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1.
Sci Total Environ ; : 174632, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38992362

ABSTRACT

Microgrids are emerging to mitigate the degradation in grid resiliency and reliability resulting from an increasing frequency of grid outages. Because microgrids incorporate a local source of power generation, the production of electricity is shifting from a centralized to distributed topology, thereby installing power generation resources and the concomitant emissions into heavily populated urban air sheds and residential communities. In this paper, the air quality and public health impacts of a mass deployment of microgrids in an urban air shed are assessed. Candidates to become microgrids are identified for both the near- and long-term deployment, and two microgrid scenarios are considered, differing by the 24/7 prime source of power: (1) combustion gas turbine (CGT)-based microgrids and (2) zero-emission FC-based microgrids complemented by solar PV and battery energy storage. Spatially and temporally resolved emissions from the microgrids are input to an air quality model and assessed for health impacts. The results show that (1) a mass deployment of CGT-based or FC-based microgrids in both the near- and long-term has a relatively small impact on air quality, (2) the health impacts are nonetheless significant for CGT-based microgrids due to the large and dense population of the area, and (3) disadvantaged communities are disproportionately impacted with the deployment of CTG-based microgrids. For example, near-term deployment of CGT-based microgrids results in an increase in the incidence of premature mortality (1 to 5 incidences per month) and an increase of $33 to $56 million per month in health costs. Deploying zero-emission FC-based microgrids mitigates the adverse health impact, prevents several incidences of premature mortality, and results in saving of ~$36M per month rather than a cost per month of ~$50M.

2.
Eur Heart J Cardiovasc Imaging ; 25(7): 996-1006, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38445511

ABSTRACT

AIMS: Variation in diagnostic performance of single-photon emission computed tomography (SPECT) myocardial perfusion imaging (MPI) has been observed, yet the impact of cardiac size has not been well characterized. We assessed whether low left ventricular volume influences SPECT MPI's ability to detect obstructive coronary artery disease (CAD) and its interaction with age and sex. METHODS AND RESULTS: A total of 2066 patients without known CAD (67% male, 64.7 ± 11.2 years) across nine institutions underwent SPECT MPI with solid-state scanners followed by coronary angiography as part of the REgistry of Fast Myocardial Perfusion Imaging with NExt Generation SPECT. Area under receiver-operating characteristic curve (AUC) analyses evaluated the performance of quantitative and visual assessments according to cardiac size [end-diastolic volume (EDV); <20th vs. ≥20th population or sex-specific percentiles], age (<75 vs. ≥75 years), and sex. Significantly decreased performance was observed in patients with low EDV compared with those without (AUC: population 0.72 vs. 0.78, P = 0.03; sex-specific 0.72 vs. 0.79, P = 0.01) and elderly patients compared with younger patients (AUC 0.72 vs. 0.78, P = 0.03), whereas males and females demonstrated similar AUC (0.77 vs. 0.76, P = 0.67). The reduction in accuracy attributed to lower volumes was primarily observed in males (sex-specific threshold: EDV 0.69 vs. 0.79, P = 0.01). Accordingly, a significant decrease in AUC, sensitivity, specificity, and negative predictive value for quantitative and visual assessments was noted in patients with at least two characteristics of low EDV, elderly age, or male sex. CONCLUSION: Detection of CAD with SPECT MPI is negatively impacted by small cardiac size, most notably in elderly and male patients.


Subject(s)
Coronary Artery Disease , Myocardial Perfusion Imaging , Registries , Tomography, Emission-Computed, Single-Photon , Humans , Male , Female , Middle Aged , Myocardial Perfusion Imaging/methods , Aged , Tomography, Emission-Computed, Single-Photon/methods , Coronary Artery Disease/diagnostic imaging , Organ Size , Sex Factors , Coronary Angiography/methods , ROC Curve , Age Factors , Sensitivity and Specificity
3.
Nat Aging ; 3(2): 162-172, 2023 02.
Article in English | MEDLINE | ID: mdl-37118113

ABSTRACT

Diminished insulin and insulin-like growth factor-1 signaling extends the lifespan of invertebrates1-4; however, whether it is a feasible longevity target in mammals is less clear5-12. Clinically utilized therapeutics that target this pathway, such as small-molecule inhibitors of phosphoinositide 3-kinase p110α (PI3Ki), provide a translatable approach to studying the impact of these pathways on aging. Here, we provide evidence that dietary supplementation with the PI3Ki alpelisib from middle age extends the median and maximal lifespan of mice, an effect that was more pronounced in females. While long-term PI3Ki treatment was well tolerated and led to greater strength and balance, negative impacts on common human aging markers, including reductions in bone mass and mild hyperglycemia, were also evident. These results suggest that while pharmacological suppression of insulin receptor (IR)/insulin-like growth factor receptor (IGFR) targets could represent a promising approach to delaying some aspects of aging, caution should be taken in translation to humans.


Subject(s)
Longevity , Phosphatidylinositol 3-Kinases , Mice , Animals , Male , Humans , Female , Aging , Phosphoinositide-3 Kinase Inhibitors/pharmacology , Mammals/metabolism , Dietary Supplements
4.
Am J Physiol Endocrinol Metab ; 323(6): E467-E479, 2022 12 01.
Article in English | MEDLINE | ID: mdl-36459047

ABSTRACT

Preptin is a 34-amino acid peptide derived from the E-peptide of pro-insulin-like growth factor 2 and is co-secreted with insulin from ß-cells. Little is understood about the effects of endogenous preptin on whole body glucose metabolism. We developed a novel mouse model in which the preptin portion of Igf2 was genetically ablated in all tissues, hereafter referred to as preptin knockout (KO), and tested the hypothesis that the removal of preptin will lead to a decreased insulin response to a metabolic challenge. Preptin KO and wild-type (WT) mice underwent weekly fasting blood glucose measurements, intraperitoneal insulin tolerance tests (ITT) at 9, 29, and 44 wk of age, and an oral glucose tolerance test (GTT) at 45 wk of age. Preptin KO mice of both sexes had similar Igf2 exon 2-3 mRNA expression in the liver and kidney compared with WT mice, but Igf2 exon 3-4 (preptin) expression was not detectable. Western blot analysis of neonatal serum indicated that processing of pro-IGF2 translated from the KO allele may be altered. Preptin KO mice had similar body weight, body composition, ß-cell area, and fasted glucose concentrations compared with WT mice in both sexes up to 47 wk of age. Female KO mice had a diminished ability to mount an insulin response following glucose stimulation in vivo. This effect was absent in male KO mice. Although preptin is not essential for glucose homeostasis, when combined with previous in vitro and ex vivo findings, these data show that preptin positively impacts ß-cell function.NEW & NOTEWORTHY This is the first study to describe a model in which the preptin-coding portion of the Igf2 gene has been genetically ablated in mice. The mice do not show reduced size at birth associated with Igf2 knockout suggesting that IGF2 functionality is maintained, yet we demonstrate a change in the processing of mature Igf2. Female knockout mice have diminished glucose-stimulated insulin secretion, whereas the insulin response in males is not different to wild type.


Subject(s)
Insulin , Peptide Fragments , Female , Male , Mice , Animals , Mice, Knockout , Glucose/pharmacology
5.
eNeuro ; 9(3)2022.
Article in English | MEDLINE | ID: mdl-35667848

ABSTRACT

As Huntington's disease (HD) progresses, there is a significant loss of neurons in the striatum in addition to a distinct thinning of the cerebral cortex. Despite an early presence of sensorimotor deficits in patients with HD, electrophysiological studies designed to assess the integrity of thalamocortical circuits are sparse. Using the R6/2 mouse model of HD, we provide evidence of reduced connectivity between thalamic cells and their targeted cortical regions. Whole-cell patch clamp recordings from ventral anterolateral nucleus (VAL; motor) and ventral posteromedial nucleus (VPM; somatosensory) thalamic neurons in ex vivo brain slices of R6/2 and wild-type (WT) mice revealed that cells in both thalamic nuclei of R6/2 mice exhibited significant differences in passive and active cell membrane properties (smaller cell membrane capacitances, faster decay time constants and increased input resistances) compared with WT cells. Although only cells in the VPM of symptomatic R6/2 mice had more depolarized resting membrane potentials compared with WTs, cells in both nuclei displayed increased excitability in symptomatic, but not presymptomatic, R6/2 mice. Optical activation of VAL and VPM terminals elicited smaller magnitude current responses in cortical pyramidal neurons (CPNs) in both motor cortex (M1CTX) and somatosensory barrel cortex (BCTX) of symptomatic R6/2 mice compared with CPNs in WT mice. Furthermore, we observed a decrease in the frequency of thalamocortical excitatory quantal events in R6/2 BCTX CPNs, with no genotype-dependent differences in AMPA:NMDA response amplitude ratios. These data suggest there is a decrease in the transmission of thalamocortical information that is likely because of impaired neurotransmitter release.


Subject(s)
Huntington Disease , Motor Cortex , Animals , Corpus Striatum , Disease Models, Animal , Humans , Huntington Disease/genetics , Mice , Mice, Transgenic , Patch-Clamp Techniques
6.
Phys Rev Lett ; 128(2): 020801, 2022 Jan 14.
Article in English | MEDLINE | ID: mdl-35089751

ABSTRACT

A global network of optical atomic clocks will enable unprecedented measurement precision in fields including tests of fundamental physics, dark matter searches, geodesy, and navigation. Free-space laser links through the turbulent atmosphere are needed to fully exploit this global network, by enabling comparisons to airborne and spaceborne clocks. We demonstrate frequency transfer over a 2.4 km atmospheric link with turbulence comparable to that of a ground-to-space link, achieving a fractional frequency stability of 6.1×10^{-21} in 300 s of integration time. We also show that clock comparison between ground and low Earth orbit will be limited by the stability of the clocks themselves after only a few seconds of integration. This significantly advances the technologies needed to realize a global timescale network of optical atomic clocks.

7.
BJS Open ; 5(1)2021 01 08.
Article in English | MEDLINE | ID: mdl-33609388

ABSTRACT

BACKGROUND: The surgical treatment of patients with complex ventral hernias is challenging. The aim of this study was to present an international overview of expert opinions on current practice. METHODS: A survey questionnaire was designed to investigate preoperative risk management, surgical approach and mesh choice in patients undergoing complex hernias repair, and treatment strategies for infected meshes. Geographical location of practice, experience and annual volumes of the surgeons were compared. RESULTS: Of 408 surgeons, 234 (57.4 per cent) were practising in the USA, 116 (28.4 per cent) in Europe, and 58 (14.2 per cent) in other countries. Some 412 of 418 surgeons (98.6 per cent) performed open repair and 322 of 416 (77.4 per cent) performed laparoscopic repair. Most recommended preoperative work-up/lifestyle changes such as smoking cessation (319 of 398, 80.2 per cent) and weight loss (254 of 399, 63.7 per cent), but the consequences of these strategies varied. American surgeons and less experienced surgeons were stricter. Antibiotics were given at least 1 h before surgery by 295 of 414 respondents (71.3 per cent). Synthetic and biological meshes were used equally in contaminated primary hernia repair, whereas for recurrent hernia repair synthetic mesh was used in a clean environment and biological or no mesh in a contaminated environment. American surgeons and surgeons with less experience preferred biological mesh in contaminated environments significantly more often. Percutaneous drainage and antibiotics were the first steps recommended in treating mesh infection. In the presence of sepsis, most surgeons favoured synthetic mesh explantation and further repair with biological mesh. CONCLUSION: There remains a paucity of good-quality evidence in dealing with these hernias, leading to variations in management. Patient optimization and issues related to mesh choice and infections require well designed prospective studies.


Subject(s)
Attitude of Health Personnel , Hernia, Ventral/surgery , Herniorrhaphy/methods , Practice Patterns, Physicians'/statistics & numerical data , Surgical Mesh , Adult , Aged , Female , Health Care Surveys , Herniorrhaphy/instrumentation , Humans , Internationality , Male , Middle Aged
8.
J Public Health (Oxf) ; 43(1): 172-177, 2021 04 12.
Article in English | MEDLINE | ID: mdl-31365091

ABSTRACT

BACKGROUND: The population of older people in residential homes is projected to rise. There are unrecognized hearing difficulties among residents and prevalence of hearing loss in this population is underreported. This can result in an overestimation of levels of cognitive impairment. Untreated hearing loss is associated with social isolation, depression, disruptive behaviour and cognitive decline. This study aimed to explore the provision of hearing care (hearing assessment, rehabilitation and staff training) in Scottish care homes for older people. METHODS: A survey comprising 18 questions was distributed to the managers (or designated staff members) of 659 care homes across Scotland. RESULTS: Responses were obtained from 154 care homes. The results support existing evidence that hearing is not assessed in the majority of homes, resulting in under detection of hearing loss. Staff lack training in supporting residents' hearing needs. Access to hearing care in residential homes differs across health board areas. CONCLUSIONS: There is an urgent requirement for hearing assessment of older adults on admission to residential care. Care providers require this information to construct effective care plans and mitigate the effects of hearing loss. Those responsible for providing hearing rehabilitation services require information about service users to address any unmet need.


Subject(s)
Homes for the Aged , Nursing Homes , Aged , Delivery of Health Care , Hearing , Humans , Scotland/epidemiology
9.
Calcif Tissue Int ; 106(2): 208-217, 2020 02.
Article in English | MEDLINE | ID: mdl-31673746

ABSTRACT

Bone is a dynamic tissue that site-specifically adapts to the load that it experiences. In response to increasing load, the cortical bone area is increased, mainly through enhanced periosteal bone formation. This increase in area is associated with an increase in the number of bone-forming osteoblasts; however, the origin of the cells involved remains unclear. Alpha-smooth muscle actin (αSMA) is a marker of early osteoprogenitor cells in the periosteum, and we hypothesized that the new osteoblasts that are activated by loading could originate from αSMA-expressing cells. Therefore, we used an in vivo fate-mapping approach in an established axial loading model to investigate the role of αSMA-expressing cells in the load-induced increase in osteoblasts. Histomorphometric analysis was applied to measure the number of cells of different origin on the periosteal surface in the most load-responsive region of the mouse tibia. A single loading session failed to increase the number of periosteal αSMA-expressing cells and osteoblasts. However, in response to multiple episodes of loading, the caudal, but not the cranial, periosteal surface was lined with an increased number of osteoblasts originating from αSMA-expressing cells 5 days after the initial loading session. The proportion of osteoblasts derived from αSMA-labeled progenitors increased by 70% (p < 0.05), and the proportion of αSMA-labeled cells that had differentiated into osteoblasts was doubled. We conclude that αSMA-expressing osteoprogenitors can differentiate and contribute to the increase in periosteal osteoblasts induced by mechanical loading in a site-specific manner.


Subject(s)
Actins/metabolism , Cell Differentiation , Osteoblasts/physiology , Stem Cells/physiology , Weight-Bearing/physiology , Animals , Cell Proliferation , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Osteoblasts/cytology , Osteoblasts/metabolism , Osteogenesis/physiology , Periosteum/cytology , Stem Cells/metabolism , Stress, Mechanical , Tibia
10.
Curr Oncol ; 26(4): 253-265, 2019 08.
Article in English | MEDLINE | ID: mdl-31548805

ABSTRACT

Diffuse large B cell lymphoma (dlbcl) is an aggressive non-Hodgkin lymphoma, accounting for approximately 30% of lymphoma cases in Canada. Although most patients will achieve a cure, up to 40% will experience refractory disease after initial treatment, or relapse after a period of remission. In eligible patients, salvage therapy followed by high-dose therapy and autologous stem-cell transplantation (asct) is the standard of care. However, many patients are transplant-ineligible, and more than half of those undergoing asct will subsequently relapse. For those patients, outcomes are dismal, and novel treatment approaches are a critical unmet need. In this paper, we present available data about emerging treatment approaches in the latter setting and provide a perspective about the potential use of those approaches in Canada.


Subject(s)
Antineoplastic Agents/therapeutic use , Lymphoma, Large B-Cell, Diffuse/drug therapy , Neoplasm Recurrence, Local/drug therapy , Adenine/analogs & derivatives , Antibodies, Monoclonal/therapeutic use , Brentuximab Vedotin/therapeutic use , Canada , Clinical Trials as Topic , Humans , Immunoconjugates/therapeutic use , Piperidines , Pyrazoles/therapeutic use , Pyrimidines/therapeutic use
11.
Int J Cosmet Sci ; 41(5): 496-508, 2019 Oct.
Article in English | MEDLINE | ID: mdl-31381160

ABSTRACT

OBJECTIVE: Recently, our group reported that extracts prepared from the Australian native plant Terminalia ferdinandiana Exell. are potent inhibitors of the growth malodorous bacteria with similar efficacy to triclosan and through these results, we highlighted a potential biological alternative to the current chemical additives. Other members of the genus Terminalia are also well documented for their antibacterial potential and tannin contents and thus were investigated as potential deodorant additives. METHODS: Solvent extractions prepared from of selected Indian, Australian and South African Terminalia spp. were screened by disc diffusion and liquid dilution assays against C. jeikeium, S. epidermidis, P. acnes and B. linens. The antibacterial activity was quantified by liquid dilution MIC assays. The extracts were screened for toxicity using Atremia franciscana nauplii and HDF cell viability bioassays. High-resolution time-of-flight (TOF) LC-MS and GC-MS headspace fingerprint analysis was used to detect tannin, flavonoid and terpenoid components in the extracts. RESULTS: Bacterial growth inhibition was observed in all Terminalia extracts with the methanolic T. chebula, T. carpenteriae and T. sericea extracts the most promising bacterial growth inhibitors, yielding MIC values as low as 200 µg mL-1 . Toxicity analyses of the extracts were favourable, and we determined that the methanolic T. chebula, T. carpenteriae and T. sericea extracts were all non-toxic. Using previously detected T. ferdinandiana antimicrobials as benchmarks, LC-MS and GC-MS fingerprint analyses revealed similar compounds in the methanolic T. chebula, T. carpenteriae and T. sericea extracts. CONCLUSION: Through these results, we propose that Terminalia spp. extracts may be useful deodorant additives to inhibit the growth of axillary and plantar malodorous bacteria, offering a biological alternative to their chemically synthesized counterparts.


OBJECTIF: notre groupe a récemment signalé que les extraits de la plante native d'Australie Terminalia ferdinandiana Exell sont de puissants inhibiteurs de croissance pour les bactéries responsables de mauvaises odeurs. Leur efficacité est comparable à celle du triclosan. Ces résultats nous ont permis de mettre en avant la possibilité d'une alternative biologique aux additifs chimiques utilisés aujourd'hui. D'autres membres du genre Terminalia, également bien connus pour leur potentiel antibactérien et leur taux de tanin, ont eux aussi été examinés comme additifs potentiels pour les déodorants. MÉTHODES: extractions par solvant préparées à partir de spécimens de Terminalia spp. d'Inde, d'Australie et d'Afrique du Sud, sélectionnés par diffusion (méthode des disques) et par des dosages de dilution liquide, contre C. Jeikeium, S. Epidermidis, P. Acnes et B. Linens. L'activité antibactérienne a été quantifiée à l'aide d'analyses de la CMI en dilution liquide. La toxicité des extraits a été recherchée à l'aide d'Atremia franciscana nauplii et de dosages biologiques de la viabilité cellulaire de fibroblastes dermiques humains (FDH). Pour détecter les composants tanniques, flavonoïdes et terpénoïdes dans les extraits, on a procédé à une analyse d'identification de l'espace de tête par LC-MS et GC-MS à temps de vol (TOF) à haute résolution. RÉSULTATS: On a observé une inhibition de la croissance bactérienne dans tous les extraits de Terminalia avec les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea, les inhibiteurs de croissance bactérienne les plus prometteurs, ayant des valeurs de CMI pouvant être aussi faibles que 200 µg/ml_ 1. Les analyses de toxicité des extraits ont donné des résultats favorables et nous avons pu établir que les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea étaient tous non toxiques. En utilisant les antimicrobiens déjà repérés T. Ferdinandiana comme des points de repère, les analyses d'identification par LC-MS et GC-MS ont révélé la présence de composés similaires dans les extraits méthanoliques de T. Chebula, T. Carpenteriae et T. Sericea. CONCLUSION: D'après ces résultats, nous pensons que les extraits de Terminalia spp. peuvent constituer des additifs utiles pour les déodorants grâce à leur pouvoir d'inhibition de la croissance des bactéries responsables des mauvaises odeurs de pieds et d'aisselles, offrant ainsi une alternative biologique à leurs équivalents d'origine chimiosynthétique.


Subject(s)
Bacteria/metabolism , Deodorants , Odorants , Terminalia/chemistry , Anti-Bacterial Agents/pharmacology , Bacteria/classification , Bacteria/drug effects , Bacteria/growth & development , Humans , Microbial Sensitivity Tests , Tannins/metabolism
12.
Hernia ; 21(6): 963-971, 2017 12.
Article in English | MEDLINE | ID: mdl-28887764

ABSTRACT

PURPOSE: Humanitarianism is by definition a moral of kindness, benevolence and sympathy extended to all human beings. In our view as surgeons working in underserved countries, humanitarianism means performing the best operation in the best possible circumstances with high income country (HIC) results and training in-country surgeons to do the same. Hernia Repair for the Underserved (HRFU), a not for profit organization, is developing a long term public health initiative for hernia surgery in Western Hemisphere countries. We report the progress of HRFUs methods to render humanitarian care. METHODS: In a collaborative effort, Creighton University and the Institute for Latin American Concern developed an outpatient surgery site for hernia surgery in Santiago, Dominican Republic. Based on this experience, we developed a sustainable care model by recruiting American and European Hernia Society expert surgeons, staff members they recommended, building relationships with local and industry partners, and selecting local surgeons to be trained in mesh hernioplasty. HRFU then extended the care model to other Western Hemisphere countries. RESULTS: Between 2004 and 2015, the HRFU elective hernia morbidity and mortality rates for 2052 hernia operations were 0.7 and 0%, respectively. This is consistent with outcomes from HICs and confirms the feasibility of a public health initiative based on the principles of the Preferential Option for the Poor. CONCLUSIONS: HRFU has recorded HIC morbidity and mortality rates for hernia surgery in low and middle income countries and has initiated a new surgical training model for sustainability of effect.


Subject(s)
Altruism , Ambulatory Surgical Procedures , Herniorrhaphy , Dominican Republic , Elective Surgical Procedures , Humans
13.
J Periodontal Res ; 52(6): 1058-1067, 2017 Dec.
Article in English | MEDLINE | ID: mdl-28691752

ABSTRACT

BACKGROUND AND OBJECTIVE: Mineral trioxide aggregate (MTA) is a biomaterial used in endodontic procedures as it exerts beneficial effects on regenerative processes. In this study, we evaluate the effect of MTA on healing of periodontal ligament (PDL) and surrounding tissue, following injury, in a transgenic mouse model and on the differentiation of murine mesenchymal progenitor cells in vitro. MATERIAL AND METHODS: We used an inducible Cre-loxP in vivo fate mapping approach to examine the effects of MTA on the contributions of descendants of cells expressing the αSMA-CreERT2 transgene (SMA9+ ) to the PDL and alveolar bone after experimental injury to the root furcation on the maxillary first molars. Col2.3GFP was used as a marker to identify mature osteoblasts, cementoblasts and PDL fibroblasts. The effects of MTA were examined 2, 17 and 30 days after injury and compared histologically with sealing using an adhesive system. The effects of two dilutions of medium conditioned with MTA on proliferation and differentiation of mesenchymal progenitor cells derived from bone marrow (BMSC) and periodontal ligament (PDLC) in vitro were examined using the PrestoBlue viability assay, alkaline phosphatase and Von Kossa staining. The expression of markers of differentiation was assessed using real-time PCR. RESULTS: Histological analyses showed better repair in teeth restored with MTA, as shown by greater expansion of SMA9+ progenitor cells and Col2.3GFP+ osteoblasts compared with control teeth. We also observed a positive effect on differentiation of SMA9+ progenitors into osteoblasts and cementoblasts in the apical region distant from the site of injury. The in vitro data showed that MTA-conditioned medium reduced cell viability and osteogenic differentiation in both PDLC and BMSC, indicated by reduced von Kossa staining and lower expression of osteocalcin and bone sialoprotein. In addition, cultures grown in the presence of MTA had marked decreases in SMA9+ and Col2.3GFP+ areas as compared with osteogenic medium, confirming reduced osteogenesis. CONCLUSION: MTA promotes regeneration of injured PDL and alveolar bone, reflected as contribution of progenitors (SMA9+ cells) into osteoblasts (Col2.3GFP+ cells). In vitro, MTA-conditioned medium fails to promote osteogenic differentiation of both PDLC and BMSC.


Subject(s)
Aluminum Compounds/pharmacology , Calcium Compounds/pharmacology , Oxides/pharmacology , Periodontium/injuries , Silicates/pharmacology , Wound Healing/drug effects , Alveolar Process/injuries , Animals , Drug Combinations , Gene Expression , Mice , Mice, Transgenic , Periodontal Ligament/injuries , Stem Cells/drug effects
14.
Int J Cosmet Sci ; 39(5): 500-510, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28488331

ABSTRACT

OBJECTIVE: Terminalia ferdinandiana extracts are potent growth inhibitors of many bacterial pathogens. They may also inhibit the growth of malodour-producing bacteria and thus be useful deodorant components, although this is yet to be tested. METHODS: Terminalia ferdinandiana fruit and leaf solvent extracts were investigated by disc diffusion and liquid dilution MIC assays against the most significant bacterial contributors to axillary and plantar malodour formation. Toxicity was determined using the Artemia franciscana nauplii bioassay. Non-targeted HPLC separation of the methanolic leaf extract coupled to high-resolution time-of-flight (TOF) mass spectroscopy was used for the identification and characterization of individual components in the extract. RESULTS: The T. ferdinandiana leaf extracts were the most potent bacterial growth inhibitors. The leaf methanolic extract was particularly potent, with low MIC values against C. jeikeium (233 µg mL-1 ), S. epidermidis (220 µg mL-1 ), P. acnes (625 µg mL-1 ) and B. linens (523 µg mL-1 ). The aqueous and ethyl acetate leaf extracts were also potent growth inhibitors of C. jeikeium and S. epidermidis (MICs < 1000 µg mL-1 ). In comparison, the fruit extracts were substantially less potent antibacterial agents, although still with MIC values indicative of moderate growth inhibitory activity. All T. ferdinandiana leaf extracts were non-toxic in the Artemia franciscana bioassay. Non-biased phytochemical analysis of the methanolic leaf extract revealed the presence of high levels of and high diversity of tannins and high levels of the flavone luteolin. CONCLUSION: The low toxicity of the T. ferdinandiana leaf extracts and their potent growth inhibition of axillary and plantar malodour-producing bacteria indicate their potential as deodorant components.


Subject(s)
Bacteria/drug effects , Deodorants/pharmacology , Odorants , Plant Extracts/pharmacology , Terminalia/chemistry , Anti-Bacterial Agents/pharmacology , Antioxidants/pharmacology , Bacteria/growth & development , Bacteria/metabolism , Chromatography, High Pressure Liquid , Humans , Mass Spectrometry , Microbial Sensitivity Tests
15.
J Dent Res ; 96(3): 323-330, 2017 03.
Article in English | MEDLINE | ID: mdl-27834664

ABSTRACT

The goal of this study was to examine the contribution of perivascular cells to odontoblasts during the development, growth, and repair of dentin using mouse molars as a model. We used an inducible, Cre-loxP in vivo fate-mapping approach to examine the contributions of the descendants of cells expressing the αSMA-CreERT2 transgene to the odontoblast lineage. In vivo lineage-tracing experiments in molars showed the contribution of αSMA-tdTomato+ cells to a small number of newly formed odontoblasts during primary dentinogenesis. Using an experimental pulp exposure model in molars to induce reparative dentinogenesis, we demonstrate the contribution of αSMA-tdTomato+ cells to cells secreting reparative dentin. Our results demonstrate that αSMA-tdTomato+ cells differentiated into Col2.3-GFP+ cells composed of both Dspp+ odontoblasts and Bsp+ osteoblasts. Our findings identify a population of mesenchymal progenitor cells capable of giving rise to a second generation of odontoblasts during reparative dentinogenesis. This population also makes a small contribution to odontoblasts during primary dentinogenesis.


Subject(s)
Actins/metabolism , Dental Pulp/cytology , Dentinogenesis/physiology , Mesenchymal Stem Cells/physiology , Odontoblasts/physiology , Osteoblasts/physiology , Animals , Cell Differentiation , Immunohistochemistry , Mice , Mice, Transgenic , Molar , Transgenes
16.
QJM ; 109(12): 777-783, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27261489

ABSTRACT

BACKGROUND/INTRODUCTION: Acute kidney injury (AKI) is common in acute hospital admission and associated with worse patient outcomes. AIM: To measure incidence, care quality and outcome of AKI in admitted hospital care. DESIGN: Forty-six of 168 acute NHS healthcare trusts in UK caring for 2 million acute hospital admissions per annum collected information on adults identified with AKI stage 3 (3-fold rise in serum creatinine or creatinine >354 µmol/l) through routine biochemical testing over a 5-month period in 2012. METHODS: Information was collected on patient and care characteristics. Primary outcomes were survival and recovery of kidney function at 1 month. RESULTS: A total of 15 647 patients were identified with biochemical AKI stage 3. Case note reviews were available for 7726 patients. In 80%, biochemical AKI stage 3 was confirmed clinically. Among this group, median age was 75 years, median length of stay was 12 days and the overall mortality within 1 month was 38%. Significant factors in a multivariable model predicting survival included age and some causes of AKI. Dipstick urinalysis, medication review, discussion with a nephrologist and acceptance for transfer to a renal unit were also associated with higher survival, but not early review by a senior doctor, acceptance for transfer to critical care or requirement for renal replacement therapy. Eighteen percent of people did not have their kidney function checked 1 month after the episode had resolved. DISCUSSION/CONCLUSIONS: This large study of in-hospital AKI supports the efficacy of biochemical detection of AKI in common usage. AKI mortality remains substantial, length of stay comparable with single-centre studies, and much of the variation is poorly explained (model Cox and Snell R2 = 0.131) from current predictors.


Subject(s)
Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Acute Kidney Injury/therapy , Quality of Health Care , Renal Replacement Therapy , Adolescent , Adult , Aged , Aged, 80 and over , Biomarkers/blood , Cohort Studies , Creatinine/blood , Female , Humans , Incidence , Kidney Function Tests , Length of Stay , Logistic Models , Male , Middle Aged , Multivariate Analysis , National Health Programs , Risk Factors , Time Factors , United Kingdom , Young Adult
17.
Hernia ; 20(2): 177-89, 2016 Apr.
Article in English | MEDLINE | ID: mdl-26936373

ABSTRACT

PURPOSE: Wide variation in care and costs exists regarding the management of abdominal wall hernias, with unproven benefit for many therapies. This work establishes a specialty society-based solution to improve the quality and value of care delivered to hernia patients during routine clinical management on a national scale. METHODS: The Americas Hernia Society Quality Task Force was charged by the Americas Hernia Society leadership to develop an initiative that utilizes the concepts of continuous quality improvement (CQI). A disease-based registry was created to collect information for CQI incorporating real-time outcome reporting, patient reported outcomes, stakeholder engagement, and collaborative learning methods to form a comprehensive quality improvement effort. RESULTS: The Americas Hernia Society Quality Collaborative (AHSQC) was formed with the mission to provide health care professionals real-time information for maximizing value in hernia care. The initial disease areas selected for CQI were incisional and parastomal hernias with ten priorities encompassing the spectrum of care. A prospective registry was created with real-time analytic feedback to surgeons. A data assurance process was implemented to ensure maximal data quality and completeness. Four collaborative meetings per year were established to meet the goals of the AHSQC. As of the fourth quarter 2014, the AHSQC includes nearly 2377 patients at 38 institutions with 82 participating surgeons. CONCLUSIONS: The AHSQC has been established as a quality improvement initiative utilizing concepts of CQI. This ongoing effort will continually refine its scope and goals based on stakeholder input to improve care delivered to hernia patients.


Subject(s)
Delivery of Health Care/standards , Hernia, Ventral/surgery , Quality Improvement/organization & administration , Registries/standards , Humans , Societies, Medical , United States
18.
J Periodontal Res ; 51(3): 304-12, 2016 Jun.
Article in English | MEDLINE | ID: mdl-26215316

ABSTRACT

BACKGROUND AND OBJECTIVE: Cementum and bone are similar mineralized tissues, but cementum accumulates much more slowly than bone, does not have vasculature or innervation and does not undergo remodeling. Despite these differences, there are no well-established markers to distinguish cementoblasts from other mature mineralizing cells such as osteoblasts and odontoblasts. The purpose of this study was to assess differences in gene expression between cementoblasts and osteoblasts using gene profiling of cell populations isolated directly from osteocalcin-green fluorescent protein (OC-GFP) transgenic mice. MATERIAL AND METHODS: OC-GFP reporter mice were used as they show labeling of cementoblasts, osteoblasts and odontoblasts, but not of periodontal ligament fibroblasts, within the periodontium. We sorted cells digested from the molar root surface to isolate OC-GFP(+) cementoblasts. Osteoblasts were isolated from calvarial digests. Microarray analysis was performed, and selected results were confirmed by real-time PCR and immunostaining or in situ hybridization. RESULTS: Microarray analysis identified 95 genes that were expressed at least two-fold higher in cementoblasts than in osteoblasts. Our analysis indicated that the Wnt signaling pathway was differentially regulated, as were genes related to skeletal development. Real-time PCR confirmed that expression of the Wnt inhibitors Wnt inhibitory factor 1 (Wif1) and secreted frizzled-related protein 1 (Sfrp1) was elevated in cementoblasts compared with osteoblasts, and Wif1 expression was localized to the apical root region. In addition, the transcription factor BARX homeobox 1 (Barx1) was expressed at higher levels in cementoblasts, and immunohistochemistry indicated that BARX1 was expressed in apical cementoblasts and cementocytes, but not in osteoblasts or odontoblasts. CONCLUSION: The OC-GFP mouse provides a good model for selectively isolating cementoblasts, and allowed for identification of differentially expressed genes between cementoblasts and osteoblasts.


Subject(s)
Dental Cementum/physiology , Gene Expression Regulation , Osteoblasts/physiology , Wnt Signaling Pathway/genetics , Adaptor Proteins, Signal Transducing , Animals , Calcification, Physiologic , Cell Differentiation/genetics , Dental Cementum/cytology , Dental Cementum/drug effects , Extracellular Matrix Proteins/pharmacology , Fibroblasts/cytology , Homeodomain Proteins/biosynthesis , Homeodomain Proteins/genetics , Intercellular Signaling Peptides and Proteins/pharmacology , Membrane Proteins/pharmacology , Mice , Mice, Transgenic , Odontoblasts/cytology , Osteoblasts/cytology , Osteoblasts/drug effects , Osteocalcin , Periodontal Ligament/cytology , RNA, Messenger/genetics , Tooth Root/cytology , Transcription Factors/biosynthesis , Transcription Factors/genetics , Wnt Signaling Pathway/drug effects
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