Search

The purpose of this study was to compare nurses' knowledge of diabetes and nursing interventions in a home health care agency (HHCA) that employed a diabetes nurse educator (DNE) and an agency that did not employ a DNE. Nurse knowledge of diabetes mellitus was measured using the Diabetes: Basic Knowledge Test (DBKT). Nursing care interventions for patients with diabetes were measured using a researcher-developed tool, the Nursing Care Intervention Tool (NCIT). The data analysis showed that the nurses in the agency with the diabetes nurse educator were significantly more knowledgeable about diabetes. The data also showed that the nurses in the HHCA with a diabetes nurse educator provided a significantly higher standard of patient care than the nurses in the agency without a diabetes nurse educator. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to characterise the presentation, treatment, and management of adolescent athlete low back pain (LBP) as diagnosed in a clinical setting. The objectives were to 1) identify diagnoses associated with LBP in adolescent athletes; 2) categorise the differences in LBP diagnosis and presentation by sport, sex, BMI, and age; and 3) examine treatment and management methods of LBP in adolescent athletes., Design: Retrospective chart review., Methods: This retrospective medical chart review was conducted in the Sports Medicine Division of Boston Children's Hospital (BCH), a tertiary paediatric academic hospital. Data were collected and analysed from 363 adolescent athletes who had experienced LBP between 2015 and 2020. Chi-squared tests for association were used to assess for associations between LBP diagnoses and age, sex, BMI, and sport. Statistical analysis was conducted using SAS software version 9.4 (SAS Institute, Cary NC)., Results: Non-specific LBP was the most common LBP diagnosis amongst 363 adolescent athletes with LBP (34 %). This was closely followed by spondylolysis (28 %). There was a higher proportion of female athletes amongst participants diagnosed with facet-joint related pain (90 %) and SI-joint related pain (89 %) compared to the proportion of female athletes amongst participants diagnosed with spondylolysis (50 %). There was a high rate of diagnostic MRI usage in this cohort. Commonly used management techniques in this cohort were diagnostic MRI, physical therapy, relative rest, and bracing., Conclusions: An awareness of the sex-based differences in adolescent athlete LBP diagnoses may be useful for clinicians. It may be important to refine methods of diagnosis of LBP in this group, as there was a high rate of diagnostic MRI use. Future research should be directed towards the development of management guidelines specific to LBP in adolescent athletes to assist in the optimal management of this diagnosis., Competing Interests: Declaration of interest statement There was no external financial support for this project. Dr. Meehan receives royalties from 1) ABC-Clio publishing for the sale of his books, Kids, Sports, and Concussion: A guide for coaches and parents, and Concussions; 2) Springer International for the book Head and Neck Injuries in Young Athlete; and 3) Wolters Kluwer for working as an author for UpToDate. His research is funded, in part, by philanthropic support from the National Hockey League Alumni Association through the Corey C. Griffin Pro-Am Tournament and a grant from the National Football League. All other authors report no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Shoulder instability in pediatric and adolescent patients can be treated operatively via arthroscopic or open procedures, but there a paucity of evidence to support the incidence of these treatment modalities over time. It is hypothesized that the overall rate of arthroscopic shoulder stabilization procedures will increase over time. Given advances in open stabilization techniques, we also hypothesized that the rate of open procedures may be increasing., Methods: The Pediatric Health Information System database was queried for patients 19 years or younger who underwent arthroscopic or open surgery for shoulder instability and pediatric orthopedic surgeries between 2009 and 2019. Data from 37 of the 52 pediatric hospitals with Pediatric Health Information System data was included in the analysis. Annual and overall incidence rates were estimated for arthroscopic and open procedures, along with 95% confidence intervals. The yearly incidence for secondary (homolateral revisions) or primary contralateral arthroscopic and open procedures was also examined., Results: 4747 patients underwent primary arthroscopic procedures and 384 patients had primary open procedures. There were 8.2 primary open shoulder stabilization procedures per 10,000 orthopedic surgical patients in 2009, which decreased by 19% to 6.7 per 10,000 orthopedic surgical patients in 2019. There was an increase seen in both arthroscopic and open secondary stabilization procedures. In 2009, there were 0.97 secondary arthroscopic procedures per 10,000 orthopedic surgical patients. This increased by 672% to 7.5 per 10,000 orthopedic surgical patients in 2019. No secondary open procedures were recorded in 2009; however, an increase to 2.6 secondary open procedures per 10,000 orthopedic surgical patients was seen by 2019., Conclusion: This study shows a rise in primary arthroscopic pediatric shoulder stabilization surgeries across the U.S. over the last decade. There was a slight decrease in the rate of primary open shoulder stabilization surgeries and an increase in both arthroscopic and open secondary (homolateral revisions or primary contralateral) shoulder stabilization surgeries, implying an increasing revision burden in this population., (© 2024 The Author(s).)

Background: Operative treatment of displaced tibial spine fractures consists of fixation and reduction of the fragment in addition to restoring tension of the anterior cruciate ligament., Purpose: To determine whether residual displacement of the anterior portion of a tibial spine fragment affects the range of motion (ROM) or laxity in operatively and nonoperatively treated patients., Study Design: Cohort study; Level of evidence, 3., Methods: Data were gathered from 328 patients younger than 18 years who were treated for tibial spine fractures between 2000 and 2019 at 10 institutions. ROM and anterior lip displacement (ALD) measurements were summarized and compared from pretreatment to final follow-up. ALD measurements were categorized as excellent (0 to <1 mm), good (1 to <3 mm), fair (3 to 5 mm), or poor (>5 mm). Posttreatment residual laxity and arthrofibrosis were assessed., Results: Overall, 88% of patients (290/328) underwent operative treatment. The median follow-up was 8.1 months (range, 3-152 months) for the operative group and 6.7 months (range, 3-72 months) for the nonoperative group. The median ALD measurement of the cohort was 6 mm pretreatment, decreasing to 0 mm after treatment ( P < .001). At final follow-up, 62% of all patients (203/328) had excellent ALD measurements, compared with 5% (12/264) before treatment. Subjective laxity was seen in 11% of the nonoperative group (4/37) and 5% of the operative group (15/285; P = .25). Across the cohort, there was no association between final knee ROM and final ALD category. While there were more patients with arthrofibrosis in the operative group (7%) compared with the nonoperative group (3%) ( P = .49), this was not different across the ALD displacement categories., Conclusion: Residual ALD was not associated with posttreatment subjective residual laxity, extension loss, or flexion loss. The results suggest that anatomic reduction of a tibial spine fracture may not be mandatory if knee stability and functional ROM are achieved., (© The Author(s) 2023.)

Background: Apophyseal avulsion fractures of the pelvis and hip are common injuries in adolescent athletes. However, high volume comparative studies elucidating the spectrum of injuries are largely absent from the literature. The current study provides a comprehensive analysis of demographic, anatomic, pathophysiological, clinical, and athletic-related variables associated with such injuries in an extensive population of affected adolescents., Methods: A retrospective review was performed of records of patients presenting to a single tertiary care pediatric hospital between January 1, 2005, and July 31, 2020, collecting variables including patient sex, age, body mass index, fracture location, injury mechanism, sport at the time of injury, and duration of prodromal symptoms., Results: Seven hundred nineteen fractures were identified in 709 patients. The average patient age was 14.6, and 78% of the fractures occurred in male patients. The anterior inferior iliac spine (33.4%), anterior superior iliac spine (30.5%), and ischial tuberosity (19.4%) were the most common fracture sites. The most common injury mechanisms were running (27.8%), kicking (26.7%), and falls (8.8%). The most common sports at the time of injury were soccer (38.1%), football (11.2%), and baseball (10.5%). Fracture site was significantly associated with patient sex, age, body mass index, laterality, mechanism, sport, time from injury, and presence of prodromal symptoms. The annual volume of pelvic avulsion fractures treated at the institution increased significantly from n=17 in 2005 to n=75 in 2019., Conclusions: Adolescent pelvic and hip avulsion fractures occur during a narrow window of age and skeletal maturation and are frequently sustained during sporting activities. Each fracture location is associated with certain demographic, mechanistic, and patient-specific characteristics. The associations between fracture site and patient-specific or injury-specific variables offer insights into the pathophysiology and possible underlying biomechanical risk factors that contribute to these injuries., Level of Evidence: This is a level III retrospective study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: The presence of seasonal patterns in pediatric septic arthritis cases is a common orthopaedic teaching. Seasonal variation has been seen in centers outside of the United States and with other inflammatory and infectious joint-related conditions within the country, but it is unknown if a seasonal pattern exists among different regions of the United States. The purpose of this study was to examine the seasonal variation of septic arthritis within specific regions across the United States., Methods: The Pediatric Health Information System database was queried for all patients 19 years or younger who were treated for septic arthritis. Data from 34 pediatric hospitals in the Pediatric Health Information System initiative were included. Centers were organized by geographical region, and season of presentation was determined using equinoxes/solstices. χ 2 tests were performed to detect seasonal differences in septic arthritis for the entire cohort and separated by geographical region. Proportion differences along with 95% CIs were provided., Results: Between 2016 and 2019, there were 5764 cases of septic arthritis. Median age at diagnosis was 6.2 years (range: 0 to 19.0 y). Each season contributed 24% to 25% of the total septic arthritis cases, and there were no significant differences detected between the 4 seasons ( P =0.66). There was no seasonal variation seen in the Midwest, South, or West ( P =0.71, 0.98, 0.36, respectively). However, there was seasonal variation in the Northeast ( P =0.05), with fall and summer having a higher percentage of cases (28%) than the winter (21%)., Conclusions: This study showed no clear seasonal variation in septic arthritis in children across the United States using a national database of pediatric hospital centers. However, there is regional seasonal variation in the Northeast, which may relate to climate differences. With no clear seasonal variation across the United States, continued diligence is needed in diagnosing septic arthritis throughout the year., Level of Evidence: Prognostic II., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Rationale & Objective: Adoption of point-of-care ultrasound (POCUS) into nephrology practice has been relatively slow. We surveyed US nephrology program directors, their fellows, and graduates from a single training program regarding current/planned POCUS training, clinical use, and barriers to training and use., Study Design: Anonymous, online survey., Setting & Participants: All US nephrology program directors (n=151), their fellows (academic year 2021-2022), and 89/90 graduates (1980-2021) of the Walter Reed Nephrology Program., Analytical Approach: Descriptive., Results: 46% (69/151) of program directors and 33% (118/361) of their fellows responded. Response rate was 62% (55/89) for Walter Reed graduates. 51% of program directors offered POCUS training, most commonly bedside training in non-POCUS oriented rotations (71%), didactic lectures (68%), and simulation (43%). 46% of fellows reported receiving POCUS training, but of these, many reported not being sufficiently trained/not confident in kidney (56%), bladder (50%), and inferior vena cava assessment (46%). Common barriers to training reported by program directors were not enough trained faculty (78%), themselves not being sufficiently trained (55%), and equipment expense (51%). 64% of program directors and 55% of fellows reported <10% of faculty were able to perform POCUS. 64% of fellows reported having too little POCUS training. 72% of program directors and 77% of graduates felt POCUS should be incorporated into the fellowship curriculum. 59% of fellows and 61% of graduates desired hands-on POCUS training rather than didactic lectures or simulation., Limitations: Loss of respondents as program directors and fellows progressed through the survey., Conclusions: Nephrology program directors, fellows, and graduates surveyed want POCUS training incorporated into the fellowship curriculum. No group felt sufficiently trained to confidently perform POCUS, and the major barrier to training was lack of sufficiently trained faculty. This highlights the need to "train the trainers" before POCUS can be fully integrated into fellowship training and regularly used in nephrology practice.

Children and young people (CYP) can be empowered to take on roles as agents of change in their own communities. CYP want to be heard and should be actively involved in the co-production, design and development of services aimed at them to ensure that the resulting services are acceptable and accessible. Little analysis of the framing and discourse of co-production in different contexts has been undertaken.Building on Children's Advocacy Center models from the United States of America (which are held in high esteem by local communities), there is perceived value of such a center in the UK. A service development initiative was designed to work with children from Greater Manchester (UK) to determine the potential for the establishment of a children's advocacy center in the North of England. This report presents the design and outcome of the initiative and contributes to the literature on the co-production of such service development projects with CYP, notably the means of achieving that outcome.Recommendations are made for the piloting of an Advocacy House model in the UK with collaborative efforts between CYP as well as health, education, law enforcement, social care providers, charities and voluntary groups. A community-inclusive partnership, underpinned by the principles of co-production and co-design, is integral to the further development of this pilot.

Background: The rate of anterior cruciate ligament (ACL) reconstruction is increasing over time in pediatric/adolescent populations, but there is less evidence to support how concomitant meniscal procedures are changing over time. There are also less data to suggest which characteristics are associated with meniscectomy versus meniscal repair treatment., Hypothesis: Age, sex, race/ethnicity, income, and insurance type may independently affect the rate of concomitant meniscal procedures and treatment modalities in pediatric patients with ACL reconstruction., Study Design: Descriptive epidemiology study., Methods: The Pediatric Health Information System database was queried for all patients aged ≤18 years who underwent ACL reconstruction with or without concomitant meniscal procedures from 2015 to 2019. Basic demographic data including age, sex, self-identified race/ethnicity, rural-urban commuting area code, predicted median income, and insurance status were collected. Linear regression was used to model trends and multiple logistic regression modeling was used to test for associations., Results: A total of 14,398 patients aged ≤18 years underwent ACL reconstruction during the study period, with 8337 patients (58%) having concomitant meniscal procedures with a 1.24-fold increase over 5 years. Of the concomitant meniscal treatment cohort, 41% had a meniscectomy and 59% had meniscal repair. There was a 0.82-fold change in meniscectomy and a 1.67-fold increase in meniscal repair during the study period. Male patients, older patients, Black race, living in an urban area, and those with nonprivate insurance had increased odds of undergoing a concomitant meniscal procedure (all P < .05). Patients of non-White race and those with nonprivate insurance had increased odds of having a meniscectomy versus meniscal repair (all P < .05). There were no associations detected between income bracket and the outcomes in this study., Conclusion: This study shows that in pediatric and adolescent patients undergoing ACL reconstruction, there was a rise in concomitant meniscal procedures from 2015 to 2019. In addition, patients of non-White race and those with nonprivate insurance have increased odds of undergoing meniscectomy versus meniscal repair.

Background: Children with medical complexity are at increased risk of low bone mineral density (BMD) and complications after spinal fusion compared with idiopathic scoliosis patients. Our aim was to compare treatments and outcomes of children with medical complexity undergoing spinal fusion in those who had dual-energy x-ray absorptiometry (DXA) scans versus those who did not in an effort to standardize the workup of these patients before undergoing spinal surgery., Methods: We conducted a retrospective review of patients with low BMD who underwent spinal fusion at a tertiary care pediatric hospital between 2004 and 2016. We consulted with a pediatric endocrinologist to create standard definitions for low BMD to classify each subject. Regardless of DXA status, all patients were given a clinical diagnosis of osteoporosis [at least 2 long bone or 1 vertebral pathologic fracture(s)], osteopenia (stated on radiograph or by the physician), or clinically low bone density belonging to neither category. The last classification was used for patients whose clinicians had documented low bone density not meeting the criteria for osteoporosis or osteopenia. Fifty-nine patients met the criteria, and 314 were excluded for insufficient follow-up and/or not meeting a diagnosis definition. BMD Z -scores compare bone density ascertained by DXA to an age-matched and sex-matched average. Patients who had a DXA scan were also given a DXA diagnosis of low bone density (≤-2 SD), slightly low bone density (-1.0 to -1.9 SD), or neither (>-1.0 SD) based on the lowest BMD Z -score recorded., Results: Fifty-nine patients were analyzed. Fifty-four percent had at least 1 DXA scan preoperatively. Eighty-one percent of DXA patients received some form of treatment compared with 52% of non-DXA patients ( P =0.03)., Conclusions: Patients referred for DXA scans were more likely to be treated for low BMD, although there is no standardized system in place to determine which patients should get scans. Our research highlights the need to implement clinical protocols to optimize bone health preoperatively., Level of Evidence: Level II-retrospective prognostic study., Competing Interests: J.G.B. is on the editorial board of JAMA Pediatrics . N.S.M. is a paid consultant for and received research support from Ascendis Pharma, research support from Ultragenyx, and financial support from UpToDate. D.J.H. is a paid consultant for Medtronic. L.I.K. received financial support from K2M. J.B.E. is a paid consultant for Biomet and Johnson & Johnson, receives IP royalties from DePuy, and is on the editorial board of the Journal of Children’s Orthopedics . M.T.H. is a board/committee member of the American College of Rheumatology Arthritis Foundation and the Pediatric Orthopaedic Society of North America, has stock/stock options in EOSI, and is on the editorial board of the New England Journal of Medicine . B.D.S. is a board/committee member of AAOS, Orthopaedic Research Society, Pediatric Orthopaedic Society of North America, and Scoliosis Research Society and an unpaid consultant for OrthoPediatrics. M.P.G. is a paid presenter for Biomet, DePuy, Medtronic, and Nuvasive, received research support as a member of HSG and PSSG, and is a paid consultant for Orthobullets and received financial support and stock/stock options from them. The remaining authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Heterotopic ossification (HO) is a known complication after hip arthroscopy in adults, positively associated with larger cam resection, male sex, older age, and obesity, and negatively associated with nonsteroidal anti-inflammatory drug (NSAID) use and capsular closure. However, it has not been well-documented in adolescents. The purpose of this study was to determine the incidence and risk factors for the development of HO in adolescent patients undergoing hip arthroscopy., Methods: Clinical and operative records from a pediatric institution were queried to identify patients aged 21 years or younger who underwent hip arthroscopy between 2008 and 2018. The 27 cases that developed HO were matched 1:4 on age and sex with 107 controls. The bivariate analysis assessed the relationship between demographic and perioperative factors on the development of HO. Multivariable logistic regression evaluated the association between prophylactic NSAID use (indomethacin 75 mg, 3 wk) and HO, controlling for surgeon and extent of cam resection (change in alpha angle)., Results: Twenty-seven of 595 (4.5%) hips that underwent hip arthroscopy developed HO within 2 years of surgery. Prophylactic indomethacin was not significantly associated with developing HO [30% (8/27), P=0.83], after controlling for surgeon and extent of cam resection-nor were age, sex, and body mass index percentile. Of patients who developed HO, a smaller proportion underwent reoperation for HO excision among those who received prophylactic indomethacin than those who did not [13% (1/8) vs. 63% (12/19), P=0.03]., Conclusions: The incidence of HO within 2 years of hip arthroscopy in this adolescent population was 4.5%. Although studies in the adult hip arthroscopy population have pointed to a protective role of NSAIDs (eg, indomethacin) in radiographic HO, the effect was less certain in this adolescent sample. Larger studies are important to further evaluate the role of prophylactic NSAIDs and variations in arthroscopic technique in developing HO., Level of Evidence: Level III-therapeutic, case-control study., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Cutaneous lymphoma is a broad term used to describe any type of lymphoma involving the skin. They may be primary, arising in the skin, or secondary, resulting from spread of a systemic lymphoma. Cutaneous involvement of mantle cell lymphoma (MCL) is extremely rare and most often occurs secondarily. To date, less than 100 cases of MCL involving the skin have been described in the English literature. We describe a case of MCL involving the skin as the clinical presentation of disease in a 74-year-old man and highlight the radiographic and pathologic findings, treatment course, and prognosis., (Copyright© by the Association of Genetic Technologists.)

Background: Recent focus on surgical site infections (SSIs) after posterior spine fusion (PSF) has lowered infection rates by standardizing perioperative antibiotic prophylaxis. However, efforts have neglected to detail antibiotic treatment of SSIs. Our aim was to document variability in antibiotic regimens prescribed for acute and latent SSIs following PSF in children with idiopathic, neuromuscular, and syndromic scoliosis., Methods: This study included patients who developed a SSI after PSF for scoliosis at a pediatric tertiary care hospital between 2004 and 2019. Patients had to be 21 years or younger at surgery. Exclusion criteria included growing rods, staged surgery, and revision or removal before SSI diagnosis. Infection was classified as acute (within 90 d) or latent. Clinical resolution of SSI was measured by return to normal lab values. Each antibiotic was categorized as empiric or tailored., Results: Eighty subjects were identified. The average age at fusion was 14.7 years and 40% of the cohort was male. Most diagnoses were neuromuscular (53%) or idiopathic (41%).Sixty-three percent of patients had an acute infection and 88% had a deep infection. The majority (54%) of subjects began on tailored antibiotic therapy versus empiric (46%). Patients with a neuromuscular diagnosis had 4.0 times the odds of receiving initial empiric treatment compared with patients with an idiopathic diagnosis, controlling for infection type and time (P=0.01). Ninety-two percent of patients with acute SSI retained implants at the time of infection and 76% retained them as of August 2020. In the latent cohort, 27% retained implants at infection and 17% retained them as of August 2020., Conclusions: Patients with acute infections were on antibiotics longer than patients with latent infections. Those with retained implants were on antibiotics longer than those who underwent removal. By providing averages of antibiotic duration and lab normalization, we hope to standardize regimens moving forward and develop SSI-reducing pathways encompassing low-risk patients., Level of Evidence: Level III., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

We present model calculations for cosmogenic production rates in order to quantify the potential effects of spallation and neutron capture reactions on Fe and Ni isotopes in iron meteorites. We aim to determine whether the magnitude of any cosmogenic effects on the isotopic ratios of Fe and/or Ni may hinder the search for nucleosynthetic variations in these elements or in the application of the 60 Fe- 60 Ni chronometer. The model shows that neutron capture reactions are the dominant source of shifts in Fe and Ni isotopic ratios and that spallation reactions are mostly negligible. The effects on 60 Ni are sensitive to the Co/Ni ratio in the metal. The total galactic cosmic ray (GCR) effects on 60 Ni and 64 Ni can be minimized through the choice of normalizing isotopes ( 61 Ni/ 58 Ni versus 62 Ni/ 58 Ni). In nearly all cases, the GCR effects (neutron capture and/or spallation) on Fe and Ni isotopic ratios are smaller than the current analytical resolution of the isotopic measurements. The model predictions are compared to the Fe and Ni isotopic compositions measured in a suite of six group IAB irons with a range of cosmic ray exposure histories. The experimental data are in good agreement with the model results. The minimal effects of GCRs on Fe and Ni isotopes should not hamper the search for nucleosynthetic variations in these two elements or the application of the 60 Fe- 60 Ni chronometer in iron meteorites or chondrites., (© 2020 The Authors. Meteoritics & Planetary Science published by Wiley Periodicals, Inc. on behalf of The Meteoritical Society (MET).)

This study was conducted to understand the reasons parents of children with minor conditions attend the Children's Emergency Department (ED), and their views about onsite pediatric same day care (SDC) service as an alternative treatment center. The study was a cross-sectional survey of parents attending an inner-city, district general hospital children's ED, with children aged under 16 years old who were allocated to low triage categories. A convenience sample of 58 parents of 58 children were recruited. All the 58 responses were analyzed. Incomplete questionnaires were not excluded. 47% of attendances were because of minor injury. Most presentations were within 24 hours of the injury or illness. 72% of parents were employed. 91% were registered with a General Practitioner (GP). 29% contacted a GP before the ED visit. The majority of participants who contacted a GP were referred to the ED; others were advised to wait to see if the child's condition improved and to attend the ED if there were any concerns or the child deteriorated in any way. About 50% of those that did not contact GP said the GP surgery was closed and 8% felt the GP could not help. 90% of parents perceived their child's condition as urgent requiring immediate treatment. About 33% of parents said they would be happy for their children to be treated at an onsite SDC center. The study showed limited access to GP services in the community and dissatisfaction with community services and perceived urgency of treatment prompted parents of children with minor conditions to attend the ED. This could mean significant ED attendance by children with minor conditions. The majority of the parents in the study would welcome an onsite pediatric SDC if appropriate to meet their children's care needs. Establishing an onsite SDC may help relieve the ED pressures to attend to more clinically urgent and emergency cases.

Objectives: Recent investigations in humans and mouse models with lupus have revealed evidence of mitochondrial dysfunction and production of mitochondrial reactive oxygen species (mROS) in T cells and neutrophils. This can provoke numerous cellular changes including oxidation of nucleic acids, proteins, lipids and even induction of cell death. We have previously observed that in T cells from patients with lupus, the increased mROS is capable of provoking oligomerisation of mitochondrial antiviral stimulator (MAVS) and production of type I interferon (IFN-I). mROS in SLE neutrophils also promotes the formation of neutrophil extracellular traps (NETs), which are increased in lupus and implicated in renal damage. As a result, in addition to traditional immunosuppression, more comprehensive treatments for lupus may also include non-immune therapy, such as antioxidants., Methods: Lupus-prone MRL- lpr mice were treated from weaning for 11 weeks with the mitochondria-targeted antioxidant, MitoQ (200 µM) in drinking water. Mice were then assessed for ROS production in neutrophils, NET formation, MAVS oligomerisation, serum IFN-I, autoantibody production and renal function., Results: MitoQ-treated mice manifested reduced neutrophil ROS and NET formation, decreased MAVS oligomerisation and serum IFN-I, and reduced immune complex formation in kidneys, despite no change in serum autoantibody ., Conclusions: These findings reveal the potential utility of targeting mROS in addition to traditional immunosuppressive therapy for lupus., Competing Interests: Competing interests: MPM helped develop MitoQ and has a commercial interest in MitoQ., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY. Published by BMJ.)

Summary: As the number and complexity of biosimulation models grows, so do demands for tools that can help users understand models and compose more comprehensive and accurate systems from existing models. SemGen is a tool for semantics-based annotation and composition of biosimulation models designed to address this demand. A key SemGen capability is to decompose and then integrate models across existing model exchange formats including SBML and CellML. To support this capability, we use semantic annotations to explicitly capture the underlying biological and physical meanings of the entities and processes that are modeled. SemGen leverages annotations to expose a model's biological and computational architecture and to help automate model composition., Availability and Implementation: SemGen is freely available at https://github.com/SemBioProcess/SemGen., Supplementary Information: Supplementary data are available at Bioinformatics online., (© The Author(s) 2018. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Life science researchers use computational models to articulate and test hypotheses about the behavior of biological systems. Semantic annotation is a critical component for enhancing the interoperability and reusability of such models as well as for the integration of the data needed for model parameterization and validation. Encoded as machine-readable links to knowledge resource terms, semantic annotations describe the computational or biological meaning of what models and data represent. These annotations help researchers find and repurpose models, accelerate model composition and enable knowledge integration across model repositories and experimental data stores. However, realizing the potential benefits of semantic annotation requires the development of model annotation standards that adhere to a community-based annotation protocol. Without such standards, tool developers must account for a variety of annotation formats and approaches, a situation that can become prohibitively cumbersome and which can defeat the purpose of linking model elements to controlled knowledge resource terms. Currently, no consensus protocol for semantic annotation exists among the larger biological modeling community. Here, we report on the landscape of current annotation practices among the COmputational Modeling in BIology NEtwork community and provide a set of recommendations for building a consensus approach to semantic annotation., (© The Author(s) 2018. Published by Oxford University Press.)

The origin of 180 W excesses in iron meteorites has been a recently debated topic. Here, a suite of IIAB iron meteorites was studied in order to accurately determine the contribution from galactic cosmic rays (GCR) and from potential decay of 184 Os to measured excesses in the minor isotope 180 W. In addition to W isotopes, trace element concentrations (Re, Os, Ir, Pt, W) were determined on the same samples, as well as their cosmic ray exposure ages, using 36 Cl- 36 Ar systematics. These data were used in combination with an improved model of GCR effects on W isotopes to correct effects resulting from neutron capture and spallation reactions. After these corrections, the residual 180 W excesses correlate with Os/W ratios and indicate a clear contribution from 184 Os decay. A newly derived decay constant is equivalent to a half-life for 184 Os of (3.38 ± 2.13) × 10 13 a. Furthermore, when the data are plotted on an Os-W isochron diagram, the intercept ( ε 180 W i = 0.63 ± 0.35) reveals that the IIAB parent body was characterized by a small initial nucleosynthetic excess in 180 W upon which radiogenic and GCR effects were superimposed. This is the first cogent evidence for p -process variability in W isotopes in early Solar System material.

Post-transplant lymphoproliferative disease (PTLD) is a rare lymphoid and/or plasmacytic proliferation that occurs in the context of immunosuppression because of solid organ transplantation (SOT) and allogeneic hematopoietic stem cell transplantation (HSCT). PTLD is the most common cancer in children who receive a SOT or HSCT, occurring in up to 13% of these patients. The majority of PTLDs are extracutaneous B-cell lymphomas, with only 12% to 14%, representing the T-cell phenotype. PTLDs can involve the skin and behave like an aggressive lymphoma, and are among the most serious and potentially fatal complications of transplantation. Here we present a case report and review of the literature of pediatric cutaneous PTLD., (© 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Chronic kidney disease affects 47 million people in the United States and is associated with significant health care costs, morbidity, and mortality. Because this disease can silently progress to advanced stages, early detection is critical for initiating timely interventions. Multiple guidelines recommend at least annual screening with serum creatinine, urine albumin/creatinine ratio, and urinalysis for patients with risk factors, particularly diabetes mellitus, hypertension, and a history of cardiovascular disease. The U.S. Preventive Services Task Force found insufficient evidence to assess the balance of benefits and harms of screening for chronic kidney disease in the general population, and the American College of Physicians recommends against screening asymptomatic adults without risk factors. Persistently elevated serum creatinine and albuminuria are diagnostic and prognostic hallmarks of chronic kidney disease. Lower levels of albuminuria are associated with adverse renal and cardiovascular outcomes. Serum cystatin C is a novel biomarker that is most useful when a false-positive decreased estimated glomerular filtration rate calculated from serum creatinine is suspected. New guidelines incorporate albuminuria into the classification framework for chronic kidney disease and elaborate on identification of the disease, the frequency of follow-up, and recommendations for nephrology referral. Nephrology consultation is indicated for patients with an estimated glomerular filtration rate less than 30 mL per minute per 1.73 m2, persistent urine albumin/creatinine ratio greater than 300 mg per g or urine protein/creatinine ratio greater than 500 mg per g, or if there is evidence of a rapid loss of kidney function. A multidisciplinary approach between primary care physicians, nephrologists, and other subspecialists for implementing early interventions, providing education, and planning for advanced renal disease is key for effective management.

Background: Research suggests that at least 10% of veterans returning from Iraq and Afghanistan meet criteria for posttraumatic stress disorder (PTSD) related to their military experiences. National dissemination initiatives have increased veterans' access to best-practice interventions. However, treatment-seeking remains low among veterans with PTSD, often due to perceived stigma and other associated barriers. The National Center for PTSD recently developed and launched AboutFace , a digital storytelling (DST) resource designed to help veterans recognize PTSD and motivate them to seek evidence-based treatment. The Ralph H. Johnson Veterans Affairs Medical Center (VAMC) and the National Center for PTSD have partnered to conduct pilot work to evaluate veterans' reactions to AboutFace to set the stage for a large-scale study to examine whether AboutFace effectively reduces stigma and improves attitudes toward treatment-seeking among veterans. If effective, this DST approach may serve as a valuable national model for a variety of treatment-seeking populations., Methods: During the first phase of the pilot, in-person usability assessments of AboutFace will be conducted via semi-structured interviews with 20 veterans. Audio recordings of interviews will undergo transcription and coding. A report of the results of qualitative analyses of these interviews will be provided to the National Center for PTSD and will inform revisions to the site. In the second phase of the pilot, 60 veterans referred to a specialized PTSD clinic will be recruited to demonstrate and refine the methodology that we propose to use in a larger randomized controlled trial evaluation of AboutFace . Veterans will be randomly assigned to receive AboutFace plus standard education vs . standard education alone. Baseline and 2-week telephone assessments will be conducted with participating veterans to measure stigma, attitudes toward seeking mental health services, and treatment access/engagement., Discussion: The feedback we receive in this pilot will be used to strengthen the quality of the DST website in preparation for a large-scale evaluation. Future work will involve evaluation of reach and impact of the site relative to stigma, attitudes toward seeking mental health service, and utilization of care. If AboutFace is found to increase access to care, this finding would have broad and significant implications for overcoming barriers to care for veterans and other populations with stigmatized conditions., Trial Registration: Clinicaltrials.gov, NCT02486692.

Objectives: Microfluidic perfusion systems are used for assessing cell and tissue function while assuring cellular viability. Low perfusate flow rates, desired both for conserving reagents and for extending the number of channels and duration of experiments, conventionally depend on peristaltic pumps to maintain flow yet such pumps are unwieldy and scale poorly for high-throughput applications requiring 16 or more channels. The goal of the study was to develop a scalable multichannel microfluidics system capable of maintaining and assessing kinetic responses of small amounts of tissue to drugs or changes in test conditions., Methods: Here we describe the BaroFuse, a novel, multichannel microfluidics device fabricated using 3D-printing technology that uses gas pressure to drive large numbers of parallel perfusion experiments. The system is versatile with respect to endpoints due to the translucence of the walls of the perifusion chambers, enabling optical methods for interrogating the tissue status. The system was validated by the incorporation of an oxygen detection system that enabled continuous measurement of oxygen consumption rate (OCR)., Results: Stable and low flow rates (1-20 μL/min/channel) were finely controlled by a single pressure regulator (0.5-2 psi). Control of flow in 0.2 μL/min increments was achieved. Low flow rates allowed for changes in OCR in response to glucose to be well resolved with very small numbers of islets (1-10 islets/channel). Effects of acetaminophen on OCR by precision-cut liver slices of were dose dependent and similar to previously published values that used more tissue and peristaltic-pump driven flow., Conclusions: The very low flow rates and simplicity of design and operation of the BaroFuse device allow for the efficient generation of large number of kinetic profiles in OCR and other endpoints lasting from hours to days. The use of flow enhances the ability to make measurements on primary tissue where some elements of native three-dimensional structure are preserved. We offer the BaroFuse as a powerful tool for physiological studies and for pharmaceutical assessment of drug effects as well as personalized medicine.

We describe an approach for performing qualitative, systems-level causal analyses on biosimulation models that leverages semantics-based modeling formats, formal ontology, and automated inference. The approach allows users to quickly investigate how a qualitative perturbation to an element within a model's network (an increment or decrement) propagates throughout the modeled system. To support such analyses, we must interpret and annotate the semantics of the models, including both the physical properties modeled and the dependencies that relate them. We build from prior work understanding the semantics of biological properties, but here, we focus on the semantics for dependencies, which provide the critical knowledge necessary for causal analysis of biosimulation models. We describe augmentations to the Ontology of Physics for Biology, via OWL axioms and SWRL rules, and demonstrate that a reasoner can then infer how an annotated model's physical properties influence each other in a qualitative sense. Our goal is to provide researchers with a tool that helps bring the systems-level network dynamics of biosimulation models into perspective, thus facilitating model development, testing, and application.

A dying massive star ends in a supernova explosion ejecting a large fraction of its mass into the interstellar medium. If this happens nearby, part of the ejecta might end on Solar System bodies and, in fact, radioactive ^{60}Fe has been detected on the Pacific ocean floor in about 2 Ma old layers. Here, we report on the detection of this isotope also in lunar samples, originating presumably from the same event. The concentration of the cosmic ray produced isotope ^{53}Mn, measured in the same samples, proves the supernova origin of the ^{60}Fe. From the ^{60}Fe concentrations found we deduce a reliable value for the local interstellar fluence in the range of 1×10^{8}  at/cm^{2}. Thus, we obtain constraints on the recent and nearby supernova(e).

Semantics-based model composition is an approach for generating complex biosimulation models from existing components that relies on capturing the biological meaning of model elements in a machine-readable fashion. This approach allows the user to work at the biological rather than computational level of abstraction and helps minimize the amount of manual effort required for model composition. To support this compositional approach, we have developed the SemGen software, and here report on SemGen's semantics-based merging capabilities using real-world modeling use cases. We successfully reproduced a large, manually-encoded, multi-model merge: the "Pandit-Hinch-Niederer" (PHN) cardiomyocyte excitation-contraction model, previously developed using CellML. We describe our approach for annotating the three component models used in the PHN composition and for merging them at the biological level of abstraction within SemGen. We demonstrate that we were able to reproduce the original PHN model results in a semi-automated, semantics-based fashion and also rapidly generate a second, novel cardiomyocyte model composed using an alternative, independently-developed tension generation component. We discuss the time-saving features of our compositional approach in the context of these merging exercises, the limitations we encountered, and potential solutions for enhancing the approach.

There is a general need to detect toxic effects of drugs during preclinical screening. We propose that increased sensitivity of xenobiotics toxicity combined with improved in vitro physiological recapitulation will more accurately assess potentially toxic perturbations of cellular biochemistry that are near in vivo pharmacological exposure levels. Importantly, measurement of such cytopathologies avoids activating mechanisms mediating toxicity at suprapharmacologic levels not relevant to in vivo effects. We present a sensitive method to measure changes in oxygen consumption rate (OCR), a well-established parameter reflecting a potential hazard, in response to exposure to pharmacologic levels of drugs using a flow culture system and state of the art oxygen sensing system. We tested metformin and acetaminophen on rat liver slices to illustrate the method. The features of the method include continuous and very stable measurement of OCR over the course of 48 h in liver slices in a continuous flow chamber with the ability to resolve changes as small as 0.3%/h. Kinetic modeling of metformin inhibition of OCR over a wide range of concentrations revealed both a slow and fast mechanism, where the fast mechanism activated only at concentrations above 0.6 mM. For both drugs, small amounts of inhibition were reversible, but higher decrements were irreversible. Overall the study highlights the advantages of measuring low-level toxicity so as to avoid the common extrapolations made about drug toxicity based on effects of drugs tested at suprapharmacologic levels., (© The Author 2015. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

The β-sitosterol concentration in pulp and paper mill effluents is typically greater than that of other phytosterols and has been shown to cause a variety of effects in fish. The authors exposed fathead minnow (Pimephales promelas) to low (22 ± 0.93 µg/L), medium-low (70 ± 2.1 µg/L), medium-high (237 ± 5.5 µg/L), and high (745 ± 16.2 µg/L) concentrations of β-sitosterol as well as negative (water), positive (ethynyl estradiol, 16 ± 0.58 ng/L), and carrier (0.6 mL/L acetone) controls. Fish were monitored over a full life cycle for population-level endpoints including growth and survival, reproductive endpoints (e.g. fecundity, sex steroids and vitellogenin, gonado-/hepatosomatic indices, and gonad histology). No significant differences were seen in fish growth, mortality, or reproduction with β-sitosterol exposure, although a trend for lower egg production in β-sitosterol exposures relative to the water control may be related to the acetone carrier. All ethynyl estradiol-exposed fish were smaller, showed female characteristics, and did not spawn. Sex steroid and vitellogenin were highly variable with no detectable treatment-related differences. Gonadal tissue showed no β-sitosterol-related differences in reproductive development and spawning capability, although most ethynyl estradiol-exposed males had ovarian tissue and were not spawning-capable. The results indicate that β-sitosterol exposure had little apparent impact on fathead minnow survival, growth, and reproduction even at concentrations >10 times that of typical effluents, although small sample size and variability precluded fully evaluating treatment responses on sex steroids and vitellogenin., (© 2013 SETAC.)

Background: In prior work, we presented the Ontology of Physics for Biology (OPB) as a computational ontology for use in the annotation and representations of biophysical knowledge encoded in repositories of physics-based biosimulation models. We introduced OPB:Physical entity and OPB:Physical property classes that extend available spatiotemporal representations of physical entities and processes to explicitly represent the thermodynamics and dynamics of physiological processes. Our utilitarian, long-term aim is to develop computational tools for creating and querying formalized physiological knowledge for use by multiscale "physiome" projects such as the EU's Virtual Physiological Human (VPH) and NIH's Virtual Physiological Rat (VPR)., Results: Here we describe the OPB:Physical dependency taxonomy of classes that represent of the laws of classical physics that are the "rules" by which physical properties of physical entities change during occurrences of physical processes. For example, the fluid analog of Ohm's law (as for electric currents) is used to describe how a blood flow rate depends on a blood pressure gradient. Hooke's law (as in elastic deformations of springs) is used to describe how an increase in vascular volume increases blood pressure. We classify such dependencies according to the flow, transformation, and storage of thermodynamic energy that occurs during processes governed by the dependencies., Conclusions: We have developed the OPB and annotation methods to represent the meaning-the biophysical semantics-of the mathematical statements of physiological analysis and the biophysical content of models and datasets. Here we describe and discuss our approach to an ontological representation of physical laws (as dependencies) and properties as encoded for the mathematical analysis of biophysical processes.

Cutaneous leiomyomas are relatively common benign smooth muscle tumors that may arise as solitary or multiple lesions. Rare forms with cytologic atypia, and features similar to symplastic leiomyomas of the uterus, have been described. We report a case of multiple cutaneous atypical leiomyomas occurring in a 43-year-old man with long history of lesions of the right lower leg and a family history of leiomyomatosis. Twenty of the lesions were excised due to pain and were examined histopathologically. All the lesions exhibited features described in atypical leiomyomas of the skin including increased cellularity, nuclear atypia and pleomorphism, and low mitotic activity. The biologic potential of cutaneous atypical leiomyomas is uncertain. Only a few case reports exist in the literature with the majority occurring as solitary lesions. Most of the reported atypical leiomyomas have behaved in a benign fashion. However, a rare account of transformation to leiomyosarcoma emphasizes the need for long-term follow up of these patients. Herein, we describe a case of multiple atypical cutaneous leiomyomas arising in the setting of familial leiomyomatosis., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: As the number and size of biological knowledge resources for physiology grows, researchers need improved tools for searching and integrating knowledge and physiological models. Unfortunately, current resources-databases, simulation models, and knowledge bases, for example-are only occasionally and idiosyncratically explicit about the semantics of the biological entities and processes that they describe., Results: We present a formal approach, based on the semantics of biophysics as represented in the Ontology of Physics for Biology, that divides physiological knowledge into three partitions: structural knowledge, process knowledge and biophysical knowledge. We then computationally integrate these partitions across multiple structural and biophysical domains as computable ontologies by which such knowledge can be archived, reused, and displayed. Our key result is the semi-automatic parsing of biosimulation model code into PhysioMaps that can be displayed and interrogated for qualitative responses to hypothetical perturbations., Conclusions: Strong, explicit semantics of biophysics can provide a formal, computational basis for integrating physiological knowledge in a manner that supports visualization of the physiological content of biosimulation models across spatial scales and biophysical domains.

Cowden syndrome is a rare, autosomal-dominant, multisystem disorder characterized by hamartomatous tissue overgrowth and an increased risk of breast, thyroid, and endometrial cancers. Most of the cases arise from germline mutations of the phosphatase and tensin homologue tumor suppressor gene. An association with colon cancer remains unproven but has been suggested in previous reports. We present the case of a 42-year-old man with colonic ganglioneuromatous polyps and an adjacent colonic adenoma giving rise to a signet-ring adenocarcinoma with lymph node metastases in the setting of Cowden syndrome. Although gastrointestinal polyps are a common feature of Cowden syndrome, reports of ganglioneuromatous polyps and malignant degeneration are rare. Cutaneous features of Cowden syndrome in our patient include "cobblestone" lesions of the tongue and oral mucosa, facial trichilemmomas, multiple acral keratoses, and a storiform collagenoma., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Systems biology is an approach to biology that emphasizes the structure and dynamic behavior of biological systems and the interactions that occur within them. To succeed, systems biology crucially depends on the accessibility and integration of data across domains and levels of granularity. Biomedical ontologies were developed to facilitate such an integration of data and are often used to annotate biosimulation models in systems biology., Results: We provide a framework to integrate representations of in silico systems biology with those of in vivo biology as described by biomedical ontologies and demonstrate this framework using the Systems Biology Markup Language. We developed the SBML Harvester software that automatically converts annotated SBML models into OWL and we apply our software to those biosimulation models that are contained in the BioModels Database. We utilize the resulting knowledge base for complex biological queries that can bridge levels of granularity, verify models based on the biological phenomenon they represent and provide a means to establish a basic qualitative layer on which to express the semantics of biosimulation models., Conclusions: We establish an information flow between biomedical ontologies and biosimulation models and we demonstrate that the integration of annotated biosimulation models and biomedical ontologies enables the verification of models as well as expressive queries. Establishing a bi-directional information flow between systems biology and biomedical ontologies has the potential to enable large-scale analyses of biological systems that span levels of granularity from molecules to organisms.

There now exists a rich set of ontologies that provide detailed semantics for biological entities of interest. However, there is not (nor should there be) a single source ontology that provides all the necessary semantics for describing biological phenomena. In the domain of physiological biosimulation models, researchers use annotations to convey semantics, and many of these annotations require the use of multiple reference ontologies. Therefore, we have developed the idea of composite annotations that access multiple ontologies to capture the physics-based meaning of model variables. These composite annotations provide the semantic expressivity needed to disambiguate the often-complex features of biosimulation models, and can be used to assist with model merging and interoperability. In this paper, we demonstrate the utility of composite annotations for model merging by describing their use within SemGen, our semantics-based model composition software. More broadly, if orthogonal reference ontologies are to meet their full potential, users need tools and methods to connect and link these ontologies. Our composite annotations and the SemGen tool provide one mechanism for leveraging multiple reference ontologies., (Copyright © 2010 Elsevier Inc. All rights reserved.)

As biomedical investigators strive to integrate data and analyses across spatiotemporal scales and biomedical domains, they have recognized the benefits of formalizing languages and terminologies via computational ontologies. Although ontologies for biological entities-molecules, cells, organs-are well-established, there are no principled ontologies of physical properties-energies, volumes, flow rates-of those entities. In this paper, we introduce the Ontology of Physics for Biology (OPB), a reference ontology of classical physics designed for annotating biophysical content of growing repositories of biomedical datasets and analytical models. The OPB's semantic framework, traceable to James Clerk Maxwell, encompasses modern theories of system dynamics and thermodynamics, and is implemented as a computational ontology that references available upper ontologies. In this paper we focus on the OPB classes that are designed for annotating physical properties encoded in biomedical datasets and computational models, and we discuss how the OPB framework will facilitate biomedical knowledge integration., (© 2011 Cook et al.)

Melanotic schwannoma is a rare markedly pigmented peripheral nerve sheath tumor comprising cells with prominent melanization and schwannian features. The psammomatous variety is associated with Carney complex, a multiple neoplasia syndrome with spotty skin pigmentation. We present the first 2 reported cases of melanotic schwannoma arising in patients with a history of nevus of Ota, a rare dermal melanosis believed to represent a failure of melanocyte migration to the epidermis during embryogenesis. Case 1 involves a 40-year-old woman with a 1.8-cm, deeply pigmented, trigeminal nerve mass and pigmentation of the maxillary sinus mucosa and bone. Case 2 involves a 53-year-old woman with a 1.5-cm mass adjacent to the clavicle. Microscopically, both masses consist of partially encapsulated epithelioid and spindle cells with abundant melanin pigment, arising in association with peripheral nerves. Morphological, immunohistochemical, and ultrastructural features support a diagnosis of melanotic schwannoma. No psammoma bodies are noted, and neither patient exhibits any additional features of Carney complex. Melanotic schwannoma is most often benign but has been associated with malignant behavior in some cases. Distinguishing this nerve sheath tumor from malignant melanoma can be difficult but is of great clinical importance due to differences in prognosis and treatment.