Plasticity of thalamocortical axons is regulated by serotonin levels modulated by preterm birth.

Sensory inputs are conveyed to distinct primary areas of the neocortex through specific thalamocortical axons (TCA). While TCA have the ability to reorient postnatally to rescue embryonic mistargeting and target proper modality-specific areas, how this remarkable adaptive process is regulated remains largely unknown. Here, using a mutant mouse model with a shifted TCA trajectory during embryogenesis, we demonstrated that TCA rewiring occurs during a short postnatal time window, preceded by a prenatal apoptosis of thalamic neurons-two processes that together lead to the formation of properly innervated albeit reduced primary sensory areas. We furthermore showed that preterm birth, through serotonin modulation, impairs early postnatal TCA plasticity, as well as the subsequent delineation of cortical area boundary. Our study defines a birth and serotonin-sensitive period that enables concerted adaptations of TCA to primary cortical areas with major implications for our understanding of brain wiring in physiological and preterm conditions.

Gene-level association analysis of bivariate ordinal traits with functional regressions.

In genetic studies, many phenotypes have multiple naturally ordered discrete values. The phenotypes can be correlated with each other. If multiple correlated ordinal traits are analyzed simultaneously, the power of analysis may increase significantly while the false positives can be controlled well. In this study, we propose bivariate functional ordinal linear regression (BFOLR) models using latent regressions with cumulative logit link or probit link to perform a gene-based analysis for bivariate ordinal traits and sequencing data. In the proposed BFOLR models, genetic variant data are viewed as stochastic functions of physical positions, and the genetic effects are treated as a function of physical positions. The BFOLR models take the correlation of the two ordinal traits into account via latent variables. The BFOLR models are built upon functional data analysis which can be revised to analyze the bivariate ordinal traits and high-dimension genetic data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Extensive simulation studies show that the likelihood ratio tests of the BFOLR models control type I errors well and have good power performance. The BFOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes, CFH and ARMS2, are found to strongly associate with eye drusen size, drusen area, age-related macular degeneration (AMD) categories, and AMD severity scale.

"People are now working together for a common good": The effect on social capital of participatory design for community-level sanitation infrastructure in urban informal settlements.

Communities with higher levels of social capital perform better than communities with lower social capital in community-level water and sanitation interventions and have better health outcomes. Although research recommends bolstering social capital to improve intervention outcomes, few studies provide empirical evidence on the effect of intervention activities on social capital. This study aimed to evaluate the effect of participatory design and community engagement activities on social capital among urban informal settlements in Suva, Fiji and Makassar, Indonesia enrolled in the Revitalizing Informal Settlements and their Environments trial using the Short Adapted Social Capital Assessment Tool. We performed confirmatory factor analyses (CFA) to test tool performance and built structural equation models to assess intervention effect on CFA-informed, sub-scale scores for cognitive and structural social capital. Qualitative in-depth interviews in Fiji and Indonesia and focus group discussions in Fiji provided nuanced understanding of intervention effects on social capital from residents' perspectives. Results confirmed the hypothesized two-factor solution but revealed differences by country and by gender in Indonesia. The intervention appeared positively related to cognitive social capital among men and women in Indonesia and negatively related to cognitive and structural social capital among men and women in Fiji. While effect sizes were small and cluster-adjustment for a small number of settlements yielded non-significant effects, trends were consistent across models and bivariate analyses and were corroborated by qualitative findings. Several contextual factors may explain these results, including timing and duration of intervention activities and influence of COVID-19. Qualitative data suggested that the relationship between participatory design and social capital may be bidirectional, helping to explain why certain settlements appeared to be better equipped to benefit from intervention activities. Practitioners and program designers should carefully consider the social pre-conditions of communities in which they intend to work to optimize program outcomes and avoid unintended consequences.

Gene-level association analysis of ordinal traits with functional ordinal logistic regressions.

In this paper, we develop functional ordinal logistic regression (FOLR) models to perform gene-based analysis of ordinal traits. In the proposed FOLR models, genetic variant data are viewed as stochastic functions of physical positions and the genetic effects are treated as a function of physical positions. The FOLR models are built upon functional data analysis which can be revised to analyze the ordinal traits and high dimension genetic data. The proposed methods are capable of dealing with dense genotype data which is usually encountered in analyzing the next-generation sequencing data. The methods are flexible and can analyze three types of genetic data: (1) rare variants only, (2) common variants only, and (3) a combination of rare and common variants. Simulation studies show that the likelihood ratio test statistics of the FOLR models control type I errors well and have good power performance. The proposed methods achieve the goals of analyzing ordinal traits directly, reducing high dimensionality of dense genetic variants, being computationally manageable, facilitating model convergence, properly controlling type I errors, and maintaining high power levels. The FOLR models are applied to analyze Age-Related Eye Disease Study data, in which two genes are found to strongly associate with four ordinal traits.

Stable isotopes and foraging behaviors support the role of antipredator benefits in driving the association between two marine fishes.

Research from terrestrial communities shows that diminished predation risk is a principal driver of heterospecific grouping behavior, with foraging ecology predicting the roles that species play in groups, as more vulnerable foragers preferentially join more vigilant ones from whom they can benefit. Meanwhile, field studies examining the adaptive significance of heterospecific shoaling among marine fish have focused disproportionately on feeding advantages such as scrounging or prey-flushing. Juvenile bonefish (Albula vulpes) occur almost exclusively among mojarras (Eucinostomus spp.) and even elect to join them over conspecifics, suggesting they benefit from doing so. We evaluated the roles of risk-related and food-related factors in motivating this pattern of affiliation, estimating: (1) the relative levels of risk associated with each species' search and prey capture activities, via behavioral vulnerability traits discerned from in situ video of heterospecific shoals, and (2) resource use redundancy, using stable isotopes (δ13C, δ15N, and δ34S) to quantify niche overlap. Across four distinct metrics, bonefish behaviors implied a markedly greater level of risk than those of mojarras, typified by higher activity levels and a reduced capacity for overt vigilance; consistent with expectations if their association conformed to patterns of joining observed in terrestrial habitats. Resource use overlap inferred from stable isotopes was low, indicating that the two species partitioned resources and making it unlikely that bonefish derived substantive food-related benefits. Collectively, these findings suggest that the attraction of juvenile bonefish to mojarras is motivated primarily by antipredator advantages, which may include the exploitation of risk-related social cues.

Gene-based analysis of bi-variate survival traits via functional regressions with applications to eye diseases.

Genetic studies of two related survival outcomes of a pleiotropic gene are commonly encountered but statistical models to analyze them are rarely developed. To analyze sequencing data, we propose mixed effect Cox proportional hazard models by functional regressions to perform gene-based joint association analysis of two survival traits motivated by our ongoing real studies. These models extend fixed effect Cox models of univariate survival traits by incorporating variations and correlation of multivariate survival traits into the models. The associations between genetic variants and two survival traits are tested by likelihood ratio test statistics. Extensive simulation studies suggest that type I error rates are well controlled and power performances are stable. The proposed models are applied to analyze bivariate survival traits of left and right eyes in the age-related macular degeneration progression.

Myocardial mesostructure and mesofunction.

The complex and highly organized structural arrangement of some five billion cardiomyocytes directs the coordinated electrical activity and mechanical contraction of the human heart. The characteristic transmural change in cardiomyocyte orientation underlies base-to-apex shortening, circumferential shortening, and left ventricular torsion during contraction. Individual cardiomyocytes shorten ∼15% and increase in diameter ∼8%. Remarkably, however, the left ventricular wall thickens by up to 30-40%. To accommodate this, the myocardium must undergo significant structural rearrangement during contraction. At the mesoscale, collections of cardiomyocytes are organized into sheetlets, and sheetlet shear is the fundamental mechanism of rearrangement that produces wall thickening. Herein, we review the histological and physiological studies of myocardial mesostructure that have established the sheetlet shear model of wall thickening. Recent developments in tissue clearing techniques allow for imaging of whole hearts at the cellular scale, whereas magnetic resonance imaging (MRI) and computed tomography (CT) can image the myocardium at the mesoscale (100 µm to 1 mm) to resolve cardiomyocyte orientation and organization. Through histology, cardiac diffusion tensor imaging (DTI), and other modalities, mesostructural sheetlets have been confirmed in both animal and human hearts. Recent in vivo cardiac DTI methods have measured reorientation of sheetlets during the cardiac cycle. We also examine the role of pathological cardiac remodeling on sheetlet organization and reorientation, and the impact this has on ventricular function and dysfunction. We also review the unresolved mesostructural questions and challenges that may direct future work in the field.

Cerebral cortex maldevelopment in syndromic craniosynostosis.

AIM: To assess the relationship of surface area of the cerebral cortex to intracranial volume (ICV) in syndromic craniosynostosis. METHOD: Records of 140 patients (64 males, 76 females; mean age 8y 6mo [SD 5y 6mo], range 1y 2mo-24y 2mo) with syndromic craniosynostosis were reviewed to include clinical and imaging data. Two hundred and three total magnetic resonance imaging (MRI) scans were evaluated in this study (148 patients with fibroblast growth factor receptor [FGFR], 19 patients with TWIST1, and 36 controls). MRIs were processed via FreeSurfer pipeline to determine total ICV and cortical surface area (CSA). Scaling coefficients were calculated from log-transformed data via mixed regression to account for multiple measurements, sex, syndrome, and age. Educational outcomes were reported by syndrome. RESULTS: Mean ICV was greater in patients with FGFR (1519cm3 , SD 269cm3 , p=0.016) than in patients with TWIST1 (1304cm3 , SD 145cm3 ) or controls (1405cm3 , SD 158cm3 ). CSA was related to ICV by a scaling law with an exponent of 0.68 (95% confidence interval [CI] 0.61-0.76) in patients with FGFR compared to 0.81 (95% CI 0.50-1.12) in patients with TWIST1 and 0.77 (95% CI 0.61-0.93) in controls. Lobar analysis revealed reduced scaling in the parietal (0.50, 95% CI 0.42-0.59) and occipital (0.67, 95% CI 0.54-0.80) lobes of patients with FGFR compared with controls. Modified learning environments were needed more often in patients with FGFR. INTERPRETATION: Despite adequate ICV in FGFR-mediated craniosynostosis, CSA development is reduced, indicating maldevelopment, particularly in parietal and occipital lobes. Modified education is also more common in patients with FGFR.

A Comprehensive Single-Center Analysis of Postoperative Nausea and Vomiting Following Orthognathic Surgery.

BACKGROUND: Postoperative nausea and vomiting (PONV) remains a major clinical end-point for directing enhanced recovery after surgery (ERAS) protocols in facial plastic surgery. This study aimed to identify risk factors for PONV and evaluate strategies for PONV reduction in orthognathic surgery patients. METHODS: A retrospective cohort study was performed among patients receiving orthognathic surgery at our institution from 2011 to 2018. Patient demographics, surgical operative and anesthesia notes, medications, and nausea/vomiting were assessed for each patient. The amount of opioid analgesia given both perioperatively and postoperatively was recorded and converted into morphine equivalents (MEQ). Stepwise regression analysis was used to identify significant risk factors for PONV. Post hoc analyses were employed to compare PONV among patients based on MEQ dosage and antiemetic prophylaxis regimes. RESULTS: A total of 492 patients were included; mean age was 23.0 years (range: 13-60); 54.4% were female. The majority of patients received concurrent Le Fort I osteotomy, BSSO, and genioplasty (70.1%). During hospitalization, 59.4% of patients experienced nausea requiring antiemetic medications and 28.4% experienced emesis. Stepwise regression yielded Apfel scores (P = 0.003) and postoperative opioids (P = 0.013) as the strongest predictors of PONV. Post hoc analyses showed that undertreatment with prophylactic antiemetics (based on Apfel) predicted increased PONV (+12.9%, P = 0.020), and that lower postoperative MEQs (<28.0) predicted decreased PONV (-11.8%, P = 0.01). CONCLUSIONS: The study findings confirm the high incidence of PONV among orthognathic surgical patients and stratify previously reported PONV risk factors. More aggressive utilization of antiemetic medications and decreased dependence on opioid analgesia may decrease nausea/vomiting following orthognathic surgery.

A novel online assessment of pragmatic and core language skills: An attempt to tease apart language domains in children.

It remains unclear whether pragmatic language skills and core language skills (grammar and vocabulary) are distinct language domains. The present work aimed to tease apart these domains using a novel online assessment battery administered to almost 400 children aged 7 to 13 years. Confirmatory factor analysis indicated that pragmatic and core language domains could be measured separately, but that both domains were highly related (r = .79). However, zero-order correlations between pragmatic tests were quite small, indicating that task-specific skills played an important role in performance, and follow-up exploratory factor analysis suggested that pragmatics might be best understood as a family of skills rather than a domain. This means that these different pragmatic skills may have different cognitive underpinnings and also need to be assessed separately. However, our overall results supported the idea that pragmatic and core aspects of language are closely related during development, with one area scaffolding development in the other.

Disappointing results of spring-assisted cranial vault expansion in patients with Crouzon syndrome presenting with sagittal synostosis.

The aim of this study was to report on a single center's experience with spring-assisted cranial vault expansion (SAE) in patients with Crouzon syndrome and sagittal suture synostosis. Strip craniotomy with SAE has resulted in successful outcomes with low complication and revision rates in patients with isolated scaphocephaly. However, recent experience suggests that outcomes in patients with Crouzon syndrome and sagittal synostosis (SS) who undergo SAE are less favorable compared with the outcomes of those who undergo frontobiparietal (FBP) expansion. The authors reviewed both operations performed at a single center and noticed an upward expansion of the skull, which may be related to ventriculomegaly, with concurrent intracranial hypertension and poor aesthetic outcome. All patients diagnosed with Crouzon syndrome and SS who were treated with SAE required a revision FBP operation. Based on this outcome, the authors consider Crouzon syndrome a contraindication for correcting SS with springs.

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.

ComPaSS-GWAS: A method to reduce type I error in genome-wide association studies when replication data are not available.

Results from association studies are traditionally corroborated by replicating the findings in an independent data set. Although replication studies may be comparable for the main trait or phenotype of interest, it is unlikely that secondary phenotypes will be comparable across studies, making replication problematic. Alternatively, there may simply not be a replication sample available because of the nature or frequency of the phenotype. In these situations, an approach based on complementary pairs stability selection for genome-wide association study (ComPaSS-GWAS), is proposed as an ad-hoc alternative to replication. In this method, the sample is randomly split into two conditionally independent halves multiple times (resamples) and a GWAS is performed on each half in each resample. Similar in spirit to testing for association with independent discovery and replication samples, a marker is corroborated if its p-value is significant in both halves of the resample. Simulation experiments were performed for both nongenetic and genetic models. The type I error rate and power of ComPaSS-GWAS were determined and compared to the statistical properties of a traditional GWAS. Simulation results show that the type I error rate decreased as the number of resamples increased with only a small reduction in power and that these results were comparable with those from a traditional GWAS. Blood levels of vitamin pyridoxal 5'-phosphate from the Trinity Student Study (TSS) were used to validate this approach. The results from the validation study were compared to, and were consistent with, those obtained from previously published independent replication data and functional studies.

Gene-based association analysis of survival traits via functional regression-based mixed effect cox models for related samples.

The importance to integrate survival analysis into genetics and genomics is widely recognized, but only a small number of statisticians have produced relevant work toward this study direction. For unrelated population data, functional regression (FR) models have been developed to test for association between a quantitative/dichotomous/survival trait and genetic variants in a gene region. In major gene association analysis, these models have higher power than sequence kernel association tests. In this paper, we extend this approach to analyze censored traits for family data or related samples using FR based mixed effect Cox models (FamCoxME). The FamCoxME model effect of major gene as fixed mean via functional data analysis techniques, the local gene or polygene variations or both as random, and the correlation of pedigree members by kinship coefficients or genetic relationship matrix or both. The association between the censored trait and the major gene is tested by likelihood ratio tests (FamCoxME FR LRT). Simulation results indicate that the LRT control the type I error rates accurately/conservatively and have good power levels when both local gene or polygene variations are modeled. The proposed methods were applied to analyze a breast cancer data set from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA). The FamCoxME provides a new tool for gene-based analysis of family-based studies or related samples.

Linear mixed models for association analysis of quantitative traits with next-generation sequencing data.

We develop linear mixed models (LMMs) and functional linear mixed models (FLMMs) for gene-based tests of association between a quantitative trait and genetic variants on pedigrees. The effects of a major gene are modeled as a fixed effect, the contributions of polygenes are modeled as a random effect, and the correlations of pedigree members are modeled via inbreeding/kinship coefficients. F -statistics and χ 2 likelihood ratio test (LRT) statistics based on the LMMs and FLMMs are constructed to test for association. We show empirically that the F -distributed statistics provide a good control of the type I error rate. The F -test statistics of the LMMs have similar or higher power than the FLMMs, kernel-based famSKAT (family-based sequence kernel association test), and burden test famBT (family-based burden test). The F -statistics of the FLMMs perform well when analyzing a combination of rare and common variants. For small samples, the LRT statistics of the FLMMs control the type I error rate well at the nominal levels α = 0.01 and 0.05 . For moderate/large samples, the LRT statistics of the FLMMs control the type I error rates well. The LRT statistics of the LMMs can lead to inflated type I error rates. The proposed models are useful in whole genome and whole exome association studies of complex traits.

Phylogenomic analysis of UDP-dependent glycosyltransferases provides insights into the evolutionary landscape of glycosylation in plant metabolism.

Glycosylated metabolites generated by UDP-dependent glycosyltransferases (UGTs) play critical roles in plant interactions with the environment as well as human and animal nutrition. The evolution of plant UGTs has previously been explored, but with a limited taxon sampling. In this study, 65 fully sequenced plant genomes were analyzed, and stringent criteria for selection of candidate UGTs were applied to ensure a more comprehensive taxon sampling and reliable sequence inclusion. In addition to revealing the overall evolutionary landscape of plant UGTs, the phylogenomic analysis also resolved the phylogenetic association of UGTs from free-sporing plants and gymnosperms, and identified an additional UGT group (group R) in seed plants. Furthermore, lineage-specific expansions and contractions of UGT groups were detected in angiosperms, with the total number of UGTs per genome remaining constant generally. The loss of group Q UGTs in Poales and Brassicales, rather than functional convergence in the group Q containing species, was supported by a gene tree of group Q UGTs sampled from many species, and further corroborated by the absence of group Q homologs on the syntenic chromosomal regions in Arabidopsis thaliana (Brassicales). Branch-site analyses of the group Q UGT gene tree allowed for identification of branches and amino acid sites that experienced episodic positive selection. The positively selected sites are located on the surface of a representative group Q UGT (PgUGT95B2), away from the active site, suggesting their role in protein folding/stability or protein-protein interactions.

A genome-wide association study implicates the BMP7 locus as a risk factor for nonsyndromic metopic craniosynostosis.

Our previous genome-wide association study (GWAS) for sagittal nonsyndromic craniosynostosis (sNCS) provided important insights into the genetics of midline CS. In this study, we performed a GWAS for a second midline NCS, metopic NCS (mNCS), using 215 non-Hispanic white case-parent triads. We identified six variants with genome-wide significance (P ≤ 5 × 10-8): rs781716 (P = 4.71 × 10-9; odds ratio [OR] = 2.44) intronic to SPRY3; rs6127972 (P = 4.41 × 10-8; OR = 2.17) intronic to BMP7; rs62590971 (P = 6.22 × 10-9; OR = 0.34), located ~ 155 kb upstream from TGIF2LX; and rs2522623, rs2573826, and rs2754857, all intronic to PCDH11X (P = 1.76 × 10-8, OR = 0.45; P = 3.31 × 10-8, OR = 0.45; P = 1.09 × 10-8, OR = 0.44, respectively). We performed a replication study of these variants using an independent non-Hispanic white sample of 194 unrelated mNCS cases and 333 unaffected controls; only the association for rs6127972 (P = 0.004, OR = 1.45; meta-analysis P = 1.27 × 10-8, OR = 1.74) was replicated. Our meta-analysis examining single nucleotide polymorphisms common to both our mNCS and sNCS studies showed the strongest association for rs6127972 (P = 1.16 × 10-6). Our imputation analysis identified a linkage disequilibrium block encompassing rs6127972, which contained an enhancer overlapping a CTCF transcription factor binding site (chr20:55,798,821-55,798,917) that was significantly hypomethylated in mesenchymal stem cells derived from fused metopic compared to open sutures from the same probands. This study provides additional insights into genetic factors in midline CS.

Intracranial hypertension and cortical thickness in syndromic craniosynostosis.

AIM: To evaluate the impact of risk factors for intracranial hypertension (ICH) on cerebral cortex thickness in syndromic craniosynostosis. METHOD: ICH risk factors including papilloedema, hydrocephalus, obstructive sleep apnea (OSA), cerebellar tonsillar position, occipitofrontal circumference (OFC) curve deflection, age, and sex were collected from the records of patients with syndromic craniosynostosis (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen syndromes) and imaging. Magnetic resonance images were analysed and exported for statistical analysis. A linear mixed model was developed to determine correlations with cerebral cortex thickness changes. RESULTS: In total, 171 scans from 107 patients (83 males, 88 females [including repeated scans], mean age 8y 10mo, range 1y 1mo-34y, SD 5y 9mo) were evaluated. Mean cortical thickness in this cohort was 2.78mm (SD 0.17). Previous findings of papilloedema (p=0.036) and of hydrocephalus (p=0.007) were independently associated with cortical thinning. Cortical thickness did not vary significantly by sex (p=0.534), syndrome (p=0.896), OSA (p=0.464), OFC (p=0.375), or tonsillar position (p=0.682). INTERPRETATION: Detection of papilloedema or hydrocephalus in syndromic craniosynostosis is associated with significant changes in cortical thickness, supporting the need for preventative rather than reactive treatment strategies. WHAT THIS PAPER ADDS: Papilloedema is associated with thinning of the cerebral cortex in syndromic craniosynostosis, independently of hydrocephalus.

Hipertensión intracraneal y grosor cortical en craneosinostosis sindrómica OBJETIVO: Evaluar el impacto de los factores de riesgo de hipertensión intracraneal (HIC) en el grosor de la corteza cerebral en la craneosinostosis sindrómica. MÉTODO: La neuroimagen, y, los factores de riesgo para HIC que incluyeron papiledema, hidrocefalia, apnea obstructiva del sueño (SAOS), posición de la tonsila cerebelosa, edad de desviación de la curva de circunferencia occipitofrontal (CFO) y el sexo, se recogieron de los registros de pacientes con craneosinostosis sindrómica (Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzensis). Las imágenes de resonancia magnética fueron analizadas y exportadas para análisis estadístico. Se desarrolló un modelo mixto lineal para determinar las correlaciones con los cambios en el espesor de la corteza cerebral. RESULTADOS: En total se evaluaron 171 exploraciones de 107 pacientes (83 varones, 88 mujeres [incluyendo escaneos repetidos], edad media 8 años 10 meses, rango 1 año 1 mes - 34 años, DE 5 años 9 meses). El espesor medio cortical en esta cohorte fue de 2,78 mm (DS 0,17). Los hallazgos anteriores de papiledema (p=0,036) y de hidrocefalia (p=0,007) se asociaron de forma independiente con el adelgazamiento cortical. El grosor cortical no varió significativamente por sexo (p=0,534), síndrome (p=0,896), SAOS (p=0,464), CFO (p=0,375), o posición tonsilar (p=0,682). INTERPRETACIÓN: La detección de papiledema o hidrocefalia en la craneosinostosis sindrómica, se asocia con cambios significativos en el grosor cortical. Esto apoya la necesidad de estrategias de tratamiento preventivo en lugar de tratamientos reactivos.

Hipertensão intracrianiana e espessura cortical na craniossinostose sindrômica OBJETIVO: Avaliar o impacto de fatores de risco para hipertensão intracraniana (HIC) na espessura cortical em craniossinostose sindrômica. MÉTODO: Fatores de risco para HIC incluindo papiloedema, hidrocefalia, apnéia obstrutiva do sono (AOS), posição das tonsilas do cerebelo, idade de deflexão da curva da circunferência occipitofrontal (COF), e sexo foram coletados dos registros de pacientes com craniossinostose sindrômica (síndromes de Apert, Crouzon, Pfeiffer, Muenke, Saethre-Chotzen) e imagens. As imagens de ressonância magnética foram analisadas e exportadas para análise estatística. Um modelo linear misto foi desenvolvido para determinar correlações com mudanças na espessura do córtex cerebral. RESULTADOS: No total, 171 imagens de 107 pacientes (83 do sexo masculino, 88 do sexo feminino [incluindo varreduras repetidas], média de idade 8a 10m, variação 1a 1m-34a, DP 5a 9m) foram avaliados. A espessura cortical média nesta coorte foi 2,78mm (DP 0,17). Achados prévios de papiloedema (p=0,036) e de hidrocefalia (p=0,007) foram independentemente associados com a redução cortical. A espessura cortical não variou significativamente com o sexo (p=0,534), síndrome (p=0,896), AOS (p=0,464), COF (p=0,375), ou posição tonsilar (p=0,682). INTERPRETAÇÃO: A detecção do papiloedema ou hidrocefalia na craniossinostose sindrômica se associa com mudanças significativas na espessura cortical, sustentando a necessidade de estratégias de tratamento preventivas e não reativas.

Falls during inpatient rehabilitation in spinal cord injury, acquired brain injury, and neurologmusculoskeletal disease programs.

STUDY DESIGN: Retrospective chart review. OBJECTIVES: To compare the proportion of fallers and the patient level and fall characteristics among inpatients who had experienced at least one fall in a spinal cord injury (SCI), an acquired brain injury (ABI), and a neuromusculoskeletal disease (NMS) rehabilitation program. SETTING: Tertiary rehabilitation hospital. SUBJECTS: Inpatients who had experienced at least one fall during rehabilitation. METHODS: Patient and fall level variables were extracted from electronic medical records over a 5-year period (January 1, 2011 to January 1, 2016): hospital program, age, sex, Functional Independence Measure (FIM) scores, length of stay, number of medications, as well as fall date, time, location, cause, harm, fall risk assessment data, and whether the fall was witnessed. The impact of hospital program on fall was examined using bivariate and multivariable analysis. RESULTS: Two hundred and thirty-seven (16%) inpatients experienced at least one fall during the study period. Inpatients with SCI had the highest proportion of fallers (20%) and fell later after admission than inpatients in the other programs. Patients with ABI were more likely to sustain moderate-to-severe physical harm from falls. Taking >5 medications at time of fall and being earlier in one's rehabilitation course were associated with increased fall rate among fallers. CONCLUSIONS: Although the type of program was not a significant predictor of fall rate in the multivariable analysis, there were some important differences among the rehabilitation programs on patient and fall level characteristics. These results may be useful when developing and timing fall prevention interventions for inpatient rehabilitation.

Classification of Subtypes of Crouzon Syndrome Based on the Type of Vault Suture Synostosis.

BACKGROUND: Patients with Crouzon syndrome develop various types of anatomic deformities due to different forms of craniosynostosis, yet they have similar craniofacial characteristics. However, exact homology is not evident. Different pathology then may be best treated by different forms of surgical technique. Therefore, precise classification of Crouzon syndrome, based on individual patterns of cranial suture involvement is needed. METHODS: Ninety-five computed tomography (CT) scans (Crouzon, n = 33; control, n = 62) were included in this study. All the CT scans are divided into 4 types based on premature closure of sutures: class I = coronal and lambdoidal synostosis; class II = sagittal synostosis; class III = pansynostosis; and class IV = "Others." The CT scan anatomy was measured by Materialise software. RESULTS: The class III, pansynostosis, is the most prevalent (63.6%). The classes I, III, and IV of Crouzon have significantly shortened entire anteroposterior cranial base length, with the shortest base length in class III. The external cranial measurements in class I show primarily a decreased posterior facial skeleton, while the class III presented with holistic facial skeleton reduction. Class II has the least severe craniofacial malformations, while class III had the most severe. CONCLUSION: The morphology of patients with Crouzon syndrome is not identical in both cranial base and facial characteristics, especially when they associated with different subtypes of cranial suture synostosis. The classification of Crouzon syndrome proposed in this study, summarizes the differences among each subgroup of craniosynostosis suture involvement, which, theoretically, may ultimately influence both the timing and type of surgical intervention.