Assembly of bacterial inner membrane proteins.

Numerous membrane proteins form multisubunit protein complexes, which contain both integral and peripheral subunits, in addition to prosthetic groups. Bacterial membrane proteins are inserted into the inner membrane by the Sec translocase and YidC insertase. Their folding can be facilitated by YidC and the phospholipid phosphatidylethanolamine (PE). Glycine zippers and other motifs promote transmembrane-transmembrane (TM-TM) helix interactions that may lead to the formation of α-helical bundles of membrane proteins. During or after membrane insertion, the subunits of oligomeric membrane proteins must find each other to build the homo-oligomeric and the hetero-oligomeric membrane complexes. Although chaperones may function as assembly factors in the formation of the oligomer, many protein oligomers appear to fold and oligomerize spontaneously. Current studies show that most subunits of hetero-oligomers follow a sequential and ordered pathway to form the membrane protein complex. If the inserted protein is misfolded or the membrane protein is misassembled, quality control mechanisms exist that can degrade the proteins.

Specialized interferon action in COVID-19.

The impacts of interferon (IFN) signaling on COVID-19 pathology are multiple, with both protective and harmful effects being documented. We report here a multiomics investigation of systemic IFN signaling in hospitalized COVID-19 patients, defining the multiomics biosignatures associated with varying levels of 12 different type I, II, and III IFNs. The antiviral transcriptional response in circulating immune cells is strongly associated with a specific subset of IFNs, most prominently IFNA2 and IFNG. In contrast, proteomics signatures indicative of endothelial damage and platelet activation associate with high levels of IFNB1 and IFNA6. Seroconversion and time since hospitalization associate with a significant decrease in a specific subset of IFNs. Additionally, differential IFN subtype production is linked to distinct constellations of circulating myeloid and lymphoid immune cell types. Each IFN has a unique metabolic signature, with IFNG being the most associated with activation of the kynurenine pathway. IFNs also show differential relationships with clinical markers of poor prognosis and disease severity. For example, whereas IFNG has the strongest association with C-reactive protein and other immune markers of poor prognosis, IFNB1 associates with increased neutrophil to lymphocyte ratio, a marker of late severe disease. Altogether, these results reveal specialized IFN action in COVID-19, with potential diagnostic and therapeutic implications.

Racial and Ethnic Disparities in Operative Experience Among General Surgery Residents: A Multi-Institutional Study from the US ROPE Consortium.

OBJECTIVE: To determine the relationship between race/ethnicity and case volume among graduating surgical residents. BACKGROUND: Racial/ethnic minority individuals face barriers to entry and advancement in surgery; however, no large-scale investigations of the operative experience of racial/ethnic minority residents have been performed. METHODS: A multi-institutional retrospective analysis of the Accreditation Council for Graduate Medical Education case logs of categorical general surgery residents at 20 programs in the US Resident OPerative Experience Consortium database was performed. All residents graduating between 2010 and 2020 were included. The total, surgeon chief, surgeon junior, and teaching assistant case volumes were compared between racial/ethnic groups. RESULTS: The cohort included 1343 residents. There were 211 (15.7%) Asian, 65 (4.8%) Black, 73 (5.4%) Hispanic, 71 (5.3%) "Other" (Native American or Multiple Race), and 923 (68.7%) White residents. On adjusted analysis, Black residents performed 76 fewer total cases (95% CI, -109 to -43, P <0.001) and 69 fewer surgeon junior cases (-98 to -40, P <0.001) than White residents. Comparing adjusted total case volume by graduation year, both Black residents and White residents performed more cases over time; however, there was no difference in the rates of annual increase (10 versus 12 cases per year increase, respectively, P =0.769). Thus, differences in total case volume persisted over the study period. CONCLUSIONS: In this multi-institutional study, Black residents graduated with lower case volume than non-minority residents throughout the previous decade. Reduced operative learning opportunities may negatively impact professional advancement. Systemic interventions are needed to promote equitable operative experience and positive culture change.

Associations between disordered eating, internalizing symptoms, and behavioral and neural correlates of response inhibition in preadolescence.

Response inhibition difficulties are reported in individuals with eating disorders (EDs), anxiety, and depression. Although ED symptoms and internalizing symptoms co-occur in preadolescence, there is limited research examining associations between these symptoms and response inhibition in this age group. This study is the first to investigate the associations between behavioral and neural markers of response inhibition, disordered eating (DE), and internalizing symptoms in a community sample of preadolescents. Forty-eight children (M age = 10.95 years, 56.3% male) completed a Go/NoGo task, whereas electroencephalography was recorded. Self-report measures of DE and internalizing symptoms were collected. Higher levels of anxiety and depression were associated with neural markers of suboptimal response inhibition (attenuated P3NoGo amplitudes) in preadolescence. In contrast, higher levels of depression were associated with greater response inhibition at a behavioral level. These findings suggest internalizing symptoms in preadolescence are associated with P3-indexed difficulties in evaluation and monitoring, but these are not sufficient to disrupt behavioral performance on a response inhibition task. This pattern may reflect engagement of compensatory processes to support task performance. DE was not significantly associated with response inhibition, suggesting that difficulties in response inhibition may only be reliably observed in more chronic and severe DE and ED presentations.

Imputation strategies for genomic prediction using nanopore sequencing.

BACKGROUND: Genomic prediction describes the use of SNP genotypes to predict complex traits and has been widely applied in humans and agricultural species. Genotyping-by-sequencing, a method which uses low-coverage sequence data paired with genotype imputation, is becoming an increasingly popular SNP genotyping method for genomic prediction. The development of Oxford Nanopore Technologies' (ONT) MinION sequencer has now made genotyping-by-sequencing portable and rapid. Here we evaluate the speed and accuracy of genomic predictions using low-coverage ONT sequence data in a population of cattle using four imputation approaches. We also investigate the effect of SNP reference panel size on imputation performance. RESULTS: SNP array genotypes and ONT sequence data for 62 beef heifers were used to calculate genomic estimated breeding values (GEBVs) from 641 k SNP for four traits. GEBV accuracy was much higher when genome-wide flanking SNP from sequence data were used to help impute the 641 k panel used for genomic predictions. Using the imputation package QUILT, correlations between ONT and low-density SNP array genomic breeding values were greater than 0.91 and up to 0.97 for sequencing coverages as low as 0.1 × using a reference panel of 48 million SNP. Imputation time was significantly reduced by decreasing the number of flanking sequence SNP used in imputation for all methods. When compared to high-density SNP arrays, genotyping accuracy and genomic breeding value correlations at 0.5 × coverage were also found to be higher than those imputed from low-density arrays. CONCLUSIONS: Here we demonstrated accurate genomic prediction is possible with ONT sequence data from sequencing coverages as low as 0.1 × , and imputation time can be as short as 10 min per sample. We also demonstrate that in this population, genotyping-by-sequencing at 0.1 × coverage can be more accurate than imputation from low-density SNP arrays.

The Severity of Initial Unilateral Cleft Lip and Nasal Deformity Predicts Long-Term Postoperative Esthetic Outcome.

BACKGROUND: Infantile cleft lip and nasal severity influence the final esthetic result of the repair. Although various authors have described methods of cleft lip and nasal repair, there is a paucity of data that correlates cleft severity with esthetic outcomes. The aim of this study was to examine the correlation between presurgical severity of unilateral cleft deformity and long-term postoperative esthetic outcomes. METHODS: This retrospective study, based at a single institution, investigated patients with complete unilateral cleft lip, with or without cleft palate, who underwent repair by a single surgeon, had preoperative infantile facial casts, and had postoperative facial photographs at 6 to 11 years of age (N=31). Preoperative nostril width ratio and columellar angle measurements were taken from facial casts. Postoperative, long-term nasolabial appearance was rated by 5 blinded observers used a modified Kuijpers-Jagtman scale. Linear regression was used to determine the relationship between preoperative cleft severity and postoperative ratings. RESULTS: Preoperative nostril width ratio directly correlated with postoperative nasal form score (r=0.40; P=0.026); likewise, preoperative columellar angle predicted postoperative nasal form score (r=0.37; P=0.040). Preoperative cleft severity was not significantly correlated with vermillion border appearance. Cronbach α values of 0.91 (nasal form) and 0.79 (vermillion border) indicated good inter-rater reliability. Kappa values of 0.87 (nasal form) and 0.70 (vermillion border) indicated good intrarater reliability. CONCLUSIONS: Preoperative unilateral cleft nose severity directly correlates with long-term postoperative nasal appearance in childhood. Outcome studies should present and control for preoperative severity to allow more accurate assessment of repair techniques.

A Longitudinal Investigation of Nasolabial Changes With and Without Revision Surgery in Patients with Non-Syndromic Unilateral Cleft Lip and Palate.

OBJECTIVE: To determine a baseline of anticipated change in nasolabial appearance following primary repair of unilateral cleft lip/palate and evaluate the degree to which revision surgery improves nasolabial appearance. DESIGN: Retrospective chart review. SETTING: Patients treated at the Lancaster Cleft Palate Clinic interdisciplinary clinic. PATIENTS: Twenty-three patients with complete unilateral cleft lip and palate who underwent primary surgical repair and 19 additional patients who underwent subsequent revision surgery were included. INTERVENTIONS: Patients in the non-revision group underwent a Tennison-Randall triangular flap lip repair at 3mo. Patients in the revision group underwent a modification of the Nakajima straight-line repair after primary Tennison-Randall triangular flap lip repair at an average age of 141mo. MAIN OUTCOME MEASURES: A modification of the Asher-McDade Aesthetic Index was utilized to evaluate Nasolabial Frontal (NLF), Nasolabial Profile (NLP), Vermillion Border (VB), and total change in appearance. Scores for patients in the revision group were evaluated before and after revision while appearance for patients without revision was evaluated at 3 distinct ages. Scores were averaged across time-points and inter-rater reliability was assessed. RESULTS: Nasolabial appearance in the non-revision sample did not change significantly over time, except for nasal profile. Scores improved after revision surgery - NLP: 3.48 to 2.97, (p = 0.001); NLF: 3.50 to 2.95 (p = 0.001); and Total Nasolabial Score: 3.29 to 3.01 (p = 0.004), with no significant change in VB. CONCLUSION: Decisions regarding need for nasolabial revision surgery may be made as early as 5yo with successful outcomes following secondary surgery improving appearance except for vermillion border appearance.

Membrane translocation of folded proteins.

An ever-increasing number of proteins have been shown to translocate across various membranes of bacterial as well as eukaryotic cells in their folded states as a part of physiological and/or pathophysiological processes. Herein, we provide an overview of the systems/processes that are established or likely to involve the membrane translocation of folded proteins, such as protein export by the twin-arginine translocation system in bacteria and chloroplasts, unconventional protein secretion and protein import into the peroxisome in eukaryotes, and the cytosolic entry of proteins (e.g., bacterial toxins) and viruses into eukaryotes. We also discuss the various mechanistic models that have previously been proposed for the membrane translocation of folded proteins including pore/channel formation, local membrane disruption, membrane thinning, and transport by membrane vesicles. Finally, we introduce a newly discovered vesicular transport mechanism, vesicle budding and collapse, and present evidence that vesicle budding and collapse may represent a unifying mechanism that drives some (and potentially all) of folded protein translocation processes.

A hydrophilic microenvironment in the substrate-translocating groove of the YidC membrane insertase is essential for enzyme function.

The YidC family of proteins are membrane insertases that catalyze the translocation of the periplasmic domain of membrane proteins via a hydrophilic groove located within the inner leaflet of the membrane. All homologs have a strictly conserved, positively charged residue in the center of this groove. In Bacillus subtilis, the positively charged residue has been proposed to be essential for interacting with negatively charged residues of the substrate, supporting a hypothesis that YidC catalyzes insertion via an early-step electrostatic attraction mechanism. Here, we provide data suggesting that the positively charged residue is important not for its charge but for increasing the hydrophilicity of the groove. We found that the positively charged residue is dispensable for Escherichia coli YidC function when an adjacent residue at position 517 was hydrophilic or aromatic, but was essential when the adjacent residue was apolar. Additionally, solvent accessibility studies support the idea that the conserved positively charged residue functions to keep the top and middle of the groove sufficiently hydrated. Moreover, we demonstrate that both the E. coli and Streptococcus mutans YidC homologs are functional when the strictly conserved arginine is replaced with a negatively charged residue, provided proper stabilization from neighboring residues. These combined results show that the positively charged residue functions to maintain a hydrophilic microenvironment in the groove necessary for the insertase activity, rather than to form electrostatic interactions with the substrates.

Mediating Photochemical Reaction Rates at Lewis Acidic Rare Earths by Selective Energy Loss to 4f-Electron States.

Manifesting chemical differences in individual rare earth (RE) element complexes is challenging due to the similar sizes of the tripositive cations and the corelike 4f shell. We disclose a new strategy for differentiating between similarly sized Dy3+ and Y3+ ions through a tailored photochemical reaction of their isostructural complexes in which the f-electron states of Dy3+ act as an energy sink. Complexes RE(hfac)3(NMMO)2 (RE = Dy (2-Dy) and Y (2-Y), hfac = hexafluoroacetylacetonate, and NMMO = N-methylmorpholine-N-oxide) showed variable rates of oxygen atom transfer (OAT) to triphenylphosphine under ultraviolet (UV) irradiation, as monitored by 1H and 19F NMR spectroscopies. Ultrafast transient absorption spectroscopy (TAS) identified the excited state(s) responsible for the photochemical OAT reaction or lack thereof. Competing sensitization pathways leading to excited-state deactivation in 2-Dy through energy transfer to the 4f electron manifold ultimately slows the OAT reaction at this metal cation. The measured rate differences between the open-shell Dy3+ and closed-shell Y3+ complexes demonstrate that using established principles of 4f ion sensitization may deliver new, selective modalities for differentiating the RE elements that do not depend on cation size.

A Per-Protocol Analysis Using Inverse-Probability-of-Censoring Weights in a Randomized Trial of Initial Protease Inhibitor Versus Nonnucleoside Reverse Transcriptase Inhibitor Regimens in Children.

Protocol adherence may influence measured treatment effectiveness in randomized controlled trials. Using data from a multicenter trial (Europe and the Americas, 2002-2009) of children with human immunodeficiency virus type 1 who had been randomized to receive initial protease inhibitor (PI) versus nonnucleoside reverse transcriptase inhibitor (NNRTI) antiretroviral therapy regimens, we generated time-to-event intention-to-treat (ITT) estimates of treatment effectiveness, applied inverse-probability-of-censoring weights to generate per-protocol efficacy estimates, and compared shifts from ITT to per-protocol estimates across and within treatment arms. In ITT analyses, 263 participants experienced 4-year treatment failure probabilities of 41.3% for PIs and 39.5% for NNRTIs (risk difference = 1.8% (95% confidence interval (CI): -10.1, 13.7); hazard ratio = 1.09 (95% CI: 0.74, 1.60)). In per-protocol analyses, failure probabilities were 35.6% for PIs and 29.2% for NNRTIs (risk difference = 6.4% (95% CI: -6.7, 19.4); hazard ratio = 1.30 (95% CI: 0.80, 2.12)). Within-arm shifts in failure probabilities from ITT to per-protocol analyses were 5.7% for PIs and 10.3% for NNRTIs. Protocol nonadherence was nondifferential across arms, suggesting that possibly better NNRTI efficacy may have been masked by differences in within-arm shifts deriving from differential regimen forgiveness, residual confounding, or chance. A per-protocol approach using inverse-probability-of-censoring weights facilitated evaluation of relationships among adherence, efficacy, and forgiveness applicable to pediatric oral antiretroviral regimens.

Embracing neurodiversity in doll play: Investigating neural and language correlates of doll play in a neurodiverse sample.

Doll play may provide opportunities for children to rehearse social interactions, even when playing alone. Previous research has found that the posterior superior temporal sulcus (pSTS) was more engaged when children played with dolls alone, compared to playing with tablet games alone. Children's use of internal state language (ISL) about others was also associated with pSTS activity. As differences in social cognition are frequently observed in autistic people, we were interested in the brain and language correlates of doll play in children with varying levels of autistic traits. We investigated children's (N = 57, mean age = 6.72, SD = 1.53) use of ISL and their pSTS brain activity using functional near-infrared spectroscopy (fNIRS) as they played with dolls and tablet games, both alone and with a social partner. We also investigated whether there were any effects of autistic traits using the parent-report Autism Spectrum Quotient-Children's Version (AQ-Child). We found that the left pSTS was engaged more as children played with dolls or a tablet with a partner, and when playing with dolls alone, compared to when playing with a tablet alone. Relations between language and neural correlates of social processing were distinct based on the degree of autistic traits. For children with fewer autistic traits, greater pSTS activity was associated with using ISL about others. For children with more autistic traits, greater pSTS activity was associated with experimenter talk during solo play. These divergent pathways highlight the importance of embracing neurodiversity in children's play patterns to best support their development through play.

Disparities in the Operative Experience Between Female and Male General Surgery Residents: A Multi-institutional Study From the US ROPE Consortium.

OBJECTIVE: To examine differences in resident operative experience between male and female general surgery residents. BACKGROUND: Despite increasing female representation in surgery, sex and gender disparities in residency experience continue to exist. The operative volume of male and female general surgery residents has not been compared on a multi-institutional level. METHODS: Demographic characteristics and case logs were obtained for categorical general surgery graduates between 2010 and 2020 from the US Resident OPerative Experience Consortium database. Univariable, multivariable, and linear regression analyses were performed to compare differences in operative experience between male and female residents. RESULTS: There were 1343 graduates from 20 Accreditation Council for Graduate Medical Education-accredited programs, and 476 (35%) were females. There were no differences in age, race/ethnicity, or proportion pursuing fellowship between groups. Female graduates were less likely to be high-volume residents (27% vs 36%, P < 0.01). On univariable analysis, female graduates performed fewer total cases than male graduates (1140 vs 1177, P < 0.01), largely due to a diminished surgeon junior experience (829 vs 863, P < 0.01). On adjusted multivariable analysis, female sex was negatively associated with being a high-volume resident (OR = 0.74, 95% CI: 0.56 to 0.98, P = 0.03). Over the 11-year study period, the annual total number of cases increased significantly for both groups, but female graduates (+16 cases/year) outpaced male graduates (+13 cases/year, P = 0.02). CONCLUSIONS: Female general surgery graduates performed significantly fewer cases than male graduates. Reassuringly, this gap in operative experience may be narrowing. Further interventions are warranted to promote equitable training opportunities that support and engage female residents.

The Bcvic1 and Bcvic2 vegetative incompatibility genes in Botrytis cinerea encode proteins with domain architectures involved in allorecognition in other filamentous fungi.

Vegetative incompatibility is a fungal allorecognition system characterised by the inability of genetically distinct conspecific fungal strains to form a viable heterokaryon and is controlled by multiple polymorphic loci termed vic (vegetative incompatibility) or het (heterokaryon incompatibility). We have genetically identified and characterised the first vic locus in the economically important, plant-pathogenic, necrotrophic fungus Botrytis cinerea. A bulked segregant approach coupled with whole genome Illumina sequencing of near-isogenic lines of B. cinerea was used to map a vic locus to a 60-kb region of the genome. Within that locus, we identified two adjacent, highly polymorphic open reading frames, Bcvic1 and Bcvic2, which encode predicted proteins that contain domain architectures implicated in vegetative incompatibility in other filamentous fungi. Bcvic1 encodes a predicted protein containing a putative serine esterase domain, a NACHT family of NTPases domain, and several Ankyrin repeats. Bcvic2 encodes a putative syntaxin protein containing a SNARE domain; such proteins typically function in vesicular transport. Deletion of Bcvic1 and Bcvic2 individually had no effect on vegetative incompatibility. However, deletion of the region containing both Bcvic1 and Bcvic2 resulted in mutant lines that were severely restricted in growth and showed loss of vegetative incompatibility. Complementation of these mutants by ectopic expression restored the growth and vegetative incompatibility phenotype, indicating that Bcvic1 and Bcvic2 are controlling vegetative incompatibility at this vic locus.

Tumour necrosis factor alpha, interleukin 1 beta and interferon gamma have detrimental effects on equine tenocytes that cannot be rescued by IL-1RA or mesenchymal stromal cell-derived factors.

Tendon injuries occur commonly in both human and equine athletes, and poor tendon regeneration leads to functionally deficient scar tissue and an increased frequency of re-injury. Despite evidence suggesting inadequate resolution of inflammation leads to fibrotic healing, our understanding of the inflammatory pathways implicated in tendinopathy remains poorly understood, meaning successful targeted treatments are lacking. Here, we demonstrate IL-1ß, TNFα and IFN-γ work synergistically to induce greater detrimental consequences for equine tenocytes than when used individually. This includes altering tendon associated and matrix metalloproteinase gene expression and impairing the cells' ability to contract a 3-D collagen gel, a culture technique which more closely resembles the in vivo environment. Moreover, these adverse effects cannot be rescued by direct suppression of IL-1ß using IL-1RA or factors produced by BM-MSCs. Furthermore, we provide evidence that NF-κB, but not JNK, P38 MAPK or STAT 1, is translocated to the nucleus and able to bind to DNA in tenocytes following TNFα and IL-1ß stimulation, suggesting this signalling cascade may be responsible for the adverse downstream consequences of these inflammatory cytokines. We suggest a superior approach for treatment of tendinopathy may therefore be to target specific signalling pathways such as NF-κB.

Controlling Extraction of Rare Earth Elements Using Functionalized Aryl-vinyl Phosphonic Acid Esters.

Ligands that can discriminate between individual rare earth elements are important for production of these critical elements. A set of aryl-vinyl phosphonic acid ligands for extracting rare earth elements were designed and synthesized under the hypothesis that the strength of the rare earth-ligand interactions could be tuned by changing the dipole moment of the ligand. The ligands were synthesized via a two-step reaction procedure using a Heck coupling reaction to functionalize vinyl phosphonic acid, followed by Steglich esterification to obtain high-purity styryl phosphonic acid monoesters with varying dipole moments along the P-C bond. The metal binding strength and composition of the rare earth complexes formed with these styryl phosphonic acid monoesters were experimentally studied by liquid-liquid extraction techniques, while DFT calculations were performed to determine the dipole moments of the free and complexed ligands and the electronic structure of the complexes formed. All three prepared ligands were much stronger extracting agents for europium(III) than the dialkylphosphonic acids usually used for this separation. However, the order of increasing extraction strength was found to match the order of the decreasing calculated dipole moment along the P-C bond of the three styryl-based ligands, rather than correlating with increasing ligand basicity, as reflected by the pKa of the ligands. These findings suggest that this approach can be used to systematically alter the extraction strength of aromatic phosphonic monoesters for rare earth element purification.

Genetic Analyses of Enamel Hypoplasia in Multiethnic Cohorts.

Enamel hypoplasia causes reduction in the thickness of affected enamel and is one of the most common dental anomalies. This defect is caused by environmental and/or genetic factors that interfere with tooth formation, emphasizing the importance of investigating enamel hypoplasia on an epidemiological and genetic level. A genome-wide association of enamel hypoplasia was performed in multiple cohorts, overall comprising 7,159 individuals ranging in age from 7-82 years. Mixed-models were used to test for genetic association while simultaneously accounting for relatedness and genetic population structure. Meta-analysis was then performed. More than 5 million single-nucleotide polymorphisms were tested in individual cohorts. Analyses of the individual cohorts and meta-analysis identified association signals close to genome-wide significance (P < 510-8), and many suggestive association signals (510-8 < P < 510-6) near genes with plausible roles in tooth/enamel development. The strongest association signal (P = 1.5710-9) was observed near BMP2K in one of the individual cohorts. Additional suggestive signals were observed near genes with plausible roles in tooth development in the meta-analysis, such as SLC4A4 which can influence enamel hypoplasia. Additional human genetic studies are needed to replicate these results and functional studies in model systems are needed to validate our findings.

Early Secondary Alveolar Bone Grafting and Facial Growth of Patients with Complete Unilateral Cleft Lip and Palate.

OBJECTIVE: To investigate the craniofacial growth outcomes of early secondary alveolar bone grafting(ABG) around 6 years of age. DESIGN: Retrospective cohort study. SETTING: 1 North-American and 5 Northern-European cleft centers. SUBJECTS: 33 subjects with CUCLP consecutively treated with secondary ABG around 6 years of age were compared to 105 subjects from 4 centers treated with late secondary ABG and 19 subjects from 1 center with primary ABG. METHODS: Preorthodontic standardized lateral cephalometric radiographs taken after 12 years of age were traced and analyzed according to the Eurocleft Study protocol. Fourteen angular and two proportional measurements were performed. Measurement means from the Study Center(SC) were compared to 5 Northern-European centers using analysis of variance and Welch's modified t-tests, and P < .05 was considered statistically significant. RESULTS: For the SC, the mean age ± SD at the time of bone graft was 5.85 ± 0.71 years and the mean age at the time of the lateral cephalogram was 13.4 ± 1.8 years. The sagittal maxillary prominence of the SC was favorably comparable to the 5 Northern-European centers. The mean SNA (78.1 ± 4.3) for the SC was significantly higher compared to 4 of the 5 Northern-European centers(all P < .05), and the mean ANB angle was comparable to 4 of the 5 centers. Similarly, the mean soft tissue ANB angle was not significantly different to the 5 centers. The soft tissue vertical proportions compared favorably to all 5 Northern-European centers(all P < .01). CONCLUSIONS: Craniofacial growth outcomes of early secondary ABG around 6 years compare favorably to the outcomes of late secondary ABG.

Evaluating SWAG and Its Validity When Compared to 3D Imagery of Secondarily Grafted Cleft Sites.

OBJECTIVE: To test validity of 2D Standardized Way to Assess Grafts (SWAG) ratings to assess 3D outcomes of bone grafting (ABG). PATIENTS: 43 patients (34 UCLP, 9 BCLP) with non-syndromic complete clefts, bone-grafted at mean age 9yrs/3mos, with available post-graft occlusal radiographs and cone beam computed tomography (CBCT) (taken mean 4yrs/9mos post-ABG). MAIN OUTCOME MEASURES: 2D occlusal radiographs rated twice using SWAG by 6 calibrated raters. 12 scores were averaged and converted to a percentage reflecting bone-fill. Weighted Kappas were assessed for SWAG reliability. 3D cleft-site bone volume was calculated by 1 rater using ITK-SNAP. 13 cleft sites were re-measured by the 'one rater' for 3D reliability using Intraclass Correlation Coefficient (ICC). 2D versus 3D ratings were compared using paired t-test, independent samples t-test, Bland-Altman and Linear Regression. Significance level was P = .5. RESULTS: 2D reliability was 0.724 (intra-rater) and 0.546 (inter-rater). 3D reliability was 0.986. Bland-Altman plot comparing 2D vs 3D showed for 45 of 47 graft-sites were within 2 SD's. Mean % bone-fill was 64.11% with 2D and 69.06% with 3D (mean difference = 4.95%) that was a non-significant difference in both t-tests. Regression showed a statistically significant relation between the two methods (r2 = 0.46; P = .0001). CONCLUSION: 2D SWAG systematically and non-significantly underestimated bone-fill. There was a significant correlation between 2D/3D methods. Bland-Altman analysis illustrated the similarity of the two methods. For comparisons of group (cleft treatment Centers') bone grafting outcomes, the 2D method may suffice as a proxy for the 3D method. However, with individual variation up to 40% in 2D estimates of actual 3D volume, 2D SWAG method cannot be used in place of 3D images.

Oxa1 Superfamily: New Members Found in the ER.

Oxa1/Alb3/YidC family members promote the insertion of proteins into the mitochondrial inner membrane, the chloroplast thylakoid membrane, and the bacterial plasma membrane. Remarkably, two recent studies identify new Oxa1 homologs that reside in the endoplasmic reticulum (ER) and function in ER membrane protein biogenesis.