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1.
Respir Res ; 25(1): 235, 2024 Jun 06.
Article in English | MEDLINE | ID: mdl-38844967

ABSTRACT

BACKGROUND: Abnormal remodeling of distal pulmonary arteries in patients with pulmonary arterial hypertension (PAH) leads to progressively increased pulmonary vascular resistance, followed by right ventricular hypertrophy and failure. Despite considerable advancements in PAH treatment prognosis remains poor. We aim to evaluate the potential for using the cytokine resistin as a genetic and biological marker for disease severity and survival in a large cohort of patients with PAH. METHODS: Biospecimens, clinical, and genetic data for 1121 adults with PAH, including 808 with idiopathic PAH (IPAH) and 313 with scleroderma-associated PAH (SSc-PAH), were obtained from a national repository. Serum resistin levels were measured by ELISA, and associations between resistin levels, clinical variables, and single nucleotide polymorphism genotypes were examined with multivariable regression models. Machine-learning (ML) algorithms were applied to develop and compare risk models for mortality prediction. RESULTS: Resistin levels were significantly higher in all PAH samples and PAH subtype (IPAH and SSc-PAH) samples than in controls (P < .0001) and had significant discriminative abilities (AUCs of 0.84, 0.82, and 0.91, respectively; P < .001). High resistin levels (above 4.54 ng/mL) in PAH patients were associated with older age (P = .001), shorter 6-min walk distance (P = .001), and reduced cardiac performance (cardiac index, P = .016). Interestingly, mutant carriers of either rs3219175 or rs3745367 had higher resistin levels (adjusted P = .0001). High resistin levels in PAH patients were also associated with increased risk of death (hazard ratio: 2.6; 95% CI: 1.27-5.33; P < .0087). Comparisons of ML-derived survival models confirmed satisfactory prognostic value of the random forest model (AUC = 0.70, 95% CI: 0.62-0.79) for PAH. CONCLUSIONS: This work establishes the importance of resistin in the pathobiology of human PAH. In line with its function in rodent models, serum resistin represents a novel biomarker for PAH prognostication and may indicate a new therapeutic avenue. ML-derived survival models highlighted the importance of including resistin levels to improve performance. Future studies are needed to develop multi-marker assays that improve noninvasive risk stratification.


Subject(s)
Resistin , Severity of Illness Index , Humans , Male , Female , Resistin/blood , Middle Aged , Adult , Biomarkers/blood , Predictive Value of Tests , Pulmonary Arterial Hypertension/blood , Pulmonary Arterial Hypertension/diagnosis , Pulmonary Arterial Hypertension/mortality , Aged , Cohort Studies , Polymorphism, Single Nucleotide , Survival Rate/trends , Hypertension, Pulmonary/blood , Hypertension, Pulmonary/diagnosis , Hypertension, Pulmonary/mortality , Hypertension, Pulmonary/genetics
2.
J Arthroplasty ; 39(7): 1811-1819, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38244641

ABSTRACT

BACKGROUND: Patients presenting with periprosthetic osteolysis or fracture between ipsilateral hip and knee arthroplasties are challenging to treat successfully. Long-stem implants, osteopenic bones, and patient comorbidities all represent considerable surgical challenges. Poor results of fracture fixation in this group, coupled with the desire to retain well-performing implants and minimize soft-tissue trauma led to the developmentof the custom cement-over megaprostheses (CCOM). The aims of the study were to evaluate implant survivals, complications, and patient outcomes in those undergoing CCOM within our institution. METHODS: A retrospective analysis of patients undergoing CCOM between 2002 and 2022 was performed. We studied 34 cases, 33 patients, one patient underwent staged bilateral surgery with 26 women and 8 men. INDICATIONS: trauma (16), failure of implants /aseptic loosening (9), or joint pathology. The mean Charlson comorbidity index was 3.5 (range, 0 to 8). All patients were followed up (mean 75 months [range, 9 to 170]) at 6 weeks, 6 months, 1 year, and annually thereafter. The VAS, EuroQol-5D-3L and MSTS scores were collected at 1 year. RESULTS: Implant survival defined by the primary outcome (all-cause revision of the implant at any time point) at 12 months of 97% (32 of 33). In surviving patients, implant survival was 90% (18 of 20) and all 7 survived at 5 and 10 years, respectively. Implant survival including those in the primary outcome group and those free of infection at 12 months was 84.8% (28 of 33) and in surviving patients, implant survival was 70% (14 of 20) and 7 out of 7 at 5 and 10 years, respectively. CONCLUSIONS: The CCOM technique demonstrates good implant survivorships and satisfactory patient-reported outcomes in complex, often frail patients who have compromised bone stock. This series confirms the technique as an established alternative to total femoral replacement in these cases.


Subject(s)
Arthroplasty, Replacement, Hip , Arthroplasty, Replacement, Knee , Bone Cements , Patient Reported Outcome Measures , Prosthesis Design , Prosthesis Failure , Reoperation , Humans , Male , Female , Retrospective Studies , Aged , Reoperation/statistics & numerical data , Middle Aged , Arthroplasty, Replacement, Knee/adverse effects , Arthroplasty, Replacement, Knee/instrumentation , Arthroplasty, Replacement, Hip/instrumentation , Arthroplasty, Replacement, Hip/adverse effects , Aged, 80 and over , Knee Prosthesis/adverse effects , Hip Prosthesis/adverse effects , Adult , Treatment Outcome
3.
Pediatr Emerg Care ; 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38950383

ABSTRACT

OBJECTIVES: The aim of this study was to create and validate a 3-dimensional (3D) ultrasound model with normal and abnormal pediatric hip joint anatomy that is comparable to a pediatric hip joint in appearance and anatomy and replicates sonographic characteristics of a pediatric hip joint. METHODS: A 3D rendering of the bone and soft tissue was created from a computed tomography pelvic scan of a pediatric patient. This rendering was modified to include a unilateral joint effusion. The bone was 3D printed with a photopolymer plastic, whereas the soft tissue was cast with a silicone mixture in a 3D-printed mold. The effusion was simulated by injecting saline into the soft tissue cavity surrounding the bone. The ultrasound model was validated by pediatric point-of-care ultrasonographers at an international pediatric ultrasound conference. RESULTS: A pediatric hip ultrasound model was developed that simulates both normal and abnormal pediatric hip joint anatomy, each with an appropriately sized, measurable joint effusion. Validation by pediatric point-of-care ultrasonographers showed that the key aspects of a normal pediatric hip joint (femoral physis, sloped femoral neck, and adequate soft tissue) with an identifiable and measurable effusion were included in the ultrasound model. CONCLUSIONS: In this study, we successfully created a cost-effective, reusable, and reproducible 3D pediatric hip ultrasound model. The majority of pediatric point-of-care ultrasonographers who evaluated the model agreed that this model is comparable to a pediatric patient for the purpose of teaching ultrasound skills and joint space measurement.

4.
Hum Genet ; 142(9): 1407-1416, 2023 Sep.
Article in English | MEDLINE | ID: mdl-37479894

ABSTRACT

Genomics research related to Indigenous people has been at worst exploitative and at best, retrospectively on a journey to improve effective engagement of Indigenous individuals and communities. Genomics can positively impact all stages of clinical management, and to improve genomic effectiveness researchers aggregate genomic data from diverse global sub-populations, such as shared ancestry groupings, as people within these groupings will have a greater proportion of shared DNA traits. While genomics is already being used worldwide to improve lives, its utility and effectiveness has not been maximized for individuals with Indigenous ancestry. Several large datasets of human genetic variation have been made publicly available, of which the most widely used is the Genome Aggregation Database (gnomAD), but none of these databases currently contain any population-specific data for Indigenous populations. There are many reasons why Indigenous people have been largely left out of genomics research and, because of this, miss out on the benefits offered. It is also clear that if research is to be effective, it needs to be done 'with' and not 'on' Indigenous communities. This systematic review of the literature regarding Indigenous peoples (in high income countries) and genomics aims to review the existing literature and identify areas of strength and weakness in study design and conduct, focusing on the effectiveness of Indigenous community engagement.


Subject(s)
Genomics , Indigenous Peoples , Humans , Developed Countries , Retrospective Studies , Indigenous Peoples/genetics , Databases, Factual
5.
Am J Hum Genet ; 107(2): 175-182, 2020 08 06.
Article in English | MEDLINE | ID: mdl-32763188

ABSTRACT

Expanded carrier screening (ECS) for recessive monogenic diseases requires prior knowledge of genomic variation, including DNA variants that cause disease. The composition of pathogenic variants differs greatly among human populations, but historically, research about monogenic diseases has focused mainly on people with European ancestry. By comparison, less is known about pathogenic DNA variants in people from other parts of the world. Consequently, inclusion of currently underrepresented Indigenous and other minority population groups in genomic research is essential to enable equitable outcomes in ECS and other areas of genomic medicine. Here, we discuss this issue in relation to the implementation of ECS in Australia, which is currently being evaluated as part of the national Government's Genomics Health Futures Mission. We argue that significant effort is required to build an evidence base and genomic reference data so that ECS can bring significant clinical benefit for many Aboriginal and/or Torres Strait Islander Australians. These efforts are essential steps to achieving the Australian Government's objectives and its commitment "to leveraging the benefits of genomics in the health system for all Australians." They require culturally safe, community-led research and community involvement embedded within national health and medical genomics programs to ensure that new knowledge is integrated into medicine and health services in ways that address the specific and articulated cultural and health needs of Indigenous people. Until this occurs, people who do not have European ancestry are at risk of being, in relative terms, further disadvantaged.


Subject(s)
Metagenomics/methods , Population Groups/genetics , Australia , Genetic Variation/genetics , Humans
6.
Int J Equity Health ; 22(1): 129, 2023 07 05.
Article in English | MEDLINE | ID: mdl-37408069

ABSTRACT

OBJECTIVE: To evaluate if existing Australian public policy related to screening, diagnosis, treatment and follow up care for breast cancer addresses the needs of and outcomes for Indigenous1 women? METHODS: This review of policy employed a modified Delphi method via an online panel of experts (n = 13), who were purposively recruited according to experience and expertise. A series of online meetings and online surveys were used for data collection. The aims of the study were to: Identify all existing and current breast cancer policy in Australia;  Analyse the extent to which consideration of Indigenous peoples is included in the development, design and implementation of the policy; and Identify policy gaps and make recommendations as to how they could be addressed. The policies were evaluated using 'A Guide to Evaluation under the Indigenous Evaluation Strategy, 2020'. RESULTS: A list of current breast cancer policies (n = 7) was agreed and analysed. Five draft recommendations to improve breast cancer outcomes for Indigenous women were developed and refined by the panel. CONCLUSIONS: Current breast cancer policy in Australia does not address the needs of Indigenous women and requires change to improve outcomes.


Subject(s)
Breast Neoplasms , Health Services, Indigenous , Humans , Female , Breast Neoplasms/therapy , Australian Aboriginal and Torres Strait Islander Peoples , Australia , Surveys and Questionnaires , Policy
7.
Med J Aust ; 219(8): 386-392, 2023 Oct 16.
Article in English | MEDLINE | ID: mdl-37716709

ABSTRACT

This consensus statement provides new recommendations for primary care assessment of ear health and hearing status of young Aboriginal and Torres Strait Islander children who are not known to have, or are not being actively managed for, ear health and hearing problems. Any child identified with otitis media should be actively managed. This national consensus statement extends existing treatment and management guidelines. MAIN RECOMMENDATIONS: Undertake checks at least 6-monthly, commencing at 6 months until 4 years of age, then at 5 years. Undertake checks more frequently in high risk settings for children under 2 years, when acceptable to families, or in response to parent/carer concerns. Ask parents/carers about concerns, signs, and symptoms; check children's listening and communication skills; and assess middle ear appearance and mobility. Otoacoustic emissions testing is suggested when equipment is available, primary health practitioners have capability and confidence to use the equipment, and there is local preference for its use. Video otoscopy is suggested for health promotion purposes, and/or for sharing images with other health practitioners. Audiometry should be done as per existing guidelines: when there are parent/carer concerns, signs of persistent/recurrent otitis media, or when listening and communication development is not yet on track. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Key practice changes include routine use of tympanometry, and listening and communication skills checklists. Implementation will require access to equipment and training; clear information on immediate, practical actions for families; timely pathways to referral services; and a change management process that shifts perception and tolerance of otitis media and its impacts and raises expectations that Aboriginal and Torres Strait Islander children can have healthy ears and hearing.

8.
BMC Health Serv Res ; 23(1): 672, 2023 Jun 21.
Article in English | MEDLINE | ID: mdl-37344905

ABSTRACT

BACKGROUND: Breast cancer continues to be the second most diagnosed cancer overall and the most diagnosed cancer for women in Australia. While mortality rates overall have declined in recent years, Indigenous women continue to be diagnosed at more marginal rates (0.9 times) and are more likely to die (1.2 times). The literature provides a myriad of reasons for this; however, the voices of Indigenous women are largely absent. This study sets out to understand what is happening from the perspectives of Australian Indigenous women with a view to charting culturally safer pathways that improve participation in screening and treatment by Indigenous women. METHODS: This co-design study was conducted using semi-structured, in-depth interviews and focus group discussions. Recruitment of study participants was via snowball sampling. Participants were subsequently consented into the study through the Aboriginal Health Service and the research team. Interviews were audio recorded and transcribed verbatim, and data coded in NVivo12 using inductive thematic analysis. RESULTS: A total of 21 Indigenous women and 14 health service providers were interviewed predominantly from the same regional/rural area in NSW, with a small proportion from other states in Australia. Six major themes were identified: Access, Awareness, Community and Family, Lack of control, Negative feelings and associations and Role of services. CONCLUSION: To improve access and participation of Indigenous women and ultimately improve mortality rates, breast cancer services must explicitly address cultural and community needs.


Subject(s)
Breast Neoplasms , Health Services, Indigenous , Female , Humans , Australia/epidemiology , Breast Neoplasms/diagnosis , Breast Neoplasms/therapy , Early Detection of Cancer , Australian Aboriginal and Torres Strait Islander Peoples
9.
J Pediatr Orthop ; 43(8): 486-491, 2023 Sep 01.
Article in English | MEDLINE | ID: mdl-37340610

ABSTRACT

BACKGROUND: Magnetically controlled growing rods (MCGRs) have a known issue with fracture of the internal locking pin resulting in early revisions. The manufacturer reported that rods manufactured before March 26, 2015, had a 5% risk of locking pin fracture. Locking pins made after this date are thicker in diameter and of a tougher alloy; their rate of pin fracture is not known. The aim of this study was to better understand the impact of the design changes on the performance of MCGRs. METHODS: This study involves 46 patients with 76 removed MCGRs. Forty-six rods were manufactured before March 26, 2015, and 30 rods after that date. Clinical and implant data were collected for all MCGRs. Retrieval analysis comprised plain radiographs evaluations, force and elongation testing, and disassembly. RESULTS: The 2 patient groups were statistically comparable. We found that 14 of 27 patients implanted with rods manufactured before March 26, 2015 (group I) had a fracture of their locking pins. Three of the 17 patients with rods manufactured after this date (group II) were also found to have a fractured pin. CONCLUSIONS: Retrieved rods collected at our center and made after March 26, 2015, had far fewer locking pin fractures than those made before this date; this may be due to the change in pin design.


Subject(s)
Fractures, Bone , Scoliosis , Humans , Prostheses and Implants , Radiography , Gravitation
10.
Aust J Rural Health ; 31(5): 1017-1026, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37706591

ABSTRACT

OBJECTIVE: To undertake an economic evaluation of community water fluoridation (CWF) in remote communities of the Northern Territory (NT). DESIGN: Dental caries experiences were compared between CWF and non-CWF communities before and after intervention. Costs and benefits of CWF are ascertained from the health sector perspective using water quality, accounting, oral health, dental care and hospitalisation datasets. SETTING AND PARTICIPANTS: Remote Aboriginal population in the NT between 1 January 2008 and 31 December 2020. INTERVENTION: CWF. MAIN OUTCOME MEASURES: Potential economic benefits were estimated by changes in caries scores valued at the NT average dental service costs. RESULTS: Given the total 20-year life span of a fluoridation plant ($1.77 million), the net present benefit of introducing CWF in a typical community of 300-499 population was $3.79 million. For each $1 invested in CWF by government, the estimated long-term economic value of savings to health services ranged from $1.1 (population ≤300) to $16 (population ≥2000) due to reductions in treating dental caries and associated hospitalisations. The payback period ranged from 15 years (population ≤300) to 2.2 years (population ≥2000). CONCLUSIONS: The economic benefits of expanding CWF in remote Aboriginal communities of NT outweigh the costs of installation, operation and maintenance of fluoridation plants over the lifespan of CWF infrastructure for population of 300 or more.


Subject(s)
Dental Caries , Fluoridation , Humans , Cost-Benefit Analysis , Dental Caries/prevention & control , Northern Territory , Indigenous Peoples
12.
J Synchrotron Radiat ; 29(Pt 6): 1480-1494, 2022 Nov 01.
Article in English | MEDLINE | ID: mdl-36345756

ABSTRACT

The highly automated macromolecular crystallography beamline AMX/17-ID-1 is an undulator-based high-intensity (>5 × 1012 photons s-1), micro-focus (7 µm × 5 µm), low-divergence (1 mrad × 0.35 mrad) energy-tunable (5-18 keV) beamline at the NSLS-II, Brookhaven National Laboratory, Upton, NY, USA. It is one of the three life science beamlines constructed by the NIH under the ABBIX project and it shares sector 17-ID with the FMX beamline, the frontier micro-focus macromolecular crystallography beamline. AMX saw first light in March 2016 and started general user operation in February 2017. At AMX, emphasis has been placed on high throughput, high capacity, and automation to enable data collection from the most challenging projects using an intense micro-focus beam. Here, the current state and capabilities of the beamline are reported, and the different macromolecular crystallography experiments that are routinely performed at AMX/17-ID-1 as well as some plans for the near future are presented.


Subject(s)
Synchrotrons , Crystallography, X-Ray , Macromolecular Substances/chemistry
13.
Am J Physiol Lung Cell Mol Physiol ; 321(2): L416-L428, 2021 08 01.
Article in English | MEDLINE | ID: mdl-34189964

ABSTRACT

Pulmonary hypertension (PH) is a devastating disease characterized by progressive elevation of pulmonary vascular resistance, right ventricular failure, and ultimately death. We have shown previously that insulin receptor substrate 2 (IRS2), a molecule highly critical to insulin resistance and metabolism, has an anti-inflammatory role in Th2-skewed lung inflammation and pulmonary vascular remodeling. Here, we investigated the hypothesis that IRS2 has an immunomodulatory role in human and experimental PH. Expression analysis showed that IRS2 was significantly decreased in the pulmonary vasculature of patients with pulmonary arterial hypertension and in rat models of PH. In mice, genetic ablation of IRS2 enhanced the hypoxia-induced signaling pathway of Akt and Forkhead box O1 (FOXO1) in the lung tissue and increased pulmonary vascular muscularization, proliferation, and perivascular macrophage recruitment. Furthermore, mice with homozygous IRS2 gene deletion showed a significant gene dosage-dependent increase in pulmonary vascular remodeling and right ventricular hypertrophy in response to hypoxia. Functional studies with bone marrow-derived macrophages isolated from homozygous IRS2 gene-deleted mice showed that hypoxia exposure led to enhancement of the Akt and ERK signaling pathway followed by increases in the pro-PH macrophage activation markers, vascular endothelial growth factor-A and arginase 1. Our data suggest that IRS2 contributes to anti-inflammatory effects by regulating macrophage activation and recruitment, which may limit the vascular inflammation, remodeling, and right ventricular hypertrophy that are seen in PH pathology. Restoring the IRS2 pathway may be an effective therapeutic approach for the treatment of PH and right heart failure.


Subject(s)
Hypertension, Pulmonary/metabolism , Hypoxia/metabolism , Insulin Receptor Substrate Proteins/metabolism , Vascular Remodeling , Animals , Disease Models, Animal , Female , Forkhead Box Protein O1/genetics , Forkhead Box Protein O1/metabolism , Humans , Hypertension, Pulmonary/genetics , Hypertension, Pulmonary/pathology , Hypoxia/genetics , Hypoxia/pathology , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Insulin Receptor Substrate Proteins/genetics , Male , Mice , Mice, Knockout , Nerve Tissue Proteins/genetics , Nerve Tissue Proteins/metabolism , Proto-Oncogene Proteins c-akt/genetics , Proto-Oncogene Proteins c-akt/metabolism , Rats , Rats, Nude
14.
J Synchrotron Radiat ; 28(Pt 5): 1649-1661, 2021 Sep 01.
Article in English | MEDLINE | ID: mdl-34475312

ABSTRACT

Here we present two robotic sample changers integrated into the experimental stations for the macromolecular crystallography (MX) beamlines AMX and FMX, and the biological small-angle scattering (bioSAXS) beamline LiX. They enable fully automated unattended data collection and remote access to the beamlines. The system designs incorporate high-throughput, versatility, high-capacity, resource sharing and robustness. All systems are centered around a six-axis industrial robotic arm coupled with a force torque sensor and in-house end effectors (grippers). They have the same software architecture and the facility standard EPICS-based BEAST alarm system. The MX system is compatible with SPINE bases and Unipucks. It comprises a liquid nitrogen dewar holding 384 samples (24 Unipucks) and a stay-cold gripper, and utilizes machine vision software to track the sample during operations and to calculate the final mount position on the goniometer. The bioSAXS system has an in-house engineered sample storage unit that can hold up to 360 samples (20 sample holders) which keeps samples at a user-set temperature (277 K to 300 K). The MX systems were deployed in early 2017 and the bioSAXS system in early 2019.


Subject(s)
Crystallography, X-Ray/methods , Macromolecular Substances/chemistry , Robotics/methods , Equipment Design , Scattering, Small Angle , Software , Synchrotrons , X-Rays
15.
J Synchrotron Radiat ; 28(Pt 2): 650-665, 2021 Mar 01.
Article in English | MEDLINE | ID: mdl-33650577

ABSTRACT

Two new macromolecular crystallography (MX) beamlines at the National Synchrotron Light Source II, FMX and AMX, opened for general user operation in February 2017 [Schneider et al. (2013). J. Phys. Conf. Ser. 425, 012003; Fuchs et al. (2014). J. Phys. Conf. Ser. 493, 012021; Fuchs et al. (2016). AIP Conf. Proc. SRI2015, 1741, 030006]. FMX, the micro-focusing Frontier MX beamline in sector 17-ID-2 at NSLS-II, covers a 5-30 keV photon energy range and delivers a flux of 4.0 × 1012 photons s-1 at 1 Šinto a 1 µm × 1.5 µm to 10 µm × 10 µm (V × H) variable focus, expected to reach 5 × 1012 photons s-1 at final storage-ring current. This flux density surpasses most MX beamlines by nearly two orders of magnitude. The high brightness and microbeam capability of FMX are focused on solving difficult crystallographic challenges. The beamline's flexible design supports a wide range of structure determination methods - serial crystallography on micrometre-sized crystals, raster optimization of diffraction from inhomogeneous crystals, high-resolution data collection from large-unit-cell crystals, room-temperature data collection for crystals that are difficult to freeze and for studying conformational dynamics, and fully automated data collection for sample-screening and ligand-binding studies. FMX's high dose rate reduces data collection times for applications like serial crystallography to minutes rather than hours. With associated sample lifetimes as short as a few milliseconds, new rapid sample-delivery methods have been implemented, such as an ultra-high-speed high-precision piezo scanner goniometer [Gao et al. (2018). J. Synchrotron Rad. 25, 1362-1370], new microcrystal-optimized micromesh well sample holders [Guo et al. (2018). IUCrJ, 5, 238-246] and highly viscous media injectors [Weierstall et al. (2014). Nat. Commun. 5, 3309]. The new beamline pushes the frontier of synchrotron crystallography and enables users to determine structures from difficult-to-crystallize targets like membrane proteins, using previously intractable crystals of a few micrometres in size, and to obtain quality structures from irregular larger crystals.


Subject(s)
Synchrotrons , Crystallography , Crystallography, X-Ray , Data Collection , Macromolecular Substances , Viscosity
16.
J Immunol ; 203(11): 2862-2871, 2019 12 01.
Article in English | MEDLINE | ID: mdl-31611261

ABSTRACT

Pulmonary hypertension (PH) is a debilitating disease characterized by remodeling of the lung vasculature. In rodents, resistin-like molecule-α (RELMα, also known as HIMF or FIZZ1) can induce PH, but the signaling mechanisms are still unclear. In this study, we used human lung samples and a hypoxia-induced mouse model of PH. We found that the human homolog of RELMα, human (h) resistin, is upregulated in macrophage-like inflammatory cells from lung tissues of patients with idiopathic PH. Additionally, at PH onset in the mouse model, we observed RELMα-dependent lung accumulation of macrophages that expressed high levels of the key damage-associated molecular pattern (DAMP) molecule high-mobility group box 1 (HMGB1) and its receptor for advanced glycation end products (RAGE). In vitro, RELMα/hresistin-induced macrophage-specific HMGB1/RAGE expression and facilitated HMGB1 nucleus-to-cytoplasm translocation and extracellular secretion. Mechanistically, hresistin promoted HMGB1 posttranslational lysine acetylation by preserving the NAD+-dependent deacetylase sirtuin (Sirt) 1 in human macrophages. Notably, the hresistin-stimulated macrophages promoted apoptosis-resistant proliferation of human pulmonary artery smooth muscle cells in an HMGB1/RAGE-dependent manner. In the mouse model, RELMα also suppressed the Sirt1 signal in pulmonary macrophages in the early posthypoxic period. Notably, recruited macrophages in the lungs of these mice carried the RELMα binding partner Bruton tyrosine kinase (BTK). hResistin also mediated the migration of human macrophages by activating BTK in vitro. Collectively, these data reveal a vascular-immune cellular interaction in the early PH stage and suggest that targeting RELMα/DAMP-driven macrophages may offer a promising strategy to treat PH and other related vascular inflammatory diseases.


Subject(s)
Hypertension, Pulmonary/immunology , Intercellular Signaling Peptides and Proteins/immunology , Macrophages, Alveolar/immunology , Pulmonary Artery/immunology , Vascular Remodeling/immunology , Adolescent , Animals , Cells, Cultured , Humans , Hypertension, Pulmonary/pathology , Intercellular Signaling Peptides and Proteins/deficiency , Macrophages, Alveolar/pathology , Mice , Mice, Inbred C57BL , Mice, Knockout , Pulmonary Artery/pathology
17.
Skeletal Radiol ; 50(2): 425-430, 2021 Feb.
Article in English | MEDLINE | ID: mdl-32856094

ABSTRACT

OBJECTIVE: To examine diagnostic and therapeutic utility of novel ultrasound-guided perineural injection of posterior antebrachial cutaneous nerve in chronic lateral elbow pain. MATERIALS AND METHODS: We performed a retrospective analysis of ultrasound-guided perineural injection of the posterior antebrachial cutaneous nerve with local anesthetic with or without corticosteroid in patients with chronic lateral elbow pain. Data variables collected included patient demographics, illness course, diagnostic ultrasound findings, immediate pre- and post-injection pain using numeric rating pain scale between 0 and 10, injection complications, and post-injection outcomes. RESULTS: Fifteen patients (9 females and 6 males) with average age 46.9 (range 16-69 years) underwent 20 perineural injections between 2009 and 2019. Patients had on average 84% reduction in pain immediately after the injection (median pre- and post-procedure numeric rating pain scale of 6 and 0, respectively, p < 0.001). Patients had pain relief for an average of 15 h (range 2-48 h) when only local anesthetic was injected, compared with average pain relief of 26.5 days (range 2 h-43 days) when local anesthetic was combined with corticosteroid, p = 0.01. CONCLUSION: Novel ultrasound-guided perineural anesthetic injections around the posterior antebrachial cutaneous nerve can be performed safely and have diagnostic and potentially therapeutic utility in select patients with chronic refractory lateral elbow pain.


Subject(s)
Elbow , Forearm , Adolescent , Adult , Aged , Female , Forearm/diagnostic imaging , Humans , Male , Middle Aged , Retrospective Studies , Ultrasonography , Ultrasonography, Interventional , Young Adult
18.
Skeletal Radiol ; 50(6): 1219-1225, 2021 Jun.
Article in English | MEDLINE | ID: mdl-33009582

ABSTRACT

OBJECTIVE: To describe the technique of sonographic ulnar nerve mapping in the postoperative elbow for surgical planning. MATERIALS AND METHODS: A retrospective review of a surgical databank identified 24 patients, all aged 18 years and older with a history of orthopedic elbow surgery, who were referred for preoperative sonographic mapping of the ulnar nerve prior to subsequent surgery. All cases were reviewed for patient demographics, clinical presentation, prior surgical interventions, and ultrasound technique. Charts were reviewed for intraoperative and postoperative outcomes, including nerve injury. RESULTS: The cohort included 12 males and 12 females with a mean age of 51 years (range 22-68 years) and a mean BMI of 29 (range 20-48). Preoperative sonographic ulnar nerve mapping occurred following various elbow surgeries including ulnar nerve transposition to assess nerve location prior to subsequent elbow surgery. Of the 24 patients with preoperative sonographic ulnar nerve mapping, subsequent surgery was performed arthroscopically in 14 and open in 10 cases. In 11 of the 24 cases, there was specific mention of a modified approach to joint access which was guided by the ulnar nerve map. There were no perioperative ulnar nerve-related complications, such as nerve transection. CONCLUSION: Preoperative mapping can facilitate planning of surgical access and ulnar nerve dissection. Sonographic mapping of the ulnar nerve reduces the potential uncertainty of nerve palpation in a complex postoperative elbow following ulnar nerve transposition. This technique may mitigate the risk of ulnar nerve injury.


Subject(s)
Elbow Joint , Orthopedic Procedures , Adult , Aged , Decompression, Surgical , Elbow , Elbow Joint/diagnostic imaging , Elbow Joint/surgery , Female , Humans , Male , Middle Aged , Retrospective Studies , Ulnar Nerve/diagnostic imaging , Ulnar Nerve/surgery , Young Adult
19.
BMC Oral Health ; 21(1): 414, 2021 08 23.
Article in English | MEDLINE | ID: mdl-34425791

ABSTRACT

BACKGROUND: Capitation models of care in dentistry started around 1973 with varying degrees of success in meeting the needs of the individuals and expectations of the participating private practitioners. These studies mostly identified that capitation payments resulted in under treatment whilst fee-for-service models often led to over treatment. The objective of this study was to develop a new way of doing business using an outsourcing capitation model of care to meet population health needs and activity-based funding requirements of rural Local Health Districts with a local university dental school. This payment model is an alternate referral pathway for public oral health practitioners from the existing New South Wales Oral Health Fee-for-Service Scheme that focuses on urgent treatment to one that offers an all-inclusive preventive approach that concentrates on sustaining good long-term oral health for the individual. METHOD: The reflective study analysed various adult age cohorts (18-24, 25-34, 35-44, 45-54, 55-64, 65-74 and 75 + years) based on 950 participants randomly selected from the Greater Southern adult public dental waiting lists. The study's capitation formula was derived from NSW government adult treatment items (n = 447,625). Dental care was provided through the local university's dental clinics utilising only dental students under clinical supervision. All data were sourced from NSW Oral Health Data Warehouse during 1 January 2012-30 June 2018 and analysed by using SAS 9.3 and Version 13 Microsoft Excel. RESULTS: There were 10,305 dental care items and 1129 capitation courses of care totalling A$599,026. This resulted in an average of 11 dental care items being provided to each participant. The capitation payment formula utilising the most provided dental care items of 100 individual patients proved to be economical and preventive focused. CONCLUSION: The systematic reflection showed that this unique methodology in developing an adult capitation payment formula associated to diagnostic pathways that resulted in: (i) more efficient usage of government expenditure on public dental services, (ii) provision of person-centred courses of dental care, and (iii) utilisation of university dental education programs to best practice treatment and holistic care.


Subject(s)
Capitation Fee , Universities , Adolescent , Adult , Australia , Fee-for-Service Plans , Humans , Oral Health , Young Adult
20.
Rural Remote Health ; 21(1): 5789, 2021 01.
Article in English | MEDLINE | ID: mdl-33497576

ABSTRACT

INTRODUCTION: The early closure of the Voluntary Dental Graduate Year Program and the Oral Health Therapy Graduate Year Program by the Australian Government adversely impacted New South Wales (NSW) Aboriginal Community Controlled Health Services (ACCHSs). This led to the co-design of a small-scale oral health therapy graduate year program for ACCHSs known as the Dalang Project, which enabled oral health therapists to engage with local Aboriginal communities and implement culturally competent, practical and evidence-based oral health promotion activities. This article provides an overview of the Dalang Project and its evaluation. METHODS: All graduates of the Dalang Project were invited via email and social media to complete an online survey. The survey included questions about their year in the Dalang Project, why they applied, what they liked and disliked about the project, where they planned to work post-placement, and examples of the most significant changes they observed in the communities where they were placed. Host sites were also surveyed and data were collated on clinical services performed as well as oral health promotion activity. RESULTS: Prior to commencing the Dalang Project only 4 of the 15 respondents came from rural or regional areas. Nine of the 15 respondents were considering working in a regional, rural or remote area prior to applying for the Dalang Project. Twelve respondents were working at the time of the survey and half were working in regional, rural or remote locations in NSW and one in the Northern Territory. All reported that they would be more likely to work in an ACCHS as a result of being a part of the Dalang Project. The majority of respondents said they would recommend the program to future graduates. A total of 63 schools, 21 preschools and 15 community health services received regular dental health education through the Dalang Project. A total of 3250 toothbrushes and fluoride toothpastes were distributed to children and families through the Dalang Project. A key part of the program was the installation of refrigerated and filtered water fountains in schools where there was no free filtered or refrigerated water supply. The inclusion of this component in the program was part of the co-design process and links the program to the wider population health strategies in NSW to help prevent childhood obesity. CONCLUSION: The Dalang Project is an example of a successful co-designed project that has positively impacted oral health service delivery for Aboriginal children and has provided a valuable experience for new graduate oral health therapists working in ACCHSs. Overall, the Dalang Project was found to be a positive professional experience for the oral health therapists with many remaining in rural, remote and regional locations after completing the program.


Subject(s)
Dental Care , Oral Health , Rural Health Services , Child , Health Promotion , Humans , Native Hawaiian or Other Pacific Islander , New South Wales , Northern Territory , Pediatric Obesity
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