RESUMEN
BACKGROUND: The purpose of this individual cohort study is to demonstrate safety and efficacy in removing the trapezium through minimally invasive arthroscopy. METHODS: A prospective case series was performed on all arthroscopic total trapeziectomy procedures for thumb basal joint arthrosis between 2018 and 2022. Patients were followed for up to 1 year. All patients received an examination at each visit to include pain, range of motion, strength, and metacarpal height. Complications, concomitant procedures, and revision procedures were recorded as well. RESULTS: A total of 49 arthroscopic trapeziectomy procedures were recorded for 46 patients. The average preoperative visual analog pain scale score was 8.8 out of 10, and the postoperative score was 1 out of 10. All patients had a resolution of the carpometacarpal grind test postoperatively. The average preoperative key pinch, 3-point chuck, and grip strength were 9.8 lbs/in2, 7.8 lbs/in2, and 45 lbs/in2, respectively. Final 6-month postoperative key pinch, 3-point chuck, and grip strength were 11.0 lbs/in2, 9.8 lbs/in2, and 49.2 lbs/in2, respectively. Metacarpal height subsided on average 50%. We report one revision and no cases of radial sensory neuritis or flexor tendon rupture. CONCLUSIONS: Arthroscopic total trapeziectomy appears to be a safe and effective treatment for end-stage arthrosis of the thumb basal joint. LEVEL OF EVIDENCE: 2b Therapeutic; Individual Cohort Study.
RESUMEN
Fractures involving the lunate facet of the distal radius (commonly called the volar ulnar corner or "critical corner") are often difficult to recognize radiographically. "Lunate facet escape" refers to the displacement of this fragment after attempted distal radius fracture closed or open reduction methods. Lunate facet escape can have severe consequences including carpal collapse with pain, instability, and arthritis. Challenges to lunate facet fixation include irregular cortical contour that makes plate fixation difficult, as well as deforming forces by inserting structures. The goal of the management of a distal radius fracture with lunate facet involvement is first identification, then adequate stabilization until osseous healing occurs. However, subsequent lunate facet escape can pose a challenging clinical and surgical dilemma. Here we discuss our preferred approach to treat lunate facet escape after distal radius fracture volar locking plating failure.
RESUMEN
Purpose: Forearm shaft fractures of the radius and/or ulna are typically repaired with plates and screws, with 3.5 mm nonlocking screws being generally recommended. However, smaller plates and screws, either nonlocking or locking, can also be applied. The purpose of this study was to retrospectively review whether fracture healing rates and related complications are affected by plate size and type. Methods: Patient demographic and descriptive data were retrospectively collected for all patients with a forearm shaft fracture treated with repair of the radial shaft and/or ulna shaft between 2017 and 2021 at a multiprovider and multilocation single institution. Inclusion criteria involved use of a locking plate with a minimum radiographic follow-up of 60 days and/or until fracture union was confirmed. Results: A total of 110 patients met inclusion criteria. There were 45 (40.9%) females and 65 (59.1%) males included with the mean age at time of injury being 47 years (± 22). There were 34 (30.1%) isolated radius fractures, 50 (45.5%) isolated ulna fractures, and 26 (23.6%) both bone forearm fractures. Screw sizes consisted of 3.5 mm (small fragment) screws in 57 (52%) cases, whereas 2.7 mm/2.5 mm/2.4 mm (mini fragment) screws were used in 53 (48%) cases. Fracture union was confirmed in 108 (98%) cases. Among the two nonunion cases, one case (50%) involved a small fragment, and one case (50%) involved a mini fragment plate. Conclusions: This study confirms that fracture union is high following any size plate fixation of radius and/or ulna fractures. Moreover, smaller screw sizes did not affect fracture union rates. Choice of plate type and screw diameter should be based on patient characteristics and surgeon preference and need not be limited to only 3.5 mm plate and screws. Type of Study/Level of Evidence: Prognosis IIb.
RESUMEN
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.
Asunto(s)
COVID-19 , Intercambio Gaseoso Pulmonar , Mecánica Respiratoria , Ventiladores Mecánicos , Animales , Porcinos , Diseño de Equipo , Respiración Artificial/instrumentación , Respiración Artificial/métodos , SARS-CoV-2 , Volumen de Ventilación PulmonarRESUMEN
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.
RESUMEN
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.
Asunto(s)
Retículo Endoplásmico , Aparato de Golgi , Animales , Retículo Endoplásmico/metabolismo , Aparato de Golgi/metabolismo , Tamaño de la CélulaRESUMEN
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.
RESUMEN
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.
RESUMEN
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.
RESUMEN
[This corrects the article DOI: 10.3389/fimmu.2022.906338.].
RESUMEN
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).
RESUMEN
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.
RESUMEN
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.
RESUMEN
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.
Asunto(s)
Esquistosomiasis mansoni , Esquistosomiasis , Animales , Antígeno CD11c , Inmunidad , Inflamación , Ratones , Schistosoma mansoniRESUMEN
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.
RESUMEN
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.
RESUMEN
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 = â¼58 Gb to 4N = â¼116 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.
Asunto(s)
5-Metilcitosina , Urodelos , Animales , Temperatura Corporal , Desaminación , Tamaño del Genoma , Metilación , Urodelos/genética , Vertebrados/genéticaRESUMEN
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.
Asunto(s)
Glutaril-CoA Deshidrogenasa , Lisina , Sirtuinas , Animales , Glutaril-CoA Deshidrogenasa/metabolismo , Lisina/metabolismo , Ratones , Oxidación-Reducción , Procesamiento Proteico-Postraduccional , Sirtuinas/metabolismo , Triptófano/metabolismoRESUMEN
BACKGROUND: Many commodity pulse oximeters are insufficiently calibrated for patients with darker skin. We demonstrate a quantitative measurement of this disparity in peripheral blood oxygen saturation (SpO2) with a controlled experiment. To mitigate this, we present OptoBeat, an ultra-low-cost smartphone-based optical sensing system that captures SpO2 and heart rate while calibrating for differences in skin tone. Our sensing system can be constructed from commodity components and 3D-printed clips for approximately US $1. In our experiments, we demonstrate the efficacy of the OptoBeat system, which can measure SpO2 within 1% of the ground truth in levels as low as 75%. OBJECTIVE: The objective of this work is to test the following hypotheses and implement an ultra-low-cost smartphone adapter to measure SpO2: skin tone has a significant effect on pulse oximeter measurements (hypothesis 1), images of skin tone can be used to calibrate pulse oximeter error (hypothesis 2), and SpO2 can be measured with a smartphone camera using the screen as a light source (hypothesis 3). METHODS: Synthetic skin with the same optical properties as human skin was used in ex vivo experiments. A skin tone scale was placed in images for calibration and ground truth. To achieve a wide range of SpO2 for measurement, we reoxygenated sheep blood and pumped it through synthetic arteries. A custom optical system was connected from the smartphone screen (flashing red and blue) to the analyte and into the phone's camera for measurement. RESULTS: The 3 skin tones were accurately classified according to the Fitzpatrick scale as types 2, 3, and 5. Classification was performed using the Euclidean distance between the measured red, green, and blue values. Traditional pulse oximeter measurements (n=2000) showed significant differences between skin tones in both alternating current and direct current measurements using ANOVA (direct current: F2,5997=3.1170 × 105, P<.01; alternating current: F2,5997=8.07 × 106, P<.01). Continuous SpO2 measurements (n=400; 10-second samples, 67 minutes total) from 95% to 75% were captured using OptoBeat in an ex vivo experiment. The accuracy was measured to be within 1% of the ground truth via quadratic support vector machine regression and 10-fold cross-validation (R2=0.97, root mean square error=0.7, mean square error=0.49, and mean absolute error=0.5). In the human-participant proof-of-concept experiment (N=3; samples=3 × N, duration=20-30 seconds per sample), SpO2 measurements were accurate to within 0.5% of the ground truth, and pulse rate measurements were accurate to within 1.7% of the ground truth. CONCLUSIONS: In this work, we demonstrate that skin tone has a significant effect on SpO2 measurements and the design and evaluation of OptoBeat. The ultra-low-cost OptoBeat system enables smartphones to classify skin tone for calibration, reliably measure SpO2 as low as 75%, and normalize to avoid skin tone-based bias.
RESUMEN
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.