Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 37
Filter
1.
J Tissue Viability ; 32(4): 508-515, 2023 Nov.
Article in English | MEDLINE | ID: mdl-37442720

ABSTRACT

Pressure ulcers (PUs) remain a chronic health problem with severe impacts on healthcare systems. Early detection is crucial to providing effective interventions. However, detecting PUs currently relies on subjective tissue evaluations, such as visual skin assessment, precluding interventions prior to the development of visible tissue damage. There is an unmet need for solutions that can detect early tissue damage before visual and tactile signs occur. Assessments based on sub-epidermal moisture (SEM) measurements represent an opportunity for robust and objective early detection of PUs, preventing broken skin PUs in more high-risk patients at high-risk anatomical locations. While SEM assessment technology has been validated in computational, bench and tissue phantom models, validation in soft tissue was absent. In this study, we successfully validated the ability of a commercially available SEM assessment device to measure and detect sub-epidermal moisture changes in a novel ex vivo porcine soft tissue model of localised oedema. When controlled and incremental fluid volumes (Phosphate Buffer Solution) were injected into porcine soft tissues, statistically significant differences were found in SEM values between fluid-injected sites, representing an inflammatory oedematous condition, and healthy tissue control sites, as measured by the SEM device. The device provided reproducible readings by detecting localised oedema changes in soft tissues, reflecting the build-up of fluid as small as 1 ml into the underlying tissue. Spatial characterization experiments described the ability of the device technology to differentiate between healthy and oedematous tissue. Our findings validate the use of SEM assessment technology to measure and quantify localized oedema.


Subject(s)
Pressure Ulcer , Humans , Swine , Animals , Pressure Ulcer/diagnosis , Pressure Ulcer/prevention & control , Epidermis , Skin , Edema/diagnosis , Suppuration
2.
ACS Appl Mater Interfaces ; 14(3): 3653-3661, 2022 Jan 26.
Article in English | MEDLINE | ID: mdl-34964593

ABSTRACT

All nanoparticles have the potential to revolutionize the delivery of therapeutic cargo such as peptides, proteins, and RNA. However, effective cytosolic delivery of cargo from nanoparticles represents a significant challenge in the design of more efficient drug delivery vehicles. Recently, research has centered on designing nanoparticles with the capacity to escape endosomes by responding to biological stimuli such as changes in pH, which occur when nanoparticles are internalized into the endo-/lysosomal pathway. Current endosomal escape assays rely on indirect measurements and yield little quantitative information, which hinders the design of more efficient drug delivery vehicles. Therefore, we adapted the highly sensitive split luciferase endosomal escape quantification (SLEEQ) assay to better understand nanoparticle-induced endosomal escape. We applied SLEEQ to evaluate the endosomal escape behavior of two pH-responsive nanoparticles: the first with a poly(2-diisopropylamino ethyl methacrylate) (PDPAEMA) core and the second with 1:1 ratio of poly(2-diethylamino ethyl methacrylate) (PDEAEMA) and PDPAEMA. SLEEQ directly measured the cytosolic delivery and showed that engineering the nanoparticle disassembly pH could improve the endosomal escape efficiency by fivefold. SLEEQ is a versatile assay that can be used for a wide range of nanomaterials and will improve the development of drug delivery vehicles in the future.


Subject(s)
Biocompatible Materials/metabolism , Endosomes/metabolism , Luciferases/metabolism , Nanoparticles/metabolism , Biocompatible Materials/chemistry , Endosomes/chemistry , Hydrogen-Ion Concentration , Luciferases/chemistry , Materials Testing , Nanoparticles/chemistry
4.
Br J Dermatol ; 184(4): 617-626, 2021 04.
Article in English | MEDLINE | ID: mdl-32510579

ABSTRACT

In order to overcome inconsistencies in the reporting of outcomes in clinical trials, core outcome sets (COSs) have been developed in many clinical areas and the awareness of this concept is growing steadily. The Outcomes for Pressure Ulcer Trials (OUTPUTs) project aims to improve the quality of evidence from pressure ulcer prevention trials by developing a COS. As an initial step in the COS process we aimed to identify and classify both outcomes and concepts that represent potential outcomes for future trials that have been reported in pressure ulcer prevention research. A review was conducted in 12 major databases covering the literature indexed until 2016. Outcomes and relevant concepts reported in primary studies and/or reviews on pressure ulcer prevention in adult patients were extracted as presented in the articles, and afterwards inductively grouped into outcome domains. The domains were then categorized according to the outcome domain taxonomy recently proposed by the COMET group. In total 332 studies were included and 68 outcome domains were identified, covering multiple aspects of pressure ulcer prevention. Pressure ulcer occurrence was reported in 71% of all included studies, representing the most frequent outcome, followed by costs (22% of all studies) and acceptability of intervention and comfort (18% of all studies). A plethora of different outcomes are applied in pressure ulcer prevention research and substantial variations in definitions and reporting of similar outcomes were observed. A COS for pressure ulcer prevention trials is needed to overcome the noncomparability of outcomes.


Subject(s)
Pressure Ulcer , Databases, Factual , Humans , Pressure Ulcer/prevention & control , Publications , Skin Care
5.
ACS Appl Mater Interfaces ; 12(5): 5593-5600, 2020 Feb 05.
Article in English | MEDLINE | ID: mdl-31917547

ABSTRACT

Nanoparticles targeted to specific cells have the potential to improve the delivery of therapeutics. The effectiveness of cell targeting can be significantly improved by optimizing how the targeting ligands are displayed on the nanoparticle surface. Crucial to optimizing the cell binding are the orientation, density, and flexibility of the targeting ligand on the nanoparticle surface. In this paper, we used an anti-EGFR single-domain antibody (sdAb or nanobody) to target fluorescent nanocrystals (Qdots) to epidermal growth factor receptor (EGFR)-positive cells. The sdAbs were expressed with a synthetic amino acid (azPhe), enabling site-specific conjugation to Qdots in an improved orientation. To optimize the targeting efficiency, we engineered the point of attachment (orientation), controlled the density of targeting groups on the surface of the Qdot, and optimized the length of the poly(ethylene glycol) linker used to couple the sdAb to the Qdot surface. By optimizing orientation, density, and flexibility, we improved cell targeting by more than an order of magnitude. This work highlights the importance of understanding the structure of the nanoparticle surface to achieve the optimal interactions with the intended receptors and how engineering the nanoparticle surface can significantly improve cell targeting.


Subject(s)
ErbB Receptors/immunology , Quantum Dots/chemistry , Single-Domain Antibodies/chemistry , A549 Cells , Endosomes/metabolism , ErbB Receptors/metabolism , Humans , Kinetics , Lysosomes/metabolism , Microscopy, Fluorescence , Polyethylene Glycols/chemistry , Recombinant Proteins/biosynthesis , Recombinant Proteins/chemistry , Recombinant Proteins/isolation & purification , Single-Domain Antibodies/genetics , Single-Domain Antibodies/metabolism
6.
Nano Lett ; 19(3): 1827-1831, 2019 03 13.
Article in English | MEDLINE | ID: mdl-30773887

ABSTRACT

Protein-conjugated nanoparticles have the potential to precisely deliver therapeutics to target sites in the body by specifically binding to cell surface receptors. To maximize targeting efficiency, the three-dimensional presentation of ligands toward these receptors is crucial. Herein, we demonstrate significantly enhanced targeting of nanoparticles to cancer cells by controlling the protein orientation on the nanoparticle surface. To engineer the point of attachment, we used amber codon reassignment to incorporate a synthetic amino acid, p-azidophenylalanine (azPhe), at specific locations within a single domain antibody (sdAb or nanobody) that recognizes the human epidermal growth factor receptor (EGFR). The azPhe modified sdAb can be tethered to the nanoparticle in a specific orientation using a bioorthogonal click reaction with a strained cyclooctyne. The crystal structure of the sdAb bound to EGFR was used to rationally select sites likely to optimally display the sdAb upon conjugation to a fluorescent nanocrystal (Qdot). Qdots with sdAb attached at the azPhe13 position showed 6 times greater binding affinity to EGFR expressing A549 cells, compared to Qdots with conventionally (succinimidyl ester) conjugated sdAb. As ligand-targeted delivery systems move toward clinical application, this work shows that nanoparticle targeting can be optimized by engineering the site of protein conjugation.


Subject(s)
Immunoconjugates/chemistry , Nanoparticles/chemistry , Single-Domain Antibodies/chemistry , A549 Cells , Azides/chemistry , Click Chemistry , Crystallography, X-Ray , Cyclooctanes/chemistry , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/chemistry , ErbB Receptors/immunology , Humans , Immunoconjugates/immunology , Ligands , Phenylalanine/analogs & derivatives , Phenylalanine/chemistry , Protein Binding , Receptors, Cell Surface/chemistry , Receptors, Cell Surface/immunology , Single-Domain Antibodies/immunology
7.
Angew Chem Int Ed Engl ; 57(51): 16678-16682, 2018 12 17.
Article in English | MEDLINE | ID: mdl-30383920

ABSTRACT

The properties and structures of viruses are directly related to the three-dimensional structure of their capsid proteins, which arises from a combination of hydrophobic and supramolecular interactions, such as hydrogen bonds. The design of synthetic materials demonstrating similar synergistic interactions still remains a challenge. Herein, we report the synthesis of a polymer/cyclic peptide conjugate that combines the capability to form supramolecular nanotubes via hydrogen bonds with the properties of an amphiphilic block copolymer. The analysis of aqueous solutions by scattering and imaging techniques revealed a barrel-shaped alignment of single peptide nanotubes into a large tubisome (length: 260 nm (from SANS)) with a hydrophobic core (diameter: 16 nm) and a hydrophilic shell. These systems, which have a structure that is similar to those of viruses, were tested in vitro to elucidate their activity on cells. Remarkably, the rigid tubisomes are able to perforate the lysosomal membrane in cells and release a small molecule into the cytosol.


Subject(s)
Nanotubes/chemistry , Peptides, Cyclic/chemistry , Polymers/chemistry , Cell Line, Tumor , Cell Survival , HEK293 Cells , Humans , Hydrogen Bonding , Hydrophobic and Hydrophilic Interactions , Lysosomes/chemistry , Macromolecular Substances/chemical synthesis , Macromolecular Substances/chemistry
8.
Int Emerg Nurs ; 37: 52-60, 2018 03.
Article in English | MEDLINE | ID: mdl-29429847

ABSTRACT

BACKGROUND: Nursing assessment of elderly patients is imperative in Emergency Departments (ED) while providing interventions that increase independence facilitating discharge to primary healthcare. AIMS: To systematically review the impact of geriatric focused nurse assessment and intervention in the ED on hospital utilisation in terms of admission rate, ED revisits and length of hospital stay (LOHS). METHODS: Search strategy used following databases; Cochrane, Medline, CINAHL, Embase, Scopus and Web of Knowledge; And terms; geriatric nurse assessment, nurse discharge planning, geriatric nurse specialist, nurse intervention, emergency department, accident and emergency, patient outcomes, discharge, admissions, readmissions, hospital utilization, hospitalization, length of stay/hospital stay. RESULTS: Nine studies were included: seven RCTs and two prospective pre/post-intervention designed studies. Geriatric focused nursing assessment and interventions did not have a statistical impact on hospitalization, readmissions, LOHS and ED revisits. Risk screening and comprehensive geriatric assessment extending into primary care may reduce readmission rates but not affect hospitalization. An increase in ED visits in the intervention group at 30 days post-intervention was noted. CONCLUSION: Inconsistencies in assessment and interventions for the older person in ED are apparent. Further research evaluating a standardised risk assessment tool and innovative interventions extending into primary healthcare is required.


Subject(s)
Geriatric Assessment/methods , Nursing Assessment/standards , Aged , Aged, 80 and over , Emergency Nursing/methods , Emergency Nursing/standards , Emergency Service, Hospital/organization & administration , Female , Humans , Length of Stay , Male , Nursing Assessment/methods , Workforce
9.
J Wound Care ; 26(11): 632-640, 2017 11 02.
Article in English | MEDLINE | ID: mdl-29131756

ABSTRACT

OBJECTIVE: Diabetic foot ulcers (DFUs) are a significant challenge in wound care practice. Our aim was to evaluate the combined use of of two therapies, ultrasound and electrostimulation, in the treatment of DFUs. METHOD: This study employed a prospective, non-comparative, case series design, undertaken in a podiatry-led diabetic foot clinic, in an acute hospital setting, in an urban location in Ireland. We recruited patinets with hard-to-heal DFUs who were treated twice a week with combined modulated ultrasound and electric current stimulation. RESULTS: We recruited seven patients with eight chronic DFUs. A mean wound size reduction of 71% was achieved and there were no adverse reactions to the therapy. CONCLUSION: The results of this small case series indicate that combined modulated ultrasound and electric current stimulation offers promise as an adjunct therapy for DFUs. Further large scale trials are now warranted.


Subject(s)
Diabetic Foot/therapy , Electric Stimulation Therapy , Pressure Ulcer/therapy , Ultrasonic Therapy , Varicose Ulcer/therapy , Adult , Aged , Aged, 80 and over , Combined Modality Therapy , Female , Humans , Ireland , Male , Middle Aged , Prospective Studies , Wound Healing
10.
Nat Commun ; 8(1): 474, 2017 09 07.
Article in English | MEDLINE | ID: mdl-28883394

ABSTRACT

When proteostasis becomes unbalanced, unfolded proteins can accumulate and aggregate. Here we report that the dye, tetraphenylethene maleimide (TPE-MI) can be used to measure cellular unfolded protein load. TPE-MI fluorescence is activated upon labelling free cysteine thiols, normally buried in the core of globular proteins that are exposed upon unfolding. Crucially TPE-MI does not become fluorescent when conjugated to soluble glutathione. We find that TPE-MI fluorescence is enhanced upon reaction with cellular proteomes under conditions promoting accumulation of unfolded proteins. TPE-MI reactivity can be used to track which proteins expose more cysteine residues under stress through proteomic analysis. We show that TPE-MI can report imbalances in proteostasis in induced pluripotent stem cell models of Huntington disease, as well as cells transfected with mutant Huntington exon 1 before the formation of visible aggregates. TPE-MI also detects protein damage following dihydroartemisinin treatment of the malaria parasites Plasmodium falciparum. TPE-MI therefore holds promise as a tool to probe proteostasis mechanisms in disease.Proteostasis is maintained through a number of molecular mechanisms, some of which function to protect the folded state of proteins. Here the authors demonstrate the use of TPE-MI in a fluorigenic dye assay for the quantitation of unfolded proteins that can be used to assess proteostasis on a cellular or proteome scale.


Subject(s)
Cells/metabolism , Molecular Probes/chemistry , Protein Folding , Proteostasis , Sulfhydryl Compounds/metabolism , Animals , Artemisinins/pharmacology , Cysteine/chemistry , Fluorescent Dyes/chemistry , HEK293 Cells , HeLa Cells , Humans , Huntingtin Protein/metabolism , Malaria/parasitology , Maleimides/chemistry , Mice , Mutant Proteins/metabolism , Oligopeptides/pharmacology , Parasites/drug effects , Parasites/metabolism , Protein Folding/drug effects , Proteome/metabolism , Proteostasis/drug effects , Solubility , Tunicamycin/pharmacology
11.
J Wound Care ; 26(Sup9): S27-S34, 2017 Sep 01.
Article in English | MEDLINE | ID: mdl-28880754

ABSTRACT

OBJECTIVE: There is a rising incidence of diabetes worldwide; however there seems to be a higher incidence and prevalence rates in the Arab world when compared with the global average. 1 Out of the top 10 countries with the highest prevalence rates, six are Arab countries and almost 20.5 million people in that part of the world live with diabetes. Despite this, published scientific research from the 22 Arab countries is limited and seems to be of lower quality when compared with the rest of the developed world. 2 Therefore, our aim was to explore the contribution of the different Arab countries in the world literature, to identify the diabetic foot ulcer (DFU) prevalence and incidence rates and to quality appraise these studies. METHOD: A systematic review, following PRISMA guidelines, was undertaken to identify the incidence and prevalence of DFUs in the Arab world. The following databases were searched: PubMed, Embase CINAHL, Web of Science (Scopus), Global Health and EBSCO Results: A total of nine papers were identified. The mean prevalence of DFU in Saudi Arabia was 11.85% (4.7-19%), in Egypt was 4.2% (1-7.4%), in Jordan was 4.65% (4-5.3%), in Bahrain was 5.9% and in Iraq was 2.7%. A single study identified DFU incidence in Saudi Arabia as 1.8% between 2009-2010. CONCLUSION: The mean prevalence rates of DFU were highest in Saudi Arabia and Bahrain and lowest in Iraq. Saudi Arabia had the only reported incidence study, thus findings could not be compared to other countries of the Arab world. There were no studies identified during our search reporting prevalence rates of DFU in 17 of the 22 Arab countries. It is clear that further research is required to determine the incidence and prevalance of DFUs in the Arab world and that progress is needed in order to improve the quality of research conducted in those countries.


Subject(s)
Diabetic Foot/epidemiology , Bahrain/epidemiology , Egypt/epidemiology , Humans , Incidence , Iraq/epidemiology , Jordan/epidemiology , Prevalence , Saudi Arabia/epidemiology
12.
Clin Interv Aging ; 12: 985-993, 2017.
Article in English | MEDLINE | ID: mdl-28721026

ABSTRACT

BACKGROUND: Globally the older population is increasing rapidly. As a result there is an increase in frail older persons living within the community, with increased risks of a hospital admission and higher mortality and morbidity rates. Due to complexity of care, health care professionals face challenges in providing effective case management and avoiding unplanned admissions to hospital. A community virtual ward (CVW) model was developed to assist health care professionals to support older persons at home during periods of illness and/or functional decline. METHODS: A quantitative observational study was conducted to examine if a CVW model of care reduced unplanned hospital admissions and emergency department (ED) presentations in 54 patients over a 12-month period. The sign-rank test examined matched data on bed days, ED presentations, and unplanned hospital admissions pre- and post-CVW implementation. Other risk factors for admission to hospital were examined using the Mann-Whitney test pre-and post-CVW admission, including falls, living alone, and cognition. Correlations between hospital admission avoidances and unplanned hospital admissions and ED presentations were tested using Spearman's ρ test. RESULTS: There was a reduction in ED presentations post-CVW admission (P<0.001), and median unscheduled admissions were reduced (P=0.001). Those living alone had a lower number of ED presentations (median 0.5, interquartile range 0-1) prior to admission in comparison to those living with a caregiver, with no differences observed during admission to CVW. For those who experienced a fall during CVW admission, the odds ratio (OR) of requiring long-term care doubled for each extra fall (OR =2.24, 95% CI 1.11 to 4.52, P=0.025). Reduced cognition was associated with an increased risk of ED presentations (ρ=0.292, P<0.05) but not associated with increased risks of unplanned hospital admissions (ρ=0.09, P=0.546). There were no significant correlations seen between admission avoidance and the number of unplanned hospital admissions or ED presentations. CONCLUSION: Through an integrated approach to care, a CVW model in the care of older persons can reduce ED presentations and unplanned hospital admissions.


Subject(s)
Case Management/organization & administration , Emergency Service, Hospital/statistics & numerical data , Independent Living , Telemedicine/organization & administration , Accidental Falls/statistics & numerical data , Aged , Aged, 80 and over , Cognition , Female , Frail Elderly , Humans , Male , Odds Ratio , Risk Factors
13.
J Wound Care ; 26(7): 381-397, 2017 Jul 02.
Article in English | MEDLINE | ID: mdl-28704150

ABSTRACT

OBJECTIVE: To assess the potential of measurements of pH, exudate composition and temperature in wounds to predict healing outcomes and to identify the methods that are employed to measure them. METHOD: A systematic review based on the outcomes of a search strategy of quantitative primary research published in the English language was conducted. Inclusion criteria limited studies to those involving in vivo and human participants with an existing or intentionally provoked wound, defined as 'a break in the epithelial integrity of the skin', and excluded in vitro and animal studies. Data synthesis and analysis was performed using structured narrative summaries of each included study arranged by concept, pH, exudate composition and temperature. The Evidence Based Literature (EBL) Critical Appraisal Checklist was implemented to appraise the quality of the included studies. RESULTS: A total of 23 studies, three for pH (mean quality score 54.48%), 12 for exudate composition (mean quality score 46.54%) and eight for temperature (mean quality score 36.66%), were assessed as eligible for inclusion in this review. Findings suggest that reduced pH levels in wounds, from alkaline towards acidic, are associated with improvements in wound condition. Metalloproteinase-9 (MMP-9), matrix metalloproteinase-2 (MMP-2), tissue inhibitor of metalloproteinase (TIMP), neutrophil elastase (NE) and albumin, in descending order, were the most frequently measured analytes in wounds. MMP-9 emerged as the analyte which offers the most potential as a biomarker of wound healing, with elevated levels observed in acute or non-healing wounds and decreasing levels in wounds progressing in healing. Combined measures of different exudate components, such as MMP/TIMP ratios, also appeared to offer substantial potential to indicate wound healing. Finally, temperature measurements are highest in non-healing, worsening or acute wounds and decrease as wounds progress towards healing. Methods used to measure pH, exudate composition and temperature varied greatly and, despite noting some similarities, the studies often yielded significantly contrasting results. Furthermore, a limitation to the generalisability of the findings was the overall quality scores of the research studies, which appeared suboptimal. CONCLUSION: Despite some promising findings, there was insufficient evidence to confidently recommend the use of any of these measures as predictors of wound healing. pH measurement appeared as the most practical method for use in clinical practice to indicate wound healing outcomes. Further research is required to increase the strength of evidence and develop a greater understanding of wound healing dynamics.


Subject(s)
Biomarkers/metabolism , Exudates and Transudates/metabolism , Skin Temperature , Wound Healing , Wounds and Injuries , Albumins/metabolism , Exudates and Transudates/chemistry , Humans , Hydrogen-Ion Concentration , Leukocyte Elastase/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Temperature , Tissue Inhibitor of Metalloproteinases/metabolism
14.
J Wound Care ; 26(6): 324-339, 2017 06 02.
Article in English | MEDLINE | ID: mdl-28598756

ABSTRACT

OBJECTIVE: To assess the impact of the multidisciplinary team in the management of the diabetic foot compared with those who did not receive multidisciplinary care. METHOD: A systematic review of the literature was conducted using the following databases: Cumulative Index to Nursing and Allied Health Literature (CINAHL), Medline, Embase and Cochrane Library. The following search terms were used: diabetic foot, multidisciplinary team, patient care team, multidisciplinary care team. Data were extracted using a bespoke data extraction tool and quality appraisal of the studies was undertaken using the EBL Critical Appraisal checklist. Data analysis was undertaken using RevMan with results presented as odds ratio for dichotomous data, or mean difference for continuous data, all with the associated 95% confidence intervals. RESULTS: The search identified 19 eligible studies. Severity of amputation, death rates and length of hospital stay of clients receiving multidisciplinary team care were improved when compared with those who did not receive multidisciplinary team care. Ulcer healing and quality of life showed an improvement but not all studies explored these outcomes. Only 7 of the 19 articles appraised were found to be of acceptable quality, questioning the generalisability of the results. CONCLUSION: From the currently available evidence a positive impact of the multidisciplinary team on diabetic foot outcomes can be seen, but due to the lack of high-quality evidence and substantial heterogeneity in the studies, these results should be interpreted with caution.


Subject(s)
Diabetic Foot/therapy , Patient Care Team , Disease Management , Humans
15.
J Wound Care ; 26(5): 199-215, 2017 May 02.
Article in English | MEDLINE | ID: mdl-28475447

ABSTRACT

OBJECTIVE: Our aims were to: establish the clinical significance of ultrasound, thermography, photography and subepidermal moisture (SEM) measurement; determine the accuracy of ultrasound, thermography, photography and SEM measurement in detecting skin/tissue damage; determine the relative accuracy of one of these assessment methods over another; make recommendations for practice pertaining to assessment of early skin/tissue damage. METHOD: The following databases, Cochrane Wounds Group Specialised Register, The Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid EMBASE, Elsevier version, EBSCO CINAHL, ClinicalTrials.gov , WHO International Clinical Trials Registry (ICTR) and The EU Clinical Trials Register were searched for terms including; thermography, ultrasound, subepidermal moisture, photograph and pressure ulcer. RESULTS: We identified four SEM, one thermography and five ultrasound studies for inclusion in this review. Data analysis indicated that photography was not a method which allowed for the early prediction of PU presence. SEM values increased with increasing tissue damage, with the sacrum and the heels being the most common anatomical locations for the development of erythema and stage I PUs. Thermography identified temperature changes in tissues and skin that may give an indication of early PU development; however the data were not sufficiently robust. Ultrasound detected pockets of fluid/oedema at different levels of the skin that were comparable with tissue damage. Thus, SEM and ultrasound were the best methods for allowing a more accurate assessment of early skin/tissue damage. Using the EBL Critical Appraisal Tool the overall validities of the studies varied between 33.3-55.6%, meaning that there is potential for bias within all the included studies. All of the studies were situated at level IV, V and VII of the evidence pyramid. Although the methodological quality of the studies warrants consideration, these studies showed the potential that SEM and ultrasound have in early PU detection. CONCLUSION: SEM and ultrasound are promising in the detection and prediction of early tissue damage and PU presence. However, these methods should be further studied to clarify their potential for use more widely in PU prevention strategies.


Subject(s)
Pressure Ulcer/diagnostic imaging , Skin/diagnostic imaging , Thermography , Ultrasonography , Early Diagnosis , Erythema , Humans
16.
J Huntingtons Dis ; 6(1): 79-91, 2017.
Article in English | MEDLINE | ID: mdl-28339398

ABSTRACT

BACKGROUND: A hallmark of Huntington's disease is the progressive aggregation of full length and N-terminal fragments of polyglutamine (polyQ)-expanded Huntingtin (Htt) into intracellular inclusions. The production of N-terminal fragments appears important for enabling pathology and aggregation; and hence the direct expression of a variety of N-terminal fragments are commonly used to model HD in animal and cellular models. OBJECTIVE: It remains unclear how the length of the N-terminal fragments relates to polyQ - mediated aggregation. We investigated the fundamental intracellular aggregation process of eight different-length N-terminal fragments of Htt in both short (25Q) and long polyQ (97Q). METHODS: N-terminal fragments were fused to fluorescent proteins and transiently expressed in mammalian cell culture models. These included the classic exon 1 fragment (90 amino acids) and longer forms of 105, 117, 171, 513, 536, 552, and 586 amino acids based on wild-type Htt (of 23Q) sequence length nomenclature. RESULTS: N-terminal fragments of less than 171 amino acids only formed inclusions in polyQ-expanded form. By contrast the longer fragments formed inclusions irrespective of Q-length, with Q-length playing a negligible role in extent of aggregation. The inclusions could be classified into 3 distinct morphological categories. One type (Type A) was universally associated with polyQ expansions whereas the other two types (Types B and C) formed independently of polyQ length expansion. CONCLUSIONS: PolyQ-expansion was only required for fragments of less than 171 amino acids to aggregate. Longer fragments aggregated predominately through a non-polyQ mechanism, involving at least one, and probably more distinct clustering mechanisms.


Subject(s)
DNA Repeat Expansion , Huntingtin Protein/metabolism , Peptides , Protein Aggregation, Pathological/metabolism , Animals , Blotting, Western , COS Cells , Cell Line, Tumor , Chlorocebus aethiops , Flow Cytometry , Fluorescent Antibody Technique , Genetic Vectors , HEK293 Cells , Humans , Huntingtin Protein/genetics , Inclusion Bodies/metabolism , Inclusion Bodies/pathology , Luminescent Proteins/genetics , Luminescent Proteins/metabolism , Mice , Microscopy, Confocal , Peptides/genetics , Peptides/metabolism , Protein Aggregation, Pathological/genetics , Protein Aggregation, Pathological/pathology , Transfection , Red Fluorescent Protein
17.
Chem Commun (Camb) ; 53(19): 2874-2877, 2017 Mar 02.
Article in English | MEDLINE | ID: mdl-28220157

ABSTRACT

We report a new strategy that allows spatiotemporal visualization of the macromolecular crowding effect in cells. An amine-reactive aggregation-induced emission fluorogen is used to label proteins in the cytoplasm and the change in the protein mobility as well as local viscosity can be monitored by using fluorescence anisotropy imaging and fluorescence lifetime imaging, respectively.


Subject(s)
Amines/chemistry , Fluorescence Polarization , Fluorescent Dyes/chemistry , Amines/chemical synthesis , Animals , Cell Line , Fluorescent Dyes/chemical synthesis , HeLa Cells , Humans , Macromolecular Substances/chemistry , Mice , Molecular Structure
18.
ACS Macro Lett ; 6(3): 315-320, 2017 Mar 21.
Article in English | MEDLINE | ID: mdl-35650909

ABSTRACT

Targeting nanoparticles to specific cellular receptors has the potential to deliver therapeutic compounds to target sites while minimizing side effects. To this end, we have conjugated a targeting protein, holo-transferrin (holo-Tf), to pH-responsive polymers, poly(2-(diethylamino)ethyl methacrylate) (PDEAEMA) and poly(2-(diethylamino)ethyl methacrylate)-ran-poly(2-(diisopropylamino)ethyl methacrylate (PDEAEMA-r-PDPAEMA). These protein-polymer hybrid materials were observed to self-assemble when the pH is increased above the pKa of the polymer. We demonstrate that their response to pH could be tuned depending on the polymer constituent attached to holo-Tf. Importantly, the targeting behavior of these nanoparticles could be maximized by tuning the density of holo-Tf on the nanoparticle surface by the introduction of a (PDEAEMA-r-PDPAEMA)-b-poly(ethylene glycol) (PEG) copolymer.

19.
J Wound Care ; 24(12): 560, 562-70, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26654736

ABSTRACT

OBJECTIVE: To compare the literature on the strengths and limitations of different offloading devices in the treatment of diabetic foot ulcers. METHOD: Systematic review of the literature in the following databases: the Cumulative Index to Nursing an Allied Health Literature (CINAHL); Medline; Embase; Cochrane Library and Web of Knowledge. The search strategy used the terms: diabetic foot; orthosis/orthotic devices/orthoses; foot orthosis/foot orthoses; casts/plaster cast/surgical cast; shoes. RESULTS: Our results identified 15 studies, which are included in this review. Healing rates, healing times and reduction in ulcer size were improved with the use of total contact casting, when compared with other offloading devices. The main adverse effects associated with the use of the device were infection, maceration and abrasion. Cost, compliance and quality of life issues were rarely included within the studies. CONCLUSION: Offloading is a key treatment strategy for the management of diabetic foot ulcers and total contact casts were found to be the most effective devices to achieve ulcer healing. However, they are not without complications and their impact on cost, compliance and quality of life is not well understood.


Subject(s)
Casts, Surgical , Diabetes Mellitus, Type 2/complications , Diabetic Foot/prevention & control , Diabetic Foot/therapy , Pressure Ulcer/prevention & control , Pressure Ulcer/therapy , Shoes , Diabetes Mellitus, Type 1 , Female , Humans , Male , Weight-Bearing , Wound Healing
20.
J Wound Care ; 24(8): 333-9, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26562375

ABSTRACT

OBJECTIVE: This study explored whether the risk assessment method, structured versus clinical judgment, influences pressure ulcer (PU) prevalence or prevention strategies. METHOD: A cross section survey design was employed with use of a pre-designed data collection instrument. Following ethical approval and consent, data was gathered from two acute care settings, one in Norway (clinical judgment) and one in Ireland (structured risk assessment using the Maelor Score). RESULTS: Data were obtained from 180 patients, 59 in Norway and 121 in Ireland. Of the patients 48% were male and 49% were female, gender was not recorded for 3%. The most common age bracket was 70-99 years of age, 46% of the study population. PU prevalence was 54% in the Norwegian site with the majority of PUs (69%) being category 1, and 12% in the Irish site with the majority (50%) being category 2. Only 8% of patients in the Norwegian site were risk assessed on admission compared with 85% in the Irish site. No dynamic mattresses and four pressure redistribution cushions were in use in the Norwegian site, whereas, in the Irish site, 27 dynamic mattresses and 11 pressure redistribution cushions were used, the majority (44%) for high-risk individuals. Of those at risk of PU development, 15% in the Norwegian site and 56% in the Irish site had a documented repositioning care plan when in bed, and 0% in the Norwegian site and 13% in the Irish site for when seated on a chair. CONCLUSION: There were inconsistencies in approach to PU risk assessment and prevention across the two clinical settings. However, prevalence rates differed, mainly relating to category 1 PU damage. Even though formal risk assessment is well established in the Irish site, this is not necessarily followed up with appropriated PU prevention. Thus, the method of risk assessment does not seem to influence subsequent care planning, questioning the role of formal risk assessment; however, despite this, risk assessment does put a focus on an important clinical problem. In the Norwegian site, a lack of risk assessment and appropriate equipment may be a confounding factor worthy of further exploration.


Subject(s)
Pressure Ulcer/epidemiology , Pressure Ulcer/prevention & control , Risk Assessment/methods , Adolescent , Adult , Aged , Aged, 80 and over , Cross-Sectional Studies , Female , Humans , Ireland/epidemiology , Male , Middle Aged , Norway , Prevalence , Risk Factors , Surveys and Questionnaires , Young Adult
SELECTION OF CITATIONS
SEARCH DETAIL