Leaf decomposition and flammability are largely decoupled across species in a tropical swamp forest despite sharing some predictive leaf functional traits.

Decomposition and fire are major carbon pathways in many ecosystems, yet potential linkages between these processes are poorly understood. We test whether variability in decomposability and flammability across species are related to each other and to key plant functional traits in tropical swamp forests, where habitat degradation is elevating decomposition and fire regimes. Using senesced and fresh leaves of 22 swamp tree species in Singapore, we conducted an in situ decomposition experiment and a laboratory flammability experiment. We analysed 16 leaf physical and biochemical traits as predictors of decomposability and components of flammability: combustibility, ignitability and sustainability. Decomposability and flammability were largely decoupled across species, despite some shared predictive traits such as specific leaf area (SLA). Physical traits predicted that thicker leaves with a smaller SLA and volume decomposed faster, while various cation concentrations predicted flammability components, particularly ignitability. We show that flammability and decomposability of swamp forest leaves are decoupled because flammability is mostly driven by biochemical traits, while decomposition is driven by physical traits. Our approach identifies species that are slow to decompose and burn (e.g. Calophyllum tetrapterum and Xanthophyllum flavescens), which could be planted to mitigate carbon losses in tropical swamp reforestation.

Loeys-Dietz and Shprintzen-Goldberg syndromes: analysis of TGF-ß-opathies with craniofacial manifestations using an innovative multimodality method.

BACKGROUND: Elevated transforming growth factor-beta (TGF-ß) signalling has been implicated in the pathogenesis of Loeys-Dietz syndrome (LDS) and Shprintzen-Goldberg syndrome (SGS). In this study, we provide a qualitative and quantitative analysis of the craniofacial and functional features among the LDS subtypes and SGS. METHODS: We explore the variability within and across a cohort of 44 patients through deep clinical phenotyping, three-dimensional (3D) facial photo surface analysis, cephalometric and geometric morphometric analyses of cone-beam CT scans. RESULTS: The most common craniofacial features detected in this cohort include mandibular retrognathism (84%), flat midface projection (84%), abnormal eye shape (73%), low-set ears (73%), abnormal nose (66%) and lip shape (64%), hypertelorism (41%) and a relatively high prevalence of nystagmus/strabismus (43%), temporomandibular joint disorders (38%) and obstructive sleep apnoea (23%). 3D cephalometric analysis demonstrated an increased cranial base angle with shortened anterior cranial base and underdevelopment of the maxilla and mandible, with evidence of a reduced pharyngeal airway in 55% of those analysed. Geometric morphometric analysis confirmed that the greatest craniofacial shape variation was among patients with LDS type 2, with distinct clustering of patients with SGS. CONCLUSIONS: This comprehensive phenotypic approach identifies developmental abnormalities that segregate to mutation variants along the TGF-ß signalling pathway, with a particularly severe phenotype associated with TGFBR2 and SKI mutations. Multimodality assessment of craniofacial anomalies objectively reveals the impact of mutations of the TGF-ß pathway with perturbations associated with the cranium and cranial base with severe downstream effects on the orbit, maxilla and mandible with the resultant clinical phenotypes.

Disruptive Therapy Using a Nonsurgical Orthodontic Airway Plate for the Management of Neonatal Robin Sequence: 1-Year Follow-up.

We recently published the 3-month follow-up of 2 neonates with Robin sequence whose mandibular hypoplasia and restricted airway were successfully treated with an orthodontic airway plate (OAP) without surgical intervention. Both infants were successfully weaned off the OAP after several months of continuous use. We present the course of OAP treatment in these patients with a focus on breathing, feeding, and facial growth during their first year of life. Both infants demonstrated stable mandibular projection, resolution of obstructive sleep apnea, and normal development.

TUBB3 Arg262His causes a recognizable syndrome including CFEOM3, facial palsy, joint contractures, and early-onset peripheral neuropathy.

Microtubules are formed from heterodimers of alpha- and beta-tubulin, each of which has multiple isoforms encoded by separate genes. Pathogenic missense variants in multiple different tubulin isoforms cause brain malformations. Missense mutations in TUBB3, which encodes the neuron-specific beta-tubulin isotype, can cause congenital fibrosis of the extraocular muscles type 3 (CFEOM3) and/or malformations of cortical development, with distinct genotype-phenotype correlations. Here, we report fourteen individuals from thirteen unrelated families, each of whom harbors the identical NM_006086.4 (TUBB3):c.785G>A (p.Arg262His) variant resulting in a phenotype we refer to as the TUBB3 R262H syndrome. The affected individuals present at birth with ptosis, ophthalmoplegia, exotropia, facial weakness, facial dysmorphisms, and, in most cases, distal congenital joint contractures, and subsequently develop intellectual disabilities, gait disorders with proximal joint contractures, Kallmann syndrome (hypogonadotropic hypogonadism and anosmia), and a progressive peripheral neuropathy during the first decade of life. Subsets may also have vocal cord paralysis, auditory dysfunction, cyclic vomiting, and/or tachycardia at rest. All fourteen subjects share a recognizable set of brain malformations, including hypoplasia of the corpus callosum and anterior commissure, basal ganglia malformations, absent olfactory bulbs and sulci, and subtle cerebellar malformations. While similar, individuals with the TUBB3 R262H syndrome can be distinguished from individuals with the TUBB3 E410K syndrome by the presence of congenital and acquired joint contractures, an earlier onset peripheral neuropathy, impaired gait, and basal ganglia malformations.

Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation.

Background Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-ß) pathway, LDS is presently classified into six subtypes. Methods We present the oro-dental features of a cohort of 40 patients with LDS from five subtypes. Results The most common oro-dental manifestations were the presence of a high-arched and narrow palate, and enamel defects. Other common characteristics included bifid uvula, submucous cleft palate, malocclusion, dental crowding and delayed eruption of permanent teeth. Both deciduous and permanent teeth had enamel defects in some individuals. We established a grading system to measure the severity of enamel defects, and we determined that the severity of the enamel anomalies in LDS is subtype-dependent. In specific, patients with TGF-ß receptor II mutations (LDS2) presented with the most severe enamel defects, followed by patients with TGF-ß receptor I mutations (LDS1). LDS2 patients had higher frequency of oro-dental deformities in general. Across all five subtypes, as well as within each subtype, enamel defects exhibited incomplete penetrance and variable expression, which is not associated with the location of the gene mutations. Conclusion This study describes, in detail, the oro-dental manifestations in a cohort of LDS, and we conclude that LDS2 has the most severely affected phenotype. This extensive characterisation, as well as some identified distinguishing features can significantly aid dental and medical care providers in the diagnosis and clinical management of patients with this rare connective tissue disorder.

Dental abnormalities in individuals with pathogenic germline variation in DICER1.

Pathogenic germline variation in the microRNA processing gene DICER1 gives rise to an autosomal dominant, tumor-predisposition disorder. Conditional deletion of Dicer1 in murine dental epithelium shows that it controls tooth patterning, size, number, and shape. The human dental phenotype of people with germline pathogenic variation in DICER1 is unknown. DICER1-carriers (n = 57) and family controls (n = 55) were evaluated at the NIH Clinical Center dental clinic as part of a comprehensive medical evaluation. Digital panoramic radiographs, bite-wing radiographs, and oral photographs were collected. A single observer, blind to DICER1 status, reviewed the dental records and determined the presence or absence of 11 dental characteristics as described in the clinic notes, radiographs, or oral photographs. Subjective phenotypes were reviewed on radiographs by two examiners (blind to DICER1 status) for the presence or absence of the dental characteristics to reduce inconsistencies. By simple association, bulbous crown, periodontitis, and taurodontism were all significant (p < .05). Logistic regression with chi-square maximum likelihood estimates showed that bulbous crown and periodontitis remained significant. Recognition of these phenotypes may aid identification of individuals and families at risk for DICER1-associated neoplasms. These findings may also guide dental care for individuals with germline DICER1 pathogenic variation.

Residency Interview Experiences in Oral and Maxillofacial Surgery Differ by Gender and Affect Residency Ranking.

PURPOSE: Resident interview experiences are crucial for applicants when ranking programs. The purpose of the present study was to evaluate the interview experience among current oral and maxillofacial surgery (OMS) residents to determine the factors that influenced their selection and ranking of training programs and whether these experiences differed between women and men. MATERIALS AND METHODS: We conducted a cross-sectional survey of OMS residents in 2018. The 12-question survey included demographics, reasons for selecting an interview and ranking programs, and positive and negative experiences during the interviews. Logistic regression models were constructed to evaluate the predictors of unprofessional or negative experiences. RESULTS: A total of 1134 surveys were emailed, with 165 completed questionnaires (14.6%) returned by 35 women (21.2%) and 130 men (78.8%). Their average age was 30.8 years (range, 25 to 42). The racial/ethnic distribution was as follows: white, 75.8%; Asian, 15.8%; and other, 8.4%. Of the 165 respondents, 52% were in MD and 48% in non-MD programs. The top factors in selecting an institution at which to interview were clinical scope and volume, and the reason for ranking a program high was resident friendliness, which was similar among the female and male respondents. Unprofessional behavior or negative experiences were reported by 62 respondents (38%) and occurred by both faculty and residents and during both interviews and social events. Demeaning behavior toward the applicant, residents, and colleagues was the most common negative experience overall, with the women experiencing more gender-specific inappropriate behavior. Female respondents and those who were in dual-degree programs were 2.4 and 2.1 times more likely to experience unprofessional conduct than their peers, respectively (P = .03). CONCLUSIONS: Female and male residents were influenced by the same factors when selecting interviews and ranking residency programs. Unprofessional and inappropriate conduct was reported by 38% of the respondents. Women and dual-degree respondents were 2.4 and 2.1 times more likely to experience unprofessionalism during interviews, respectively. This might have contributed to the low number of current female OMS residents.

Temporomandibular Joint Condyle-Disc Morphometric Sexual Dimorphisms Independent of Skull Scaling.

PURPOSE: Approximately 2 to 4% of the US population have been estimated to seek treatment for temporomandibular symptoms, predominately women. The study purpose was to determine whether sex-specific differences in temporomandibular morphometry result from scaling with sex differences in skull size and shape or intrinsic sex-specific differences. MATERIALS AND METHODS: A total of 22 (11 male [aged 74.5 ± 9.1 years]; 11 female [aged 73.6 ± 12.8 years]) human cadaveric heads with no history of temporomandibular disc derangement underwent cone beam computed tomography and high-resolution magnetic resonance imaging scanning to determine 3-dimensional cephalometric parameters and temporomandibular morphometric outcomes. Regression models between morphometric outcomes and cephalometric parameters were developed, and intrinsic sex-specific differences in temporomandibular morphometry normalized by cephalometric parameters were determined. Subject-specific finite element (FE) models of the extreme male and extreme female conditions were developed to predict variations in articular disc stress-strain under the same joint loading. RESULTS: In some cases, sex differences in temporomandibular morphometric parameters could be explained by linear scaling with skull size and shape; however, scaling alone could not fully account for some differences between sexes, indicating intrinsic sex-specific differences. The intrinsic sex-specific differences in temporomandibular morphometry included an increased condylar medial length and mediolateral disc lengths in men and a longer anteroposterior disc length in women. Considering the extreme male and female temporomandibular morphometry observed in the present study, subject-specific FE models resulted in sex differences, with the extreme male joint having a broadly distributed stress field and peak stress of 5.28 MPa. The extreme female joint had a concentrated stress field and peak stress of 7.37 MPa. CONCLUSIONS: Intrinsic sex-specific differences independent of scaling with donor skull size were identified in temporomandibular morphometry. Understanding intrinsic sex-specific morphometric differences is critical to determining the temporomandibular biomechanics given the effect of anatomy on joint contact mechanics and stress-strain distributions and requires further study as one potential factor for the increased predisposition of women to temporomandibular disc derangement.

Development and Validation of Novel Three-Dimensional Craniofacial Landmarks on Cone-Beam Computed Tomography Scans.

As cone-beam computed tomography (CBCT) scans become increasingly common, it is vital to have reliable 3-dimensional (3D) landmarks for quantitative analysis of craniofacial skeletal morphology. While some studies have developed and used 3D landmarks, these landmark sets are generally small and derived primarily from previous 2-dimensional (2D) cephalometric landmarks. These derived landmarks lack information in parts of the skull such as the cranial base, which is an important feature for cranial growth and development. The authors see a real need for development and validation of 3D landmarks, particularly bilateral landmarks, across the skull for improved cephalometric analysis. The primary objective of this study is to develop and validate a set of 61 3D anatomical landmarks on the face, cranial base, mandible, and teeth for use in clinical and research studies involving CBCT imaging. Each landmark was placed 3 times by 3 separate trained observers on a set of 10 anonymized CBCT patient scans. Intra-rater and inter-rater estimates of consistency and agreement were calculated using the intraclass correlation coefficient. Measurement error was calculated per landmark and per X, Y, and Z landmark coordinate. The authors had high ICC estimates within rates, indicating high consistency, and high ICC estimates among raters, indicate good agreement across raters. Overall measurement error for each landmark and each X, Y, and Z coordinate was low. Our results confirm the accuracy of novel 3D landmarks including several on the cranial base that will serve researchers and clinicians for use in future studies involving 3D CBCT imaging and craniofacial development.

Comparison of Three-Dimensional Surface Imaging Systems Using Landmark Analysis.

Numerous 3d imaging systems are now available commercially for the capture of facial shape data via landmarking or surface shape comparisons but it is not known whether these systems produce data of comparable quality. This study investigates the error associated with landmark coordinate data collected on facial surface images taken using three 3d imaging systems: the 3dMDface system (3dMD, Atlanta, GA), the Planmeca ProFace system (Planmeca, Roselle, IL), and the Vectra H1 handheld system (Canfield Scientific, Parsippany, NJ). This was a retrospective study involving 3d imaging data that used geometric morphometric analysis to assess overall shape differences as well as landmark-specific differences among the systems. Ten individuals evaluated at the NIDCR dental clinic on various protocols were imaged on all 3 systems. The subject pool consisted of syndromic and unaffected subjects, as disease status was irrelevant to the question of reproducibility and variability. Variation in landmark placement across systems was assessed by ANOVA, covariance matrix, and summary statistics. No overall shape or size differences were found among the systems. However, there was some landmark-specific variation and the 3dMD and Vectra systems were generally more similar to each other than either was to the Planmeca system. The data acquired by these 3 systems are comparable, although landmarks on the eyes and ears are noisy and most different among systems.

Leveraging human genetic and adverse outcome pathway (AOP) data to inform susceptibility in human health risk assessment.

Estimation of susceptibility differences in human health risk assessment (HHRA) has been challenged by a lack of available susceptibility and variability data after exposure to a specific environmental chemical or pharmaceutical. With the increasingly large number of available data sources that contain polymorphism and other genetic data, human genetic variability that informs susceptibility can be better incorporated into HHRA. A recent policy, the 2016 The Frank R. Lautenberg Chemical Safety for the twenty-first Century Act, requires the US Environmental Protection Agency to evaluate new and existing toxic chemicals with explicit consideration of susceptible populations of all types (life stage, exposure, genetic, etc.). We propose using the adverse outcome pathway (AOP) construct to organize, identify, and characterize human genetic susceptibility in HHRA. We explore how publicly available human genetic datasets can be used to gain mechanistic understanding of molecular events and characterize human susceptibility for an adverse outcome. We present a computational method that implements publicly available human genetic data to prioritize AOPs with potential for human genetic variability. We describe the application of this approach across multiple described AOPs for health outcomes of interest, and by focusing on a single molecular initiating event. This contributes to a long-term goal to improve estimates of human susceptibility for use in HHRA for single and multiple chemicals.

Facial surface morphology predicts variation in internal skeletal shape.

INTRODUCTION: The regular collection of 3-dimensional (3D) imaging data is critical to the development and implementation of accurate predictive models of facial skeletal growth. However, repeated exposure to x-ray-based modalities such as cone-beam computed tomography has unknown risks that outweigh many potential benefits, especially in pediatric patients. One solution is to make inferences about the facial skeleton from external 3D surface morphology captured using safe nonionizing imaging modalities alone. However, the degree to which external 3D facial shape is an accurate proxy of skeletal morphology has not been previously quantified. As a first step in validating this approach, we tested the hypothesis that population-level variation in the 3D shape of the face and skeleton significantly covaries. METHODS: We retrospectively analyzed 3D surface and skeletal morphology from a previously collected cross-sectional cone-beam computed tomography database of nonsurgical orthodontics patients and used geometric morphometrics and multivariate statistics to test the hypothesis that shape variation in external face and internal skeleton covaries. RESULTS: External facial morphology is highly predictive of variation in internal skeletal shape ([Rv] = 0.56, P <0.0001; partial least squares [PLS] 1-13 = 98.7% covariance, P <0.001) and asymmetry (Rv = 0.34, P <0.0001; PLS 1-5 = 90.2% covariance, P <0.001), whereas age-related (r(2) = 0.84, P <0.001) and size-related (r(2) = 0.67, P <0.001) shape variation was also highly correlated. CONCLUSIONS: Surface morphology is a reliable source of proxy data for the characterization of skeletal shape variation and thus is particularly valuable in research designs where reducing potential long-term risks associated with radiologic imaging methods is warranted. We propose that longitudinal surface morphology from early childhood through late adolescence can be a valuable source of data that will facilitate the development of personalized craniodental and treatment plans and reduce exposure levels to as low as reasonably achievable.

Development and application of a rat PBPK model to elucidate kidney and liver effects induced by ETBE and tert-butanol.

Subchronic and chronic studies in rats of the gasoline oxygenates ethyl tert-butyl ether (ETBE) and tert-butanol (TBA) report similar noncancer kidney and liver effects but differing results with respect to kidney and liver tumors. Because TBA is a major metabolite of ETBE, it is possible that TBA is the active toxic moiety in all these studies, with reported differences due simply to differences in the internal dose. To test this hypothesis, a physiologically-based pharmacokinetic (PBPK) model was developed for ETBE and TBA to calculate internal dosimetrics of TBA following either TBA or ETBE exposure. This model, based on earlier PBPK models of methyl tert-butyl ether (MTBE), was used to evaluate whether kidney and liver effects are consistent across routes of exposure, as well as between ETBE and TBA studies, on the basis of estimated internal dose. The results demonstrate that noncancer kidney effects, including kidney weight changes, urothelial hyperplasia, and chronic progressive nephropathy (CPN), yielded consistent dose-response relationships across routes of exposure and across ETBE and TBA studies using TBA blood concentration as the dose metric. Relative liver weights were also consistent across studies on the basis of TBA metabolism, which is proportional to TBA liver concentrations. However, kidney and liver tumors were not consistent using any dose metric. These results support the hypothesis that TBA mediates the noncancer kidney and liver effects following ETBE administration; however, additional factors besides internal dose are necessary to explain the induction of liver and kidney tumors.

Correlation of Airway Volume With Orthognathic Surgical Movement Using Cone-Beam Computed Tomography.

PURPOSE: Orthognathic surgery can induce changes in airway volume. The aim of this study was to determine whether there is a correlation of surgical movement of the maxilla or mandible to airway volume changes. MATERIALS AND METHODS: This was a prospective cohort study and the sample was composed of patients undergoing single-jaw orthognathic procedures from 2004 through 2007. Cone-beam computed tomograms were obtained before surgery (T0), immediately after surgery (T1), and at least 6 months after surgery (T2). The airway was segmented from 3-dimensional images and identified as the whole airway, consisting of the naso-, oro-, and hypopharynx. The volumetric percentage of change of the airway between time points was compared and correlated to the surgical movements using paired t test and cubic regression analysis. The level of statistical significance was set at a P value less than or equal to .05. RESULTS: The sample was composed of 33 patients. Sixteen patients underwent maxillary advancement with mean advancement of 5.4 mm (3 to 8 mm), 13 underwent mandibular advancement with mean advancement of 8.0 mm (5 to 15 mm), and 4 underwent mandibular setback of 4.0 mm. For maxillary advancement at T1, volume percentages of change for the whole airway and the naso-, oro-, and hypopharynx were 18.4 (P ≤ .05), 53.8 (P ≤ .05), 26.3, and 5.5%, respectively, and at T2, the changes were 10.0, 46.7 (P ≤ .05), 6.8, and 1.0%, respectively. For mandibular advancement at T1, volume percentages of change were 34.6 (P ≤ .05), 26.1, 54.1 (P ≤ .05), and 17.4%, respectively, and at T2, the changes were 15.0 (P ≤ .05), -3.7, 23.5 (P ≤ .05), and 12.1%, respectively. There were no meaningful long-term airway changes with mandibular setback. CONCLUSION: The study results suggest that there might be an anatomic limit to pharyngeal airway expansion associated with single-jaw orthognathic surgery.

Cone-beam computed tomographic comparison of surgically assisted rapid palatal expansion and multipiece Le Fort I osteotomy.

PURPOSE: To examine and compare the skeletal and dental effects of surgically assisted rapid palatal expansion (SARPE) and multipiece Le Fort osteotomy using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: This was a prospective cohort study. Patients underwent SARPE or multipiece Le Fort I osteotomy to address maxillary transverse deficiency. CBCT scans were taken preoperatively, immediately postoperatively or after retention, and at least 6 months postoperatively. Four landmark measurements and ratios of dental-to-skeletal change were used to follow skeletal and dental widths in the posterior and anterior maxillary regions. Wilcoxon signed-rank test and Wilcoxon 2-sample rank-sum test were used to compare the landmark measurements and the ratio of dental-to-skeletal change for the 2 surgeries. A P value less than .05 was statistically significant. RESULTS: Thirteen patients (mean, 28.3 yr old; 7 women) were enrolled: 9 were treated by multipiece Le Fort I osteotomy and 4 were treated by SARPE. The ratios of dental-to-skeletal expansion in the posterior maxilla for the Le Fort procedure and SARPE were 0.70 ± 0.41 and 25.20 ± 15.8, respectively, and the dental-to-skeletal relapses were 1.17 ± 0.80 and -3.63 ± 3.70, respectively. The ratios of dental-to-skeletal expansion in the anterior maxilla for the Le Fort procedure and SARPE were 0.58 ± 0.38 and 31.80 ± 59.4, respectively, and the dental-to-skeletal relapses were 2.25 ± 3.41 and 4.86 ± 8.10, respectively. CONCLUSION: There was greater correlation between dental and skeletal changes in the multipiece Le Fort procedure, indicating bodily separation of the segments, whereas the SARPE showed noteworthy dental and skeletal tipping. Dental relapse was greater than skeletal relapse for these 2 procedures.

Proceedings from the 2013 American Association of Oral and Maxillofacial Surgeons Research Summit.

The American Association of Oral and Maxillofacial Surgeons, the Oral and Maxillofacial Surgery Foundation, and the International Association of Oral and Maxillofacial Surgeons sponsored the fifth research summit, which convened on May 2 and 3 in Rosemont, Illinois. The Research Summits are convened biennially to facilitate the discussion and collaboration of oral and maxillofacial surgeons with clinical and basic science researchers in fields affecting the specialty. The goal is to advance the field of oral and maxillofacial surgery through exposure and education in topics that ultimately benefit the oral and maxillofacial surgical patient. This edition of the research summit included the topics of robotic surgery and antiresorptive-related osteonecrosis of the jaws (ARONJ). Most importantly, this research summit saw the development of research interest groups (RIGs) in the fields of anesthesia, maxillofacial oncology and reconstructive surgery, obstructive sleep apnea and orthognathic surgery, temporomandibular joint surgery, and trauma. These RIGs developed specific research goals with a plan to continue working on potential projects at the AAOMS Clinical Trials Course on May 7 to 9, 2013 at the University of Michigan in Ann Arbor. The summit program was developed by the AAOMS Committee on Research Planning and Technology Assessment. The charge of the committee is to encourage and promote research within the specialty and to encourage interdisciplinary collaboration. The research summit serves as a platform for oral and maxillofacial surgeons to lead the goal of advancement of research relevant to the specialty. This article provides an overview of the presentations that were made in the sessions on robotic surgery and ARONJ. The research summit keynote address and two additional presentations on patient registries are summarized and updates from the RIGs that were formed at the 2013 research summit are highlighted.

Integrin signalling in joint development, homeostasis and osteoarthritis.

Integrins are key regulators of cell-matrix interactions during joint development and joint tissue homeostasis, as well as in the development of osteoarthritis (OA). The signalling cascades initiated by the interactions of integrins with a complex network of extracellular matrix (ECM) components and intracellular adaptor proteins orchestrate cellular responses necessary for maintaining joint tissue integrity. Dysregulated integrin signalling, triggered by matrix degradation products such as matrikines, disrupts this delicate balance, tipping the scales towards an environment conducive to OA pathogenesis. The interplay between integrin signalling and growth factor pathways further underscores the multifaceted nature of OA. Moreover, emerging insights into the role of endocytic trafficking in regulating integrin signalling add a new layer of complexity to the understanding of OA development. To harness the therapeutic potential of targeting integrins for mitigation of OA, comprehensive understanding of their molecular mechanisms across joint tissues is imperative. Ultimately, deciphering the complexities of integrin signalling will advance the ability to treat OA and alleviate its global burden.

Essential and Toxic Elements in Infant Cereal in Brazil: Exposure Risk Assessment.

Infant cereals, one of the first solid foods introduced to infants, have been reported to pose risks to human health because they contain toxic elements and an excess of essential elements. The objective of this study was to assess the cancer and non-cancer risk of exposure to essential and toxic elements in infant cereal in Brazil. In our analyses, we included data from 18 samples of infant cereals made from different raw materials and estimated the incremental lifetime cancer risks and non-cancer hazard quotients (HQs) for their consumption. Rice cereal is particularly concerning because it is immensely popular and usually contains high levels of inorganic arsenic. In addition to arsenic, we assessed aluminum, boron, barium, cadmium, chromium, copper, lead, manganese, nickel, selenium, silver, strontium, and zinc. The cancer risk was highest for rice cereal, which was also found to have an HQ > 1 for most of the tested elements. Inorganic As was the element associated with the highest cancer risk in infant cereal. All of the infant cereals included in this research contained at least one element with an HQ > 1. The essential and non-essential elements that presented HQ > 1 more frequently were zinc and cadmium, respectively. The cancer and non-cancer risks could potentially be decreased by reducing the amount of toxic and essential elements (when in excess), and public policies could have a positive influence on risk management in this complex scenario.

The National Institutes of Health Lasker Clinical Research Scholars Program: A Decade of Launching Clinician-Scientist Careers.

PURPOSE: In response to the decades-long decrease in U.S. clinician-scientists, the National Institutes of Health (NIH) and the Albert and Mary Lasker Foundation launched the Lasker Clinical Research Scholars Program in academic year 2011 to 2012. The investigators examined the early outcomes of this program. METHOD: Thirty-nine scholars have matriculated into the program as of May 2023. Productivity was assessed for all scholars who joined the program before October 2020 (n = 31). Extramural early-stage investigators (ESIs) were used as a control group, and coarsened exact matching was used to compare the groups. The scholars were compared with the matched ESIs on 4 productivity metrics: publication count, weighted relative citation ratio, clinical impact, and approximate potential to translate. Publication records for both groups were compiled using the NIH Office of Portfolio Analysis' name disambiguation method and manually curated to ensure integrity of the data set. RESULTS: Of the 39 scholars, 29 were compared with 121 matched extramural ESIs. Five years before matriculation, the 2 groups had comparable numbers of publications, but scholars had a higher median weighted relative citation ratio, clinical impact, and approximate potential to translate score. Five years after matriculation, the scholars had a higher median number of publications than the ESIs, and the gap between scholars and ESIs, with scholars having higher scores, had widened for all metrics except approximate potential to translate scores. Of 10 of the 39 scholars at or approaching tenure eligibility, 6 have attained tenure (3 at NIH and 3 in academic institutions), and 4 are on track to attain tenure at NIH. CONCLUSIONS: All the Lasker clinical research scholars are substantially involved in clinical and translational research. Their productivity matches or exceeds that of a matched cohort of ESIs at U.S. academic institutions.