SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines.

Proteinaceous cysteine residues act as privileged sensors of oxidative stress. As reactive oxygen and nitrogen species have been implicated in numerous pathophysiological processes, deciphering which cysteines are sensitive to oxidative modification and the specific nature of these modifications is essential to understanding protein and cellular function in health and disease. While established mass spectrometry-based proteomic platforms have improved our understanding of the redox proteome, the widespread adoption of these methods is often hindered by complex sample preparation workflows, prohibitive cost of isotopic labeling reagents, and requirements for custom data analysis workflows. Here, we present the SP3-Rox redox proteomics method that combines tailored low cost isotopically labeled capture reagents with SP3 sample cleanup to achieve high throughput and high coverage proteome-wide identification of redox-sensitive cysteines. By implementing a customized workflow in the free FragPipe computational pipeline, we achieve accurate MS1-based quantitation, including for peptides containing multiple cysteine residues. Application of the SP3-Rox method to cellular proteomes identified cysteines sensitive to the oxidative stressor GSNO and cysteine oxidation state changes that occur during T cell activation.

A Systematic Review of Idiopathic Secondary Stenosis Following Index Surgery for Craniosynostosis.

BACKGROUND: Primary craniosynostosis is a congenital craniofacial disorder in which cranial sutures prematurely close. Iatrogenic secondary stenosis is abnormal cranial suture closure caused by surgical manipulation of the suture. In contrast, idiopathic secondary stenosis develops in a suture that did not undergo surgical manipulation. The objective of this systematic review was to consolidate and characterize the incidence, classification, and management of idiopathic secondary stenosis in the literature. METHODS: Literature from PubMed, Web Of Science, and EMBASE from 1970 to March 2022 was reviewed. The following information was extracted for individual patients: incidence of idiopathic secondary stenosis, index primary craniosynostosis, primary surgical correction, presenting signs of secondary stenosis, management, and further complications. RESULTS: Seventeen articles detailing 1181 patients were included. Ninety-one developed idiopathic secondary stenosis (7.7%). Only 3 of these patients were syndromic. The most common index craniosynostosis was sagittal synostosis (83.5%). The most common suture undergoing idiopathic secondary stenosis was the coronal suture (91.2%). Patients presented at a median age of 24 months. The most common presenting sign was a radiologic finding (85.7%), although some patients presented with headache or head deformity. Only 2 patients, both syndromic, had complications following surgical correction of secondary stenosis. CONCLUSIONS: Idiopathic secondary stenosis is a rare, long-term complication following index surgical repair of craniosynostosis. It can occur following any surgical technique. It most commonly affects the coronal suture but can affect any of the sutures, including pansynostosis. Surgical correction is curative in nonsyndromic patients.

Facial Dermal Filler Injection and Vaccination: A 12-Year Review of Adverse Event Reporting and Literature Review.

BACKGROUND: Following authorization of 2 COVID-19 vaccines in December 2020, media attention increased towards postvaccine adverse events (AEs) in patients with facial dermal filler injections. OBJECTIVES: The purpose of this study was to characterize vaccine-related facial dermal filler AEs by scrutinizing the FDA's Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: The MAUDE database was queried from January 1, 2011 to January 28, 2023 for facial dermal filler medical device reports (MDRs) discussing vaccination-related AEs. A PubMed (National Institutes of Health, Bethesda, MD) literature review on dermal filler AEs was then conducted. Data were analyzed with descriptive statistics. RESULTS: Of 10,637 MDRs identified, 33 were included. There were 25 MDRs (75.8%) related to COVID-19 vaccination. Hyaluronic acid-based fillers were described in 31 MDRs (93.9%). AEs were mostly reported within days postinjection (n = 7, 21.2%), but ranged from immediately (n = 2, 6.1%) to months (n = 6, 18.2%) postinjection. Most AEs were reported postvaccine (n = 17, 51.5%) vs postfiller (n = 14, 42.4%). In 26 reports (78.8%), AEs occurred at the site of filler injection. Most MDRs described inflammation/swelling (n = 21, 28.0%). The literature review returned 302 articles, of which 14 were included. Only 1 article (7.1%) was published in a plastic surgery journal. CONCLUSIONS: Although the pandemic brought attention to COVID-19 vaccine-related facial dermal filler AEs, this study shows a low incidence compared with the millions of vaccine and filler injections administered. Reactions with non-COVID-19 vaccines were also documented. Increased awareness may help providers counsel patients undergoing vaccination and dermal filler implantation.

Multimodal Intervention Assessing the Appropriateness of Acid Suppression Therapy is Associated With Reduced Prescriptions at the Time of Discharge for Hospitalized Inpatients.

Background: Acid suppression therapy (AST), including proton pump inhibitors and histamine 2 receptor antagonists, are an overused class of medications. When used inappropriately, AST leads to polypharmacy, increased healthcare costs, and possible negative health consequences. Objective: To assess whether an intervention including prescriber education combined with a pharmacist-driven protocol was effective in reducing the percentage of patients who were discharged with inappropriate AST. Methods: This was a prospective pre-post study of adult patients who were prescribed AST before or during their admission to an internal medicine teaching service. All internal medicine resident physicians received education on appropriate AST prescribing. During the 4-week intervention period, dedicated pharmacists assessed the appropriateness of AST and made recommendations regarding deprescribing if no appropriate indication was identified. Results: During the study period, there were 14 166 admissions during which patients were prescribed AST. Out of the 1143 admissions during the intervention period, appropriateness of AST was assessed by a pharmacist for 163 patients. AST was determined to be inappropriate for 52.8% (n = 86) of patients and discontinuation or de-escalate of therapy occurred in 79.1% (n = 68) of these cases. The percentage of patients discharged on AST decreased from 42.5% before the intervention to 39.9% after the intervention (P = .007). Conclusion: This study suggests that a multimodal deprescribing intervention reduced prescriptions for AST without an appropriate indication at the time of discharge. To increase the efficiency of the pharmacist assessment several workflow improvements were identified. Further study is necessary to understand the long-term outcomes of this intervention.

Global models underestimate large decadal declining and rising water storage trends relative to GRACE satellite data.

Assessing reliability of global models is critical because of increasing reliance on these models to address past and projected future climate and human stresses on global water resources. Here, we evaluate model reliability based on a comprehensive comparison of decadal trends (2002-2014) in land water storage from seven global models (WGHM, PCR-GLOBWB, GLDAS NOAH, MOSAIC, VIC, CLM, and CLSM) to trends from three Gravity Recovery and Climate Experiment (GRACE) satellite solutions in 186 river basins (∼60% of global land area). Medians of modeled basin water storage trends greatly underestimate GRACE-derived large decreasing (≤-0.5 km3/y) and increasing (≥0.5 km3/y) trends. Decreasing trends from GRACE are mostly related to human use (irrigation) and climate variations, whereas increasing trends reflect climate variations. For example, in the Amazon, GRACE estimates a large increasing trend of ∼43 km3/y, whereas most models estimate decreasing trends (-71 to 11 km3/y). Land water storage trends, summed over all basins, are positive for GRACE (∼71-82 km3/y) but negative for models (-450 to -12 km3/y), contributing opposing trends to global mean sea level change. Impacts of climate forcing on decadal land water storage trends exceed those of modeled human intervention by about a factor of 2. The model-GRACE comparison highlights potential areas of future model development, particularly simulated water storage. The inability of models to capture large decadal water storage trends based on GRACE indicates that model projections of climate and human-induced water storage changes may be underestimated.

Does Surgical Specialty Impact Mandibular Fracture Outcomes?

PURPOSE: Maxillofacial trauma is treated by two medical specialties, plastic surgery (PRS) and otolaryngology (ENT). Differences in training exposure and practice patterns exist between specialties, but their respective outcomes have never been compared. METHODS: Mandible fracture data were reviewed from the National Surgical Quality Improvement Program from 2005 to 2016. Demographics variables, repair types, and adverse outcomes were compared between PRS and ENT. RESULTS: From 2005 to 2016, one thousand two hundred eighty-two cases were identified with 756 cases managed by ENT and 526 cases managed by PRS. Mean patient age was 34.6 years for both specialties (P = 0.95). Patient demographics between both cohorts were not statistically different except for higher rates of hypertension among ENT patients (10.2% for ENT versus 6.7% for PRS, P = 0.027) and higher rates of smoking history among PRS patients (46.8% versus 52.3%, P = 0.055). Mean operative time (131.3 versus 124.0 min, P = 0.090) had a trend toward being longer for ENT and mean length of stay (1.3 versus 2.0, P = 0.002) was significantly longer for PRS. Despite a greater proportion of high ASA class patients in the ENT group (P = 0.012) and patients with dirty/infected wounds in the PRS group (P = 0.013), there were no significant differences in 30-day readmission rates, 30-day reoperation rates, or wound infection rates. CONCLUSIONS: No significant differences in 30-day readmission rates, reoperation rates, or wound infection rates for mandible fracture management exist between specialties. Despite differences in training between PRS and ENT, both specialties have comparable perioperative outcomes for mandible fracture management.

Spatial Analysis of the Temporomandibular Joint and Condyle Following Mandibular Distraction in Robin Sequence.

ABSTRACT: To comprehensively assess changes in temporomandibular joint and mandibular condyle morphology in Robin sequence (RS) patients undergoing mandibular distraction osteogenesis (MDO). A retrospective analysis of pediatric patients with RS and functional temporomandibular joints who underwent MDO by a single surgeon was performed. Preoperative and postoperative computed tomography (CT) scans were morphometrically analyzed three-dimensional in 3-matic and Mimics (Materialise). Comparative analysis was performed using Wilcoxon signed-rank tests. Fourteen RS patients were included (28 condyles, 56 CT scans), 78% male and 22% females. The mean age at surgery was 9.4 weeks (range 1.6-46.7 weeks). The average age at initial CT was 5.3 days (range 0-11 days). The mean time interval for CT scan before MDO and after hardware removal were 8.8 ±â€Š6.4 days and 11.2 ±â€Š25.8 days, respectively. Rotatory changes of the condyle revealed a significantly decreased horizontal angle following MDO (-7.55°, 95% confidence interval -11.13° to -3.41°; P < 0.001). Anteroposteriorly, the angle between condylar process and ramus (incline) increased significantly (14.14°, 95% confidence interval 10.71°-19.59°; P < 0.001). Intragroup analysis revealed no difference between left versus right condylar position measurements. The condyle itself increased in size and length and the intercondylion distance increased post-MDO. There were no complications and all patients achieved relief of airway obstruction without tracheostomy. Morphologic and positional changes of the mandibular condyle following MDO in RS patients parallel changes that occur during normal development in non-RS patients. As a result, MDO may facilitate normal condylar morphology and function in RS patients.

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.

The Zoom Boom: How Video Calling Impacts Attitudes Towards Aesthetic Surgery in the COVID-19 Era.

BACKGROUND: The COVID-19 pandemic has led to the widespread adoption of video calling. A parallel growth in aesthetic surgery demand has been documented. OBJECTIVES: The authors sought to identify associations between video call engagement and aesthetic surgery attitudes. METHODS: We distributed a cross-sectional survey via Amazon Mechanical Turk in November 2020. Respondents were asked to report their time spent video calling, video calling applications and features (eg, virtual backgrounds) they utilized, and aesthetic surgery attitudes employing the 15-item Acceptance of Cosmetic Surgery Scale (ACSS; higher scores indicate greater acceptance). ACSS scores were compared between video call users and non-users employing t tests. Pearson's correlation coefficient was employed to quantify associations between ACSS scores and time spent on calls and multivariable analysis to estimate associations between video call engagement and ACSS scores. RESULTS: A total of 295 respondents (mean age, 37.6 years; 49.5% female) completed the survey. Across all video call applications surveyed, video call users had higher ACSS scores than non-users. Increased time respondents spent looking at their own face on video call was moderately associated with higher ACSS scores (r = 0.48, P < 0.01), whereas time spent looking at another person's face was not associated with a change in ACSS scores (r = 0.09, P = 0.11). Increased video call utilization was associated with higher ACSS scores. CONCLUSIONS: Increased video calling utilization is associated with increased acceptance of aesthetic surgery. Although the clinical significance of ACSS scores can be better elucidated, plastic surgeons should consider the effects of video calling on patient motivations for aesthetic surgery in the COVID-19 era.

Projected Landscape Impacts from Oil and Gas Development Scenarios in the Permian Basin, USA.

Projecting landscape impacts from energy development is essential to land management decisions. We forecast landscape alteration resulting from oil and gas well-pad construction across the economically important Permian Basin of Texas and New Mexico, USA, by projecting current landscape trends through 2050. We modeled three landscape-impact scenarios (low, medium, and high) using recent (2008-2017) trends in well-pad construction and energy production. The results of low-, medium-, and high-impact scenarios suggest that ~60,000, ~180,000, and ~430,000 new well pads could be constructed, potentially causing ~1000, ~2800, and ~6700 km2 of new direct landscape alteration. Almost two-thirds of all new well pads will be constructed within the geologic boundaries of the Delaware and Midland Basins. This translates into a 40, 120, and 300% increase in direct landscape alteration compared with direct alteration from existing well pads. We found that indirect effects (from edges) could increase by twofold, and that the ratio between indirect and direct alteration could decline by half as alteration intensifies and overlaps with existing alteration. The Chihuahuan Desert occupies the largest portion of the study area, and is projected to experience the largest area of alteration from future well-pad construction in the Permian Basin; the degree of direct alteration could increase by 70, 200, and 500% in this desert region, under low-, medium-, and high-impact scenarios. These scenarios can be used to design proactive conservation strategies to reduce landscape impacts from future oil and gas development.

Management of intussusception in patients with melanoma.

BACKGROUND: Increased cross-sectional imaging for surveillance of metastatic melanoma has led to more diagnoses of asymptomatic intussusception. METHODS: We performed a multi-institutional retrospective review of patient records with a history of metastatic melanoma and a diagnosis of intussusception. Patients were divided into three groups: 1) asymptomatic patients without current evidence of melanoma (no evidence of disease [NED]); 2) asymptomatic intussusception and known active metastatic melanoma; 3) symptomatic intussusception and known active metastatic melanoma; the number of patients requiring surgery and intraoperative findings were recorded. RESULTS: We reviewed 73 patients diagnosed with intussusception from 2004 to 2017. Among asymptomatic patients with NED (n = 16), 14 spontaneously resolved and 2 underwent pre-emptive surgery without abnormal intraoperative findings. Of asymptomatic patients with active metastatic disease (n = 32), 25 were initially observed and 7 underwent pre-emptive surgery and 9 of the 25 initially observed patients required surgery for development of symptoms. In this group, all 16 patients undergoing surgery (50% of the group) had intraoperative findings of intussusception and/or metastatic intestinal melanoma.. All symptomatic patients with metastatic melanoma (n = 25) underwent surgery; all had intraoperative findings of intussusception and/or metastatic melanoma except 1 (Meckel's diverticulum). CONCLUSION: Asymptomatic patients with NED do not require surgery and intussusception will likely resolve spontaneously. Asymptomatic patients with known metastatic melanoma may be initially observed, but a low threshold for surgery should be maintained. Symptomatic patients with known metastases should undergo surgery.

Incorporation of a chiral gem-disubstituted nitrogen heterocycle yields an oxazolidinone antibiotic with reduced mitochondrial toxicity.

gem-Disubstituted N-heterocycles are rarely found in drugs, despite their potential to improve the drug-like properties of small molecule pharmaceuticals. Linezolid, a morpholine heterocycle-containing oxazolidinone antibiotic, exhibits significant side effects associated with human mitochondrial protein synthesis inhibition. We synthesized a gem-disubstituted linezolid analogue that when compared to linezolid, maintains comparable (albeit slightly diminished) activity against bacteria, comparable in vitro physicochemical properties, and a decrease in undesired mitochondrial protein synthesis (MPS) inhibition. This research contributes to the structure-activity-relationship data surrounding oxazolidinone MPS inhibition, and may inspire investigations into the utility of gem-disubstituted N-heterocycles in medicinal chemistry.

Clinical Value of Single-photon Emission Computed Tomography Combined With Computed Tomography for Sentinel Lymph Node Identification in Melanoma.

INTRODUCTION: Melanoma is the deadliest form of skin cancer and has the ability to metastasize widely. Accurate diagnosis of sentinel lymph nodes (SLN) is crucial to its management. The gold standard for SLN identification is planar lymphoscintigraphy. Recently, single-photon emission computed tomography combined with computed tomography (SPECT/CT) has been used as a hybrid method to map lymphatic drainage networks. We aim to better characterize the utility of this tool in head and neck melanoma by evaluating its effectiveness in the preoperative setting for melanoma patients undergoing sentinel lymph node biopsy (SLNB). METHODS: We performed a retrospective chart review at the West Haven Veterans Affairs Hospital. Inclusion criteria were patients with melanoma with a thickness greater than 0.75 mm and SPECT/CT use before operative sentinel lymph node excision. Exclusion criteria included clinically palpable lymph nodes, evidence of distant metastatic disease, melanoma with a Breslow depth less than 0.75 mm, and melanoma in situ. Our primary endpoints were correlation with intraoperative findings and whether the test had any influence on the operative plan. RESULTS: Thirty-five patients between 2011 and 2017 met our criteria. SPECT/CT correlated with the sentinel node biopsy based on intraoperative lymphoscintigraphy in 30 (86%) of 35 cases, and there were no changes to the operative plan after SPECT/CT was performed. Sentinel lymph nodes were correctly identified in all 35 cases. CONCLUSIONS: The role of SPECT/CT in SLNB is uncertain. According to some studies, SPECT/CT can help decision making and change surgical approach in up to 35% of patients. However, other studies have reported questionable correlation with intraoperative findings and no added intraoperative value in over 50% of patients. We have demonstrated that preoperative SPECT/CT was consistent with intraoperative findings in 86.0% of cases but did not change the surgical approach for the SLNB. Surveillance over a period of 12 months did not reveal any signs of melanoma recurrence. A possible advantage of SPECT/CT is potentially decreasing costs by lowering operative time. However, financial cost in the literature suggests SPECT/CT is costlier than lymphoscintigraphy and therefore this must be weighed against any potential benefit. Overall, we did not find that SPECT/CT gives added value when compared with lymphoscintigraphy.

An Investigation of Brain Functional Connectivity by Form of Craniosynostosis.

PURPOSE: Long-term neurocognitive sequelae of nonsyndromic craniosynostosis (NSC) patients are just beginning to be clarified. This study uses functional MRI (fMRI) to determine if there is evidence of altered brain functional connectivity in NSC, and whether these aberrations vary by form of synostosis. METHODS: Twenty adolescent participants with surgically treated NSC (10 sagittal synostosis, 5 right unilateral coronal synostosis [UCS], 5 metopic synostosis [MSO]) were individually matched to controls by age, gender, and handedness. A subgroup of MSO was classified as severe metopic synostosis (SMS) based on the endocranial bifrontal angle. Resting state fMRI was acquired in a 3T Siemens TIM Trio scanner (Erlangen, Germany), and data were motion corrected and then analyzed with BioImage Suite (Yale School of Medicine). Resulting group-level t-maps were cluster corrected with nonparametric permutation tests. A region of interest analysis was performed based on the left Brodmann's Areas 7, 39, and 40. RESULTS: Sagittal synostosis had decreased whole-brain intrinsic connectivity compared to controls in the superior parietal lobules and the angular gyrus (P = 0.071). Unilateral coronal synostosis had decreased intrinsic connectivity throughout the prefrontal cortex (P = 0.031). The MSO cohort did not have significant findings on intrinsic connectivity, but the SMS subgroup had significantly decreased connectivity among multiple subcortical structures. CONCLUSION: Sagittal synostosis had decreased connectivity in regions associated with visuomotor integration and attention, while UCS had decreased connectivity in circuits crucial in executive function and cognition. Finally, severity of metopic synostosis may influence the degree of neurocognitive aberration. This study provides data suggestive of long-term sequelae of NSC that varies by suture type, which may underlie different phenotypes of neurocognitive impairment.

Understanding the Learning Disabilities Linked to Sagittal Craniosynostosis.

OBJECTIVE: The purpose of this study is to investigate further findings that corroborate similarities between corrected sagittal craniosynostosis and attention deficit hyperactivity disorder (ADHD). The aim is to further characterize the neurocognitive deficits seen in adolescents with corrected craniosynostosis by comparing it to established learning deficits such as ADHD. METHODS: A total of 30 functional magnetic resonance imaging (fMRI) of 10 sagittal nonsyndromic craniosynostosis (sNSC), 10 ADHD-combined, and 10 control adolescents were studied. The fMRI scans were analyzed utilizing Statistical Parametric Mapping (University College London, UK) and analyzed with BioImageSuite (Yale University, New Haven, CT). RESULTS: The ADHD has lower connectivity to Brodmann area (BA) 11 (Montreal Neurological Institution [MNI]: -12,26,-21), BA20 (MNI: 62,-24,-25), and BA21 (MNI: 62,-32,-23) compared to sNSC and controls (P < 0.001). The sNSC has a unique visuospatial defect, compared to ADHD, created by decreased connectivity to BA31 (MNI: -3,-68,37), BA7 (MNI: -4,-68,41), BA19 (MNI: 0,-83,31), visual association cortex (MNI: -4,-78,22), and primary visual cortex (MNI: 7,-74,21) (P < 0.001). CONCLUSION: Patients born with sNSC have different neural connections than children born with ADHD. Patients born with sNSC have decreased connections in areas of visual processing and increased connections in areas of attention and auditory processing than patients with ADHD. Therefore, children with sagittal craniosynsotosis may have learning difficulties that, similar, yet different from ADHD.

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.

High-Density Redox Amplified Coulostatic Discharge-Based Biosensor Array.

High-density biosensor arrays are essential for many cutting-edge biomedical applications including point-of-care vaccination screening to detect multiple highly-contagious diseases. Typical electrochemical biosensing techniques are based on the measurement of sub-pA currents for micron-sized sensors requiring highly-sensitive readout circuits. Such circuits are often too complex to scale down for high-density arrays. In this paper, a high-density 4,096-pixel electrochemical biosensor array in 180 nm CMOS is presented. It uses a coulostatic discharge sensing technique and interdigitated electrode geometry to reduce both the complexity and size of the readout circuitry. Each biopixel contains an interdigitated microelectrode with a 13 aA low-leakage readout circuit directly underneath. Compared to standard planar electrodes, the implemented interdigitated electrodes achieve a maximum amplification factor of 10.5× from redox cycling. The array's sensor density is comparable to state-of-the-art arrays, all without augmenting the sensors with complex post-processing. The detection of anti-Rubella and anti-Mumps antibodies in human serum is demonstrated.

Osseous Convexity at the Anterior Fontanelle: A Presentation of Metopic Fusion?

BACKGROUND: Craniosynostosis, or a premature fusion of 1 or more cranial vault sutures, results in characteristic head shape deformities. In previous reports, an osseous prominence at the anterior fontanelle has been suggestive of adjacent suture fusion and local elevation in intracranial pressure (ICP). This prominence has been termed the "volcano" sign, and has been described in the anterior fusion of the sagittal suture and serves as an indication for surgery. METHODS: Two patients presented for head shape evaluation with mild metopic ridging and anterior fontanellar osseous convexities consistent with the volcano sign. Low-dose computed tomography imaging was performed in both patients due to concern for underlying craniosynostosis with elevated locoregional ICP. RESULTS: In both patients, imaging was significant for a localized, superior forehead metopic fusion, as well as a bony, convex prominence at the site of the ossified anterior fontanelle. There were no other clinical or radiologic signs or symptoms to suggest elevated ICP. Surgery was not indicated in either patient. CONCLUSIONS: Here the authors present 2 patients with osseous convexities at the site of the closed anterior fontanelle without signs or symptoms of elevated ICP, or classic signs of metopic synostosis. The authors hypothesize that this pattern may be due to a form of mechanically induced premature fusion of a normal metopic suture that is focused superiorly at the bregma, with minimal resultant restriction of overall skull growth. This is in contrast to metopic synostosis, which primarily has a sutural pathology and leads to characteristic findings of hypotelorism and trigonocephaly.

Temporal Progression of Craniofacial Dysmorphology in Unilateral Coronal Synostosis: A Mechanistic Hypothesis.

AIM: This study chronicles skull base and face development in nonsyndromic unilateral coronal synostosis (UCS) during infancy, to characterize the mechanistic progression of facial dysmorphology. METHODS: Computed tomography scans from 51 subjects were reviewed (26 UCS, 25 controls) and data were reconstructed. Patients were stratified into 5 age groups. A series of measurements were taken from the reconstructions. RESULTS: All patients had a unilaterally fused coronal suture at the time of analysis. Asymmetry of the sphenoid wings was present across all age groups. The sphenoid wing ipsilateral to the fused suture consistently had a more acute angle from the midline. At 19 days of age, ipsilateral nasal root and cribriform plate deviation are noted, as well as increased contralateral zygoma antero-posterior length. Patients younger than 2 months also had elongated posterior cranial bases. At 2 to 3 months of age, the cranial base widens in the anterior portion of the middle cranial fossa with an increased ipsilateral pterion to sella distance. The most delayed change observed was the increase in contralateral orbital rim angle at 7 to 12 months of age compared to normal. CONCLUSION: After suture fusion, sphenoid wing changes are among the earliest restructural malformations to take place. This suggests that the cascade of dysmorphology in UCS originates in the cranial vault, then progresses to the skull base, and lastly to the facial structures. Ipsilateral orbital changes are early facial changes in UCS that begin before 2 months of age. This is then followed by changes in the contralateral face later in development.

The Etiology of Neuronal Development in Craniosynostosis: A Working Hypothesis.

Craniosynostosis is one of the most common craniofacial conditions treated by neurologic and plastic surgeons. In addition to disfigurement, children with craniosynostosis experience significant cognitive dysfunction later in life. Surgery is performed in infancy to correct skull deformity; however, the field is at a crossroads regarding the best approach for correction. Since the cause of brain dysfunction in these patients has remained uncertain, the role and type of surgery might have in attenuating the later-observed cognitive deficits through impact on the brain has been unclear. Recently, however, advances in imaging such as event-related potentials, diffusion tensor imaging, and functional MRI, in conjunction with more robust clinical studies, are providing important insight into the potential etiologies of brain dysfunction in syndromic and nonsyndromic craniosynostosis patients. This review aims to outline the cause(s) of such brain dysfunction including the role extrinsic vault constriction might have on brain development and the current evidence for an intrinsic modular developmental error in brain development. Illuminating the cause of brain dysfunction will identify the role of surgery can play in improving observed functional deficits and thus direct optimal primary and adjuvant treatment.