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1.
Arthrosc Tech ; 12(2): e297-e300, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36879875

ABSTRACT

There are several techniques used for tendon fixation in distal biceps tendon repair. Intramedullary unicortical button fixation has the advantage of high biomechanical strength, minimal proximal radial bone removal, and low risk of injury to the posterior interosseous nerve. One disadvantage in revision surgery is retained implants in the medullary canal. This article describes a novel technique for revision distal biceps repair initially fixed with intramedullary unicortical buttons, using the original implants.

2.
PeerJ ; 11: e14598, 2023.
Article in English | MEDLINE | ID: mdl-36710873

ABSTRACT

Gut microbiota studies often rely on a single sample taken per individual, representing a snapshot in time. However, we know that gut microbiota composition in many animals exhibits intra-individual variation over the course of days to months. Such temporal variations can be a confounding factor in studies seeking to compare the gut microbiota of different wild populations, or to assess the impact of medical/veterinary interventions. To date, little is known about the variability of the koala (Phascolarctos cinereus) gut microbiota through time. Here, we characterise the gut microbiota from faecal samples collected at eight timepoints over a month for a captive population of South Australian koalas (n individuals = 7), and monthly over 7 months for a wild population of New South Wales koalas (n individuals = 5). Using 16S rRNA gene sequencing, we found that microbial diversity was stable over the course of days to months. Each koala had a distinct faecal microbiota composition which in the captive koalas was stable across days. The wild koalas showed more variation across months, although each individual still maintained a distinct microbial composition. Per koala, an average of 57 (±16) amplicon sequence variants (ASVs) were detected across all time points; these ASVs accounted for an average of 97% (±1.9%) of the faecal microbial community per koala. The koala faecal microbiota exhibits stability over the course of days to months. Such knowledge will be useful for future studies comparing koala populations and developing microbiota interventions for this regionally endangered marsupial.


Subject(s)
Microbiota , Phascolarctidae , Animals , Phascolarctidae/genetics , Individuality , RNA, Ribosomal, 16S/genetics , Australia
3.
J Wrist Surg ; 12(1): 32-39, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36644727

ABSTRACT

Introduction As the popularity of wrist arthroscopy grows, it continues to prove useful in the treatment of ganglion cysts. Previous studies comparing an arthroscopic technique to traditional open excision have demonstrated generally equivalent results regarding complications and cyst recurrence. However, this systematic review compares the two treatment methods not only regarding cyst recurrence but also regarding patient-centered outcomes. Additionally, new studies in the available literature may allow for further analysis. Methods This systematic review identified 23 articles published between 2000 and 2021 that met inclusion criteria. Articles were assessed for quality, and reported cyst recurrence rates, patient satisfaction, patients' preoperative and postoperative pain, and complications associated with either open or arthroscopic excisions were pooled into open excision and arthroscopic excision groups for analysis. Results In total, 23 studies accounted for 1,670 cases. Pooled data for patient-centered outcomes indicated a significantly higher patient satisfaction rate (89.2 vs 85.6%, p < 0.001) and higher reported pain relief (69.5 vs. 66.7%, p = 0.011) associated with arthroscopic excision versus open excision. Recurrence rates were also significantly lower for the arthroscopic excision group (9.4 vs. 11.2%, p < 0.001). Overall, the complication rate was significantly lower for arthroscopic excision (7.5 vs. 10.7%, p < 0.001), but the complication profile distinctly differed between the two methods. Conclusions Both arthroscopic and open excision of dorsal wrist ganglions are viable treatment options. However, the results of this meta-analysis suggest benefits associated with the arthroscopic technique in both patient-centered outcomes and in traditional, surgical outcomes. This may prove advantageous as wrist arthroscopy becomes more common.

4.
J Hand Surg Am ; 48(7): 736.e1-736.e7, 2023 07.
Article in English | MEDLINE | ID: mdl-35256227

ABSTRACT

PURPOSE: Several improvised dynamic external fixation devices are used for treating unstable dorsal proximal interphalangeal (PIP) joint fracture-dislocations. We compared the effectiveness of 3 constructs for simulated dorsal PIP joint fracture-dislocations in a cadaver model. METHODS: We tested 30 digits from 10 fresh-frozen, thawed cadaver hands. We aimed to remove the palmar 50% of the base of each digit's middle phalanx (P2), simulating an unstable dorsal PIP joint fracture-dislocation. Each PIP joint was then stabilized via external fixation with either a pins-and-rubber-bands construct, pins-only construct, or tuberculin syringe-pins construct. We allocated 10 digits per fixation group. The finger tendons were secured to a computer-controlled stepper motor-driven linear actuator. Via this mechanism, all PIP joints were taken through 1,400 cycles of flexion-extension. With the PIP joint in neutral extension, we measured the P2 dorsal translation at baseline, after fixator stabilization, and after the motion protocol. RESULTS: The actual mean P2 palmar defect created was 48% of the base. All PIP joints were unstable after creating the defect, with a mean initial P2 dorsal displacement of 3.7 mm. After application of the fixators, all PIP joint dislocations were reduced. The median residual P2 dorsal displacements were 0.0 mm for the pins-rubber bands group, 0.1 mm for the pins-only group, and 0.5 mm for the syringe-pins group. There were no cases of PIP joint redislocation after flexion-extension cycling, and the median dorsal P2 displacements were 0.0 mm for the pins-rubber bands group; 0.0 mm for the pins-only group; and 0.5 mm for the syringe-pins group. CONCLUSIONS: All 3 external fixators restored PIP joint stability following simulated dorsal fracture-dislocation, with all reductions maintained after motion testing. The syringe-pins construct had significantly greater median residual P2 dorsal displacement after the initial reduction and motion testing, which is of unclear clinical importance. CLINICAL RELEVANCE: This study informs surgeon decision-making when considering dynamic external fixator options for dorsal PIP joint fracture-dislocations.


Subject(s)
Finger Injuries , Fracture Dislocation , Fractures, Bone , Joint Dislocations , Humans , External Fixators , Fracture Fixation/methods , Finger Joint/surgery , Fracture Dislocation/surgery , Fractures, Bone/surgery , Joint Dislocations/surgery , Cadaver , Finger Injuries/surgery , Range of Motion, Articular
5.
Lancet Planet Health ; 6(9): e769-e773, 2022 09.
Article in English | MEDLINE | ID: mdl-36087607

ABSTRACT

COVID-19 has devastated global communities and economies. The pandemic has exposed socioeconomic disparities and weaknesses in health systems worldwide. Long-term health effects and economic recovery are major concerns. Ecosystem restoration-ie, the repair of ecosystems that have been degraded-relates directly to tackling the health and socioeconomic burdens of COVID-19, because stable and resilient ecosystems are fundamental determinants of health and socioeconomic stability. Here, we use COVID-19 as a case study, showing how ecosystem restoration can reduce the risk of infection and adverse sequelae and have an integral role in humanity's recovery from COVID-19. The next decade will be crucial for humanity's recovery from COVID-19 and for ecosystem repair. Indeed, in the absence of effective, large-scale restoration, 95% of the Earth's land could be degraded by 2050. The UN Decade on Ecosystem Restoration (2021-30) declaration reflects the growing urgency and scale at which we should repair ecosystems. Importantly, ecosystem restoration could also help to combat the health and socioeconomic issues that are associated with COVID-19, yet it is poorly integrated into current responses to the disease. Ecosystem restoration can be a core public health intervention and assist in COVID-19 recovery if it is closely integrated with socioeconomic, health, and environmental policies.


Subject(s)
COVID-19 , Ecosystem , Conservation of Natural Resources , Environmental Policy , Humans
6.
Plast Reconstr Surg ; 148(6): 1301-1305, 2021 Dec 01.
Article in English | MEDLINE | ID: mdl-34644265

ABSTRACT

BACKGROUND: Osteotomy-site nonunion after distal radius corrective osteotomy is a detrimental complication. This retrospective study aims to identify patient and surgical factors associated with nonunion risk to help mitigate this. The authors hypothesize that patient factors and potentially modifiable surgical factors are contributory. METHODS: Thirty-three patients who underwent corrective osteotomy of the distal radius for prior fracture malunion were identified. Radiographs and patient records were reviewed for demographics, comorbidities, nutritional status, plate position, angle and length of osteotomy correction, and graft used. The primary study outcome was osteotomy nonunion. Descriptive and bivariate statistics were used to identify covariates relevant to nonunion. Backward, stepwise logistic regression was applied to investigate the multivariate effects on outcome, and regression analysis was adjusted for confounders. RESULTS: Seven patients (21 percent) experienced nonunion after initial corrective osteotomy. Risk factors associated with nonunion included correction length of osteotomy of 5 mm or greater and prior treatment with open reduction and internal fixation. Autograft use was protective against nonunion. History of osteoporosis showed a trend toward increased risk. Angle of osteotomy correction, nutritional deficit, age, diabetes, smoking status, and obesity were not identified as risk factors by the multivariate model. CONCLUSIONS: Distraction length at the osteotomy site, graft selection, and prior internal fixation were significant risk factors for distal radius osteotomy nonunion, but other factors traditionally associated with nonunion did not appear to impact risk. The authors recommend using autograft bone augmentation, particularly when distracting the osteotomy beyond 5 mm or after prior internal fixation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.


Subject(s)
Fracture Fixation/adverse effects , Fractures, Malunited/surgery , Osteotomy/adverse effects , Postoperative Complications/epidemiology , Radius/pathology , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Postoperative Complications/etiology , Postoperative Complications/pathology , Radius/injuries , Radius/surgery , Radius Fractures/complications , Radius Fractures/surgery , Retrospective Studies , Risk Factors
7.
Curr Opin Otolaryngol Head Neck Surg ; 29(2): 100-106, 2021 Apr 01.
Article in English | MEDLINE | ID: mdl-33664195

ABSTRACT

PURPOSE OF REVIEW: To provide a summary of the current evidence, with a focus on recent publications, pertaining to indications for postoperative radiation therapy for cutaneous squamous-cell carcinoma (cSCC), basal-cell carcinoma, Merkel-cell carcinoma and melanoma of the head and neck. RECENT FINDINGS: Meta-analyses in cSCC and Merkel-cell carcinoma have shown an association between postoperative radiation therapy and overall survival. Prospective phase III data in head and neck cSCC has shown excellent locoregional control following surgery and postoperative radiation therapy. The addition of concurrent cytotoxic chemotherapy to postoperative radiation therapy has not improved outcomes in either of these two entities. Postoperative immune checkpoint inhibition or combined BRAF and MEK blockade in stage-III melanoma improves progression-free survival whereas postoperative radiation therapy does not. SUMMARY: Further improvement in outcomes with high-risk cSCC and Merkel-cell carcinoma might be achieved with concurrent or sequential immune checkpoint inhibition and postoperative radiation therapy. Postoperative radiation therapy for cutaneous melanoma should be reserved for patients in whom novel systemic therapies are not a treatment option.


Subject(s)
Carcinoma, Squamous Cell , Head and Neck Neoplasms , Melanoma , Skin Neoplasms , Carcinoma, Squamous Cell/radiotherapy , Carcinoma, Squamous Cell/surgery , Head and Neck Neoplasms/radiotherapy , Head and Neck Neoplasms/surgery , Humans , Melanoma/therapy , Prospective Studies , Skin Neoplasms/therapy
8.
Head Neck ; 43(5): 1440-1450, 2021 05.
Article in English | MEDLINE | ID: mdl-33427358

ABSTRACT

BACKGROUND: Smoking status at point of diagnosis is not used in defining risk groups for human papillomavirus (HPV)-associated oropharyngeal cancer (OPC) despite its prognostic value in head and neck cancer. METHODS: Retrospective analysis of consecutive patients treated with chemoradiotherapy between January 2005 and July 2017 was performed with multivariable analysis to explore the impact of smoking status at diagnosis (current/former/never) on overall survival (OS), cancer-specific survival (CSS) and progression-free survival (PFS). RESULTS: Median follow-up was 61 months. Four hundred and four patients were included. Current smokers had inferior OS versus never and former smokers [adjusted HR 2.37 (95% CI 1.26-4.45, p < 0.01) and 2.58 (95% CI 1.40-4.73, p < 0.01), respectively] and inferior PFS versus never smokers [adjusted HR 1.83 (95% CI 1.00-3.35, p = 0.04)]. Smoking status did not predict for CSS. CONCLUSION: Detailed smoking behavior should be considered in refining risk groups in HPV-associated OPC treated with radiotherapy and in future trial design eligibility and stratification.


Subject(s)
Alphapapillomavirus , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Oropharyngeal Neoplasms/diagnosis , Oropharyngeal Neoplasms/therapy , Papillomaviridae , Papillomavirus Infections/complications , Papillomavirus Infections/diagnosis , Papillomavirus Infections/epidemiology , Retrospective Studies , Smoking/adverse effects
9.
Stem Cell Res Ther ; 12(1): 6, 2021 01 06.
Article in English | MEDLINE | ID: mdl-33407850

ABSTRACT

BACKGROUND: Multipotent progenitor cells have been harvested from different human tissues, including the bone marrow, adipose tissue, and umbilical cord blood. Previously, we identified a population of mesenchymal progenitor cells (MPCs) isolated from the traumatized muscle of patients undergoing reconstructive surgery following a war-related blast injury. These cells demonstrated the ability to differentiate into multiple mesenchymal lineages. While distal radius fractures from a civilian setting have a much lower injury mechanism (low-energy trauma), we hypothesized that debrided traumatized muscle near the fracture site would contain multipotent progenitor cells with the ability to differentiate and regenerate the injured tissue. METHODS: The traumatized muscle was debrided from the pronator quadratus in patients undergoing open reduction and internal fixation for a distal radius fracture at the Walter Reed National Military Medical Center. Using a previously described protocol for the isolation of MPCs from war-related extremity injuries, cells were harvested from the low-energy traumatized muscle samples and expanded in culture. Isolated cells were characterized by flow cytometry and q-RT-PCRs and induced to adipogenic, osteogenic, and chondrogenic differentiation. Downstream analyses consisted of lineage-specific staining and q-RT-PCR. RESULTS: Cells isolated from low-energy traumatized muscle samples were CD73+, CD90+, and CD105+ that are the characteristic of adult human mesenchymal stem cells. These cells expressed high levels of the stem cell markers OCT4 and NANOG 1-day after isolation, which was dramatically reduced over-time in monolayer culture. Following induction, lineage-specific markers were demonstrated by each specific staining and confirmed by gene expression analysis, demonstrating the ability of these cells to differentiate into adipogenic, osteogenic, and chondrogenic lineages. CONCLUSIONS: Adult multipotent progenitor cells are an essential component for the success of regenerative medicine efforts. While MPCs have been isolated and characterized from severely traumatized muscle from high-energy injuries, here, we report that cells with similar characteristics and multipotential capacity have been isolated from the tissue that was exposed to low-energy, community trauma.


Subject(s)
Mesenchymal Stem Cells , Multipotent Stem Cells , Adult , Cell Differentiation , Cells, Cultured , Chondrogenesis , Humans , Stem Cells
10.
Radiother Oncol ; 151: 242-248, 2020 10.
Article in English | MEDLINE | ID: mdl-32798595

ABSTRACT

BACKGROUND AND PURPOSE: Human papillomavirus-associated oropharyngeal cancer (HPV+ OPC) with regional lymph node metastases has a good prognosis following (chemo)radiation therapy (C/RT) but lymph nodes may remain detectable for several months. Delayed [18F]-Fluorodeoxyglucose positron emission tomography/computed tomography (PET) can identify patients who may avoid post-treatment neck dissection (PTND). We investigated the rate of PTND in HPV+ OPC treated with C/RT and delayed PET-directed management of the neck. MATERIALS AND METHODS: This is a retrospective cohort study from a prospectively updated institutional database. Eligible patients were treated between January 2005 and July 2017 with a minimum of 18 months follow up, had node-positive, non-distant metastatic HPV+ OPC and were treated with RT (70 Gy/35#/5 per week) with concurrent Cisplatin or Cetuximab, or accelerated RT alone (68 Gy/34#/6 per week). The primary endpoint was rate of PTND. Secondary endpoints were locoregional failure free survival (LRFFS), regional failure free survival (RFFS), distant metastatic failure free survival (DMFFS), overall survival (OS) and oropharyngeal cancer-specific survival (CSS). RESULTS: 418 patients were eligible. Nineteen patients (4.5%) received a PTND. None of the tested variables were associated with an increased risk of PTND. Five-year probabilities for LRFFS, RFFS, DMFS, OS and CSS were, 91.2% (95% CI 88.3-94.2), 93.4% (95% CI 90.8-96.0), 91.2% (95% CI 88.3-94.2), 86.4% (95% CI 83.0-90.1) and 90.2% (95% CI 87.1-93.4), respectively. CONCLUSION: In a large cohort with good median follow up and protocolized C/RT, delayed PET-directed management of the neck affords a lower rate of PTND than reported in historical series without compromising disease control and survival.


Subject(s)
Alphapapillomavirus , Oropharyngeal Neoplasms , Papillomavirus Infections , Humans , Neck Dissection , Oropharyngeal Neoplasms/therapy , Papillomaviridae , Papillomavirus Infections/complications , Retrospective Studies
11.
Int J Radiat Oncol Biol Phys ; 107(4): 641-651, 2020 07 15.
Article in English | MEDLINE | ID: mdl-32289475

ABSTRACT

Radiation therapy (RT) consensus contouring guidelines in the postoperative setting for complex cutaneous squamous cell carcinoma of the head and neck have been developed by expert clinicians in the field of head and neck and dermato-oncology and members of the Head and Neck Cancer International Group to assist radiation oncologists involved in the management of this disease. These guidelines present a set of principles used to define postoperative RT volumes and corresponding minimum doses after resection of all macroscopic tumor with or without microscopic residual disease. It is anticipated they will promote the harmonization of postoperative RT globally and contribute to a reduction in treatment variation among clinicians, allowing for RT quality and outcomes assessment across institutions.


Subject(s)
Consensus , Practice Guidelines as Topic , Societies, Medical , Squamous Cell Carcinoma of Head and Neck/radiotherapy , Humans , Postoperative Period , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Squamous Cell Carcinoma of Head and Neck/surgery
12.
Biochem Cell Biol ; 98(4): 492-501, 2020 08.
Article in English | MEDLINE | ID: mdl-31967865

ABSTRACT

Exogenous ubiquitin (UB) plays a protective role in ß-adrenergic receptor-stimulated and ischemia/reperfusion (I/R)-induced myocardial remodeling. Here, we report that UB treatment inhibits hypoxia/reoxygenation (H/R)-induced apoptosis in adult rat ventricular myocytes (ARVMs). The activation of Akt was elevated, whereas the activation of glycogen synthase kinase-3ß was reduced in UB-treated cells post-H/R. The level of oxidative stress was lower, whereas the number of ARVMs with polarized mitochondria was significantly greater in the UB-treated samples. ARVMs express CXCR4 with majority of CXCR4 localized in the membrane fraction. CXCR4 antagonism using AMD3100, and siRNA-mediated knockdown of CXCR4 negated the protective effects of UB. Two mutated UB proteins (unable to bind CXCR4) had no effect on H/R-induced apoptosis, activation of Akt and GSK-3ß, or oxidative stress. UB treatment enhanced mitochondrial biogenesis, and inhibition of mitochondrial fission using mdivi1 inhibited H/R-induced apoptosis. Ex vivo, UB treatment significantly decreased infarct size and improved functional recovery of the heart following global I/R. Activation of caspase-9, a key player of the mitochondrial death pathway, was significantly lower in UB-treated hearts post-I/R. UB, most likely acting via CXCR4, plays a protective role in H/R-induced myocyte apoptosis and myocardial I/R injury via modulation of mitochondrial homeostasis and the mitochondrial death pathway of apoptosis.


Subject(s)
Cardiovascular Diseases/prevention & control , Mitochondria, Heart/metabolism , Myocytes, Cardiac/metabolism , Receptors, CXCR4/metabolism , Ubiquitin/metabolism , Animals , Apoptosis/physiology , Cardiovascular Diseases/etiology , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Cells, Cultured , Disease Models, Animal , Hypoxia/physiopathology , Male , Mice , Mice, Inbred C57BL , Myocytes, Cardiac/pathology , Oxygen/metabolism , Rats , Rats, Sprague-Dawley
13.
Pract Radiat Oncol ; 10(1): 29-35, 2020.
Article in English | MEDLINE | ID: mdl-31606546

ABSTRACT

PURPOSE: Treatment package time (TPT) prolongation is associated with lower overall survival and locoregional control in mucosal head and neck squamous cell carcinoma (SCC), but there are few reports in cutaneous HNSCC (cHNSCC). We sought to test the effect of TPT in a cohort of patients with cHNSCC. METHODS: This is a single institution retrospective study of node-positive cHNSCC patients involving either the parotid or cervical nodes treated with curative intent surgery with macroscopic tumor clearance followed by standard fractionation postoperative radiation therapy (PORT) from 2001 to 2014. We assessed the effect of TPT and other prognostic variables on overall survival (OS), cHNSCC specific survival (CSS) progression free survival (PFS), and freedom from locoregional failure (FFLRF). RESULTS: In the present study, 152 patients met the inclusion criteria. The 5-year OS, CSS, PFS, and FFLRF were 62% (95% confidence interval [CI], 54-71), 78% (95% CI, 71-87), 54% (95% CI, 46-64), and 76% (95% CI ,68-85), respectively. In a multivariable model, TPT ≥14 weeks was associated with worse outcomes in all endpoints (OS [hazard ratio (HR) 4.93; 95% CI, 2.54-9.56, P < .001], CSS [HR 6.09; 95% CI, 2.33-15.92; P = .001], PFS [HR 4.29; 95% CI, 2.21-8.34; P < .001], and FFLRF [HR 4.63; 95% CI, 1.71-12.51; P = .007]). Immunosuppression and the presence of ≥2 pathologically involved lymph nodes were also significant adverse factors for both OS and FFLRF, although extracapsular extension was also associated with lower FFRLF. Delays to commencing PORT rather than treatment breaks accounted for the majority of cases with prolonged TPT. CONCLUSIONS: Prolongation of TPT to 14 weeks or longer may confer a lower probability of locoregional control and survival in patients with lymph node-positive cHNSCC treated with surgery and PORT. Timely referral and commencement of PORT is necessary to maximize long-term disease outcomes.


Subject(s)
Head and Neck Neoplasms/therapy , Neoplasm Recurrence, Local/epidemiology , Skin Neoplasms/therapy , Squamous Cell Carcinoma of Head and Neck/therapy , Time-to-Treatment , Adult , Aged , Aged, 80 and over , Dermatologic Surgical Procedures , Dose Fractionation, Radiation , Female , Follow-Up Studies , Head and Neck Neoplasms/mortality , Head and Neck Neoplasms/pathology , Humans , Kaplan-Meier Estimate , Lymph Nodes/pathology , Lymph Nodes/radiation effects , Male , Middle Aged , Neoplasm Recurrence, Local/pathology , Neoplasm Recurrence, Local/prevention & control , Progression-Free Survival , Radiotherapy, Adjuvant/methods , Retrospective Studies , Skin/pathology , Skin/radiation effects , Skin Neoplasms/mortality , Skin Neoplasms/pathology , Squamous Cell Carcinoma of Head and Neck/mortality , Squamous Cell Carcinoma of Head and Neck/pathology , Time Factors
14.
Am J Physiol Heart Circ Physiol ; 316(3): H617-H628, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30681370

ABSTRACT

ß-Adrenergic receptor (ß-AR) stimulation increases extracellular levels of ubiquitin (UB) in myocytes, and exogenous UB decreases ß-AR-stimulated myocyte apoptosis and myocardial fibrosis. Here, we hypothesized that exogenous UB modulates the inflammatory response, thereby playing a protective role in cardiac remodeling after ischemia-reperfusion (I/R) injury. C57BL/6 mice infused with vehicle or UB (1 µg·g-1·h-1) were subjected to myocardial I/R injury. Functional and biochemical parameters of the heart were examined 3 days post-I/R. Heart weight-to-body weight ratios were similarly increased in I/R and UB + I/R groups. The area at risk and infarct size were significantly lower in UB + I/R versus I/R groups. Measurement of heart function using echocardiography revealed that I/R decreases percent fractional shortening and percent ejection fraction. However, the decrease in fractional shortening and ejection fraction was significantly lower in the UB + I/R group. The UB + I/R group displayed a significant decrease in inflammatory infiltrates, neutrophils, and macrophages versus the I/R group. Neutrophil activity was significantly lower in the UB + I/R group. Analysis of the concentration of a panel of 23 cytokines/chemokines in the serum using a Bio-Plex assay revealed a significantly lower concentration of IL-12 subunit p40 in the UB + I/R versus I/R group. The concentration of monocyte chemotactic protein-1 was lower, whereas the concentration of macrophage inflammatory protein-1α was significantly higher, in the UB+I/R group versus the sham group. Expression of matrix metalloproteinase (MMP)-2 and activity of MMP-9 were higher in the UB + I/R group versus the I/R group. Levels of ubiquitinated proteins and tissue inhibitor of metalloproteinase 2 expression were increased to a similar extent in both I/R groups. Thus, exogenous UB plays a protective role in myocardial remodeling post-I/R with effects on cardiac function, area at risk/infarct size, the inflammatory response, levels of serum cytokines/chemokines, and MMP expression and activity. NEW & NOTEWORTHY Stimulation of ß-adrenergic receptors increases extracellular levels of ubiquitin (UB) in myocytes, and exogenous UB decreases ß-adrenergic receptor-stimulated myocyte apoptosis and myocardial fibrosis. Here, we provide evidence that exogenous UB decreases the inflammatory response and preserves heart function 3 days after myocardial ischemia-reperfusion injury. Further identification of the molecular events involved in the anti-inflammatory role of exogenous UB may provide therapeutic targets for patients with ischemic heart disease.


Subject(s)
Heart/physiopathology , Inflammation/drug therapy , Myocardial Reperfusion Injury/drug therapy , Myocardial Reperfusion Injury/physiopathology , Ubiquitin/therapeutic use , Animals , Body Weight , Chemokines/metabolism , Cytokines/metabolism , Heart/diagnostic imaging , Inflammation/etiology , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Inbred C57BL , Myocardial Reperfusion Injury/diagnostic imaging , Neutrophil Infiltration/drug effects , Organ Size , Stroke Volume/drug effects , Ventricular Remodeling/drug effects
15.
Life Sci ; 211: 8-16, 2018 Oct 15.
Article in English | MEDLINE | ID: mdl-30195032

ABSTRACT

AIMS: ß-adrenergic receptor (ß-AR) stimulation increases extracellular levels of ubiquitin (UB), and exogenous UB plays an important role in ß-AR-stimulated myocardial remodeling with effects on heart function, fibrosis and myocyte apoptosis. Cardiac fibroblasts are vital for maintaining the normal function of the heart, and in the structural remodeling of the heart in response to injury. Here we hypothesized that extracellular UB modulates cardiac fibroblast phenotype and function via its interaction with CXC chemokine receptor type 4 (CXCR4). MAIN METHODS: Serum starved adult cardiac fibroblasts were used to identify CXCR4 as a receptor for UB. Fluorescent microscopy, co-immunoprecipitation, western blot, proliferation, migration and collagen contraction assays were performed to investigate the role of UB/CXCR4 axis on cell signaling, and modulation of fibroblast phenotype and function. KEY FINDINGS: Using fluorescent microscopy and co-immunoprecipitation assay, we provide evidence that extracellular UB interacts with CXCR4. CXCR4 antagonist, AMD3100, inhibited interaction of UB with CXCR4. UB activated ERK1/2, not Akt. It enhanced VEGF-A expression, while decreasing ß3 integrins expression. Two mutated UB proteins (V70A and F4A; unable to interact with CXCR4) failed to affect the expression of VEGF-A and ß3 integrins. UB treatment inhibited migration of cells into the wound and FBS-stimulated cell proliferation. UB enhanced expression of α-smooth muscle actin (marker of myofibroblast differentiation) and contraction of fibroblast-populated collagen gel pads. Most of the effects of UB were negated by AMD3100. SIGNIFICANCE: The data presented here suggest that UB interacts with CXCR4, and UB/CXCR4 interaction affects intracellular signaling, and modulates fibroblast phenotype and function.


Subject(s)
Fibroblasts/physiology , Myocytes, Cardiac/physiology , Receptors, CXCR4/metabolism , Ubiquitin/pharmacology , Animals , Apoptosis/drug effects , Cell Movement/drug effects , Cell Proliferation/drug effects , Cells, Cultured , Fibroblasts/cytology , Fibroblasts/drug effects , Male , Myocytes, Cardiac/cytology , Myocytes, Cardiac/drug effects , Phenotype , Rats , Rats, Sprague-Dawley , Signal Transduction/drug effects
16.
J Orthop Trauma ; 32(6): 283-287, 2018 06.
Article in English | MEDLINE | ID: mdl-29533305

ABSTRACT

OBJECTIVES: To determine what proportion of residual limbs formed heterotopic ossification (HO) in amputations sustained by US service members, the injury profile of these amputations, and what effect the number of limb amputations sustained has on resource utilization. DESIGN: Retrospective review. SETTING: A tertiary military medical center. PATIENTS: Four-hundred seventy-one consecutive patients with 714 combat-related amputations were treated at our institution between September 2009 and August 2014. Four-hundred thirty-nine amputations had radiographic follow-up beyond 2 months of injury and met the criteria for study inclusion. MAIN OUTCOME MEASURE: Formation and grade of HO. RESULTS: HO was present in 399 of 439 (91%) residual limbs, including 211 of 216 (98%) transfemoral amputations. Dismounted improvised explosive device blast injury resulted in HO development in 346 of 372 (93%) residual limbs compared with 36 of 44 (82%) in mounted improvised explosive device blast injury [P = 0.014; odds ratio (OR) 2.96, 95% confidence interval (CI), 1.25-7.04]. As the number of amputations per patient increased, so too did blood product utilization [including packed red blood cells (P < 0.001), fresh frozen plasma (P < 0.001), and platelets (P < 0.001)]; the number of days on a ventilator (P < 0.001), in the intensive care unit (P < 0.001), and in the hospital (P = 0.007). CONCLUSIONS: HO prevalence in the traumatic amputations of war wounded has increased compared with earlier studies, which is temporally associated with higher rates of increasingly severe injuries due to dismounted blast. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.


Subject(s)
Amputation, Traumatic/complications , Blast Injuries/complications , Ossification, Heterotopic/etiology , Adult , Blast Injuries/diagnosis , Female , Humans , Iraq War, 2003-2011 , Male , Middle Aged , Military Personnel , Odds Ratio , Ossification, Heterotopic/diagnosis , Ossification, Heterotopic/epidemiology , Prevalence , Prognosis , Radiography , Retrospective Studies , United States/epidemiology , Young Adult
17.
Mil Med ; 183(1-2): e162-e166, 2018 01 01.
Article in English | MEDLINE | ID: mdl-29401339

ABSTRACT

INTRODUCTION: Women account for approximately 15% of the active duty US Army, and studies show that women may be at an increased risk of musculoskeletal injury during sport and military training. Nationally, the field of orthopedic surgery comprises 14% women, lagging behind other surgical fields. Demographics for US Military orthopedic surgeons are not readily available. Similarly, demographic data of graduating medical students entering Military Medicine are not reported. We hypothesize that a gender disparity within military orthopedics will be apparent. We will compare the demographic profile of providers to our patients and hypothesize that the two groups are dissimilar. Secondarily, we examine the demographics of military medical students potentially entering orthopedics from the Uniformed Services University of the Health Sciences (USUHS) or the Health Professions Scholarship Program. METHODS: A census was formed of all US Army active duty orthopedic surgeons to include staff surgeons and residents, as well as US Army medical student graduates and orthopedic patients. RESULTS: There are 252 Army orthopedic surgeons and trainees; 26 (10.3%) are women and 226 (89.7%) are men. There were no significant demographic differences between residents and staff. Between 2014 and 2017, the 672 members of the USUHS graduating classes included 246 Army graduates. Of those, 62 (25%) were female. Army Health Professions Scholarship Program graduated 1,072 medical students, with women comprising 300 (28%) of the group. No statistical trends were seen over the 4 yr at USUHS or in Health Professions Scholarship Program. In total, 2,993 orthopedic clinic visits during the study period were by Army service members, 23.6% were women. CONCLUSION: There exists a gender disparity among US Army orthopedic surgeons, similar to that seen in civilian orthopedics. Gender equity is also lacking among medical students who feed into Army graduate medical education programs. The gender profile of our patient population is not reflected by that of providers. Because patients prefer providers of the same gender, this is a limitation to patient satisfaction and access to care for musculoskeletal injuries. Further study is underway to identify perceptions and potential causes of these disparities, including the critical perspective of our patients. In addition to the inherent benefits offered by diversity (e.g., expanding the talent pool and more perspectives for decision-making), ultimately it affords a greater ability to maintain a fit and ready force.


Subject(s)
Military Personnel/statistics & numerical data , Orthopedic Procedures/statistics & numerical data , Sexism/statistics & numerical data , Adult , Career Choice , Education, Medical, Graduate/statistics & numerical data , Female , Humans , Male , Orthopedic Procedures/methods , Orthopedics/education , Orthopedics/statistics & numerical data , Personnel Selection/standards , Personnel Selection/statistics & numerical data , United States
18.
Front Psychol ; 8: 2094, 2017.
Article in English | MEDLINE | ID: mdl-29250016

ABSTRACT

Although the restorative benefits of nature are widely acknowledged, there is a limited understanding of the attributes of natural environments that are fundamental to restorative experiences. Faced with growing human populations and a greater awareness of the wellbeing benefits natural environments provide, park agencies and planners are increasingly challenged with balancing human and ecological outcomes in natural areas. This study examines the physical and experiential qualities of natural environments people referred to when describing their connection to their most valued natural environments in an online questionnaire. Recruited primarily via a public radio program, respondents were asked to identify their favorite places and explain what they loved about those places. Favorite places are considered exemplars of restorative environments and were classified based on an existing park typology. Reasons people liked particular sites were classified into three domains: setting, activity, or benefit. Content analysis was used to identify the attributes most commonly associated with favorite places. These attributes were then related to the four components of restorative environments according to Attention Restoration Theory. In contrast to previous research, we found that "fascination" was the most important component of favorite places. Possible reasons for this contrast, namely, respondents' median age, and the likelihood of a high degree of ecological literacy amongst the study population are discussed. South Australians' favorite environments comprise primarily hilly, wooded nature parks, and botanical gardens, in stark contrast to the vast arid areas that dominate the state. Micro-variables such as birds, plants, wildlife, native species, and biodiversity appear particularly important elements used to explain people's love of these sites. We discuss the implications of these findings and their potential value as an anchor for marketing campaigns seeking to encourage contact with nature, as well as education programs designed to improve people's understanding of important but intangible concepts such as biodiversity. The findings have clear, practical implications for park managers given the modifiable nature of many of the attributes identified as being most important to our respondents, and we believe attention to such elements has the potential to simultaneously enhance people's nature experiences, optimize restorative outcomes, and improve environmental stewardship.

19.
Biochem Biophys Rep ; 7: 130-137, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27957549

ABSTRACT

Sepsis is an exaggerated systemic inflammatory response to persistent bacteria infection with high morbidity and mortality rate clinically. ß-arrestin 2 modulates cell survival and cell death in different systems. However, the effect of ß-arrestin 2 on sepsis-induced cardiac dysfunction is not yet known. Here, we show that ß-arrestin 2 overexpression significantly enhances animal survival following cecal ligation and puncture (CLP)-induced sepsis. Importantly, overexpression of ß-arrestin 2 in mice prevents CLP-induced cardiac dysfunction. Also, ß-arrestin 2 overexpression dramatically attenuates CLP-induced myocardial gp130 and p38 mitogen-activated protein kinase (MAPK) phosphorylation levels following CLP. Therefore, ß-arrestin 2 prevents CLP-induced cardiac dysfunction through gp130 and p38. These results suggest that modulation of ß-arrestin 2 might provide a novel therapeutic approach to prevent cardiac dysfunction in patients with sepsis.

20.
Am J Physiol Heart Circ Physiol ; 311(2): H445-52, 2016 08 01.
Article in English | MEDLINE | ID: mdl-27288435

ABSTRACT

Ataxia telangiectasia-mutated kinase (ATM), a cell cycle checkpoint protein, is activated in response to DNA damage and oxidative stress. We have previously shown that ATM deficiency is associated with increased apoptosis and fibrosis and attenuation of cardiac dysfunction early (1-7 days) following myocardial infarction (MI). Here, we tested the hypothesis that enhanced fibrosis and apoptosis, as observed early post-MI during ATM deficiency, exacerbate cardiac dysfunction and remodeling in ATM-deficient mice late post-MI. MIs were induced in wild-type (WT) and ATM heterozygous knockout (hKO) mice by ligation of the left anterior descending artery. Left ventricular (LV) structural and functional parameters were assessed by echocardiography 14 and 28 days post-MI, whereas biochemical parameters were measured 28 days post-MI. hKO-MI mice exhibited exacerbated LV dysfunction as observed by increased LV end-systolic volume and decreased percent fractional shortening and ejection fraction. Infarct size and thickness were not different between the two genotypes. Myocyte cross-sectional area was greater in hKO-MI group. The hKO-MI group exhibited increased fibrosis in the noninfarct and higher expression of α-smooth muscle actin (myofibroblast marker) in the infarct region. Apoptosis and activation of GSK-3ß (proapoptotic kinase) were significantly lower in the infarct region of hKO-MI group. Matrix metalloproteinase 2 (MMP-2) expression was not different between the two genotypes. However, MMP-9 expression was significantly lower in the noninfarct region of hKO-MI group. Thus ATM deficiency exacerbates cardiac remodeling late post-MI with effects on cardiac function, fibrosis, apoptosis, and myocyte hypertrophy.


Subject(s)
Myocardial Infarction/complications , Myocardium/pathology , Ventricular Dysfunction, Left/genetics , Ventricular Remodeling/genetics , Actins/metabolism , Animals , Apoptosis/genetics , Ataxia Telangiectasia Mutated Proteins/genetics , Blotting, Western , Cell Size , Coronary Vessels/surgery , Echocardiography , Female , Fibrosis , Glycogen Synthase Kinase 3 beta/metabolism , Immunohistochemistry , In Situ Nick-End Labeling , Ligation , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Knockout , Myocardium/metabolism , Myocytes, Cardiac/pathology , Stroke Volume , Ventricular Dysfunction, Left/etiology
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