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OBJECTIVES: Despite data linking smoking to increased risk of fetal morbidity and mortality, 11% of pregnant women continue to smoke or use alternative nicotine products. Studies confirm that nicotine exposure during pregnancy increases the incidence of birth defects; however, little research has focused on specific anatomic areas based on timing of exposure. We aim to determine critical in utero and postnatal periods of nicotine exposure that affect craniofacial development, specifically palate growth. Malformation of the palatal structures can result in numerous complications including facial growth disturbance, or impeding airway function. We hypothesized that both in utero and postnatal nicotine exposure will alter palate development. MATERIALS AND METHODS: We administered pregnant C57BL6 mice water supplemented with 100 µg/mL nicotine during early pregnancy, throughout pregnancy, during pregnancy and lactation, or lactation only. Postnatal day 15 pups underwent micro-computed tomography (µCT) analyses specific to the palate. RESULTS: Resultant pups revealed significant differences in body weight from lactation-only nicotine exposure, and µCT investigation revealed several dimensions affected by lactation-only nicotine exposure, including palate width, palate and cranial base lengths, and mid-palatal suture width. CONCLUSIONS: These results demonstrate the direct effects of nicotine on the developing palate beyond simple tobacco use. Nicotine exposure through tobacco alternatives, cessation methods, and electronic nicotine delivery systems (ENDS) may disrupt normal growth and development of the palate during development and the postnatal periods of breastfeeding. Due to the recent dramatic increase in the use of ENDS, future research will focus specifically on this nicotine delivery method.
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Selective serotonin re-uptake inhibitors (SSRI) widely used in the treatment of depression, anxiety, obsessive compulsive disorder, fibromyalgia, and migraine are among the most heavily prescribed drug class in the United States (US). Along with an overall rise in SSRI use, these medications are increasingly used by pregnant individuals and recent preclinical and clinical studies have indicated that SSRIs may increase the prevalence of congenital abnormalities and birth defects of the craniofacial region. Our group has developed pre-clinical models of study, including those that mimic the clinical use of SSRI in mice. Here we designed a study to interrogate a commonly prescribed SSRI drug, Citalopram, for its effects on craniofacial and dental development when introduced in utero. Pre-natal exposure to a clinically relevant dose of citalopram resulted in changes in craniofacial form identified by an increase in endocast volume in SSRI exposed postnatal day 15 mouse pups. More specifically, cranial length and synchondrosis length increased in SSRI exposed pups as compared to control pups of the same age. Additionally, growth center (synchondrosis) height and width and palate length and width decreased in SSRI exposed pups as compared to control un-exposed pups. Effects of SSRI on the molars was minimal. Craniofacial growth and development continue to be an area of interest in the investigation of in utero pharmaceutical drug exposure. Altogether these data indicate that prenatal SSRI exposure affects craniofacial form in multiple tissues and specifically at growth sites and centers of the skull.
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Citalopram , Anormalidades Craniofaciais , Inibidores Seletivos de Recaptação de Serotonina , Crânio , Animais , Inibidores Seletivos de Recaptação de Serotonina/farmacologia , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Camundongos , Feminino , Gravidez , Citalopram/farmacologia , Crânio/efeitos dos fármacos , Anormalidades Craniofaciais/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Modelos Animais de Doenças , MasculinoRESUMO
Post-traumatic stress disorder (PTSD) is associated with osteopenia, osteoporosis and increased fracture risk in the clinical population. Yet, the development of preclinical models to study PTSD-induced bone loss remains limited. In this study, we present a previously unreported model of PTSD in adult female C57BL/6 mice, by employing inescapable foot shock and social isolation, that demonstrates high face and construct validity. A subset of mice exposed to this paradigm (i.e. PTSD mice) display long-term alterations in behavioral and inflammatory indices. Using three-dimensional morphometric calculations, cyclic reference point indentation (cRPI) testing and histological analyses, we find that PTSD mice exhibit loss of trabecular bone, altered bone material quality, and aberrant changes in bone tissue architecture and cellular activity. This adult murine model of PTSD exhibits clinically relevant changes in bone physiology and provides a valuable tool for investigating the cellular and molecular mechanisms underlying PTSD-induced bone loss.
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Transtornos de Estresse Pós-Traumáticos , Feminino , Camundongos , Animais , Transtornos de Estresse Pós-Traumáticos/complicações , Camundongos Endogâmicos C57BL , Fenótipo , Osso e Ossos , Modelos Animais de DoençasRESUMO
OBJECTIVES: Antidepressants, specifically Selective Serotonin Re-uptake Inhibitors (SSRIs), that alter serotonin metabolism are currently the most commonly prescribed drugs for the treatment of depression. There is some evidence to suggest these drugs contribute to birth defects. As jaw development is often altered in craniofacial birth defects, the purpose of this study was to interrogate the effects of in utero SSRI exposure in a preclinical model of mandible development. MATERIALS AND METHODS: Wild-type C57BL6 mice were used to produce litters that were exposed in utero to an SSRI, Citalopram (500 µg/day). Murine mandibles from P15 pups were analysed for a change in shape and composition. RESULTS: Analysis indicated an overall shape change with total mandibular length and ramus height being shorter in exposed pups as compared to controls. Histomorphometric analysis revealed that first molar length was longer in exposed pups while third molar length was shorter in exposed as compared to control. Histological investigation of molars and surrounding periodontium revealed no change in collagen content of the molar in exposed pups, some alteration in collagen composition in the periodontium, increased alkaline phosphatase in molars and periodontium and decreased mesenchymal cell marker presence in exposed mandibles. CONCLUSION: The results of this study reveal SSRI exposure may interrupt mandible growth as well as overall dental maturation in a model of development giving insight into the expectation that children exposed to SSRIs may require orthodontic intervention.
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Inibidores Seletivos de Recaptação de Serotonina , Serotonina , Animais , Camundongos , Inibidores Seletivos de Recaptação de Serotonina/efeitos adversos , Serotonina/metabolismo , Camundongos Endogâmicos C57BL , Citalopram/efeitos adversos , Mandíbula/metabolismoRESUMO
INTRODUCTION: Alveolar bone grafting aims to restore bony continuity of the alveolus and provide optimal periodontal support for teeth adjacent to the cleft. We created a survey of cleft surgeons to assess the current standard of care regarding this procedure. METHODS: A multiple choice survey was implemented using Qualtrics software and emailed to a list of 708 surgeons from the ACPA membership directory. Correlation between various provider factors and treatment practices was assessed with Fisher's exact test and likelihood ratio tests. RESULTS: The response rate was 17.5%. Eighty-seven percent of providers preferred to perform grafts prior to secondary canine eruption while 10% favored before central incisor eruption. Eighty-one percent favored palatal expansion prior to bone grafting. Wide variability existed regarding the time to initiate postoperative orthodontics; 43% waited 4 to 6 months. Sixty-four percent of surgeons now utilize cone beam CT to assess graft take. The majority of respondents utilized cancellous bone autograft (92%) from the anterior iliac crest (97%) as graft material. Seventy percent used three or more modalities for post-operative pain control management. Early career surgeons (0-5 years) appeared more likely to use non-autologous materials (p < .01) for grafting. CONCLUSION: Alveolar bone grafting prior to secondary canine eruption remains the most common strategy but other protocols are employed. Surgeons utilize multiple modalities for radiographic evaluation and most often use autologous cancellous bone as the primary grafting material. There is no true consensus on the perioperative timing and sequencing of orthodontic manipulation while principles of multimodal perioperative pain control appear widely accepted.
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Enxerto de Osso Alveolar , Fenda Labial , Fissura Palatina , Cirurgiões , Humanos , Transplante Ósseo/métodos , Fissura Palatina/cirurgia , Fenda Labial/cirurgia , Técnica de Expansão Palatina , Enxerto de Osso Alveolar/métodos , América do Norte , Estudos RetrospectivosRESUMO
AIMS: Evidence suggests alterations of thyroid hormone levels can disrupt normal bone development. Most data suggest the major targets of thyroid hormones to be the Htra1/Igf1 pathway. Recent discovery by our group suggests involvement of targets WNT pathway, specifically overexpression of antagonist Sfrp4 in the presence of exogenous thyroid hormone. MAIN METHODS: Here we aimed to model these interactions in vitro using primary and isotype cell lines to determine if thyroid hormone drives increased Sfrp4 expression in cells relevant to craniofacial development. Transcriptional profiling, bioinformatics interrogation, protein and function analyses were used. KEY FINDINGS: Affymetrix transcriptional profiling found Sfrp4 overexpression in primary cranial suture derived cells stimulated with thyroxine in vitro. Interrogation of the SFRP4 promoter identified multiple putative binding sites for thyroid hormone receptors. Experimentation with several cell lines demonstrated that thyroxine treatment induced Sfrp4 expression, demonstrating that Sfrp4 mRNA and protein levels are not tightly coupled. Transcriptional and protein analyses demonstrate thyroid hormone receptor binding to the proximal promoter of the target gene Sfrp4 in murine calvarial pre-osteoblasts. Functional analysis after thyroxine hormone stimulation for alkaline phosphatase activity shows that pre-osteoblasts increase alkaline phosphatase activity compared to other cell types, suggesting cell type susceptibility. Finally, we added recombinant SFRP4 to pre-osteoblasts in combination with thyroxine treatment and observed a significant decrease in alkaline phosphatase positivity. SIGNIFICANCE: Taken together, these results suggest SFRP4 may be a key regulatory molecule that prevents thyroxine driven osteogenesis. These data corroborate clinical findings indicating a potential for SFRP4 as a diagnostic or therapeutic target for hyperostotic craniofacial disorders.
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Fosfatase Alcalina , Tiroxina , Camundongos , Animais , Tiroxina/metabolismo , Fosfatase Alcalina/metabolismo , Osteoblastos/metabolismo , Via de Sinalização Wnt/genética , Osteogênese/genética , Proteínas Proto-Oncogênicas/metabolismoRESUMO
The human temporomandibular joint (TMJ) lateral capsule ligament (LCL) complex is debated as a fibrous capsule with distinct ligaments or ligamentous thickening, necessitating further evaluation of the complex and its role in TMJ anatomy and mechanics. This study explores the ultrastructural arrangement, biomechanical tensile properties, and biochemical composition of the human LCL complex including region-specific differences to explore the presence of a distinct temporomandibular ligament and sex-specific differences to inform evaluations of potential etiological mechanisms. LCL complex ultrastructural arrangement, biomechanical properties, and biochemical composition were determined using cadaveric samples. Statistical modeling assessed sex- and region-specific effects on LCL complex tissue properties. Collagen fiber coherency, collagen fiber bundle size, and elastin fiber count did not differ between sexes, but females trended higher in elastin fiber count. LCL complex water and sGAG content did not differ between sexes or regions, but collagen content was higher in the anterior region (311.0 ± 185.6 µg/mg) compared to the posterior region (221.0 ± 124.9 µg/mg) (p = 0.045) across sexes and in males (339.6 ± 170.6 µg/mg) compared to females (204.5 ± 130.7 µg/mg) (p = 0.006) across regions. Anterior failure stress (1.1 ± 0.7 MPa) was larger than posterior failure stress (0.6 ± 0.4 MPa) (p = 0.024). Regional differences confirm the presence of a mechanically and compositionally distinct temporomandibular ligament. Baseline sex-specific differences are critical for etiological investigations of sex disparities in TMJ disorders. These results have important biomechanical and clinical ramifications, providing critical baseline tissue material properties, informing the development of TMJ musculoskeletal models, and identifying new areas for etiologic investigations for temporomandibular disorders.
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Transtornos da Articulação Temporomandibular , Articulação Temporomandibular , Fenômenos Biomecânicos , Colágeno , Feminino , Humanos , Ligamentos Articulares , Masculino , Relação Estrutura-AtividadeRESUMO
OBJECTIVE: We aimed to assess significant ethnic variabilities in infants' nasolabial anthropometry to motivate variations in surgical correction of a synchronous bilateral cleft lip/nasal anomaly, specifically whether a long columella is a European feature, therefore accepting a short columella and/or delayed columellar lengthening suitable for reconstruction in ethnic patients. METHODS: Thirty-three infants without craniofacial pathology (10 African American [AA], 7 Hispanic [H], and 16 of European descent [C]), ages 3 to 8 months, presenting to the Johns Hopkins All Children's general pediatric clinic were recruited. Four separate 3D photographs (2 submental and frontal views each) were taken using the Vectra H1 handheld camera (Canfield Imaging). Eighteen linear facial distances were measured using Mirror 3D analysis (Canfield Imaging Systems). Difference between ethnicities was measured using analysis of variance with the Bonferroni/Dunn post hoc comparisons. Pearson correlation was employed for interrater reliability. All statistical analyses were carried out using SPSS version 21.0 (IBM Corp), with statistical significance set at P < .05. RESULTS: Nasal projection (sn-prn) and columella length (sn-c) did not differ significantly between groups (P = .9). Significant differences were seen between ethnic groups in nasal width (sbal-sbal [C-AA; P = .02]; ac-ac [C-AA; P = .00; H-AA; P = .04]; al-al [C-AA; P = .00; H-AA; P = .001]) and labial length (sn-ls [C-AA; P = .041]; sn-sto [C-AA; P = .005]; Cphs-Cphi L [C-AA; P = .013]; Cphs-Cphi R [C-AA; P = .015]). Interrater reliability was good to excellent and significantly correlated for all measures. CONCLUSIONS: African American infants exhibited wider noses and longer lips. No difference was noted in nasal projection or columella length, indicating that these structures should be corrected during the primary cleft lip and nasal repair for all patients and should not be deferred to secondary correction.
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Fenda Labial , Doenças Nasais , Antropometria , Criança , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Etnicidade , Humanos , Lactente , Septo Nasal , Nariz/anormalidades , Reprodutibilidade dos TestesRESUMO
Several teaching resources are used to enhance the learning of anatomy. The purpose of this study was to examine the preference of medical students on the use of various resources to learn anatomy and their link to 12 learning outcomes. A selected response item questionnaire was administered that asked students to rank six laboratory teaching resources from most to least preferred, and rate how useful these six resources were towards achieving 12 learning outcomes. These learning outcomes covered many of the learning domains such as demonstrating an understanding of anatomy, visualizing structures, appreciating clinical correlations, and understanding anatomical variations. Medical students ranked cadaveric prosections paired with an active learning clinical tutorial as the highest rank and most useful resource for learning anatomy, followed by dissection videos, electronic resources, and printed material, followed by plastinated specimens and plastic models. Overall, cadaveric prosections were also rated as the most helpful teaching resource in achieving various learning outcomes. In conclusion, anatomy teachers should provide prosections coupled with clinical tutorials as well as electronic resources as students prefer these and think they help them learn anatomy. Future studies will investigate the impact of using these resources on students' performance. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s40670-021-01436-2.
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Timing of craniofacial suture fusion is important for the determination of demographics and primate ontogeny. There has been much work concerning the timing of fusion of calvarial sutures over the last century, but little comprehensive work focusing on facial sutures. Here we assess the relationships of facial suture fusion across ontogeny among select catarrhines. Fusion timing patterns for 5 facial sutures were examined in 1,599 crania of Homo, Pan, Gorilla, Pongo, Hylobatidae, Papio, and Macaca. Calvarial volume (early ontogeny) and dental eruption (late ontogeny) were used as indicators of stage of development. General linear models, test for homogeneity of slopes, and ANOVA were used to determine differences in timing of fusion by taxon. For calvarial volume, taxonomic groups segregated by regression slopes, with models for Homo indicating sutural fusion throughout ontogeny, Pongo, Macaca, and Papio representing earlier and more complete suture fusion, and Pan, Gorilla, and Hylobatidae indicating very early facial suture fusion. Similar patterns are observed when dental eruption is used for developmental staging. Only Gorilla and Hylobatidae are observed to, generally, fuse all facial suture sites in adulthood. Finally, Homo appears to be unique in its delay and patency of sutures into late ontogeny. The taxonomic patterns of facial suture closure identified in this study likely reflect important evolutionary shifts in facial growth and development in catarrhines.
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Suturas Cranianas , Hominidae , Crânio , Animais , Hominidae/anatomia & histologia , Crânio/anatomia & histologiaRESUMO
BACKGROUND: The submucous cleft palate can be overt or occult and may require surgical repair. The double-opposing Z-plasty (Furlow repair) is the authors' center's preferred approach. This study evaluated complication rates, differences in outcome between overt and occult types, and patient factors associated with surgical failure. METHODS: This retrospective study reviewed documentation on all patients who underwent Furlow Z-plasty for submucous cleft palate at a single center between 2004 and 2018. Speech pathology was quantified using the Pittsburgh Weighted Speech Score. RESULTS: A total of 351 patients were included (125 overt and 226 occult cases). Furlow Z-plasty was successful (postoperative Pittsburgh Weighted Speech Score <7 without recommendation for secondary speech surgery) in 291 patients (82.1 percent). Apart from those requiring secondary surgery, there were no documented complications. Occult-type patients were 7.5 years old at palatoplasty with a speech score of 14.1; overt-type patients were 6.5 years old with a score of 15.7. Postoperative speech scores were similar for both groups. Secondary speech surgery patients had a higher preoperative score (16.9 versus 14.2). Age at time of palatoplasty and submucous cleft palate type were not predictive of the need for secondary surgery. Syndromic patients had higher preoperative and postoperative speech scores (15.6 and 7.5, respectively) than nonsyndromic patients (14.3 and 4.3) and needed secondary surgery more often (24.4 percent versus 9.2 percent). V-shaped velar vaulting on preoperative assessment was present in 92 percent of occult-type patients. CONCLUSIONS: Furlow palatoplasty is a safe and effective means of repairing submucous cleft palate. Patients with the occult type presented later with a lower Pittsburgh Weighted Speech Score. High preoperative speech score and syndromic status were associated with the need for secondary speech surgery. V-shaped velar vaulting is a reliable sign of occult submucous cleft palate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.
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Fissura Palatina/cirurgia , Palato/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Adolescente , Criança , Pré-Escolar , Fissura Palatina/patologia , Feminino , Humanos , Lactente , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Living primates show a complex trend in reduction of nasal cavity spaces and structures due to moderate to severe constraint on interorbital breadth. Here we describe the ontogeny of the posterior end of the primate cartilaginous nasal capsule, the thimble shaped posterior nasal cupula (PNC), which surrounds the hind end of the olfactory region. We used a histologically sectioned sample of strepsirrhine primates and two non-primates (Tupaia belangeri, Rousettus leschenaulti), and histochemical and immunohistochemical methods to study the PNC in a perinatal sample. At birth, most strepsirrhines possess only fragments of PNC, and these lack a perichondrium. Fetal specimens of several species reveal a more complete PNC, but the cartilage exhibits uneven or weak reactivity to type II collagen antibodies. Moreover, there is relatively less matrix than in the septal cartilage, resulting in clustering of chondrocytes, some of which are in direct contact with adjacent connective tissues. In one primate (Varecia spp.) and both non-primates, the PNC has a perichondrium at birth. In older, infant Varecia and Rousettus, the perichondrium of the PNC is absent, and PNC fragmentation at its posterior pole has occurred in the former. Loss of the perichondrium for the PNC appears to precede resorption of the posterior end of the nasal capsule. These results suggest that the consolidation of the basicranial and facial skeletons happens ontogenetically earlier in primates than other mammals. We hypothesize that early loss of cartilage at the sphenoethmoidal articulation limits chondral mechanisms for nasal complexity, such as interstitial expansion or endochondral ossification.
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Quirópteros/anatomia & histologia , Face/anatomia & histologia , Cavidade Nasal/anatomia & histologia , Primatas/anatomia & histologia , Base do Crânio/anatomia & histologia , Tupaia/anatomia & histologia , Animais , Evolução Biológica , Especificidade da EspécieRESUMO
Cranial synchondroses are cartilaginous joints between basicranial bones or between basicranial bones and septal cartilage, and have been implicated as having a potential active role in determining craniofacial form. However, few studies have examined them histologically. Using histological and immunohistochemical methods, we examined all basicranial joints in serial sagittal sections of newborn heads from nine genera of primates (five anthropoids, four strepsirrhines). Each synchondrosis was examined for characteristics of active growth centers, including a zonal distribution of proliferating and hypertrophic chondrocytes, as well as corresponding changes in matrix characteristics (i.e., density and organization of Type II collagen). Results reveal three midline and three bilateral synchondroses possess attributes of active growth centers in all species (sphenooccipital, intrasphenoidal, presphenoseptal). One midline synchondrosis (ethmoseptal) and one bilateral synchondrosis (alibasisphenoidal synchondrosis [ABS]) are active growth centers in some but not all newborn primates. ABS is oriented more anteriorly in monkeys compared to lemurs and bushbabies. The sphenoethmoidal synchondrosis (SES) varies at birth: in monkeys, it is a suture-like joint (i.e., fibrous tissue between the two bones); however, in strepsirrhines, the jugum sphenoidale is ossified while the mesethmoid remains cartilaginous. No species possesses an SES that has the organization of a growth plate. Overall, our findings demonstrate that only four midline synchondroses have the potential to actively affect basicranial angularity and facial orientation during the perinatal timeframe, while the SES of anthropoids essentially transitions toward a "suture-like" function, permitting passive growth postnatally. Loss of cartilaginous continuity at SES and reorientation of ABS distinguish monkeys from strepsirrhines.
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Cartilagem/crescimento & desenvolvimento , Suturas Cranianas/crescimento & desenvolvimento , Crânio/crescimento & desenvolvimento , Strepsirhini/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Osteogênese/fisiologiaRESUMO
INTRODUCTION: Surgical outcomes for patients with complete cleft lips are not as ideal as those achieved for milder phenotypes. We hypothesized that in addition to the greater width of the cleft, patients with complete cleft lip and palate exhibit a greater degree of hypoplasia and asymmetry. METHODS: Stereophotographs of 14 infants with unrepaired unilateral complete and 14 with incomplete cleft lips were measured using Vectra imaging software (Canfield Imaging). Unpaired t tests were used to compare measured asymmetry between groups. Measurements included nasion to endocathion, sn-sbal, subnasale to alare (sn-al), subnasale to crista philtra, subalare to crista philtra (sbal-cphi), chelion to crista philtra, lateral lip element fullness, medial lip element fullness (mef), and non-cleft lip fullness. Duplicate measurements allowed Pearson correlation to be used to determine intra-rater reliability. Statistical significance was set at P < .05. RESULTS: Degree of asymmetry of the nasal base, sn-al, and sn-sbal was significantly greater for patients with complete clefts (P = .0001, P = .0001). Hypoplasia of the lateral lip element was seen when comparing lateral and mef (P = .04, P = .004) and lateral lip height (sbal-cphi''; P = .002). The degree of cupid's bow asymmetry did not differ between groups (P = .23). Intrarater reliability was high for all facial measures, ranging from 0.70 to 0.99. CONCLUSIONS: More severe, complete cleft lips demonstrate statistically significant greater asymmetry in surgically relevant dimensions. There was greater width of the nasal base. Vertical asymmetry of cupid's bow was unaffected by cleft severity, but that asymmetry was greater in patients with complete clefts due to hypoplasia of the lateral lip element. This may contribute to the less favorable results in these patients.
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Fenda Labial , Fissura Palatina , Fenda Labial/diagnóstico por imagem , Fenda Labial/cirurgia , Fissura Palatina/diagnóstico por imagem , Fissura Palatina/cirurgia , Humanos , Lactente , Lábio/diagnóstico por imagem , Nariz , Reprodutibilidade dos TestesRESUMO
INTRODUCTION: Oronasal fistulae following palatoplasty may affect patients' quality of life by impacting their ability to eat, speak, and maintain oral hygiene. We aimed to quantify the impact of previous oronasal fistula repair on patients' quality of life using patient-reported outcome psychometric tools. METHODS: A cross-sectional study of 8- to 9-year-old patients with cleft palate and/or lip was completed. Patients who had a cleft team clinic between September 2018 and August 2019 were recruited. Participants were divided into 2 groups (no fistula, prior fistula repair). Differences in the individual CLEFT-Q and Child Oral Health Impact Profile-Short Form 19 (COHIP-SF 19) Oral Health scores between the 2 groups were evaluated using a multivariate analysis controlling for Veau classification and syndromic diagnosis. RESULTS: Sixty patients with a history of cleft palate were included. Forty-two (70%) patients had an associated cleft lip. Thirty-two (53.3%) patients had no history of fistula and 28 (46.7%) patients had undergone a fistula repair. CLEFT-Q Dental, Jaw, and Speech Function were all higher in patients without a history of a fistula repair; however, none of these differences were statistically significant. The COHIP-SF 19 Oral Health score demonstrated a significantly lower score in the fistula group, indicating poorer oral health (P = .05). CONCLUSIONS: One would expect that successful repair of a fistula would result in improved function and patient satisfaction, but the consistent trend toward lower CLEFT-Q scores and significantly increased COHIP-SF 19 Oral Health scores in our study group suggests that residual effects linger and that the morbidity of a fistula may not be completely treated with a secondary correction.
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Fenda Labial , Fissura Palatina , Fístula , Criança , Fenda Labial/cirurgia , Fissura Palatina/cirurgia , Estudos Transversais , Humanos , Fístula Bucal , Saúde Bucal , Assistência Centrada no Paciente , Complicações Pós-Operatórias , Qualidade de Vida , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Although bone repair is typically an efficient process, an inadequate healing response can occur, with approximately 5-20% of fractures developing nonunion. Even with improved healing strategies and external fixation devices, overall rate of nonunion has not been significantly reduced, particularly for atrophic nonunion. Atrophic nonunion is characterized by sparse or no callus formation and is difficult to treat clinically, resulting in long-term pain and functional limitation. Reliable preclinical models are needed to study the pathophysiology of atrophic nonunion to create better treatment options. The MouseNail kit (RISystem, Landquart, Switzerland) provides a highly standardized approach in which stabilized segmental bone defects are achieved through interlocked intramedullary nailing. However, reliably performing this surgery is technically challenging, particularly while maintaining strict asepsis. Skilled and aseptic surgical execution is important and necessary because it ensures optimal animal welfare and reproducibility. Therefore, the aim of this paper is to describe:â¢Novel modifications to the MouseNail kit that allow for: 1) a completely aseptic surgical environment, including description of a hanging limb orthopedic aseptic preparation and 2) a reduction in fracture gap size necessary for induction of atrophic nonunion.â¢Pre- to post-operative recommendations to facilitate successful performance of murine orthopedic survival surgery.
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Progressive curricular changes in medical education over the past two decades have resulted in the diaspora of gross anatomy content into integrated curricula while significantly reducing total contact hours. Despite the development of a wide range of alternative teaching modalities, gross dissection remains a critical component of medical education. The challenge posed to modern anatomists is how to maximize and integrate the time spent dissecting under the current curricular changes. In this study, an alternative approach to the dissection of the pelvis and perineum is presented in an effort to improve content delivery and student satisfaction. The approach involves removal of the perineum en bloc from the cadaver followed by excision of the pubic symphysis, removal and examination of the bladder and associated structures, examination and bisection of the midline pelvic organs in situ, and midsagittal hemisection of the pelvis for identification of the neurovasculature. Results indicate that this novel dissecting approach increases the number of structures identified by 46% ± 14% over current dissecting methods. Survey results indicate that students were better able to integrate lecture and laboratory concepts, understand the concepts, and successfully identify more structures using the new approach (P < 0.05). The concept of anatomic efficiency is introduced and proposed as a standard quantitative measure of gross dissection proficiency across programs and institutions. These findings provide evidence that innovative solutions to anatomy education can be found that help to maintain critical content and student satisfaction in a modern medical curriculum.
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Anatomia/educação , Dissecação/métodos , Pelve/anatomia & histologia , Períneo/anatomia & histologia , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Once thought to have revolutionized therapeutic intervention in surgery, Recombinant Human Bone Morphogenic Protein 2 (rhBMP2) is now in its second decade of sustained controversy over the side effects associated with its use. Side effects associated with clinical use of rhBMP2 (Infuse, Medtronic Inc) include a marked inflammatory response, pain, therapeutic failures, ectopic bone, tissue degradation, and death. What is missing, despite the depth of literature on the subject, is a direct interrogation of rhBMP2, specifically for inflammation. Here we set out to determine if rhBMP2 alters traditional macrophage markers associated with pro-inflammatory responses, and pro-reparative responses to injury. Based on our previous work, we hypothesized there would be no direct effect of the peptide on macrophage polarization. Here we utilized commercially available murine macrophages, RAW 264.7, and treated these cells with rhBMP2 in standard growth media or macrophage polarizing media (M1 and M2) at several doses of the peptide. Our readouts were cell viability, apoptosis, gene expression of M1 and M2 markers, and ELISA for M1 marker iNOS, and M2 marker Arg1. Our data give very little evidence to support an alteration in macrophage phenotype by rhBMP2 alone, or alteration of the phenotype when cultured in enriched M1 or M2 media. These results further suggest that other factors associated with the clinical use of Infuse, likely supraphysiological rhBMP2 doses and off label usage, are more likely the culprit for poor outcomes. This further reinforces the utility of rhBMP2 and other peptides in tissue engineering therapies when conditions are tightly controlled.
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Proteína Morfogenética Óssea 2/farmacologia , Diferenciação Celular/efeitos dos fármacos , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Fator de Crescimento Transformador beta/farmacologia , Animais , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Humanos , Inflamação/imunologia , Camundongos , Células RAW 264.7 , Proteínas Recombinantes/farmacologiaRESUMO
BACKGROUND: Previous attempts to study the effect of prophylactic antibiotics on the outcomes of cleft palate surgery have been hampered by the need for a very large sample size to provide adequate power to discern a potentially small therapeutic effect. This limitation can be overcome by querying large databases created by health care governing bodies. METHODS: Data from the Pediatric Health Information System database were used for this analysis. Patients, aged 6 to 18 months, who had undergone primary palatoplasty (International Classification of Diseases, Ninth Revision, code 27.62) between 2004 and 2009 were included. Subsequent repair of an oronasal fistula between 2004 and 2015 was identified by International Classification of Diseases, Ninth Revision, procedure code 21.82. Pharmacy billing records were used to determine antibiotic administration. Associations between antibiotic administration and fistula repair were assessed using random-intercept logistic regression adjusting for age, sex, race, and cleft type. RESULTS: Seven thousand one hundred sixty patients were available for analysis; of these, 460 (6.4 percent) had a subsequent repair of an oronasal fistula. Fistula rates were 5.9, 11.4, and 5.2 percent among patients given preoperative antibiotics, only postoperative antibiotics, and no antibiotics, respectively (p < 0.001). Multivariable analysis results showed that the odds of having an oronasal fistula among patients who were administered preoperative antibiotics did not differ significantly (statistically) from patients who did not receive antibiotics (OR, 0.88; 95 percent CI, 0.59 to 1.31). CONCLUSIONS: The treatment goal of primary palatoplasty is the successful repair of the cleft without an oronasal fistula. Administration of preoperative antibiotics did not significantly reduce the odds of subsequent fistula repair within the same Pediatric Health Information System institution following primary palatoplasty. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.
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Antibioticoprofilaxia/estatística & dados numéricos , Fissura Palatina/cirurgia , Fístula/cirurgia , Doenças Nasais/cirurgia , Fístula Bucal/cirurgia , Fenda Labial/cirurgia , Feminino , Humanos , Lactente , Masculino , Complicações Pós-Operatórias/cirurgia , Reoperação/estatística & dados numéricos , Infecção da Ferida Cirúrgica/prevenção & controle , Estados UnidosRESUMO
Physiological responses to psychological stressors are protective in acute fight or flight situations; however, there is increasing evidence suggesting the detrimental impact of chronic psychological stress on disease. Chronic stress has been associated with inflammation, poor prognosis, increased morbidity, and poor outcome in many diseases including atherosclerosis, cancer, and pulmonary disease. Given the systemic impact of stress, and the role of the hematopoietic system as a rapid responder to homeostatic insults, we hypothesized that early blood profile changes and biochemical alterations could be detected in a model of chronic stress. To test this hypothesis, a variation of the chronic unpredictable stress (CUS) model was employed. Following 10 days of CUS, C57BL/6 mice exhibited a chronic-stress-associated corticosterone profile. Complete blood count (CBC) revealed mild normochromic, normocytic anemia, and reduced monocyte and lymphocyte count. Serum analysis demonstrated hypoferremia with unchanged total iron binding capacity and serum ferritin levels. These findings are consistent with clinical diagnostic parameters for anemia of chronic disease and indicate that CUS results in significant changes in blood and serum biochemical profile in C57BL/6 mice. These studies identify early changes in blood parameters in response to CUS and identify hematopoietic and biochemical alterations that are often associated with increased morbidity in patients experiencing chronic-stress-associated mental health disease.