Development and performance evaluation of a solenoid valve assisted low-cost ventilator on gas exchange and respiratory mechanics in a porcine model.

INTRODUCTION: During the COVID-19 pandemic, ventilator shortages necessitated the development of new, low-cost ventilator designs. The fundamental requirements of a ventilator include precise gas delivery, rapid adjustments, durability, and user-friendliness, often achieved through solenoid valves. However, few solenoid-valve assisted low-cost ventilator (LCV) designs have been published, and gas exchange evaluation during LCV testing is lacking. This study describes the development and performance evaluation of a solenoid-valve assisted low-cost ventilator (SV-LCV) in vitro and in vivo, focusing on gas exchange and respiratory mechanics. METHODS: The SV-LCV, a fully open ventilator device, was developed with comprehensive hardware and design documentation, utilizing solenoid valves for gas delivery regulation. Lung simulator testing calibrated tidal volumes at specified inspiratory and expiratory times, followed by in vivo testing in a porcine model to compare SV-LCV performance with a conventional ventilator. RESULTS: The SV-LCV closely matched the control ventilator's respiratory profile and gas exchange across all test cycles. Lung simulator testing revealed direct effects of compliance and resistance changes on peak pressures and tidal volumes, with no significant changes in respiratory rate. In vivo testing demonstrated comparable gas exchange parameters between SV-LCV and conventional ventilator across all cycles. Specifically, in cycle 1, the SV-LCV showed arterial blood gas (ABG) results of pH 7.54, PCO2 34.5 mmHg, and PO2 91.7 mmHg, compared to the control ventilator's ABG of pH 7.53, PCO2 37.1 mmHg, and PO2 134 mmHg. Cycle 2 exhibited ABG results of pH 7.53, PCO2 33.6 mmHg, and PO2 84.3 mmHg for SV-LCV, and pH 7.5, PCO2 34.2 mmHg, and PO2 93.5 mmHg for the control ventilator. Similarly, cycle 3 showed ABG results of pH 7.53, PCO2 32.1 mmHg, and PO2 127 mmHg for SV-LCV, and pH 7.5, PCO2 35.5 mmHg, and PO2 91.3 mmHg for the control ventilator. CONCLUSION: The SV-LCV provides similar gas exchange and respiratory mechanic profiles compared to a conventional ventilator. With a streamlined design and performance akin to commercially available ventilators, the SV-LCV presents a viable, readily available, and reliable short-term solution for overcoming ventilator supply shortages during crises.

Extensor tendon transfer for fracture-related extensor pollicis longus rupture: Long-term outcome case series.

BACKGROUND: Spontaneous rupture of the extensor pollicis longus (EPL) tendon following both nonoperative and operative treatment of distal radius fractures has been well described. PURPOSE: The purpose of this study was to assess long-term outcomes of extensor indicis proprius to EPL tendon transfers for patients following distal radius fracture and EPL tendon repair. STUDY DESIGN: Retrospective case series focusing on long-term clinical outcomes. METHODS: A retrospective review was conducted for patients who sustained a distal radius fracture and subsequently underwent extensor tendon transfer from 2005-2015 at a private practice center. Outcome measures including index finger (IF) metacarpophalangeal (MCP) and thumb interphalangeal (IP) active range of motion (ROM), digital extension against resistance, subjective complaints, and QuickDASH scores were recorded at final follow-up. RESULTS: Seven patients were included in the study. There were six females and one male subject, mean age of 54 ± 13 years at injury of EPL, and 5/7 involved the left upper extremity. For isolated function, 7/7 (100%) patients had isolated, active IF MCP extension, 6/7 (86%) could extend IF MCP and thumb IP against resistance. Mean IF MCP extension was 1° ± 2°, mean IF MCP flexion was 89° ± 2°, mean thumb IP extension was -5° ± 4°, and mean thumb IP flexion was 67° ± 15°. Mean QuickDASH score was 16 ± 14. CONCLUSIONS: This series shows good long-term functional and patient reported outcomes in patients following extensor indicis proprius to EPL tendon transfers at a single center.

Gigantic animal cells suggest organellar scaling mechanisms across a 50-fold range in cell volume.

The largest cells are orders of magnitude bigger than the smallest cells. Organelle content scales to maintain cell function, with different organelles increasing in volume, length, or number as cells increase in size. Scaling may also reflect functional demands placed on organelles by increased cell size. Amphibians exhibit exceptional diversity in cell size. Using transmission electron microscopy, we analyzed 3 species whose enterocyte cell volumes range from 228 to 10,593 µm3. We show that nuclear volume increases by an increase in radius while mitochondrial volume increases by an increase in total network length; the endoplasmic reticulum and Golgi apparatus, with their complex shapes, are intermediate. Notably, all 4 organelle types increase in total volume proportional to cell volume, despite variation in functional (i.e., metabolic, transport) demands. This pattern suggests that organellar building blocks are incorporated into more or larger organelles following the same rules across species that vary ~50-fold in cell sizes, consistent with a "limited precursor" model for organellar scaling that, in turn, assumes equivalent cytoplasmic concentrations of organellar building block proteins. Taken together, our results lead us to hypothesize that salamanders have evolved increased biosynthetic capacity to maintain functional protein concentrations despite huge cell volumes.

Nonunion After Using Procedure-Specific Instrumentations for Ulnar Shortening Osteotomy.

Objectives: The primary purpose of this study was to compare the rates of nonunion among different osteotomy designs (company brand) and the rates of nonunion between oblique and transverse osteotomies. We secondarily aimed to assess the differences in reoperation and hardware removal rates after ulnar shortening osteotomy (USO). Methods: A retrospective cohort study of patients undergoing ulnar shortening osteotomy between 2015 and 2022 in our institute amongst 17 providers resulted in 92 consecutive patients. We included skeletally mature patients who underwent USO for the ulnar impingement abutment diagnosis. Demographic information was collected, including age, gender, race/ethnicity, BMI, and medical comorbidities. Six brand-specific devices were used and compared to the conventional plate fixation. Nonunion was determined based on the final available radiograph with a minimum follow-up of four months. Results: Of the 92 patients, 83 (90%) had a bone union. There is a remarkable difference in union among implant brands, although statistical analysis was not performed due to the small number of patients in each group. Transverse osteotomy was significantly related to a higher nonunion rate. Out of nine patients with resultant nonunion (10%), three healed after revision surgery (3.2%), two were lost to follow-up (2.2%), and four remained asymptomatic despite radiographic nonunion (4.6%). Plate removal was performed in four patients (4.3%), all of whom were in the union group. Conclusion: Patients should be informed about the nonunion rate with possible subsequent secondary surgery. Using procedure-specific devices may have mitigated the risk of nonunion.

Pulmonary Complications and Mortality in Patients with SARS-CoV-2 Undergoing Elective and Emergent Hand Surgery.

Background Patients acutely infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may have increased risk for postsurgical pulmonary complications and mortality, particularly with general anesthesia. Surgery is often delayed to mitigate risk; however, excessive delays may result in morbidity. Optimal criteria for delaying surgery in patients with or without symptoms are unknown. This study aimed to evaluate any complications following hand surgery in patients testing positive for SARS-CoV-2. Methods We retrospectively reviewed patients with a positive polymerase chain reaction test within 60 days before or after hand surgery between March 31, 2020 and March 31, 2021. Patients were telephoned also to supplement records. Type of surgery, type of anesthesia, comorbidities, timing of surgery, onset of symptoms, and complications were recorded. Results We identified 21 patients undergoing 26 procedures, of which 21 (81%) were emergency procedures and 5 (19%) were elective. Mean age was 37 years (range: 17-71). General anesthesia was used in 88% of cases, with mean duration of 110 minutes. SARS-CoV-2 was diagnosed on average 6 days preoperatively (range: 39 days preop-14 days postop). Positive tests were usually identified preoperatively (50%), versus day-of-surgery (25%) or postoperatively (25%). Patients were symptomatic in only 27% of cases, and completely asymptomatic in 73%. No asymptomatic patients developed complications. One patient suffered a fracture malunion after delayed surgery. Pulmonary complications were noted in 3 patients; all had prior pulmonary disease and underwent emergency surgeries under general anesthesia. Overall mortality rate was 0%. Conclusion Pulmonary complications and mortality are low following hand surgery in asymptomatic patients with a positive SARS-CoV-2 test.

Rate of Complications After Capitellum Fracture Fixation: A Systematic Review and Meta-Analysis.

PURPOSE: This systematic review aimed to determine the incidence of complications following surgical fixation of an acute capitellum fracture. We secondarily aimed to compare the complication rate between anterior-to-posterior (A-P) versus posterior-to-anterior (P-A) screw insertion. METHODS: PubMed, EMBASE, and Scopus were searched to identify studies on surgical fixation of capitellum fractures in skeletally mature patients. The main outcome was the rate of complication after fracture fixation. Subgroup analysis was performed to assess the impact of the fixation technique on the outcomes after surgery. An inverse variance method using random or fixed effects models was used to perform a meta-analysis based on the degree of heterogeneity between studies. Study heterogeneity was evaluated using Q statistics to calculate the I2 index. RESULTS: We included 42 studies in the final analysis. The most reported complications after surgical fixation of capitellum fractures included elbow pain (21%), radiocapitellar arthritis (19%), hardware removal (17%), and heterotopic ossification (13%). When groups were stratified based on the direction of screw insertion, the mean rate of avascular necrosis was higher in the P-A direction (29% vs 11%). In comparison, the rate of revision fixation (2.9% vs 6.7%) and heterotopic ossification (7.3% vs 22%) were higher in the A-P direction. Transient posterior interosseous nerve palsy was reported in four patients in four studies, of whom three patients had A-P screw fixation. CONCLUSION: Fixation of a displaced capitellum fracture is recommended when possible. However, patients should be counseled about the potential risk of complications and chances of undergoing an unplanned surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Corrigendum: Dynamics of host immune response development during Schistosoma mansoni infection.

[This corrects the article DOI: 10.3389/fimmu.2022.906338.].

Analyses of Orthopaedic Surgery Residency Interviews.

Interviews are a critical component of orthopaedic surgery residency selection for both the applicant and the program. Some institutions no longer report Alpha Omega Alpha (AOA) designation or class rank, and US Medical Licensing Examination (USMLE) Step 1 recently switched to pass/fail scoring. During the coronavirus disease 2019 (COVID-19) pandemic, all Accreditation Council for Graduate Medical Education programs conducted virtual interviews and subinternship rotations were restricted. These changes offer significant challenges to the residency match process. The purpose of this study was to examine the residency applicant interview and ranking process at a large urban academic university setting. We hypothesized that large variability exists among evaluations submitted by faculty interviewers and also that applicant academic factors (i.e., USMLE Step 1 score) would show association with final ranking. Methods: We retrospectively reviewed the 2020-2021 and 2021-2022 residency interview cycles, both conducted virtually due to the COVID-19 pandemic. Residency application (i.e., applicant demographic and academic backgrounds) and interview data (i.e., faculty interviewer scores) were recorded. Interobserver reliability among faculty interviewers was calculated. Statistical analysis was performed to determine factors associated with ranking of applicants. Results: There were 195 included applicants from the 2020 and 2021 interview cycles. There was no true agreement of interviewers' scoring of shared applicants (kappa intraclass coefficient range 0-0.2). Applicant factors associated with being ranked include applying to the match for the first time, USMLE Step 1 and 2 scores, educational break (vs. consecutive completion of college and medical school in 4 years each), higher class rank, and greater interviewer scores. Factors associated with better rank included additional degrees (i.e., PhD or MBA), couples match, AOA designation, educational break, underrepresented minority status, and notable attributes (i.e., collegiate athletics or Eagle Scout participation). Factors associated with worse rank included male sex, international medical graduate, prior match history, science major, extended research (i.e., >1 year spent in a research role), and home medical school students. Conclusions: There was significant variability and no reliability at our institution among faculty interviewers' applicant ratings. Being ranked was based more on academic record and interview performance while final rank number seemed based on applicant qualities. The removal of merit-based objective applicant measurements offers challenges to optimal residency applicant and program match. Level of Evidence: III (retrospective cohort study).

The Impact of Preoperative Symptom Duration on Patient Outcomes After Posterior Cervical Decompression and Fusion.

STUDY DESIGN: Retrospective Cohort Study. OBJECTIVES: To determine if decreased preoperative symptom duration is associated with greater clinical improvement in function and myelopathic symptoms after posterior cervical decompression and fusion (PCDF). METHODS: All patients over age 18 who underwent primary PCDF for cervical myelopathy or myeloradiculopathy at a single institution between 2014 and 2020 were retrospectively identified. Patient demographics, surgical characteristics, duration of symptoms, and preoperative and postoperative patient reported outcomes measures (PROMs) including modified Japanese Orthopaedic Association (mJOA), Neck Disability Index (NDI), Visual Analogue Scale (VAS) Neck, VAS Arm, and SF-12 were collected. Univariate and multivariate analyses were performed to compare change in PROMs and minimum clinically important difference achievement (%MCID) between symptom duration groups (< 6 months, 6 months-2 years, > 2 years). RESULTS: Preoperative symptom duration groups differed significantly by sex and smoking status. Patients with < 6 months of preoperative symptoms improved significantly in all PROMs. Patients with 6 months-2 years of preoperative symptoms did not improve significantly in mJOA, Physical Component Scores (PCS), or NDI. Patients with > 2 years of symptoms failed to demonstrate significant improvement in mJOA, NDI, or Mental Component Scores (MCS). Univariate analysis demonstrated significantly decreased improvement in mJOA with longer symptom durations. Increased preoperative symptom duration trended toward decreased %MCID for mJOA and MCS. Regression analysis demonstrated that preoperative symptom duration of > 2 years relative to < 6 months predicted decreased improvement in mJOA and NDI and decreased MCID achievement for mJOA and MCS. CONCLUSION: Increased duration of preoperative symptoms (> 2 years) before undergoing PCDF was associated with decreased postoperative improvement in myelopathic symptoms.

Evidenced-Based Opioid Prescribing Recommendations Following Hand and Upper-Extremity Surgery.

The United States' opioid epidemic has taken an immense toll over the past 2 decades when assessed by morbidities, mortalities, and economic costs. Prescription opioids are a substantial contribution to this public health emergency, and it is critical for health care providers to practice good analgesic stewardship. Interventions have effectively curtailed opioid overuse, including prescription drug monitoring programs, educational initiatives, and multimodal analgesia strategies. Surgeons, particularly hand surgeons or those who perform musculoskeletal procedures, have been implicated as high-volume opioid prescribers. Guidelines for appropriate opioid dosing and analgesic management strategies after common hand and upper-extremity surgeries are sparse and offer an area for meaningful improvement. We sought to generate comprehensive, evidence-based recommendations for postoperative analgesia regimens for common hand and upper-extremity procedures.

Dynamics of Host Immune Response Development During Schistosoma mansoni Infection.

Schistosomiasis is a disease of global significance, with severity and pathology directly related to how the host responds to infection. The immunological narrative of schistosomiasis has been constructed through decades of study, with researchers often focussing on isolated time points, cell types and tissue sites of interest. However, the field currently lacks a comprehensive and up-to-date understanding of the immune trajectory of schistosomiasis over infection and across multiple tissue sites. We have defined schistosome-elicited immune responses at several distinct stages of the parasite lifecycle, in three tissue sites affected by infection: the liver, spleen, and mesenteric lymph nodes. Additionally, by performing RNA-seq on the livers of schistosome infected mice, we have generated novel transcriptomic insight into the development of schistosome-associated liver pathology and fibrosis across the breadth of infection. Through depletion of CD11c+ cells during peak stages of schistosome-driven inflammation, we have revealed a critical role for CD11c+ cells in the co-ordination and regulation of Th2 inflammation during infection. Our data provide an updated and high-resolution account of how host immune responses evolve over the course of murine schistosomiasis, underscoring the significance of CD11c+ cells in dictating host immunopathology against this important helminth infection.

Reliability of Assessing Distal Radius Fractures on a Smartphone Versus PACS.

BACKGROUND: Communication between health care providers is becoming more intertwined with technology. During the pandemic, telehealth strategies grew exponentially. Remote viewing of imaging on a smartphone may offer efficient communication; however, the reliability of injury assessment when compared with traditional methods is not known. The purpose of this study was to evaluate intraobserver and interobserver reliability of distal radius fracture radiograph review for smartphone versus traditional Picture Archiving and Communication System (PACS). METHODS: Eight evaluators (3 attending hand surgeons, 3 hand surgery fellows, 2 orthopedic residents) evaluated 26 distal radius fracture radiographs on 2 different viewers: smartphone or PACS. The reviewers were asked to record: (1) operative or nonoperative preference; (2) fracture classification (based on Fernandez and Jupiter); and (3) treatment strategy (volar plate, dorsal plate, pins, cast, bridge plate, or fragment-specific fixation). The percentage of intraobserver agreement was recorded for each observer. Reliability was calculated using Fleiss' kappa coefficient for intraobserver and interobserver agreement and graded by strength of correlation. RESULTS: Intraobserver agreement averaged 97% when deciding between operative and nonoperative treatment, 76% for classification, and 84% for treatment. Kappa scores were graded as "excellent" for operative decision and "substantial" for classification and treatment. Attendings and fellows generally had higher agreement than that of residents. Interobserver agreement was graded as "substantial" for all categories for both PACS and smartphone. CONCLUSIONS: Evaluation of radiographs on a smartphone for the purpose of treating distal radius fractures does not appear to be significantly different from an evaluation on traditional PACS.

Preoperative Opioid Use Results in Greater Postoperative Opioid Consumption After Thumb Basal Joint Arthroplasty.

Purpose: Thumb basal joint arthroplasty surgery is a common hand surgery after which patients often require opioids. To better understand safe opioid consumption patterns, this study sought to identify risk factors for filling a second prescription and/or prolonged opioid use (prescription over 6 months after the surgery). Preoperative opioid use was hypothesized to show an association with greater postoperative opioid use. Methods: A retrospective review of consecutive patients who underwent primary thumb basal joint arthroplasty was conducted, yielding 110 patients for analysis. Demographic and clinical data were collected. Opioid prescription data were extracted from 6 months before the surgery to 9 months after the surgery using a state prescription drug monitoring program. Bivariate and multivariate analyses were performed for filling a second opioid prescription or filling an opioid prescription over 6 months after the surgery. Results: All the patients filled their initial postoperative prescription. Of the 110 patients, 26.4% filled an opioid prescription before the surgery, 42% filled a second postoperative prescription, and 14.5% were still consuming opioids over 6 months after the surgery. Patients using preoperative opioids had 7-fold higher odds of filling a second opioid prescription and 37-fold higher odds of prolonged use. No other demographic or clinical factors, including the type of procedure or number of initial opioids prescribed, were associated with increased use of postoperative opioids. Of all the opioid prescriptions filled after the initial postoperative prescription, only 9.3% were prescribed by a surgeon's office. Conclusions: Patients who undergo thumb basal joint arthroplasty with preoperative opioid use have much greater odds of filling a second opioid prescription and prolonged use after the surgery. Low initial surgeon-provided opioid dosages did not correlate to filling a second prescription, indicating that lower initial doses are feasible. Finally, nearly all opioid-naïve patients who filled a second opioid prescription received them from providers other than a surgeon, indicating the need for greater communication with nonsurgical providers simultaneously caring for patients in the perioperative period. Type of study/level of evidence: Therapeutic III.

Gigantic genomes of salamanders indicate that body temperature, not genome size, is the driver of global methylation and 5-methylcytosine deamination in vertebrates.

Transposable elements (TEs) are sequences that replicate and move throughout genomes, and they can be silenced through methylation of cytosines at CpG dinucleotides. TE abundance contributes to genome size, but TE silencing variation across genomes of different sizes remains underexplored. Salamanders include most of the largest C-values - 9 to 120 Gb. We measured CpG methylation levels in salamanders with genomes ranging from 2N = ∼58 Gb to 4N = ∼116 Gb. We compared these levels to results from endo- and ectothermic vertebrates with more typical genomes. Salamander methylation levels are approximately 90%, higher than all endotherms. However, salamander methylation does not differ from other ectotherms, despite an approximately 100-fold difference in nuclear DNA content. Because methylation affects the nucleotide compositional landscape through 5-methylcytosine deamination to thymine, we quantified salamander CpG dinucleotide levels and compared them to other vertebrates. Salamanders and other ectotherms have comparable CpG levels, and ectotherm levels are higher than endotherms. These data show no shift in global methylation at the base of salamanders, despite a dramatic increase in TE load and genome size. This result is reconcilable with previous studies that considered endothermy and ectothermy, which may be more important drivers of methylation in vertebrates than genome size.

Deglutarylation of glutaryl-CoA dehydrogenase by deacylating enzyme SIRT5 promotes lysine oxidation in mice.

A wide range of protein acyl modifications has been identified on enzymes across various metabolic processes; however, the impact of these modifications remains poorly understood. Protein glutarylation is a recently identified modification that can be nonenzymatically driven by glutaryl-CoA. In mammalian systems, this unique metabolite is only produced in the lysine and tryptophan oxidative pathways. To better understand the biology of protein glutarylation, we studied the relationship between enzymes within the lysine/tryptophan catabolic pathways, protein glutarylation, and regulation by the deglutarylating enzyme sirtuin 5 (SIRT5). Here, we identify glutarylation on the lysine oxidation pathway enzyme glutaryl-CoA dehydrogenase (GCDH) and show increased GCDH glutarylation when glutaryl-CoA production is stimulated by lysine catabolism. Our data reveal that glutarylation of GCDH impacts its function, ultimately decreasing lysine oxidation. We also demonstrate the ability of SIRT5 to deglutarylate GCDH, restoring its enzymatic activity. Finally, metabolomic and bioinformatic analyses indicate an expanded role for SIRT5 in regulating amino acid metabolism. Together, these data support a feedback loop model within the lysine/tryptophan oxidation pathway in which glutaryl-CoA is produced, in turn inhibiting GCDH function via glutaryl modification of GCDH lysine residues and can be relieved by SIRT5 deacylation activity.

Plasmacytoid Dendritic Cells Facilitate Th Cell Cytokine Responses throughout Schistosoma mansoni Infection.

Plasmacytoid dendritic cells (pDCs) are potent producers of type I IFN (IFN-I) during viral infection and respond to IFN-I in a positive feedback loop that promotes their function. IFN-I shapes dendritic cell responses during helminth infection, impacting their ability to support Th2 responses. However, the role of pDCs in type 2 inflammation is unclear. Previous studies have shown that pDCs are dispensable for hepatic or splenic Th2 responses during the early stages of murine infection with the trematode Schistosoma mansoni at the onset of parasite egg laying. However, during S. mansoni infection, an ongoing Th2 response against mature parasite eggs is required to protect the liver and intestine from acute damage and how pDCs participate in immune responses to eggs and adult worms in various tissues beyond acute infection remains unclear. We now show that pDCs are required for optimal Th2 cytokine production in response to S. mansoni eggs in the intestinal-draining mesenteric lymph nodes throughout infection and for egg-specific IFN-γ at later time points of infection. Further, pDC depletion at chronic stages of infection led to increased hepatic and splenic pathology as well as abrogated Th2 cell cytokine production and activation in the liver. In vitro, mesenteric lymph node pDCs supported Th2 cell responses from infection-experienced CD4+ T cells, a process dependent on pDC IFN-I responsiveness, yet independent of Ag. Together, these data highlight a previously unappreciated role for pDCs and IFN-I in maintaining and reinforcing type 2 immunity in the lymph nodes and inflamed tissue during helminth infection.

A temperature-sensitive FERONIA mutant allele that alters root hair growth.

In plants, root hairs undergo a highly polarized form of cell expansion called tip-growth, in which cell wall deposition is restricted to the root hair apex. In order to identify essential cellular components that might have been missed in earlier genetic screens, we identified conditional temperature-sensitive (ts) root hair mutants by ethyl methanesulfonate mutagenesis in Arabidopsis thaliana. Here, we describe one of these mutants, feronia-temperature sensitive (fer-ts). Mutant fer-ts seedlings were unaffected at normal temperatures (20°C), but failed to form root hairs at elevated temperatures (30°C). Map based-cloning and whole-genome sequencing revealed that fer-ts resulted from a G41S substitution in the extracellular domain of FERONIA (FER). A functional fluorescent fusion of FER containing the fer-ts mutation localized to plasma membranes, but was subject to enhanced protein turnover at elevated temperatures. While tip-growth was rapidly inhibited by addition of rapid alkalinization factor 1 (RALF1) peptides in both wild-type and fer-ts mutants at normal temperatures, root elongation of fer-ts seedlings was resistant to added RALF1 peptide at elevated temperatures. Additionally, at elevated temperatures fer-ts seedlings displayed altered reactive oxygen species (ROS) accumulation upon auxin treatment and phenocopied constitutive fer mutant responses to a variety of plant hormone treatments. Molecular modeling and sequence comparison with other Catharanthus roseus receptor-like kinase 1L (CrRLK1L) receptor family members revealed that the mutated glycine in fer-ts is highly conserved, but is not located within the recently characterized RALF23 and LORELI-LIKE-GLYCOPROTEIN 2 binding domains, perhaps suggesting that fer-ts phenotypes may not be directly due to loss of binding to RALF1 peptides.

Producing a new website for a paediatric liaison mental health team with our service users.

INTRODUCTION: Online resources are an important source of information about mental health issues and services for children and young people. Our service's website had an out-of-date appearance and was aimed at professionals. More importantly, comments in our routinely collected patient experience data indicated that service users did not know what to expect when coming to our service. METHODS: We followed the model for improvement by testing out changes in plan, do, study and act cycles that included a review of recently updated child and adolescent mental health services' and youth charities' websites, designing a new web page for our service and then testing out the website in focus groups. We used routinely collected patient experience data to assess impact on wider patient satisfaction. RESULTS: Focus groups involving patients, parents and professionals judged the new website to be clearer, more attractive and easier to understand. Routine patient experience data did not reveal any website-specific feedback. CONCLUSION: This study demonstrates that it is easy and possible to create an attractive and accessible website for a mental health service using quality improvement methodology. In order to capture and integrate ongoing feedback about a service's website from service users, routinely collected patient experience measures would need to ask specific questions related to this area. In this study, preproject and postproject patient experience data did not generate any specific comments.

Loss of Extreme Long-Range Enhancers in Human Neural Crest Drives a Craniofacial Disorder.

Non-coding mutations at the far end of a large gene desert surrounding the SOX9 gene result in a human craniofacial disorder called Pierre Robin sequence (PRS). Leveraging a human stem cell differentiation model, we identify two clusters of enhancers within the PRS-associated region that regulate SOX9 expression during a restricted window of facial progenitor development at distances up to 1.45 Mb. Enhancers within the 1.45 Mb cluster exhibit highly synergistic activity that is dependent on the Coordinator motif. Using mouse models, we demonstrate that PRS phenotypic specificity arises from the convergence of two mechanisms: confinement of Sox9 dosage perturbation to developing facial structures through context-specific enhancer activity and heightened sensitivity of the lower jaw to Sox9 expression reduction. Overall, we characterize the longest-range human enhancers involved in congenital malformations, directly demonstrate that PRS is an enhanceropathy, and illustrate how small changes in gene expression can lead to morphological variation.

Effects of toothbrushing on surface characteristics of microhybrid and nanofilled resin composites following different finishing and polishing procedures.

OBJECTIVES: To evaluate the effects of simulated tooth brushing (STB) on the surface roughness of microhybrid and nanofilled resin composites following different finishing and polishing procedures. MATERIALS AND METHODS: Ninety cylindrical-shaped specimens of Filtek Supreme XT (a universal nano resin composite) and Filtek Z250 (a universal microhybrid resin composite) were prepared. The specimens were allocated at random into 9 paired groups each of 10 specimens. The finishing and polishing systems included were Tungsten Carbide bur (TC); Diamond bur (Db); Sof-Lex discs (S); PoGo discs (PG); TC + S; Db + S; TC + PG; Db + PG. Polymerisation against a Mylar strip without finishing and polishing acted as the control. Surface roughness was measured using a 3D non-contact optical profilometer and surface morphology was examined by scanning electron microscopy. Specimens were subjected to the equivalent of four years STB and surface roughness was measured again. RESULTS: Mylar formed surfaces were the smoothest for both composites before and after STB. Finishing with the diamond finishing bur caused significantly greater surface irregularity (p < 0.0001) before and after STB compared to the tungsten carbide bur. The surface treatment with Db + PG resulted in significantly greater surface roughness following STB than all other regimes of finishing and polishing (p < 0.01). CONCLUSION: Where indicated clinically, finishing is better conducted using a tungsten carbide bur rather than a diamond finishing bur. The combination of tungsten carbide bur/Enhance PoGo and tungsten carbide bur/Sof-Lex surface protocols produced a similarly smooth finish for both composites. The composite surfaces in all groups increased in surface irregularity following STB. CLINICAL SIGNIfiCANCE: Whilst finishing using a tungsten carbide finishing bur followed by either the Sof-Lex or PoGo polishing system may be found to result in a smooth surface finish, all the surfaces investigated increased in surface roughness following toothbrushing.