrane capable of being used in a guided bone regeneration (GBR) procedure. METHODS:Human venous blood samples were placed into 10 9-ml silica-lined test tubes. Two of the tubes were doped with rhPDGF-ßß, two tubes were doped with rhBMP-2, and two were doped with alpha-2 antiplasmin plus rhBMP-2. Four tubes with no growth factors added served as controls. After centrifugation the blood clots were separated from the red blood cell fraction and platelet poor plasma. The clots were placed into wells with liquid growth medium except for the platelet poor plasma and the serum squeezed from the clots. These solutions were measured directly. One milliliter of growth medium from the clots was removed at 20 minutes, 4 hours, 72 hours, 168 hours, 312 hours, and 336 hours and replaced with 1 ml of fresh growth medium. All samples were analyzed using indirect ELISA assay. Six 9-ml plastic-lined test tubes were filled with venous blood. After centrifugation the uncoagulated plasma was separated from the red blood cell layer and placed into a surgical bowl. Coagulation was initiated with 500 µl of calcium chloride for 30 minutes. RESULTS:The indirect ELISA assay for rhPDGF-ßß at 116 hours showed 1,583 pg/ml compared to 8 pg/ml from the average of the control samples with no growth factor added. The ELISA assay for rhBMP-2 at 324 hours showed 9,606 pg/ml, and for alpha-2 antiplasmin plus rhBMP-2 12,788 pg/ml, compared to no detectable growth factor from the controls. After 30 minutes of incubating the 25 ml of separated plasma, the coagulated clot produced a biologic membrane approximately 40 mm x 45 mm. CONCLUSIONS:The current pilot study showed fibrin can bind and release rhBMP-2 and rhPDGF-ßß over a 7- to 14-day period allowing the fibrin matrix to become an osseoconductive scaffold. Both growth factors can be incorporated into fibrin to create a biologic membrane to be used for GBR, sinus augmentation, and ridge augmentation.

Tumor necrosis factor-alpha (TNF-α) inhibitors and other biologics used for autoimmune diseases are associated with low-grade immunosuppression. Treatment with these and the presence of prosthetic mechanical cardiac valves both increase the risk of infective endocarditis (IE). However, evidence on the risk of prosthetic valve endocarditis (PVE) among patients treated with TNF-α inhibitors is limited. This study reports a 41-year-old man with a prosthetic aortic valve who was on treatment with golimumab and presented with low-grade fevers and positive blood cultures for Staphylococcus epidermidis. Transesophageal echocardiogram revealed vegetations adjacent to the valve sewing ring and an inflammatory phlegmon in the right atrium, leading to a diagnosis of prosthetic valve endocarditis. The patient was referred to a higher level of care center and underwent urgent surgical intervention. The study highlights that TNF-α inhibitors and other biologics may increase the risk of prosthetic heart valve endocarditis and the importance of early imaging for diagnosis.

BACKGROUND:Cardiac positron emission tomography (PET) and single-photon emission computed tomography (SPECT) are widely used for the assessment of coronary artery disease. While SPECT remains more available, workforce shortages and training demands contribute to geographic disparities in PET availability, impacting patient access to advanced imaging. Therefore, we assessed trends in the U.S. cardiac nuclear imaging workforce. METHODS:Data from Medicare Part B (2013-2022), provided by the Centers for Medicare & Medicaid Services, were analyzed to assess trends in cardiac nuclear imaging services billed by physicians. The analysis focused on the number of readers, their gender, specialty, geographic distribution, and workload. RESULTS:From 2013 to 2022, the proportion of SPECT procedures declined from 95.8% (2,303,194 scans; 4393 per 100,000 Medicare beneficiaries) to 86.3% (1,386,358 scans; 2130 per 100,000 Medicare beneficiaries) of total nuclear cardiology procedures, while the proportion of PET procedures increased from 4.2% (99,861 scans; 190 per 100,000 Medicare beneficiaries) to 13.7% (220,366 scans; 339 per 100,000 Medicare beneficiaries). The majority of studies were interpreted by readers performing 50 or more studies annually. From 2013 to 2022, the number of SPECT-only readers declined from 17,013 to 13,491, while PET-only readers increased from 66 to 386. Readers interpreting both SPECT and PET doubled from 822 to 1643. Only 1 in 10 nuclear imaging readers were women and the majority were cardiologists. The median (interquartile range) number of studies per reader was higher for cardiologists compared to those of other specialties. Geographic disparities were evident, with most nuclear imaging readers practicing in Texas, Florida, and California, while the fewest were in Wyoming, Alaska, Vermont, and Washington, D.C. CONCLUSIONS:While SPECT remained the most commonly used modality in 2022, its use has declined, whereas PET use has increased, accompanied by similar trends in the number of readers. Gender and geographic disparities persist in the distribution of nuclear cardiology imaging specialists. Addressing these gaps is essential to ensuring equitable access to nuclear imaging expertise.

BACKGROUND/OBJECTIVES/UNASSIGNED:Emotional fear memories are increasingly recognized as contributors to the development of specific fears and phobias. Despite this, relatively little dental fear research has specifically focused on patient memories or their potential role in the etiology of dental fear. METHODS/UNASSIGNED:This two-study paper employs qualitative thematic analysis of memories for dental visits among traumatized patients (study 1) and the general patient population (ranging from endorsing no dental fear to severe fear). Recollections were evaluated based on the characteristics (i.e., sensory descriptors, affectively laden, intrusive) of emotional fear memories (studies 1 and 2) and according to a modified cognitive vulnerability model of dental fear (study 2). RESULTS/UNASSIGNED:Characteristics of emotional fear memories were ubiquitous across recollections of individuals who endorsed traumatic dental visits in childhood. Among the general patient population, these characteristics and cognitive vulnerability themes (particularly perceptions of the visit and dentist as dangerous and untrustworthy) were more prevalent in the earliest remembered visits for fearful individuals. When individuals were asked to recall their worst dental visits, emotional fear memory characteristics and vulnerability perceptions were evident across the spectrum of current fear (none to severe). CONCLUSIONS/UNASSIGNED:This study contributes to nascent work examining memory in specific fears and phobias and suggests that worst recollections across a general sample share many of the characteristics that might otherwise imply vulnerability for anxiety. We recommend that dental practices universally screen patients for fear, inquire about past negative experiences, partner with patients to minimize evoking their specific vulnerabilities, and diligently implement these personalized care plans.

Craniofacial spliceosomopathies are syndromes resulting from mutations in components of the spliceosome, presenting with facial dysostosis in combination with other phenotypes. An outstanding question in the field is how mutations in the ubiquitously expressed spliceosome lead to such cell- and tissue-specific disorders. To understand the etiology of these diseases and decipher the underlying mechanisms, scientists have turned to modeling these disorders in the laboratory. In vivo modeling of these disorders includes the use of mice, zebrafish, and frogs, whereas in vitro modeling typically uses embryonic stem cells (ESCs) and induced pluripotent stem cells (iPSCs). The goal with these models is to recapitulate the human disorders in a manner that is conducive to scientific exploration. In this review, we briefly describe the major craniofacial spliceosomopathies and discuss recent advances using model systems that have helped understand the root cause of these conditions.

Advancements in spinal cord stimulation (SCS) have enhanced patient outcomes, improved durability, and broadened the range of treatable pain conditions. Technological improvements in battery design have led to smaller implant size, while evolving societal guidelines have played a critical role in optimizing implant safety and quality. This review summarizes recent technological developments in SCS, the impact of such developments on patient satisfaction, and provides an overview of the major systems currently available. We also introduce and explore the emerging concept, "pocket awareness" - referring to a patient's conscious perception of their implant. Several modifiable factors involving physicians, patients, and manufacturers can influence this awareness, and by extension, patient satisfaction. While pain relief is certainly the primary objective, fostering a comfortable and positive relationship between the patient and their device is essential and merits further clinical attention.