Neurologic Characterization of Craniosynostosis: Can Direct Brain Recordings Predict Language Development?

PURPOSE: Nonsyndromic craniosynostosis (NSC) is associated with language deficits. Conventional tests, such as the Bayley Scales of Infant Development (BSID), may not reflect accurate long-term cognition. Alternatively, mismatch negativity (MMN) waves recorded via electroencephalogram (EEG) measure neural responses to speech and may objectively predict language development. This study aimed to (1) correlate infant MMN to future language achievement and (2) compare MMN among subtypes of NSC. METHODS: Pre and postoperatively (mean operative age 9.5 months), NSC participants received the BSID and EEG phoneme-discrimination paradigm(80 dB,250 Hz). The MMN was the largest negative amplitude in the difference wave 80 to 300 ms after stimuli. To measure cognitive outcome, patients completed a neurodevelopmental battery (Wechsler-Abbreviated Scale of Intelligence and Wechsler-Fundamentals) at >6 years of age. RESULTS: Eleven NSC patients with EEG testing in infancy were neurocognitively tested (average age 8.0 years; 27% female; 55% sagittal, 27% metopic, 9% unicoronal, 9% sagittal/metopic). The left frontal cluster MMN strongly correlated with word-reading (r = 0.713, P = 0.031), reading-comprehension (r = 0.745, P = 0.021), and language-composites (r = 0.0771, P = 0.015). Conversely, BSID scores did not yield significant predictive value (r < 0.5, P > 0.05). Follow-up event related potentials (ERP) comparison included 39 normal control, 18 sagittal, 17 metopic, 6 unilateral-coronal infants. Preoperatively, sagittal (P = 0.003) and metopic (P = 0.003) patients had attenuated left frontal MMN compared to controls. Postoperatively, the sagittal cohort was normalized to controls while metopic patients retained attenuations (P = 0.041). CONCLUSION: ERP assessment in NSC had significantly better predictive value for future neurocognition than the BSID. Preoperatively, sagittal and metopic patients had attenuated neural response to language; postoperatively, sagittal patients had improved responses in comparison to metopic patients. Use of ERP assessment may help tailor treatment for language deficits earlier in development.

Functional Network Development in Sagittal Craniosynostosis Treated With Whole Vault Cranioplasty.

INTRODUCTION: In this study, the authors seek to clarify the neurological changes before and after whole vault cranioplasty (WVC) in patients born with sagittal craniosynostosis. METHODS: A case control study design was performed that included thirty functional MRI scans, from 25 individual patients. Functional MRI and diffusion tension imaging data were analyzed with BioImageSuite (Yale University, USA). 9 functional brain networks were analyzed, with appropriate correlated functional regions of the brain and utilized for analysis. RESULTS: Comparing functional MRI the infants after WVC versus infants before WVC group, the after WVC group demonstrated an increased connectivity in the left frontoparietal, secondary (V2), and third (V3) visual networks (P < 0.001). The right frontoparietal (RFPN) had decreased connectivity (P < 0.001). There is also a decrease and increase in anisotropy in the cingulum and precuneus despite surgery, respectively (P < 0.05). Adolescents treated with WVC compared to controls, demonstrated an increased connectivity in the salience and decreased connectivity in the RFPN relative to adolescent controls. CONCLUSIONS: Patients born with sagittal craniosynostosis have different connections in infancy in most of the defined cerebral networks compared to controls. After surgery, there are specific connectivity changes that occur in the RFPN, left frontoparietal, V2, and V3 networks, which are areas associated with executive function and emotional control. Changes identified in white matter tract microstructure connections could be influential in changes in functional connectivity. Although, as a child with sagittal craniosynostosis develops, much of the abnormal network connections, seen in infancy preoperatively, corrects to some degree after surgery. However, some aberrancies in the salience and RFPN networks remain potentially affecting executive functioning.

Impact of socioeconomic status on psychological functioning in survivorship following breast cancer and reconstruction.

Socioeconomic status (SES) remains an important population health risk factor and impacts a patient's experience of care during breast cancer. This study explored the relationship between SES and quality of life and satisfaction in survivorship following breast cancer and reconstruction. All patients underwent breast reconstruction at a single academic center from 2013 to 2017. Patients completed the five quality of life and satisfaction domains of the BREAST-Q, a validated patient-reported outcome measure. Estimated home value using a web-based real estate website was used to approximate a patient's socioeconomic status. Correlations were evaluated using Pearson's correlation methods, where appropriate, as well as analysis of covariance. Data were stratified for comparison utilizing t tests and linear regression models. Significance was defined as P ≤ .05. Four hundred patients underwent 711 breast reconstructions during the study time period. Satisfaction with the breast (P = .038) and psychosocial well-being (P = .012) had significant positive correlations with increasing socioeconomic status. When stratifying patients' socioeconomic status into thirds, the upper third had significantly higher psychosocial well-being (P = .001), satisfaction with breasts (P = .010), and physical well-being of the chest (P = .001) than the lower third. Significance persisted even after controlling for cancer stage, treatment, complications, and baseline comorbidities. Higher socioeconomic status is associated with greater satisfaction with breast reconstruction and psychosocial well-being following breast cancer treatment. Providing added social, psychological, and emotional support networks may be beneficial long after the initial cancer treatment and reconstruction are complete. Patients of lower socioeconomic status may benefit from additional resources.

Breast reconstruction patterns and outcomes in academic and community practices within a single institution.

Breast reconstruction is a common procedure that is performed in both community and academic settings. At Yale-New Haven Hospital (YNHH), both academic (AP) and community-based (CP) plastic surgeons perform breast reconstructions. We aim to compare practice patterns in breast reconstruction between two practice environments within a single institution. A retrospective chart review of all breast reconstructions at YNHH between 2013 and 2018 was performed. Data collected included demographics, preoperative history, and postoperative outcomes. Results were further subdivided by practice setting. A total of 1045 patients (1683 breasts) underwent breast reconstruction during the study period. About 52.8% were performed by AP while 47.2% were performed by CP. CP had higher rates of autologous reconstruction (P < .001) and nipple-sparing mastectomy (P < .0001). Age and BMI were similar between the cohorts. However, patients cared for by AP had 2.6% increased prevalence of diabetes (P = .064), 5.5% greater prevalence of psychiatric diagnoses (P = .004), and 7.1% higher open abdominal surgery rates (P < .001). Outcomes were similar between the groups except for higher infection rates (P = .027) and explant rates (P = .003) in the CP cohort. When evaluating insurance status, the AP cohort had 30.5% fewer patients with commercial insurance, 16.7% more patients with Medicaid and 6.1% more patients with Medicare (P < .001). Within our institution, academic and community-based plastic surgeons perform breast reconstruction with overall similar complication rates. Patients treated by AP have a higher rate of preoperative medical and psychiatric comorbidities. Patients treated by CP have higher rates of infection and implant explant. AP plastic surgeons care for a significantly higher rate of Medicare and Medicaid patients with proportionally fewer patients with commercial insurance.

Patients with psychiatric illness report worse patient-reported outcomes and receive lower rates of autologous breast reconstruction.

Psychiatric well-being impacts on general satisfaction and quality of life. This study explored how the presence of psychiatric diagnoses affects patient-reported outcomes in breast reconstruction and on selection of reconstructive modality. Patients who received breast reconstruction at a tertiary hospital between 2013 and 2018 and completed the BREAST-Q survey were included. BREAST-Q module scores were compared between patients who had a psychiatric diagnosis at presentation and the remaining cohort using t tests. General linear models (GLMs) were used to control for confounding factors. A chi-squared test was used to assess the effect on reconstructive modality, and binary logistic regression was used to control for confounding factors. Of the 471 patients included, 93 (19.7%) had at least one psychiatric diagnosis. Cohorts did not differ significantly by age, BMI, race, ASA classification, or insurance status. Patients with a psychiatric diagnosis experienced a decrease in BREAST-Q scores for the Psychosocial Wellbeing (B = 9.16, P = .001) and Sexual Wellbeing (B = 9.29, P = .025) modules. On binary logistic regression, patients with a psychiatric diagnosis were less likely to receive autologous reconstruction compared with implant reconstruction (OR = 0.489, P = .010). The presence of psychiatric diagnoses is an independent predictor of decreased BREAST-Q. Furthermore, there is a significant disparity in modality of reconstruction given to patients with psychiatric diagnoses. Further study is needed to evaluate interventions to improve satisfaction among at-risk populations and evaluate the reason for low autologous reconstruction in this population.

Radiographic Predictors of FACE-Q Outcomes Following Non-Operative Orbital Floor Fracture Management.

BACKGROUND: Orbital floor fractures are common injuries treated by multiple surgical subspecialties. Controversy exists regarding the operative indications. This study sought to correlate radiographic characteristics of orbital floor fractures with validated patient reported outcome measures following non-operative management. MATERIALS AND METHODS: Patients who underwent non-operative management of an orbital floor fracture at Yale New Haven Hospital from 2013 to 2018 were queried retrospectively. Patients with GCS < 15 and/or distracting facial soft tissue or bony injuries were excluded from analysis. CT images, demographic information, and FACE-Q patient reported outcomes (Satisfaction with Eyes, Psychological Function, Social Function, and Appearance Related Psychosocial Distress) were reviewed. Statistical analysis was performed with SPSS with statistical significance set at P < .05. RESULTS: Eighteen patients were included in the study. The mean time between injury and completion of the survey was 3.6 years. Fifty-six percent of patients had a right-sided fracture. The mean fracture area was 73.6 mm (Range:15-172 mm), and 913 mm (Range: 0-3106) was the mean volume displaced into the maxillary sinus. The unaffected inferior rectus muscle shape (height/width) was 0.5 (Range: 0.2-0.98) compared to 0.8 (Range 0.4-1.6) for the affected inferior rectus. After controlling for the time interval between survey and injury, gender, income, and education, rounding of the inferior rectus muscle was a significant predictor of appearance related psychosocial distress (P = 0.006). Inferior rectus rounding was stratified into "severe" (75%) and "moderate" (25%) categories. Severe rounding was associated with a larger orbital floor fracture area (110 versus 64 mm; P = 0.074), volume displaced into the maxillary sinus (1,716 versus 610 mm; P = 0.024), and worse appearance-related psychosocial distress (70 versus 25; P = 0.013). Sixty-one percent of patients followed up in clinic with a mean duration of 194 days. CONCLUSION: Prior studies have correlated presenting radiographic findings to follow-up clinical findings. However, this study is the first to assess long-term outcomes using validated patient-reported questionnaires. Inferior rectus muscle belly rounding significantly correlated with appearance related psychosocial distress. This radiographic finding may be valuable to consider in orbital floor fracture management.

Assessing Facial Asymmetry in Postoperative Patients With Unilateral Coronal Craniosynostosis.

BACKGROUND: Despite surgical correction of unilateral craniosynostosis (ULC), complex cranial base angulation can result in partial reversion to preoperative deformity with growth and time. Using 3-dimensional imaging, dysmorphic facial features of ULC in school-age patients were quantified and related to how they contribute to overall facial asymmetry and patient-reported outcomes. METHODS: Children who underwent surgical correction of ULC were recruited from Yale University and Children's Hospital of Philadelphia. The 3D photographs were analyzed utilizing a Procrustes analysis of shape. Pearson's correlation was used to determine dysmorphic features' impact on overall asymmetry. Patients were stratified into "moderate" and "severe" asymmetry. Finally, asymmetry was correlated to patient-reported outcome scores. Statistical analysis was performed with SPSS-25 with P < 0.05 as statistically significant. RESULTS: Twenty-one patients were included with average age at analysis of 12.3 years. Fifty-seven percent of patients had right-sided fusion. The overall Procrustes analysis indicated a root mean square difference of 2.21 mm. Pearson's correlation indicated that the facial middle 3rd (P ≤ 0.001), orbital dystopia (P < 0.001), chin point deviation (P = 0.011), and nasal root angulation (P = 0.019) contributed most to overall asymmetry. Patients in the severe asymmetry cohort had greater facial middle-third asymmetry (P < 0.001) and orbital dystopia (P < 0.001). Asymmetry did not correlate with patient-reported outcomes. CONCLUSION: Patients with ULC have persistent facial asymmetry at school-age with the greatest levels of asymmetry in the facial middle-third, orbit, and nasal root. Beyond the cranial dysmorphology, initial skull base angulation in unilateral coronal craniosynostosis manifests in long-term mid and lower-third facial asymmetry.

Outcomes of Endoscopic Versus Open Spring Assisted Surgery for Sagittal Craniosynostosis.

Spring-assisted surgery (SAS) has been shown to be an effective technique for correction of isolated sagittal craniosynostosis in patients less than 6 months of age. At their institution, the authors adopted a minimally invasive technique in 2010, using a shorter incision and an endoscope. A retrospective chart review of 101 patients with isolated, nonsyndromic, sagittal craniosynostosis, who underwent SAS, was performed in order to compare perioperative and clinical outcomes of the open (n = 51) and minimally-invasive (n = 50) approaches. Surgeries were performed by 2 neurosurgeons and 3 plastic surgeons, between 2005 and 2018. The pre and postoperative cephalic indices were not significantly different in both groups. Minimally-invasive spring placement required a longer operative time than the open approach, with the mean minimally-invasive operative time at 65 minutes, compared to 53 minutes (P < 0.0001). Spring removal operative time was not significantly different, with the minimally-invasive operative time at 31 minutes versus 29 minutes (P = 0.48). There were no significant differences in major or minor complications when comparing the open and minimally-invasive approaches. In conclusion, both the open and the minimally-invasive SAS techniques are effective for early correction of isolated sagittal craniosynostosis, although the minimally-invasive approach requires a longer operative time for spring placement.

Spring-Assisted Strip Craniectomy Versus Cranial Vault Remodeling: Long-Term Psychological, Behavioral, and Executive Function Outcomes.

BACKGROUND: Controversy exists regarding the optimal surgical approach for non-syndromic sagittal synostosis. This study provides the first comparative analysis of the long-term behavioral, psychological, and executive function outcomes for patients who underwent either cranial vault remodeling (CVR) or spring-assisted strip craniectomy (SAS). METHODS: Thirty-six CVR patients and 39 SAS patients were evaluated. Parents and caregivers completed the Behavior Rating Inventory of Executive Function (BRIEF) and the Behavior Assessment System for Children, Second Edition (BASC-2) to evaluate behavioral, emotional, social, adaptive, and executive functioning skills. RESULTS: There were no statistically significant differences between the CVR and the SAS groups (P > 0.05) in any of the BRIEF areas of function. Furthermore, the BASC-2 battery illustrated no significant differences in all areas analyzed except one. Among the 2 groups, the CVR group was rated as having fewer social withdrawal symptoms on the BASC-2 (47.00 ±â€Š10.27) compared to the SAS cohort (54.64 ±â€Š10.96), F = 6.79, P = 0.012, Cohen d = 0.688. However, both means were still within the normal range. CONCLUSIONS: Children undergoing SAS and CVR procedures for isolated sagittal synostosis were not rated as having clinically significant behavioral, emotional, social, adaptive, or executive functioning problems on parental forms.

Secondary Cleft Rhinoplasty in 1720 Patients: Are National Practices Consistent With Guidelines?

OBJECTIVE: To assess the timing, type, and associated adjunct procedures for secondary cleft rhinoplasty nationally. DESIGN: Data were extracted from a national database of all secondary cleft rhinoplasty procedures (Current Procedural Terminology [CPT] codes 30460 and 30462). Frequency statistics were utilized to analyze demographics, comorbidities, surgical procedures, and timing. Chi-squared analysis and Fisher exact test were used for analysis. SETTING: National Surgical Quality Improvement Program-Pediatric Database. PARTICIPANTS: A total of 1720 patients met inclusion criteria for secondary cleft rhinoplasty repair. INTERVENTIONS: No relevant intervention. MAIN OUTCOMES AND MEASURES: Age, demographics, comorbidities, and associated procedures. RESULTS: Over 5 consecutive years, 1720 patients underwent secondary cleft lip rhinoplasty nationally. Mean patient age was 9.3 ± 5.3 years. Unilateral cleft rhinoplasty patients were older (9.0 years) than bilateral patients (7.8 years; P = .001). Rib grafting was performed in 6.3% of patients at a mean age of 10.6 years with a higher proportion of Asian and female patients. Auricular grafts were more commonly performed by otolaryngology than plastic surgery. The most common adjunct procedures included secondary cleft lip revision (33.1%) and tympanostomy tube placement (10.2%). When subdividing by type of cleft rhinoplasty, tip rhinoplasty was performed at a mean age of 7.3 years compared to rhinoplasty with osteotomies and a major septal component at 12.1 years (P < .001). CONCLUSIONS: This study reveals that a large proportion of cleft rhinoplasties are performed in skeletally immature patients. Although patients undergoing rib grafting, nasal osteotomies, and a major septal component were older, these procedures are still performed in a large proportion of patients who are younger than expected.

The Effect of Autologous Fat Grafting on Edema and Ecchymoses in Primary Open Rhinoplasty.

BACKGROUND: Autologous fat is a safe and effective soft tissue filler. Recent evidence also suggests improved wound healing and immune modulation with fat grafting. OBJECTIVES: The aim of this study was to describe a novel technique utilizing fat grafting during primary open rhinoplasty. We hypothesize a more rapid resolution of bruising and edema. METHODS: Patients who underwent rhinoplasty were reviewed and compared by presence or absence of concurrent fat grafting. Three-dimensional images were analyzed employing Mirror (Vectra, Canfield Scientific, NJ). Ecchymoses were outlined utilizing a magnetic lasso followed by an area measurement. Volumetric edema measurements were also taken and assessed. Edema and ecchymosis were measured at 2 and 6 weeks postoperatively. Statistical significance was defined as P < 0.05. RESULTS: Sixty-two patients were included. Thirty-three patients (53.2%) received autologous fat grafting and 29 (46.8%) did not. Age, gender, surgical approach, and osteotomy distribution were similar between the groups. The fat grafted group showed 7.29 cm2 fewer ecchymoses (P < 0.001) and 0.73 cc less edema (P = 0.68) in the early postoperative interval. Six weeks postoperatively, the fat grafted group showed 1 cc less edema (P = 0.36) with negligible differences in bruising. CONCLUSIONS: Autologous fat grafting is a useful adjunct to rhinoplasty and is associated with significantly fewer ecchymoses in the acute postoperative period.

Veau III and Veau IV Cleft Palate: Do Peri-Operative Complications Differ?

OBJECTIVE: The Veau classification represents the most commonly used system for characterizing cleft palate severity. Conflicting evidence exists as to how increasing Veau classification affects outcomes. This study compared perioperative outcomes between Veau III and IV cleft palate repairs. METHODS: The National Surgical Quality Improvement Program Pediatric (NSQIP-P) database was used to identify cleft palate repairs between 2012 and 2016 using CPT codes. Patients with alveolar bone grafts were excluded. Veau III (unilateral) and Veau IV (bilateral) cleft palate repairs were identified using International Classification of Disease code 9 and 10 (ICD-9 and -10 codes. Patient demographics, comorbidities, and adverse events were compared between the cohorts. RESULTS: A total of 5026 patients underwent cleft palate repair between 2012 and 2016. Of the 2114 patients with identifiable Veau classification, 1302 had Veau III cleft palates and 812 had Veau IV cleft palates.The Veau IV cleft palate patient population was older (377.8 versus 354.1 days, P < 0.001) and had significantly more comorbidities including a higher incidence of chronic lung disease (P = 0.014), airway abnormalities (P = 0.001), developmental delay (P = 0.018), structural central nervous system deformities (P < 0.001), and nutritional support (P < 0.001). Veau IV cleft palate repairs also had longer operative times (153.2 versus 140.2 minutes, P < 0.001). Despite significant differences in comorbidities and perioperative factors, there were no differences in 30-day complications, readmissions, or reoperation rates between Veau III and IV cleft palate repairs. CONCLUSIONS: Patients undergoing Veau IV cleft palate repair have a significantly greater number of comorbidities than Veau III cleft palate repairs. Despite differences in patient populations, 30-day surgical outcomes are comparable between the cohorts.

Fat Grafting in Orthognathic Surgery.

BACKGROUND: Fat grafting is widely utilized in craniofacial surgery. The authors describe a series of consecutive patients who underwent orthognathic surgery with fat grafting by the senior author and review relevant literature in the field; fat grafting technique is discussed in detail. The authors also highlight 3 patients to illustrate postoperative outcomes. METHODS: A retrospective cohort of consecutive orthognathic surgery patients was reviewed. Age, sex, BMI, procedure, area of harvest, location of injection, donor site complications, and need for repeat fat grafting were analyzed. Inclusion criteria included history of orthognathic surgery and concomitant fat grafting performed by the senior author in 2015. RESULTS: Fifty-three orthognathic surgery patients with concurrent fat grafting were reviewed. The cohort comprised 20 males (37.7%) and 33 females (62.3%). Thirty-three patients (62.3%) underwent Le Fort I operations either in conjunction with genioplasty and/or bilateral sagittal split osteotomies. Twenty-eight patients (52.8%) underwent second operations involving additional fat grafting. The majority of these patients (15/28, 53.6%) received additional fat grafting during ensuing rhinoplasty. There were no donor site complications (ie, infection, wound breakdown) recorded in the authors' patient cohort. Amount of fat injected averaged 13.1 cc (range 5-25 cc). Follow-up generally occurred through the 1-year mark. CONCLUSIONS: Fat grafting is a proven technique to facilitate optimal postoperative wound-healing in orthognathic surgery. The senior author uses Telfa processing and the Coleman system to deliver the fat atraumatically. The authors' cohort of consecutive patients corroborates the benefits of fat grafting in craniofacial surgery; the authors observe wound-healing benefits, enhanced aesthetic outcomes and an anti-inflammatory effect with this technique.

Temporal Evaluation of Craniofacial Relationships in Apert Syndrome.

Complicated craniofacial malformations interfacing with multiple intracellular regulatory mechanisms, lead to ambiguous growth patterns in Apert syndrome. This study aims to explore the chronology and pathogenesis of the development of craniofacial anatomic relationships and to verify the positional correlates between skull and facial structures in Apert syndrome. Fifty-four computed tomography scans (Apert, n = 18; control, n = 36) were included and divided into 3 age subgroups. Craniofacial 3-dimensional cephalometries were analyzed by Materialize software. The angle between sella-nasion plane and maxillary plane widens 7.74° (P = 0.003) prior to 6 months of age; thereafter, this widening increases by 10.36° (P < 0.001) in 6 months to 2 years of age, and remains increased by 8.9° (P = 0.046) throughout childhood. The angle between Frankfort horizontal plane and maxillary plane widens 5.17° (P = 0.022) before 6 months. Angles SNA, SNB, and ANB showed decreases, averaging 12.23° (P < 0.001), 5.19° (P = 0.004), and 6.72° (P = 0.001), respectively. The linear measurements showed synchronicity and continuing deformity into adulthood. Between 6 months to 2 years of age, the distance from sella to nasion (S-N), anterior nasal spine (S-ANS), and posterior nasal spine (S-PNS) decreased 8% (P = 0.006), 16% (P < 0.001), and 19% (P = 0.002), respectively, and remained shortened into adulthood. The angulation changes occur earlier in development than linear distance reduction in Apert syndrome patients compared with controls. Angular adjustments were not sufficient to maintain normal cranial base length. Facial deformity of Apert syndrome temporally begins with the midface, and affects orbit and mandible later in life.

What is the Functional Difference Between Sagittal With Metopic and Isolated Sagittal Craniosynotosis?

INTRODUCTION: The purpose of this study is to understand the neurological differences between patients born with combined sagittal and metopic craniosynostosis (SMc) and isolated sagittal craniosynostosis (ISc) by studying aberrations in functional brain connectivity and white matter microstructure, before surgery, utilizing functional magnetic resonance imaging (fMRI) and diffusion tensor imaging (DTI). METHODS: The authors collected DTI and resting-state (ie, no sedation and asleep) functional connectivity MRI data in 10 infant patients preoperatively: 5 in the SMc group (4.3 ±â€Š1 months) and 5 in the ISc group (4.8 ±â€Š1.1 months). Resting state fMRI imaging and DTI data were acquired using a 3-T Siemens Trio MRI system (Erlangen, Germany) while the infant patients slept. fMRI data were corrected for movement using SPM, underwent cerebrospinal fluid and white matter signal regression and further analyzed with BioImageSuite. For the DTI data, 3 diffusion runs were averaged, processed utilizing FMRIB Software Library, and analyzed statistically using BioImageSuite. RESULTS: Comparing the SMc versus ISc groups, SMc demonstrated that there was increased connectivity, statistically significant differences, in neural networks between children with sagittal synostosis alone versus those with sagittal with metopic synostosis, in the right BA 31 and BA 23 (corresponding to the posterior cingulate cortex (PCC) (P < 0.001). Analysis of the DTI revealed increased fractional anisotropy (normal maturation of white tracts) in the SMc group in the cingulum compared to the ISc group (P < 0.05). Differences in the functional networks include increased connectivity right frontoparietal network (RFPN) in ISc and increased connectivity in the primary visual network (V1) in SMc (P < 0.001). CONCLUSION: The SMc had increased connectivity as measured by fMR in the PCC, an area associated with attention deficit hyperactivity disorder. The DTI analysis demonstrated an increase in fractional anisotropy of the cingulum in the SMc group, a white matter tract projecting from the cingulate cortex; connections of the limbic (emotional regulation) system are instrumental. In SMc, increase of connectivity in the PCC correlates with an increase in maturation of the cingulum compared to ISc. There is increased connectivity of the RFPN network in the ISc and increased connectivity of the V1 network in the SMc patients. The SMc group has increased connectivity in the PCC, the original seed of the DMN network, and decreased connectivity to the RFPN network. The pattern of increased connectivity in the area of the DMN and decreased connectivity in the RFPN network is similar to the trend when comparing ADHD patients to normal controls. SMc has more similar functional network connectivity to ADHD as compared to ISc.

National Longitudinal Comparison of Patients Undergoing Surgical Management of Craniosynostosis.

PURPOSE: Limited cross-institutional studies compare strip craniectomy versus cranial vault remodeling (CVR) for craniosynostosis management. Given competing surgical preferences, the authors conducted a large-scale analysis of socioeconomic differences, costs, and complications between treatment options. METHODS: Nonsyndromic craniosynostosis patients receiving strip craniectomies or CVR were identified in the Kids' Inpatient Database for years 2000 to 2009. Demographics, socioeconomic background, hospital characteristics, charge, and outcomes were tabulated. Univariate and multivariate analyses were performed for comparison. RESULTS: Two hundred fifty-one strip craniectomies and 1811 CVR patients were captured. Significantly more strip craniectomy patients were White while more CVR patients were Hispanic or Black (P < 0.0001). Strip craniectomy patients more often had private insurance and CVR patients had Medicaid (P < 0.0001). Over time, CVR trended toward treating a higher proportion of Hispanic and Medicaid patients (P = 0.036). Peri-operative charges associated with CVR were $27,962 more than strip craniectomies, and $11,001 after controlling for patient payer, income, bedsize, and length of stay (P < 0.0001). Strip craniectomies were performed more frequently in the West and Midwest, while CVR were more common in the South (P = 0.001). Length of stay was not significant. Postsurgical complications were largely equivocal; CVR was associated with increased accidental puncture (P = 0.025) and serum transfusion (P = 0.002). CONCLUSION: Our national longitudinal comparison demonstrates widening socioeconomic disparities between strip craniectomy and CVR patients. Cranial vault remodeling is more commonly performed in underrepresented minorities and patients with Medicaid, while strip craniectomy is common in the White population and patients with private insurance. While hospital charges and complications were higher among CVR, differences were smaller than expected.

Dynamic regulation of ß1 subunit trafficking controls vascular contractility.

Ion channels composed of pore-forming and auxiliary subunits control physiological functions in virtually all cell types. A conventional view is that channels assemble with their auxiliary subunits before anterograde plasma membrane trafficking of the protein complex. Whether the multisubunit composition of surface channels is fixed following protein synthesis or flexible and open to acute and, potentially, rapid modulation to control activity and cellular excitability is unclear. Arterial smooth muscle cells (myocytes) express large-conductance Ca(2+)-activated potassium (BK) channel α and auxiliary ß1 subunits that are functionally significant modulators of arterial contractility. Here, we show that native BKα subunits are primarily (∼95%) plasma membrane-localized in human and rat arterial myocytes. In contrast, only a small fraction (∼10%) of total ß1 subunits are located at the cell surface. Immunofluorescence resonance energy transfer microscopy demonstrated that intracellular ß1 subunits are stored within Rab11A-postive recycling endosomes. Nitric oxide (NO), acting via cGMP-dependent protein kinase, and cAMP-dependent pathways stimulated rapid (≤1 min) anterograde trafficking of ß1 subunit-containing recycling endosomes, which increased surface ß1 almost threefold. These ß1 subunits associated with surface-resident BKα proteins, elevating channel Ca(2+) sensitivity and activity. Our data also show that rapid ß1 subunit anterograde trafficking is the primary mechanism by which NO activates myocyte BK channels and induces vasodilation. In summary, we show that rapid ß1 subunit surface trafficking controls functional BK channel activity in arterial myocytes and vascular contractility. Conceivably, regulated auxiliary subunit trafficking may control ion channel activity in a wide variety of cell types.

Biology of Bone Formation, Fracture Healing, and Distraction Osteogenesis.

Distraction osteogenesis is a bone-regenerative process in which an osteotomy is followed by distraction of the surrounding vascularized bone segments, with formation of new bone within the distraction gap. Distraction osteogenesis is efficacious for reconstructing critical sized bony defects in the appendicular and craniofacial skeleton. To provide opportunity to expand applications of distraction osteogenesis, it is important to have a thorough understanding of the underlying molecular biology and physiology of bone development and fracture healing. To accomplish these objectives a review of the literature was performed using search terms "endochondral ossification, intramembranous ossification, craniofacial skeleton, appendicular skeleton, fracture healing, bone development, and distraction osteogenesis." Bones of the craniofacial and appendicular skeleton have distinct mechanisms of embryonic development. The former develops from growth centers of mesenchymal precursors through intramembranous ossification. The latter forms though endochondral ossification in growth plates. However, both endochondral and intramembranous bone share similar master regulatory transcription factors and downstream growth factors. Fracture healing mirrors the pathway by which these bones developed embryonically. In contrast, bone formed by distraction osteogenesis does so by intramembranous ossification, regardless of whether it occurs within the appendicular or craniofacial skeleton. Understanding molecular pathway differences between bone formation by these mechanisms may allow for optimization and expansion of skeletal reconstruction by distraction osteogenesis.

Smooth muscle cell transient receptor potential polycystin-2 (TRPP2) channels contribute to the myogenic response in cerebral arteries.

Intravascular pressure-induced vasoconstriction is a smooth muscle cell-specific mechanism that controls systemic blood pressure and organ regional blood flow. Smooth muscle cell polycystin-1 and -2 (TRPP1 and -2) proteins modulate the myogenic response in mesenteric arteries, but involvement in other vascular beds is unclear. Here, we examined TRPP2 expression, cellular distribution, cation currents (ICat), and physiological functions in smooth muscle cells of rat and human cerebral arteries. We demonstrate that TRPP2 is the major TRPP isoform expressed in cerebral artery smooth muscle cells, with message levels higher than those of TRPP1. Arterial biotinylation and immunofluorescence indicated that TRPP2 is located primarily (∼88%) in the smooth muscle cell plasma membrane. RNA interference reduced TRPP2 expression by ∼55% compared to control, but did not alter levels of TRPP1, TRPC1, TRPC3, TRPC6, TRPM4, ANO1/TMEM16A, or voltage-dependent Ca(2+) (CaV1.2) channels, other ion channel proteins that modulate myogenic tone. Cell swelling induced by hyposmotic (250 osmol (l solution)(-1)) bath solution stimulated Gd(3+)-sensitive ICat in smooth muscle cells that were reduced by selective TRPP2 knockdown. TRPP2 knockdown did not alter myogenic tone at 20 mmHg but reduced tone between ∼28 and 39% over an intravascular pressure range between 40 and 100 mmHg. In contrast, TRPP2 knockdown did not alter depolarization-induced (60 mmol l K(+)) vasoconstriction. In summary, we show that TRPP2 is expressed in smooth muscle cells of resistance-size cerebral arteries, resides primarily in the plasma membrane, and contributes to the myogenic response. Data also suggest that TRPP2 differentially regulates the myogenic response in cerebral and mesenteric arteries.