Biogeographical Impacts of Dental, Oral, and Craniofacial Microbial Reservoirs.

The human mouth, or oral cavity, is at the crossroads of our external and internal environments, and it is increasingly evident that local colonization of dental, oral, and craniofacial (DOC) tissues and cells by bacteria and viruses may also have systemic effects across myriad diseases and disorders. Better understanding of this phenomenon will require a holistic understanding of host-microbial interactions in both spatiotemporal and biogeographical contexts while also considering person-, organ-, tissue-, cell-, and molecular-level variation. After the acute phase interaction with microbes, the establishment of site-specific reservoirs constitutes an important relationship to understand within the human body; however, despite a preliminary understanding of how viral reservoirs originate and persist across the human body, the landscape of single-cell and spatial multiomic tools has challenged our current understanding of what cells and niches can support microbial reservoirs. The lack of complete understanding impacts research into these relevant topics and implementing precision care for microbial-induced or microbial-influenced diseases. Here, via the lens of acute and chronic microbial infections of the DOC tissues, the goal of this review is to highlight and link the emerging spatiotemporal biogeography of host-viral interactomics at 3 levels: (1) DOC cell types in distinct tissues, (2) DOC-associated microbes, and (3) niche-specific DOC pathologies. Further, we will focus on the impact of postacute infectious syndromes such as long COVID, neurodegenerative disorders, and other underappreciated postviral conditions. We will provide hypotheses about how DOC tissues may play roles systemically in these conditions. Throughout, we will underscore how COVID-19 has catalyzed a new understanding of these biological questions, discuss future directions to study these phenomena, and highlight the utility of noninvasive oral biofluids in screening, monitoring, and intervening to prevent and/or ameliorate human infectious diseases.

A Roadmap for the Human Oral and Craniofacial Cell Atlas.

Oral and craniofacial tissues are uniquely adapted for continuous and intricate functioning, including breathing, feeding, and communication. To achieve these vital processes, this complex is supported by incredible tissue diversity, variously composed of epithelia, vessels, cartilage, bone, teeth, ligaments, and muscles, as well as mesenchymal, adipose, and peripheral nervous tissue. Recent single cell and spatial multiomics assays-specifically, genomics, epigenomics, transcriptomics, proteomics, and metabolomics-have annotated known and new cell types and cell states in human tissues and animal models, but these concepts remain limitedly explored in the human postnatal oral and craniofacial complex. Here, we highlight the collaborative and coordinated efforts of the newly established Oral and Craniofacial Bionetwork as part of the Human Cell Atlas, which aims to leverage single cell and spatial multiomics approaches to first understand the cellular and molecular makeup of human oral and craniofacial tissues in health and to then address common and rare diseases. These powerful assays have already revealed the cell types that support oral tissues, and they will unravel cell types and molecular networks utilized across development, maintenance, and aging as well as those affected in diseases of the craniofacial complex. This level of integration and cell annotation with partner laboratories across the globe will be critical for understanding how multiple variables, such as age, sex, race, and ancestry, influence these oral and craniofacial niches. Here, we 1) highlight these recent collaborative efforts to employ new single cell and spatial approaches to resolve our collective biology at a higher resolution in health and disease, 2) discuss the vision behind the Oral and Craniofacial Bionetwork, 3) outline the stakeholders who contribute to and will benefit from this network, and 4) outline directions for creating the first Human Oral and Craniofacial Cell Atlas.

Use of sport-related concussion information sources among parents of United States middle school children.

OBJECTIVE: Parents may use various information sources to obtain information about sport-related concussions (SRC). This study examined SRC-related information sources used by parents of United States middle school children (age: 10-15 years). METHODS: A panel of 1083 randomly selected U.S. residents, aged ≥18 years and identifying as parents of middle school children, completed an online questionnaire capturing parental and child characteristics, and utilization and perceived trustworthiness of various sources of SRC-related information. Multivariable logistic regression models identified factors associated with utilizing each source. Adjusted odds ratios (OR) with 95% confidence intervals (95%CIs) excluding 1.00 were deemed significant. RESULTS: Doctors/healthcare providers (49.9%) and other healthcare-related resources (e.g., Centers for Disease Control and Prevention, WebMD) (37.8%) were common SRC-related information sources; 64.0% of parents utilized ≥1 of these sources. Both sources were considered "very" or "extremely" trustworthy for SRC-related information among parents using these sources (doctors/healthcare providers: 89.8%; other healthcare-related resources: 70.9%). A 10-year increase in parental age was associated with higher odds of utilizing doctors/healthcare providers (adjusted odd ratio (ORadjusted) = 1.09, 95%CI: 1.02-1.16) and other healthcare-related resources (ORadjusted = 1.11, 95%CI: 1.03-1.19). The odds of utilizing doctors/healthcare providers (ORadjusted = 0.58, 95%CI: 0.40-0.84) and other healthcare-related resources (ORadjusted = 0.64, 95%CI: 0.44-0.93) were lower among parents whose middle school children had concussion histories versus the parents of children who did not have concussion histories. CONCLUSION: One-third of parents did not report using doctors/healthcare providers or other healthcare-related resources for SRC-related information. Factors associated with underutilization of these sources may be targets for future intervention. Continuing education for healthcare providers and educational opportunities for parents should highlight accurate and up-to-date SRC-related information.

Factors associated with concussion-symptom knowledge and attitudes toward concussion care seeking in a national survey of parents of middle-school children in the US.

BACKGROUND: Developing appropriate concussion prevention and management paradigms in middle school (MS) settings requires understanding parents' general levels of concussion-related knowledge and attitudes. This study examined factors associated with concussion-symptom knowledge and care-seeking attitudes among parents of MS children (aged 10-15 years). METHODS: A panel of 1224 randomly selected U.S. residents, aged ≥ 18 years and identifying as parents of MS children, completed an online questionnaire capturing parental and child characteristics. The parents' concussion-symptom knowledge was measured using 25 questions, with possible answers being "yes", "maybe", and "no". Correct answers earned 2 points, "maybe" answers earned 1 point, and incorrect answers earned 0 point (range: 0-50; higher scores = better knowledge). Concussion care-seeking attitudes were also collected using five 7-point scale items (range: 5-35; higher scores = more positive attitudes). Multivariable ordinal logistic regression models identified predictors of higher scores. Models met proportional odds assumptions. Adjusted odds ratios (aORs) with 95% confidence intervals (95%CIs) (excluding 1.00) were deemed statistically significant. RESULTS: Median scores were 39 (interquartile range: 32-44) for symptom knowledge and 32 (interquartile range: 28-35) for care-seeking attitude. In multivariable models, odds of better symptom knowledge were higher in women vs. men (aOR = 2.28; 95%CI: 1.71-3.05), white/non-Hispanics vs. other racial or ethnic groups (aOR = 1.88; 95%CI: 1.42-2.49), higher parental age (10-year-increase aOR = 1.47; 95%CI: 1.26-1.71), and greater competitiveness (10%-scale-increase aOR = 1.24; 95%CI: 1.13-1.36). Odds of more positive care-seeking attitudes were higher in white/non-Hispanics vs. other racial or ethnic groups (aOR = 1.45; 95%CI: 1.06-1.99) and in older parental age (10-year-increase aOR = 1.24; 95%CI: 1.05-1.47). CONCLUSION: Characteristics of middle school children's parents (e.g., sex, race or ethnicity, age) are associated with their concussion-symptom knowledge and care-seeking attitudes. Parents' variations in concussion knowledge and attitudes warrant tailored concussion education and prevention.

Approaching community priorities in youth sports injury prevention research.

BACKGROUND: Research in youth sports is often complex. As interest in youth sports injury prevention grows, scientists should consider community priorities beyond a specific research study. MAIN TEXT: This commentary discusses the authors' personal experiences researching concussion prevention in middle school sports, as the overarching community faced multiple challenges. These challenges included a series of weather-related emergencies that resulted in a shift in the community's priorities, multi-day school closures, and cancellations of sports activities and meetings. We discuss the importance of considering community priorities and providing support as scientists, colleagues, and members of the communities in which we conduct research. CONCLUSION: Scientists should consider the changing circumstances and dynamics surrounding community priorities in order to help drive their research-based decisions and ensure successful and respectful applications of research based on community values and priorities.

Flossing Is Associated with Improved Oral Health in Older Adults.

The effect of preventive oral habits is largely unexplored in older individuals. The purpose of this study was to evaluate the associations between home use of flossing and prevalence of periodontal disease and caries in older adults. Five-year incident tooth loss was also evaluated. Data on 686 individuals ≥65 y-old from the Piedmont 65+ Dental Study were examined including: 1) interproximal clinical attachment level (iCAL), 2) interproximal probing depth (iPD), 3) numbers of caries, and 4) missing teeth. Flossing behavior was evaluated according to the Periodontal Profile Class (PPC) system. Five-year follow-up data (n = 375) was evaluated for incident tooth loss. Dichotomous and categorical variables were analyzed using Pearson chi-square tests as well as covariate-adjusted Cochran-Mantel-Haenszel tests. Multiple linear regression compared clinical parameters based on flossing behavior. Elderly flossers had lower (mean, SE) %iCAL≥3 mm (38.2, 2.38 vs. 48.8, 1.56) and %iPD≥4 mm (8.70, 1.41 vs. 14.4, 0.93) compared to nonflossers (P ≤ 0.005). Flossers showed less coronal caries compared to nonflossers (P = 0.02). Baseline number of missing teeth (mean, SE) was 11.5 (0.35) in nonflossers compared to 8.6 (0.53) in flossers (P < 0.0001). Regular dental visitors had lower oral disease levels compared to episodic dental users. The majority of flossers classified into PPC-Stage I (health) whereas nonflossers classified as PPC-Stages V, VI, and VII (disease). At the 5-y follow-up visit, the average tooth loss for flossers was ~1 tooth compared to ~4 teeth lost for nonflossers (P < 0.0001). Among all teeth, molars showed the highest benefit (>40%) for flossing behavior (P = 0.0005). In conclusion, the extent of oral disease for older individuals was significantly less in flossers than in nonflossers. Flossers showed less periodontal disease, fewer dental caries, and loss of fewer teeth over a 5-y period. These findings further support flossing as an important oral hygiene behavior to prevent oral disease progression in older adults.

Transcriptomic profiling of tantalum metal implant osseointegration in osteopenic patients.

OBJECTIVES: The long-term success of dental implants is established by literature. Although clinically well defined, the complex genetic pathways underlying osseointegration have not yet been fully elucidated. Furthermore, patients with osteopenia/osteoporosis are considered to present as higher risk for implant failure. Porous tantalum trabecular metal (PTTM), an open-cell porous biomaterial, is suggested to present enhanced biocompatibility and osteoconductivity. The goal of this study was to evaluate the expression patterns of a panel of genes closely associated with osteogenesis and wound healing in osteopenic patients receiving either traditional titanium (Ti) or PTTM cylinders to assess the pathway of genes activation in the early phases of osseointegration. MATERIAL AND METHODS: Implant cylinders made of Ti and PTTM were placed in osteopenic volunteers. At 2- and 4 weeks of healing, one Ti and one PTTM cylinder were removed from each subject for RT-PCR analysis using osteogenesis PCR array. RESULTS: Compared to Ti, PTTM-associated bone displayed upregulation of bone matrix proteins, BMP/TGF tisuperfamily, soluble ligand and integrin receptors, growth factors, and collagen genes at one or both time points. Histologically, PTTM implants displayed more robust osteogenesis deposition and maturity when compared to Ti implants from the same patient. CONCLUSIONS: Our results indicate that PTTM properties could induce an earlier activation of genes associated with osteogenesis in osteopenic patients suggesting that PTTM implants may attenuate the relative risk of placing dental implants in this population.

Using opinion leaders to address intervention gaps in concussion prevention in youth sports: key concepts and foundational theory.

Behavioral interventions to increase disclosure and proper management of concussion in youth sports have unrealized potential when it comes to preventing concussion. Interventions have focused on changing individual athlete behavior and have fallen short of the potential for sustained systemic behavioral change. One potentially critical reason for this shortfall is that other key determinants of risk behaviors at all levels of the socio-ecological model (e.g. interpersonal, community, policy) are not addressed in extant programming. There is a critical need for theory-driven interventions that address concussion prevention and education at the community level and target sustainable culture change. The Popular Opinion Leader (POL) intervention, a multi-level intervention model previously successfully employed in multiple public health contexts, is theoretically well positioned to affect such change. POL is based on the Diffusion of Innovations framework and involves identifying, recruiting, and training well-respected and trusted individuals to personally endorse prevention and risk-reduction within their social networks. Critical behavioral changes related to concussion disclosure and management have been shown to diffuse to others if enough opinion leaders endorse and support the behaviors. This article summarizes the concepts and principles of POL and describes how it could be adapted for and implemented in youth sport settings. For optimal impact, POL needs to adapt to several factors unique to youth sports settings and culture. First, adult involvement may be important, given their direct involvement in the athlete's medical care. However, parents and coaches' opinions on injury care-seeking, competition, and safety may affect their perceptions of POL. Second, youth sports are structured settings both physically and socioculturally. Games and practices may provide opportunities for the informal interactions that are critical to the success of POL. However, youth sport setting membership is transient as players get older and move to other sport settings; POL approaches need to be self-sustaining despite this turnover. Moreover, stakeholder value placed on athlete development and competition, alongside safety, must be considered. Formative research is needed to ensure that POL principles are translated into the youth sport setting while maintaining fidelity to the concepts and principles that have made POL successful for other health outcomes.

Closing the Gap: Mouse Models to Study Adhesion in Secondary Palatogenesis.

Secondary palatogenesis occurs when the bilateral palatal shelves (PS), arising from maxillary prominences, fuse at the midline, forming the hard and soft palate. This embryonic phenomenon involves a complex array of morphogenetic events that require coordinated proliferation, apoptosis, migration, and adhesion in the PS epithelia and underlying mesenchyme. When the delicate process of craniofacial morphogenesis is disrupted, the result is orofacial clefting, including cleft lip and cleft palate (CL/P). Through human genetic and animal studies, there are now hundreds of known genetic alternations associated with orofacial clefts; so, it is not surprising that CL/P is among the most common of all birth defects. In recent years, in vitro cell-based assays, ex vivo palate cultures, and genetically engineered animal models have advanced our understanding of the developmental and cell biological pathways that contribute to palate closure. This is particularly true for the areas of PS patterning and growth as well as medial epithelial seam dissolution during palatal fusion. Here, we focus on epithelial cell-cell adhesion, a critical but understudied process in secondary palatogenesis, and provide a review of the available tools and mouse models to better understand this phenomenon.

Impact of providing in-home water service on the rates of infectious diseases: results from four communities in Western Alaska.

Approximately 20% of rural Alaskan homes lack in-home piped water; residents haul water to their homes. The limited quantity of water impacts the ability to meet basic hygiene needs. We assessed rates of infections impacted by water quality (waterborne, e.g. gastrointestinal infections) and quantity (water-washed, e.g. skin and respiratory infections) in communities transitioning to in-home piped water. Residents of four communities consented to a review of medical records 3 years before and after their community received piped water. We selected health encounters with ICD-9CM codes for respiratory, skin and gastrointestinal infections. We calculated annual illness episodes for each infection category after adjusting for age. We obtained 5,477 person-years of observation from 1032 individuals. There were 9,840 illness episodes with at least one ICD-9CM code of interest; 8,155 (83%) respiratory, 1,666 (17%) skin, 241 (2%) gastrointestinal. Water use increased from an average 1.5 gallons/capita/day (g/c/d) to 25.7 g/c/d. There were significant (P-value < 0.05) declines in respiratory (16, 95% confidence interval (CI): 11-21%), skin (20, 95%CI: 10-30%), and gastrointestinal infections (38, 95%CI: 13-55%). We demonstrated significant declines in respiratory, skin and gastrointestinal infections among individuals who received in-home piped water. This study reinforces the importance of adequate quantities of water for health.

fMRI study of brain activity elicited by oral parafunctional movements.

Parafunctional masticatory activity, such as the tooth clenching and grinding that is associated with bruxism, is encountered by clinicians in many disciplines, including dentistry, neurology and psychiatry. Despite this, little is known about the neurological basis for these activities. To identify the brain network engaged in such complex oromotor activity, functional magnetic resonance imaging (fMRI) was used to elucidate the brain activation patterns of 20 individuals (10 males and 10 females, mean s.d. age of 26.3+/-4.1 years) with (parafunctional, PFx group, 5M/5F) and without (normal functional, NFx group, 5 M/5F) self-reported parafunctional grinding and clenching habits during clenching and grinding tasks. Subject group classification was based on: (i) self-reported history, (ii) clinical examination, (iii) evaluation of dental casts and (iv) positive responses to the temporomandibular disorder (TMD) History Questionnaire [Dworkinand LeResche, Journal of Craniomandibular Disorders, (1992) 6:301]. While subjects performed these oromotor tasks, each wore a custom-designed oral appliance minimizing head motion during imaging. Mean per cent signal changes showed significant between group differences in motor cortical (supplementary motor area, sensorimotor cortex and rolandic operculum) and subcortical (caudate) regions. Supplementary motor area data suggest that motor planning and initiation, particularly during the act of clenching, are less prominent in individuals with oromotor parafunctional behaviours. The overall extent of activated areas was reduced in subjects with self-reported parafunctional masticatory activity compared with the controls. This study's methodology and findings provide an initial step in understanding the neurological basis of parafunctional masticatory activities that are relevant for therapeutic research applications of temporomandibular joint and muscle disorders and associated comorbidities.

Effects of post-natal serotonin levels on craniofacial complex.

Although the role of serotonin (5-hydroxytryptamine or 5-HT) in pre-natal craniofacial growth and development has been studied, no research has been done on the effects of serotonin on post-natal craniofacial growth and development. The following experimental question was tested: What effect does increasing in vivo serotonin levels adjacent to trigeminal motoneurons have on post-natal craniofacial structures in young, actively growing rats? Forty male Sprague-Dawley rats were divided into 4 experimental groups (10% serotonin microspheres, 15% serotonin microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at post-natal day 35; 5 rats of each group were killed at 14 and 21 post-surgical days for data collection. Statistical analyses by mixed-model, 4 x 2 repeated-measures ANOVA, and post hoc Fisher LSD tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for muscle weight, cranial dimension, and TMJ dimension data. Data described here indicate that significant alterations of post-natal craniofacial structures can be caused by altered in vivo levels of serotonin adjacent to trigeminal motoneurons.

A chromatin insulator determines the nuclear localization of DNA.

Chromatin insulators might regulate gene expression by controlling the subnuclear organization of DNA. We found that a DNA sequence normally located inside of the nucleus moved to the periphery when the gypsy insulator was placed within the sequence. The presence of the gypsy insulator also caused two sequences, normally found in different regions of the nucleus, to come together at a single location. Alterations in this subnuclear organization imposed by the gypsy insulator correlated with changes in gene expression that took place during the heat-shock response. These global changes in transcription were accompanied by dramatic alterations in the distribution of insulator proteins and DNA. The results suggest that the nuclear organization imposed by the gypsy insulator on the chromatin fiber is important for gene expression.

The role of density on the release profiles of hydrophobic and hydrophilic compounds from TCPL delivery systems.

Several studies have shown that tri-calcium phosphate lysine drug delivery systems (TCPL) are capable of releasing various organic compounds at a sustained manner for long duration. The fabrication of TCPL devices is complex and the manipulation of various factors can alter drug release profiles. The compression of the TCPL material into the capsular form is an instrumental factor when studying the desired release profile. The objectives of this investigation were: 1) to study the interrelationship between the release profiles of devices that had been cold pressed at two different densities (1.53 +/- 0.15 (Low density, TCPL-LD) and 1.98 +/- 0.7 gm/cm3 (High density, TCPL-HD)), and 2) to evaluate the role of the change in density that might have on the release of hydrophobic and hydrophilic compounds in an in vitro environment. A total of 16 serum bottles were used and later subdivided into four groups (n = 4). Groups I and II contained TCPL-HD and TCPL-LD capsules each loaded with 20 mg of progesterone (P). Groups III & IV contained TCPL-HD and TCPL-LD capsules that were loaded with 20 mg of Bovine Serum Albumin (BSA). Each serum bottle in groups III and IV was filled with 100 mL of phosphate buffer saline (pH 7.4) and 10 microL of sodium azide (antibacterial agent). Serum bottles in groups I and II were filled with 50% alcohol (wt/vol). Samples were withdrawn at various time intervals and the release profiles were analyzed by using standard spectrophotometer techniques. Data analysis was conducted by using Jandel Sigma Stat Statistical software. Results of this investigation suggest that: 1) TCPL-HD and TCPL-LD devices were capable of releasing P and BSA at sustained levels, 2) regardless of the loaded drugs, the release profiles from TCPL-LD devices was found to be significantly higher (p < 0.05) than the release profiles of P and BSA from TCPL-HD, and 3) physiochemical characteristics of the drug to be delivered are instrumental in regulating the rate of release and duration or availability of an effective and safe dose (BSA > P).

Increased in vivo levels of neurotransmitters to trigeminal motoneurons: effects on craniofacial bone and TMJ.

The results of chronic, in vivo delivery of excitatory and inhibitory neurotransmitter substances upon the craniofacial skeleton are of ongoing interest to clinician and basic scientist alike. Our purpose was to document and compare the effects of biodegradable glycine, glutamate, and thyrotropin-releasing hormone (TRH) microspheres upon the craniofacial skeleton and TMJ of actively growing rats. Glycine, glutamate, TRH, and blank microspheres were stereotactically implanted in proximity to motoneurons within the trigeminal motor nucleus in order to test the following null hypotheses: (1) neurotransmitter microspheres implanted near trigeminal motoneurons of growing rats have no significant effect on the craniofacial skeleton and temporomandibular joints of implanted animals, and (2) there are no significant differences between the relative effects of glutamate, TRH (excitatory to trigeminal motoneurons), and glycine (inhibitory to trigeminal motoneurons) implants upon the craniofacial skeleton and temporomandibular joint. Fifty male Sprague-Dawley rats underwent stereotactic neurosurgery at 35 days; five rats each were killed at 14 and 21 days postoperative for data collection and comparison between glycine-, glutamate-, TRH-, blank-microsphere, and sham-surgery rats. Glycine rats had significantly (P < or = 0.05, 0. 01) smaller implant-side cranial dimensions and mandibular condyles, all glycine rats showed increased gracility of implant-side bones, and deviation of their facial skeleton away from the implant-side; this was in contrast to the generally larger implant-side bony structures in both glutamate and TRH rats. The two null hypotheses were both rejected. Due to their inhibitory and excitatory effects upon trigeminal motoneurons, masticatory muscles, and their neuromuscular generation of biomechanical forces that affect bone, the neurotransmitter substances glycine, glutamate, and TRH appear to play an important role in the growth and development of the mammalian craniofacial skeleton and TMJ.

Prolonged seizure suppression by a single implantable polymeric-TRH microdisk preparation.

Thyrotropin-releasing hormone (TRH; Protirelin) is an endogenous neuropeptide known to have anticonvulsant effects in several seizure models and in intractable epileptic patients. Like most neuropeptides, its duration of action may be limited by a lack of sustained site-specific bioavailability. To attempt to provide long-term delivery, we attached TRH to a biodegradable polyanhydride copolymer as a sustained-release carrier. Utilizing the rat kindling model of temporal lobe epilepsy, a single TRH microdisk implanted stereotaxically into the seizure focus (amygdala) significantly suppressed kindling expression when assessed by the number of stimulations required to reach each behavioral stage and to become fully kindled (8.63 +/- 0.92 vs. 16.17 +/- 1.37; Mean +/- S.E.M.). Two indices of seizure severity, afterdischarge duration (Mean +/- S.E.M., sec.) (stimulated amygdala [87.40 +/- 5.47 vs. 51.80 +/- 15.65] and unstimulated amygdala [89.60 +/- 5.55 vs. 48.67 +/- 15.8] and clonus duration (71.2 +/- 5.94 vs. 29.40 +/- 8.87; Mean +/- S.E.M., sec.), were also significantly reduced by a single polymeric-TRH implant. Fifty days after initiation of the study a significant reduction in clonus duration (53.90 +/- 3.27 vs. 40.09 +/- 4.14) still remained in the TRH-implanted groups. This report is the first to provide evidence in support of in situ microdisk pharmacotherapy for potential neuropeptide delivery in intractable epilepsy and possibly other neurological disorders.

Oxidative capacity of rat masseter muscle after implantation of thyrotropin-releasing hormone microspheres in proximity to trigeminal motoneurones.

Earlier work has shown that two important consequences of implanting thyrotropin-releasing hormone (TRH) microspheres near motoneurones within the trigeminal motor nucleus of actively growing rats are increased muscle mass and a darkening of the implant-side masticatory muscles. These phenomena have been associated with altered neuromuscular activity patterns and biomechanical forces that directly influence craniofacial growth and development. Now, whether the implantation of TRH microspheres in proximity to trigeminal motoneurones would affect the oxidative capacity of the implant-side masseter muscles was investigated. Cytochrome C oxidase (COX) assays were carried out for both implant- and non-implant-side masseters of TRH (n = 5) and blank microsphere (n = 6) Sprague-Dawley rats after stereotactic surgery at 35 days of age. Analyses of both groups at 14 days post-implantation revealed that the COX activity levels of implant-side masseters in TRH-implanted rats was significantly (P< or =0.05) greater than that of non-implant-side masseters; rats implanted with blank microsphere exhibited no significant difference between implant- and non-implant-side masseter COX activity levels. The stated null hypothesis was therefore rejected. These data suggest that TRH implants in proximity to trigeminal motoneurones effect increased oxidative capacity of the masseter muscle as measured by COX activity.

Death anxiety in young adults as a function of religious orientation, guilt, and separation-individuation conflict.

Seventy undergraduate participants between the ages of 19 and 30 were assessed with measures of death anxiety, religious orientation, separation--individuation conflict, and two dimensions of guilt (need for reparation and fear of punishment). A multiple regression with death anxiety as the criterion variable revealed the following variables, listed in order of their contributions to R2, to be significant predictors: fear of punishment, extrinsic religious orientation, need for reparation, and separation--individuation conflict. A model of death anxiety for young adults that addresses the developmental tasks of this stage is proposed.

Craniofacial and TMJ effects after glutamate and TRH microsphere implantation in proximity to trigeminal motoneurons of growing rats.

The sequelae of sustained, in vivo delivery of two important neurotransmitter substances, glutamate and thyrotropin-releasing hormone (TRH), upon craniofacial growth and development have previously not been investigated. Our purpose was to document and compare the relative effects of glutamate and TRH microspheres stereotactically placed in proximity to trigeminal motoneurons within the trigeminal motor nucleus. The following null hypotheses were tested: (1) TRH microspheres in proximity to trigeminal motoneurons have no significant effect upon the craniofacial skeleton, and (2) there are no significant differences between the relative effects of chronic, long-term delivery of glutamate and TRH upon the neuromusculoskeletal system of growing rats. Forty male Sprague-Dawley rats were divided into 4 experimental groups (glutamate microspheres, TRH microspheres, blank microspheres, sham surgeries) and underwent stereotactic neurosurgery at 35 days; 5 rats of each group were killed at 14 and 21 days for data collection. Histology revealed that implants were clustered in the pontine reticular formation, close to the ventrolateral tegmental nucleus. Both glutamate and TRH rats had implant-side deviation of their facial skeleton and snout regions; 4 x 2 ANOVA and post hoc t-tests revealed significant (P < or = 0.05, 0.01) differences between groups and sides for motoneuron count, muscle weight, and osteometric data. TRH rats also demonstrated larger implant-side TMJ discs and mandibular fossae in comparison with the other groups. The stated null hypotheses were therefore rejected.

Prevalence of retinal hemorrhages in pediatric patients after in-hospital cardiopulmonary resuscitation: a prospective study.

OBJECTIVE: Child abuse occurs in 1% of children in the United States every year; 10% of the traumatic injuries suffered by children under 5 years old are nonaccidental, and 5% to 20% of these nonaccidental injuries are lethal. Rapid characterization of the injury as nonaccidental is of considerable benefit to child protection workers and police investigators seeking to safeguard the child care environment and apprehend and prosecute those who have committed the crime of child abuse. Physically abused children present with a variety of well-described injuries that are usually easily identifiable. In some cases, however, particularly those involving children with the shaken baby syndrome, obvious signs of physical injury may not exist. Although external signs of such an injury are infrequent, the rapid acceleration-deceleration forces involved often cause subdural hematomas and retinal hemorrhages, hallmarks of the syndrome. Frequently, retinal hemorrhages may be the only presenting sign that child abuse has occurred. Complicating the interpretation of the finding of retinal hemorrhages is the belief by some physicians that retinal hemorrhages may be the result of chest compressions given during resuscitative efforts. The objective of this study is to determine the prevalence of retinal hemorrhages after inpatient cardiopulmonary resuscitation (CPR) in pediatric patients hospitalized for nontraumatic illnesses in an intensive care unit. DESIGN: Prospective clinical study. SETTING: Pediatric intensive care unit. PATIENTS: Forty-three pediatric patients receiving at least 1 minute of chest compressions as inpatients and surviving long enough for a retinal examination. Patients were excluded if they were admitted with evidence of trauma, documented retinal hemorrhages before the arrest, suspicion of child abuse, or diagnosis of near-drowning or seizures. All of the precipitating events leading to cardiopulmonary arrest occurred in our intensive care unit, eliminating the possibility of physical abuse as an etiology. INTERVENTIONS: None. MEASUREMENTS: Examination of the retina was performed by one of two pediatric ophthalmologists within 96 hours of CPR. The chart was reviewed for pertinent demographic information; the platelet count, prothrombin time, and partial thromboplastin time proximate to the CPR were recorded if they had been determined. RESULTS: A total of 43 pediatric patients hospitalized with nontraumatic illnesses survived 45 episodes of inpatient CPR. The mean age was 23 months (range, 1 month to 15.8 years), and 84% of the patients were under 2 years old. The majority of the patients (44%) were admitted to the intensive care unit after surgery for congenital heart disease, and another 21% were admitted for respiratory failure. The mean duration of chest compressions was 16.4 minutes +/- 17 minutes with 58% lasting between 1 and 10 minutes. Five patients had chest compressions lasting >40 minutes, and two patients had open chest cardiac massage. All patients survived their resuscitative efforts. Ninety-three percent of patients had an elevated prothrombin time and/or partial thromboplastin time while 49% were thrombocytopenic. Sixty-two percent of the patients had low platelet counts and an elevated prothrombin time and/or partial thromboplastin time. Small punctate retinal hemorrhages were found in only one patient. CONCLUSIONS: Retinal hemorrhages are rarely found after chest compressions in pediatric patients with nontraumatic illnesses, and those retinal hemorrhages that are found appear to be different from the hemorrhages found in the shaken baby syndrome. Despite the small number of patients in this prospective study, we believe that these data support the idea that chest compressions do not result in retinal hemorrhages in children with a normal coagulation profile and platelet count. A larger number of patients should be evaluated in a prospective multi-institutional study to achieve statistical significance