Are There Identifiable Risk Factors Associated With Heterotopic Ossification of the Temporomandibular Joint?

PURPOSE: Heterotopic ossification (HO) is defined as bone where it does not belong and as the abnormal presence of calcifications within soft tissues or joints. The purpose of this study was to answer the following clinical question: Are there identifiable risk factors associated with HO in and around the temporomandibular joint (TMJ)? METHODS: We designed a retrospective review of patients seen at the Department of Oral and Maxillofacial Surgery, Massachusetts General Hospital, between January 1985 and December 2019 and diagnosed with HO involving the TMJ. Variables studied included demographic factors, medical history including hereditary conditions, and specific TMJ history including past interventions. The primary outcome variable was the diagnosis of HO based on radiographic findings using the classification system described by Turlington and Durr. Inclusion criterion was clinical or radiographic evidence of TMJ HO. RESULTS: A total of 67 patients met the inclusion criteria. There were 48 females and 19 males (2.5:1) with an average age of 44.1 ± 16.7 years (range, 5-76 years). Risk factors associated with TMJ HO included musculoskeletal disease, psychiatric illness, history of trauma or previous TMJ surgeries, and congenital conditions. Of these, a history of nonsurgical TMJ therapy (odds ratio [OR], 3.5; P < .00) was most closely associated with HO. This was followed by male sex (OR, 3.1; P = .001), other craniofacial or musculoskeletal surgeries (OR, 2.4; P = .004), TMJ surgeries (OR, 1.9; P = .012), and neurogenic injury (OR, 1.8; P = .018). The results also demonstrated that patients diagnosed with TMJ HO were medically complex, with 86.6% presenting with other systemic conditions. CONCLUSION: This study identifies several risk factors which differ from those reported in the orthopedic literature. The Turlington and Durr classification is only partially helpful in clinical decision-making and needs to include HO associated with TMJ alloplasts and autogenous bone grafts (eg, costochondral grafts).

Natural History and Progression of Craniofacial Fibrous Dysplasia: A Retrospective Evaluation of 114 Patients From Massachusetts General Hospital.

PURPOSE: The natural history of fibrous dysplasia (FD) is poorly understood. The purpose of this study was to identify differences in demographic, clinical, and radiographic characteristics among patients with craniofacial FD, including McCune-Albright syndrome (MAS), polyostotic fibrous dysplasia (PFD), and monostotic fibrous dysplasia (MFD). We hypothesized that patients with MAS would show higher disease severity, have more complications, and undergo more operations than those with PFD or MFD. PATIENTS AND METHODS: A retrospective cohort study of patients with MAS or FD, evaluated at Massachusetts General Hospital from 2000 to 2018, was implemented. Patients of all ages and genders were identified through Massachusetts General Hospital Data Registries using International Classification of Diseases, Ninth Revision (ICD-9) and International Classification of Diseases, Tenth Revision (ICD-10) codes. Those with adequate clinical and radiographic data were included. Predictor variables were diagnosis of MAS, PFD, or MFD; age; and gender. Outcome variables included severity of disease at initial presentation (aggressive, nonaggressive and slow growing, or quiescent), number of operations, and complications: pain, sensory disturbances, pathologic fracture, airway obstruction, osteomyelitis, and dental findings. Data were analyzed with descriptive statistics and assessed for significance using χ2 tests and analysis of variance (P < .05). RESULTS: A total of 229 patients were identified: 114 had craniofacial FD, and 70 of these 114 (61.4%) met the inclusion criteria (48 of whom were female patients). The average age at diagnosis was 23.5 years; mean length of follow-up, 5.8 years. Diagnoses included MAS in 9 patients, PFD in 24, and MFD in 37. Signs and symptoms at initial presentation were pain (n = 29), sensory abnormalities (n = 13), facial deformity or swelling (n = 54), and dental findings (n = 25). At presentation, the biological behavior of disease was 77.8% aggressive, 11.1% nonaggressive, and 11.1% quiescent in the MAS group; 41.7%, 41.7%, and 16.7%, respectively, in the PFD group; and 29.7%, 29.7%, and 40.5%, respectively, in the MFD group. Patients with MAS were younger and were more likely to have pain, pathologic fractures, more bones involved, bilateral disease, and visual symptoms than those with PFD or MFD. MAS patients underwent more operations (mean, 4.2 ± 4.18) than those with PFD (mean, 2.6 ± 2.31; P = not significant) or MFD (mean, 1.7 ± 1.28; P = .010). CONCLUSIONS: The results of this study indicate that patients with MAS, presumably with the same mutation, are more likely to have aggressive disease, complications, and more operations than those with PFD or MFD.

Calibrating Pediatric Dental Faculty: Caries Management in Primary Teeth.

PURPOSE: The purpose of this study was to evaluate caries treatment decisions agreement in primary teeth among board-certified pedi- atric dentistry faculty at a single teaching institution. METHODS: Ten full-time faculty selected a treatment for each of 64 primary teeth in 17 children based on clinical photos and radiographs. Cases were presented under three different social and behavioral scenarios. Descriptive and kappa statistics were calculated. RESULTS: The interrater reliability was 0.59 for the decision at the surgical versus nonsurgical level and 0.55 for the treatment-specific decision (e. g., crown versus extraction). Surgical treatments were the predominant preference (76 percent of responses). Non- surgical treatments were preferred for early-stage lesions and in nonideal social and behavioral scenarios. Surgical options were unanimously preferred in sedation or general anesthesia. CONCLUSIONS: Different clinical scenarios highlight different treatment preferences among faculty. Further emphasis should be placed on calibrating the decision-making process for selecting caries treatment in primary teeth among pediatric dentists.

Toxoplasma gondii activates hypoxia-inducible factor (HIF) by stabilizing the HIF-1alpha subunit via type I activin-like receptor kinase receptor signaling.

Toxoplasma gondii is an intracellular protozoan parasite that can cause devastating disease in fetuses and immune-compromised individuals. We previously reported that the alpha subunit of the host cell transcription factor, hypoxia-inducible factor-1 (HIF-1), is up-regulated by infection and necessary for Toxoplasma growth. Under basal conditions, HIF-1alpha is constitutively expressed but rapidly targeted for proteasomal degradation after two proline residues are hydroxylated by a family of prolyl hydroxylases (PHDs). The PHDs are alpha-ketoglutarate-dependent dioxygenases that have low K(m) values for oxygen, making them important cellular oxygen sensors. Thus, when oxygen levels decrease, HIF-1alpha is not hydroxylated, and HIF-1 is activated. How Toxoplasma activates HIF-1 under normoxic conditions remains unknown. Here, we report that Toxoplasma infection increases HIF-1alpha stability by preventing HIF-1alpha prolyl hydroxylation. Infection significantly decreases PHD2 abundance, which is the key prolyl hydroxylase for regulating HIF-1alpha. The effects of Toxoplasma on HIF-1alpha abundance and prolyl hydroxylase activity require activin-like receptor kinase signaling. Finally, parasite growth is severely diminished when signaling from this family of receptors is inhibited. Together, these data indicate that PHD2 is a key host cell factor for T. gondii growth and represent a novel mechanism by which a microbial pathogen subverts host cell signaling and transcription to establish its replicative niche.

Host cell invasion by Toxoplasma gondii is temporally regulated by the host microtubule cytoskeleton.

Toxoplasma gondii is an obligate intracellular protozoan parasite that invades and replicates within most nucleated cells of warm-blooded animals. The basis for this wide host cell tropism is unknown but could be because parasites invade host cells using distinct pathways and/or repertoires of host factors. Using synchronized parasite invasion assays, we found that host microtubule disruption significantly reduces parasite invasion into host cells early after stimulating parasite invasion but not at later time points. Host microtubules are specifically associated with the moving junction, which is the site of contact between the host cell and the invading parasite. Host microtubules are specifically associated with the moving junction of those parasites invading early after stimulating invasion but not with those invading later. Disruption of host microtubules has no effect on parasite contact, attachment, motility, or rate of penetration. Rather, host microtubules hasten the time before parasites commence invasion. This effect on parasite invasion is distinct from the role that host microtubules play in bacterial and viral infections, where they function to traffic the pathogen or pathogen-derived material from the host cell's periphery to its interior. These data indicate that the host microtubule cytoskeleton is a structure used by Toxoplasma to rapidly infect its host cell and highlight a novel function for host microtubules in microbial pathogenesis.

Dependence of stress resistance on a spore coat heteropolysaccharide in Dictyostelium.

In Dictyostelium, sporulation occurs synchronously as prespore cells approach the apex of the aerial stalk during culmination. Each prespore cell becomes surrounded by its own coat comprised of a core of crystalline cellulose and a branched heteropolysaccharide sandwiched between heterogeneous cysteine-rich glycoproteins. The function of the heteropolysaccharide, which consists of galactose and N-acetylgalactosamine, is unknown. Two glycosyltransferase-like genes encoding multifunctional proteins, each with predicted features of a heteropolysaccharide synthase, were identified in the Dictyostelium discoideum genome. pgtB and pgtC transcripts were modestly upregulated during early development, and pgtB was further intensely upregulated at the time of heteropolysaccharide accumulation. Disruption of either gene reduced synthase-like activity and blocked heteropolysaccharide formation, based on loss of cytological labeling with a lectin and absence of component sugars after acid hydrolysis. Cell mixing experiments showed that heteropolysaccharide expression is spore cell autonomous, suggesting a physical association with other coat molecules during assembly. Mutant coats expressed reduced levels of crystalline cellulose based on chemical analysis after acid degradation, and cellulose was heterogeneously affected based on flow cytometry and electron microscopy. Mutant coats also contained elevated levels of selected coat proteins but not others and were sensitive to shear. Mutant spores were unusually susceptible to hypertonic collapse and damage by detergent or hypertonic stress. Thus, the heteropolysaccharide is essential for spore integrity, which can be explained by a role in the formation of crystalline cellulose and regulation of the protein content of the coat.

Toxoplasma gondii rhoptry discharge correlates with activation of the early growth response 2 host cell transcription factor.

Toxoplasma gondii is a ubiquitous apicomplexan parasite that can cause severe disease in fetuses and immune-compromised patients. Rhoptries, micronemes, and dense granules, which are secretory organelles unique to Toxoplasma and other apicomplexan parasites, play critical roles in parasite growth and virulence. To understand how these organelles modulate infected host cells, we sought to identify host cell transcription factors triggered by their release. Early growth response 2 (EGR2) is a host cell transcription factor that is rapidly upregulated and activated in Toxoplasma-infected cells but not in cells infected with the closely related apicomplexan parasite Neospora caninum. EGR2 upregulation occurred only when live parasites were in direct contact with the host cell and not from exposure to cell extracts that contain dense granule or micronemal proteins. When microneme-mediated attachment was blocked by pretreating parasites with a calcium chelator, EGR2 expression was significantly reduced. In contrast, when host cells were infected with parasites in the presence of cytochalasin D, which allows rhoptry secretion but prevents parasite invasion, EGR2 was activated. Finally, we demonstrate that Toxoplasma activation of host p38 mitogen-activated protein kinase is necessary but not sufficient for EGR2 activation. Collectively, these data indicate that EGR2 is specifically upregulated by a parasite-derived secreted factor that is most likely a resident rhoptry protein.

Not a "mom thing": Predictors of gatekeeping in same-sex and heterosexual parent families.

The current study is the first to examine parental gatekeeping in both same-sex (57 female, 51 male) and heterosexual (n = 82) couples, all of whom became parents via adoption. Aspects of the individual, the couple, and the work context, measured preadoption, were examined as predictors of gatekeeping. Gatekeeping refers to attitudes and behaviors aimed at regulating and limiting the involvement of the other parent in housework and child care and was measured 2 years postadoption. Findings revealed that women in heterosexual relationships reported higher gatekeeping compared with all other groups, and men in same-sex relationships reported higher gatekeeping compared with women in same-sex relationships and men in heterosexual relationships. Across the full sample, lower job autonomy predicted higher gatekeeping in both housework and child care, whereas greater relationship ambivalence, greater perceived parenting skill, and lower perceived partner parenting skill predicted higher gatekeeping in child care. Findings provide insight into how gatekeeping behaviors and beliefs are enacted in diverse types of couples and suggest that work factors should be taken into account when conducting research on, and seeking to improve, coparenting relationships. (PsycINFO Database Record

African American Gay Family Networks: An Entry Point for HIV Prevention.

Gay families are constructed support networks that gay, bisexual, and transgender individuals of color form, often in response to societal marginalization and rejection from biological families. Research on these family structures has been scarce, with little focus on the experience of African American gay family networks in the South. The current grounded theory qualitative study focused on the experiences of 10 African American male and transgender individuals between the ages of 18 and 29 from gay families in the Mid-South, and explored the ways these families addressed safe-sex issues and human immunodeficiency virus (HIV) risk prevention. Results revealed that families can play a role in either increasing HIV risk (e.g., ignoring HIV issues, encouraging such unsafe behaviors as exchanging sex for money or drugs, stigmatizing HIV-positive people) or decreasing it (e.g., intensive, family-level prevention efforts at safe-sex practices and family support for HIV treatment adherence). The potential of these family networks for HIV prevention and adherence efforts is considered.

Heat-related deaths.

Risk factors and criteria for classifying deaths as heat related are discussed with emphasis on investigation of the circumstances.