Single-molecule Sequencing of an Animal Mitochondrial Genome Reveals Chloroplast-like Architecture and Repeat-mediated Recombination.

Recent advances in long-read sequencing technology have allowed for single-molecule sequencing of entire mitochondrial genomes, opening the door for direct investigation of the mitochondrial genome architecture and recombination. We used PacBio sequencing to reassemble mitochondrial genomes from two species of New Zealand freshwater snails, Potamopyrgus antipodarum and Potamopyrgus estuarinus. These assemblies revealed a ∼1.7 kb structure within the mitochondrial genomes of both species that was previously undetected by an assembly of short reads and likely corresponding to a large noncoding region commonly present in the mitochondrial genomes. The overall architecture of these Potamopyrgus mitochondrial genomes is reminiscent of the chloroplast genomes of land plants, harboring a large single-copy (LSC) region and a small single-copy (SSC) region separated by a pair of inverted repeats (IRa and IRb). Individual sequencing reads that spanned across the Potamopyrgus IRa-SSC-IRb structure revealed the occurrence of a "flip-flop" recombination. We also detected evidence for two distinct IR haplotypes and recombination between them in wild-caught P. estuarinus, as well as extensive intermolecular recombination between single-nucleotide polymorphisms in the LSC region. The chloroplast-like architecture and repeat-mediated mitochondrial recombination we describe here raise fundamental questions regarding the origins and commonness of inverted repeats in cytoplasmic genomes and their role in mitochondrial genome evolution.

Sulfonamide Per- and Polyfluoroalkyl Substances Can Impact Microorganisms Used in Aromatic Hydrocarbon and Trichloroethene Bioremediation.

Per- and polyfluoroalkyl substances (PFASs) from aqueous film forming foams (AFFFs) can hinder bioremediation of co-contaminants such as trichloroethene (TCE) and benzene, toluene, ethylbenzene, and xylene (BTEX). Anaerobic dechlorination can require bioaugmentation of Dehalococcoides, and for BTEX, oxygen is often sparged to stimulate in situ aerobic biodegradation. We tested PFAS inhibition to TCE and BTEX bioremediation by exposing an anaerobic TCE-dechlorinating coculture, an aerobic BTEX-degrading enrichment culture, and an anaerobic toluene-degrading enrichment culture to n-dimethyl perfluorohexane sulfonamido amine (AmPr-FHxSA), perfluorohexane sulfonamide (FHxSA), perfluorohexanesulfonic acid (PFHxS), or nonfluorinated surfactant sodium dodecyl sulfate (SDS). The anaerobic TCE-dechlorinating coculture was resistant to individual PFAS exposures but was inhibited by >1000× diluted AFFF. FHxSA and AmPr-FHxSA inhibited the aerobic BTEX-degrading enrichment. The anaerobic toluene-degrading enrichment was not inhibited by AFFF or individual PFASs. Increases in amino acids in the anaerobic TCE-dechlorinating coculture compared to the control indicated stress response, whereas the BTEX culture exhibited lower concentrations of all amino acids upon exposure to most surfactants (both fluorinated and nonfluorinated) compared to the control. These data suggest the main mechanisms of microbial toxicity are related to interactions with cell membrane synthesis as well as protein stress signaling.

Effect of pharmacist interventions on the management of overweight and obesity: A systematic review.

BACKGROUND: Pharmacists are underused healthcare professionals who are well positioned to provide weight management interventions; however, a systematic review of the literature supporting the role of pharmacists in weight management is lacking. OBJECTIVES: To conduct a systematic review to assess the body of evidence supporting the role of pharmacists in the management of obesity. METHODS: A literature search of OVID MEDLINE, Embase, Web of Science, and CINAHL was conducted from inception through February 23, 2023, to identify studies involving pharmacist interventions for weight management. Included studies were retrospective or prospective studies reporting a change in body weight, body mass index (BMI), or waist circumference as a primary endpoint; and a weight management intervention involving a pharmacist. Studies were excluded if they did not report the desired outcomes, involved pediatric populations, or lacked a pharmacist in the intervention. RESULTS: Twenty-nine studies met the eligibility criteria. A total of 6,423 study participants were enrolled with a mean BMI of 27 to 46 kg/m2. The included studies were conducted across 8 different countries with 15 from the United States. The primary approach was a prepost/quasi-experimental study design, typically conducted in community pharmacies. The pharmacists' role varied widely but mainly involved educational counseling as the pharmacist made medication recommendations in only 5 studies. Multidisciplinary collaboration was infrequent. All but 3 studies reported a significant improvement in the weight loss outcome of interest, although most study durations were less than 6 months. A critical appraisal of the 29 studies found the overall quality of the available studies to be relatively poor. CONCLUSION: Pharmacist interventions for weight management were mostly effective in reducing body weight; however, more robust clinical trials with a comparator group and for longer duration are warranted. The pharmacist's role in managing weight loss medications also requires further study.

Tibial Component Subsidence in a Total Ankle System Comparing Standard Technique Versus a Hybrid Technique.

Total ankle arthroplasty (TAA) is a viable treatment option for end-stage ankle arthritis. However, implant survivorship remains an important consideration. Concerns regarding early component loosening with the low-profile tibial tray utilized by fourth-generation TAA systems have been raised in the literature. We have previously described our preliminary outcomes of a hybrid technique combining a stemmed intramedullary tibial component with a chamfer-cut talar component for TAA. A retrospective study comparing short-term outcomes of the tibial component between a standard fourth-generation TAA system versus our hybrid technique was performed. 46 patients with a minimum of 1-year follow up were included in the analyses. There were 25 subjects in the standard implant cohort utilizing a low-profile tibial tray, and 21 subjects in the hybrid group utilizing a stemmed intramedullary tibial component. No statistically significant difference between the demographics of each group was found. The rate of tibial component subsidence was 8% (n = 2) in the standard implant group, and 0% (n = 0) in the hybrid group, though this did not meet statistical significance (p = .49). Mean time to subsidence was 6 months, and revision rate due to tibial component subsidence was 2.1% (n = 1). Periprosthetic lucency was present on most recent follow-up radiographs in 32% and 9.5% of ankles in the standard and hybrid groups, respectively (p = .08). Despite prior concerns for tibial component subsidence with the standard fourth-generation system, we demonstrated low rates in both implant groups. Additional studies are needed to further explore factors that may predispose patients to early tibial component subsidence and resulting implant failure.

Biological and Chemical Transformation of the Six-Carbon Polyfluoroalkyl Substance N-Dimethyl Ammonio Propyl Perfluorohexane Sulfonamide (AmPr-FHxSA).

Sites impacted by aqueous film-forming foam (AFFF) contain co-contaminants that can stimulate biotransformation of polyfluoroalkyl substances. Here, we compare how microbial enrichments from AFFF-impacted soil amended with diethyl glycol monobutyl ether (found in AFFF), aromatic hydrocarbons (present in co-released fuels), acetate, and methane (substrates used or formed during bioremediation) impact the aerobic biotransformation of an AFFF-derived six-carbon electrochemical fluorination (ECF) precursor N-dimethyl ammonio propyl perfluorohexane sulfonamide (AmPr-FHxSA). We found that methane- and acetate-oxidizing cultures resulted in the highest yields of identifiable products (38 and 30%, respectively), including perfluorohexane sulfonamide (FHxSA) and perfluorohexane sulfonic acid (PFHxS). Using these data, we propose and detail a transformation pathway. Additionally, we examined chemical oxidation products of AmPr-FHxSA and FHxSA to provide insights on remediation strategies for AmPr-FHxSA. We demonstrate mineralization of these compounds using the sulfate radical and test their transformation during the total oxidizable precursor (TOP) assay. While perfluorohexanoic acid accounted for over 95% of the products formed, we demonstrate here for the first time two ECF-based precursors, AmPr-FHxSA and FHxSA, that produce PFHxS during the TOP assay. These findings have implications for monitoring poly- and perfluoroalkyl substances during site remediation and application of the TOP assay at sites impacted by ECF-based precursors.

Environment-dependent fitness gains can be driven by horizontal gene transfer of transporter-encoding genes.

Many microbes acquire metabolites in a "feeding" process where complex polymers are broken down in the environment to their subunits. The subsequent uptake of soluble metabolites by a cell, sometimes called osmotrophy, is facilitated by transporter proteins. As such, the diversification of osmotrophic microorganisms is closely tied to the diversification of transporter functions. Horizontal gene transfer (HGT) has been suggested to produce genetic variation that can lead to adaptation, allowing lineages to acquire traits and expand niche ranges. Transporter genes often encode single-gene phenotypes and tend to have low protein-protein interaction complexity and, as such, are potential candidates for HGT. Here we test the idea that HGT has underpinned the expansion of metabolic potential and substrate utilization via transfer of transporter-encoding genes. Using phylogenomics, we identify seven cases of transporter-gene HGT between fungal phyla, and investigate compatibility, localization, function, and fitness consequences when these genes are expressed in Saccharomyces cerevisiae Using this approach, we demonstrate that the transporters identified can alter how fungi utilize a range of metabolites, including peptides, polyols, and sugars. We then show, for one model gene, that transporter gene acquisition by HGT can significantly alter the fitness landscape of S. cerevisiae We therefore provide evidence that transporter HGT occurs between fungi, alters how fungi can acquire metabolites, and can drive gain in fitness. We propose a "transporter-gene acquisition ratchet," where transporter repertoires are continually augmented by duplication, HGT, and differential loss, collectively acting to overwrite, fine-tune, and diversify the complement of transporters present in a genome.

Risk Stratification for Revision Surgery Following Total Ankle Replacement.

As a result of improved implants total ankle replacement (TAR) is becoming a more reliable option for end stage ankle arthritis. As with any surgery there are numerous complications that can occur intraoperatively and postoperatively with TAR. The primary aim of this study is to use recent data on implants currently on the market to develop a well-defined and comprehensive complication classification system which stratifies risk of subsequent surgery for TAR. A systematic review of studies on TARs from 2013 to 2018 was performed. Inclusion criteria were studies published between 2013 and August 2018, studies having at least 20 patients, data with at least 1-year follow-up and use of implants currently on the market. Studies were excluded if they involved revision cases, case reports, basic science articles and studies published in non-peer-reviewed journals. Sixteen studies fit inclusion criteria involving 3,305 implants. Overall survival of all implants was found to be 93% with a pooled complication rate of 75.6% using criteria for classifying complications by Glazebrook et al. Previously published classification systems did not clearly define complication categories leading to inconsistency in complication reporting and inaccurate complication rates. There are also several complications that are unclassifiable with the classifications developed by Gadd et al and Glazebrook et al. Our proposed updated classification system provides more inclusive tier profiles to capture the complications that can occur with implants currently on the market. Furthermore, this system provides a stratification of risk that these complications pose to ultimate procedure success.

Fitness and Productivity Increase with Ecotypic Diversity among Escherichia coli Strains That Coevolved in a Simple, Constant Environment.

The productivity of a biological community often correlates with its diversity. In the microbial world this phenomenon can sometimes be explained by positive, density-dependent interactions such as cross-feeding and syntrophy. These metabolic interactions help account for the astonishing variety of microbial life and drive many of the biogeochemical cycles without which life as we know it could not exist. While it is difficult to recapitulate experimentally how these interactions evolved among multiple taxa, we can explore in the laboratory how they arise within one. These experiments provide insight into how different bacterial ecotypes evolve and from these, possibly new "species." We have previously shown that in a simple, constant environment a single clone of Escherichia coli can give rise to a consortium of genetically and phenotypically differentiated strains, in effect, a set of ecotypes, that coexist by cross-feeding. We marked these different ecotypes and their shared ancestor by integrating fluorescent protein into their genomes and then used flow cytometry to show that each evolved strain is more fit than the shared ancestor, that pairs of evolved strains are fitter still, and that the entire consortium is the fittest of all. We further demonstrate that the rank order of fitness values agrees with estimates of yield, indicating that an experimentally evolved consortium more efficiently converts primary and secondary resources to offspring than its ancestor or any member acting in isolation.IMPORTANCE Polymicrobial consortia occur in both environmental and clinical settings. In many cases, diversity and productivity correlate in these consortia, especially when sustained by positive, density-dependent interactions. However, the evolutionary history of such entities is typically obscure, making it difficult to establish the relative fitness of consortium partners and to use those data to illuminate the diversity-productivity relationship. Here, we dissect an Escherichia coli consortium that evolved under continuous glucose limitation in the laboratory from a single common ancestor. We show that a partnership consisting of cross-feeding ecotypes is better able to secure primary and secondary resources and to convert those resources to offspring than the ancestral clone. Such interactions may be a prelude to a special form of syntrophy and are likely determinants of microbial community structure in nature, including those having clinical significance such as chronic infections.

Total Ankle Arthroplasty Survivorship: A Meta-analysis.

The gold standard for management of end-stage ankle arthritis was previously ankle arthrodesis; however, improvements in total ankle replacements are making this a more viable treatment option. The primary aim of this meta-analysis was to evaluate the survivorship of total ankle replacement implants currently in use. An extensive search strategy initially captured 20,842 citations that were evaluated for relevance. Abstract screening produced 97 articles to be read in entirety, of which 10 articles studying 1963 implants met all prospective inclusion criteria for analysis. Overall survivorship of all implants was 93.0% (95% confidence interval, 85.2-96.9) using a random effect model. There was significant heterogeneity between the studies (Q = 131.504). Meta-regression identified an inverse relationship between survivorship and study follow-up duration (p < .0001). Furthermore, age (p = .36) and implant type (fixed-bearing [95.6%, 95% confidence interval, 85.9-98.7] versus mobile-bearing ]89.4%, 95% confidence interval, 79.6%-94.8%]) did not have a statistically significant impact on survivorship, p = .213. However, patients with higher preoperative functional scores had improved survivorship (p = .001). Complications were inconsistently reported with varied definitions. In order of reported frequency, complications were classified into technical error (28.15%), subsidence (16.89%), implant failure (13.28%), aseptic loosening (6.3%), intraoperative fracture (5.67%), wound problems (4.3%), deep infection (1%), and postoperative fracture (0.0001%). Overall study quality was low, with only 10% being prospective and 90% from nonregistry data. The results from this meta-analysis revealed a promising overall survivorship of current implants in use for total ankle replacement; however higher quality studies with standardized outcomes measures are needed.

Cerebral organoids derived from Sandhoff disease-induced pluripotent stem cells exhibit impaired neurodifferentiation.

Sandhoff disease, one of the GM2 gangliosidoses, is a lysosomal storage disorder characterized by the absence of ß-hexosaminidase A and B activity and the concomitant lysosomal accumulation of its substrate, GM2 ganglioside. It features catastrophic neurodegeneration and death in early childhood. How the lysosomal accumulation of ganglioside might affect the early development of the nervous system is not understood. Recently, cerebral organoids derived from induced pluripotent stem (iPS) cells have illuminated early developmental events altered by disease processes. To develop an early neurodevelopmental model of Sandhoff disease, we first generated iPS cells from the fibroblasts of an infantile Sandhoff disease patient, then corrected one of the mutant HEXB alleles in those iPS cells using CRISPR/Cas9 genome-editing technology, thereby creating isogenic controls. Next, we used the parental Sandhoff disease iPS cells and isogenic HEXB-corrected iPS cell clones to generate cerebral organoids that modeled the first trimester of neurodevelopment. The Sandhoff disease organoids, but not the HEXB-corrected organoids, accumulated GM2 ganglioside and exhibited increased size and cellular proliferation compared with the HEXB-corrected organoids. Whole-transcriptome analysis demonstrated that development was impaired in the Sandhoff disease organoids, suggesting that alterations in neuronal differentiation may occur during early development in the GM2 gangliosidoses.

Affective and physiological response to a novel parent-adolescent conflict stressor.

Few laboratory paradigms exist that expose adolescents to conflict that might commonly be experienced in parent-adolescent relationships. Given the continued importance of parent-adolescent relationships on adolescent development, as well as the changing expectations in these relationships, we examined the effect of a novel parent-adolescent conflict paradigm on physiological and affective response in a sample of 52 adolescents. The parent-adolescent conflict stressor (PACS) involved adolescent participants (50% girls; M = 14.75, SD = 0.88) watching a 12-minute scripted video that asked youth to imagine that they were the teenager in the video, which consisted of parent and adolescent actors having discussions about conflict in their relationship and solving this conflict in either a positive, typical, or hostile manner. Cortisol, alpha amylase, and self-report of negative and positive affect were collected at baseline, following the video, and during a recovery period. Heart rate also was taken continuously while adolescents watched the videos. Hierarchical linear modeling (HLM) analyses indicated significant linear change in alpha amylase and linear and quadratic change in negative affect to the PACS. There also was a significant linear and quadratic change in heart rate during the portion of the video where teens and parents discussed issues of personal responsibility. The PACS marks a preliminary but important first step in developing a parent-adolescent conflict paradigm that can be used across studies to understand the impact of parent-adolescent conflict on affective and physiological markers associated with stress response.

Interactions between intersubunit transmembrane domains regulate the chaperone-dependent degradation of an oligomeric membrane protein.

In the kidney, the epithelial sodium channel (ENaC) regulates blood pressure through control of sodium and volume homeostasis, and in the lung, ENaC regulates the volume of airway and alveolar fluids. ENaC is a heterotrimer of homologous α-, ß- and γ-subunits, and assembles in the endoplasmic reticulum (ER) before it traffics to and functions at the plasma membrane. Improperly folded or orphaned ENaC subunits are subject to ER quality control and targeted for ER-associated degradation (ERAD). We previously established that a conserved, ER lumenal, molecular chaperone, Lhs1/GRP170, selects αENaC, but not ß- or γ-ENaC, for degradation when the ENaC subunits were individually expressed. We now find that when all three subunits are co-expressed, Lhs1-facilitated ERAD was blocked. To determine which domain-domain interactions between the ENaC subunits are critical for chaperone-dependent quality control, we employed a yeast model and expressed chimeric α/ßENaC constructs in the context of the ENaC heterotrimer. We discovered that the ßENaC transmembrane domain was sufficient to prevent the Lhs1-dependent degradation of the α-subunit in the context of the ENaC heterotrimer. Our work also found that Lhs1 delivers αENaC for proteasome-mediated degradation after the protein has become polyubiquitinated. These data indicate that the Lhs1 chaperone selectively recognizes an immature form of αENaC, one which has failed to correctly assemble with the other channel subunits via its transmembrane domain.

An interprofessional patient assessment involving medical and nursing students: a qualitative study.

Interprofessional collaboration is fundamental to providing optimal patient care. The readiness of the team entering a framework of interprofessional collaborative practice is critical to its success. In this study, we conducted an interprofessional education (IPE) activity for medical and nursing students in an acute care setting. Over nine occasions, 21 student pairs (one nursing and one medical student per pair) jointly assessed a patient and created a list of problems and interventions to achieve the patient's goals. Immediately after the activity, students were debriefed to gain insight into their experiences. Debriefing sessions were audiotaped and analysed using a phenomenological approach and four major themes were identified. Overall, students felt responsible for representing their profession and were initially apprehensive about the interprofessional task. Nevertheless, they identified their own shortcomings and recognized the value in their partner's approach. These realizations promoted convergence on a shared vision to provide optimal care for patients as a team. Acknowledging and understanding these perceptions may help design better ways to improve patient care. This educational model may be utilized by others who are seeking IPE activities in acute care.

Individual Differences in Adolescents' Emotional Reactivity across Relationship Contexts.

Understanding individual differences in adolescents' ability to regulate emotions within interpersonal relationships is paramount for healthy development. Thus, the effect of individual vulnerabilities (depressive affect, social anxiety, self-blame, and coping efficacy problems) on the transmission of emotional reactivity in response to conflict from family to peers (friends and romantic partners) was prospectively examined across six waves of data in a community-based sample of 416 adolescents (Mage Wave 1 = 11.90, 51% girls). Multiple-group models estimated in structural equation modeling suggested that youth who were higher in social anxiety or coping efficacy problems were more likely to transmit emotional reactivity developed in the family-of-origin to emotional reactivity in response to conflict in close friendships. Additionally, those youth higher in self-blame and depressive affect were more likely to transmit emotional reactivity from friendships to romantic relationships.

Anatomic Reconstruction Versus Traditional Rebalancing in Lesser Metatarsophalangeal Joint Reconstruction.

Traditional rebalancing techniques, such as capsulotomies and capsulorrhaphies, are commonly performed during complex hammertoe and lesser metatarsal osteotomy procedures involving metatarsophalangeal joint (MTPJ) contractures; however, floating toes, digital instability, and malalignment are concerns. We critically analyzed the outcomes after anatomic reconstruction of the plantar plate and collateral ligaments compared with those after traditional rebalancing techniques. A case-control study was conducted of 54 patients who had undergone surgical correction of lesser MTPJ imbalances due to complex hammertoe deformities (power 80%, type I error = 0.05). Cases were defined as consecutive patients treated with anatomic plantar plate and collateral ligament reconstruction. Controls had undergone traditional lesser MTPJ rebalancing and were matched to cases by age, gender, follow-up duration (minimum 12 months), and concomitant procedures of the same lesser ray. Multivariate logistic regression demonstrated that patients treated with anatomic reconstruction had greater digital stability (negative dorsal drawer and negative paper pull-out test findings) at final follow-up examination compared with the controls. American College of Foot and Ankle Surgeons (ACFAS) forefoot module scores were greater in the anatomic group in all domains (p ≤ .05). Controls had greater postoperative radiographic MTPJ angles than the cases, with no differences detected between the 2 groups in visual analog scale scores or proximal interphalangeal joint angles. The importance of restoration of the plantar plate and collateral ligament integrity as a digital stabilizer is generally accepted but has not been well studied. We found that anatomic reconstruction yielded greater digital stability, greater ACFAS Forefoot module scores, and better radiographic MTPJ alignment than controls. Additional studies are warranted to assess the long-term viability of anatomic lesser MTPJ reconstruction.

Radiographic Union Scoring Scale for Determining Consolidation Rates in the Calcaneus.

The reliable evaluation of osseous consolidation after hindfoot osteotomy can be difficult. Concomitant hindfoot osteotomies often dictate the advancement of weightbearing, and radiographs are the mainstay imaging tool owing to cost, efficiency, and radiation exposure. Understanding the radiographic parameters that can be used to reliably determine osseous healing is paramount. However, currently, no reliable or validated method is available to determine osseous healing of hindfoot osteotomies in irregular bones of the foot. The purpose of the present study was to develop a radiographic healing scoring system that would enhance the diagnostic healing assessment after elective calcaneal osteotomy. We adapted existing orthopedic scales validated for healing in the leg for application in the irregular bones of the foot. A total of 168 cases were evaluated by 6 blinded assessors to test the interrater reliability of subjective healing assessment compared with the proposed scoring system. The radiographs were classified by postoperative period: ≤4 weeks, 5 to 12 weeks, and >12 weeks. The proposed scale had high interrater reliability but was burdensome. Using a priori item reduction protocols, a limited 6-item scale further improved internal consistency and reduced the burden. The result was excellent interrater reliability (α = 0.98, standard deviation 0.02, 95% confidence interval 0.91 to 0.96) among all assessors when using the scoring scale compared with unacceptable reliability (α = 0.438) for subjective osteotomy healing. The reliability of our system appeared superior to that of subjective assessment of osseous healing alone, even in the absence of clinical correlates after osteotomy of the calcaneus.

Long-Term Outcomes of Corrective Osteotomies Using Porous Titanium Wedges for Flexible Flatfoot Deformity Correction.

Common corrective osteotomies used in flexible flatfoot deformity reconstruction include Cotton and Evans osteotomies, which require structural graft to maintain correction. Auto-, allo-, and xenografts are associated with a number of limitations, including disease transmission, rejection, donor site morbidity, technical challenges related to graft fashioning, and graft resorption. Porous titanium is a synthetic substance designed to address these flaws; however, few studies have been reported on the efficacy, safety, and long-term outcomes. A multicenter retrospective cohort of 63 consecutive preconfigured porous titanium wedges (PTWs) used in flexible flatfoot reconstructions from June 1, 2009 to June 30, 2015 was evaluated. The primary outcome measure was the pre- to postdeformity correction efficacy. The secondary outcomes included maintenance of correction at a minimum follow-up point of 12 months, complications, graft incorporation, and graft safety profile. Multivariate linear regression found a statistically significant improvement in all radiographic parameters from preoperatively to the final weightbearing radiographs (calcaneocuboid 18.850 ± 4.020 SE, p < .0001; Kite's, 7.810 ± 3.660 SE, p = .04; Meary's 13.910 ± 3.100 SE, p = .0001; calcaneal inclination, 5.550 ± 2.140 SE, p = .015). When restricted to patients with >4 years of follow-up data, maintenance of correction appeared robust in all 4 measurements, demonstrating a lack of bone or graft resorption. No patients were lost to follow-up, no major complications or implant explantation or migration occurred, and all implants were incorporated. Minor complications included hardware pain from plates over grafts (8%), 1 case of scar neuritis, and a 5% table incidence of transfer pain associated with the PTWs. These results support the use of PTWs for safety and degree and maintenance of correction in flatfoot reconstruction.

Development and Validation of the Foot Union Scoring Evaluation Tool for Arthrodesis of Foot Structures.

Reliable evaluation of osseous consolidation after pedal arthrodesis can be difficult, and the presence or absence of radiographic healing often dictates care. Plain radiographs remain the mainstay imaging tool owing to their cost, efficiency, and low radiation exposure. Applying radiographic parameters that can reliably determine osseous healing is essential. However, currently, no reliable or validated measures are available to determine osseous union of any joint in the foot or ankle. The purpose of the present study was to develop a radiographic healing scoring system that would enhance the diagnostic healing assessment after joint arthrodesis of the foot or ankle. We adapted several existing scales previously validated for fracture healing in the leg, because no study has attempted to apply this to a joint fusion model. A total of 150 cases were evaluated by 6 blinded assessors to test the interrater reliability of the subjective healing assessment compared with the proposed scoring system. The radiographs were classified by the postoperative period: ≤4 weeks, 5 to 12 weeks, and >12 weeks. The initial proposed scale was found to have high interrater reliability but was burdensome. Using a priori item reduction protocols, a limited 5-item scale further improved the internal consistency and reduced the burden. The result was excellent interrater reliability (α = 0.978, standard deviation 0.02, 95% confidence interval 0.96 to 0.99) among all assessors compared with the reduced reliability (α = 0.752) for subjective arthrodesis healing. Intrarater reliability was also found to be superior using a test-retest method. The reliability of this system appeared superior to the subjective assessment of arthrodesis healing, even in the absence of clinical correlates, after foot arthrodesis.

Sphingosine-1-phosphate Phosphatase 2 Regulates Pancreatic Islet ß-Cell Endoplasmic Reticulum Stress and Proliferation.

Sphingosine-1-phosphate (S1P) is a sphingolipid metabolite that regulates basic cell functions through metabolic and signaling pathways. Intracellular metabolism of S1P is controlled, in part, by two homologous S1P phosphatases (SPPases), 1 and 2, which are encoded by the Sgpp1 and Sgpp2 genes, respectively. SPPase activity is needed for efficient recycling of sphingosine into the sphingolipid synthesis pathway. SPPase 1 is important for skin homeostasis, but little is known about the functional role of SPPase 2. To identify the functions of SPPase 2 in vivo, we studied mice with the Sgpp2 gene deleted. In contrast to Sgpp1(-/-) mice, Sgpp2(-/-) mice had normal skin and were viable into adulthood. Unexpectedly, WT mice expressed Sgpp2 mRNA at high levels in pancreatic islets when compared with other tissues. Sgpp2(-/-) mice had normal pancreatic islet size; however, they exhibited defective adaptive ß-cell proliferation that was demonstrated after treatment with either a high-fat diet or the ß-cell-specific toxin, streptozotocin. Importantly, ß-cells from untreated Sgpp2(-/-) mice showed significantly increased expression of proteins characteristic of the endoplasmic reticulum stress response compared with ß-cells from WT mice, indicating a basal islet defect. Our results show that Sgpp2 deletion causes ß-cell endoplasmic reticulum stress, which is a known cause of ß-cell dysfunction, and reveal a juncture in the sphingolipid recycling pathway that could impact the development of diabetes.

The Interactive Effects of Stressful Family Life Events and Cortisol Reactivity on Adolescent Externalizing and Internalizing Behaviors.

This study investigated the associations between stressful family life events and adolescent externalizing and internalizing behaviors, and the interactive effects of family life events and cortisol reactivity on problem behaviors. In a sample of 100 mothers and their adolescents (M age = 15.09; SD age = .98; 68 % girls), adolescent cortisol reactivity was measured in response to a mother-adolescent conflict interaction task designed to elicit a stress response. Mothers reported on measures of family life events and adolescent problem behaviors. Results indicated that a heightened adolescent cortisol response moderated the relations between stressful family life events and both externalizing and internalizing behaviors. Results support context-dependent theoretical models, suggesting that for adolescents with higher cortisol reactivity (compared to those with lower cortisol reactivity), higher levels of stressful family life events were associated with greater problem behaviors, whereas lower levels of stressful family life events were related to fewer problem behaviors.