Publications by authors named "Sarah Walsh"

99 Publications

A preliminary prospective observational study of the effectiveness of high-concentration capsaicin cutaneous patch in the management of chronic post-surgical neuropathic pain.

Ir J Med Sci 2021 May 13. Epub 2021 May 13.

Department of Anaesthesiology and Pain Medicine, St. James's Hospital, Dublin, Ireland.

Introduction: Chronic post-surgical neuropathic pain is difficult to treat. Topically applied analgesics provide an alternative to systemic therapy in localised neuropathic pain syndromes. The aim of this study was to prospectively assess whether 8% capsaicin is effective in surgically induced neuropathic pain.

Methodology: Patients were screened for neuropathic pain using DN4 questionnaire. Validated questionnaires were completed at baseline and at 6 and 12 weeks (BPI, HADS, PGIC), and the affected area was mapped. The study received ethical approval from the local research ethics committee.

Results: There were 12 participants. The most common operation was open thoracotomy (n = 8). There was a significant improvement in pain-interference from baseline to 12 weeks (p = .018). There were no significant changes in pain intensity or in the HADS. Repeat patches were performed for 4 participants on a second occasion (33%) and for 3 participants a third time (25%). There was a significant reduction in the surface area of the painful region on second (p = .04) and third applications (p = .023). At 12 weeks, 17% rated their symptoms very much better, 8% were much better, and 33% were minimally better, while 42% rated their symptoms no better.

Conclusions: This prospective study provides preliminary evidence for an improvement in patient outcomes with 8% capsaicin in surgically induced neuropathic pain. Improvements were noted in pain interference, and significant reductions in the painful surface area were noted for those who underwent subsequent treatments. Findings should be replicated in a randomised control trial to establish causation.
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http://dx.doi.org/10.1007/s11845-021-02632-0DOI Listing
May 2021

Discriminating 'DRESS minor' from 'DRESS major': facial oedema aligns to the severe phenotype.

J Am Acad Dermatol 2021 Apr 16. Epub 2021 Apr 16.

Department of Dermatology, King's College Hospital, Denmark Hill, London, SE5 9RS, U.K.

Background: DRESS is a cutaneous and systemic drug allergy disorder. Patients exist on a severity spectrum with some developing a mild form of the disorder which fails to meet the RegiSCAR diagnostic criteria for DRESS.

Objective: We sought to determine if there were any cutaneous or dermatopathological features which discriminate between the mild form of DRESS ('DRESS minor') and the severe phenotype ('DRESS major').

Methods: Inpatients from a single centre with a diagnosis of DRESS were prospectively recruited over a 7-year period. Clinical and dermatopathological features were analysed to discriminate between DRESS minor and DRESS major.

Results: 45 patients were included: 19 patients had a RegiSCAR score of ≤3 (DRESS minor), and 26 patients had a score ≥4 (DRESS major). The mean latency period (P=0.001), fever >38.5 C (P=0.001), and a reaction lasting >15 days (P=0.010) discriminated DRESS major from DRESS minor. Facial oedema was the sole discerning cutaneous feature(P=0.025). Discriminating histopathological features included basal squamatisation (P=0.005), dermal red cell extravasation (P=0.009), and interface inflammation (P=0.005).

Conclusion: We propose a new classification system: DRESS minor, to distinguish the milder illness from the severe form, DRESS major. Facial oedema and certain histopathological features can help discriminate between major and minor versions.
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http://dx.doi.org/10.1016/j.jaad.2021.04.020DOI Listing
April 2021

GPR55 regulates the responsiveness to, but does not dimerise with, α-adrenoceptors.

Biochem Pharmacol 2021 May 1;188:114560. Epub 2021 May 1.

Cardiometabolic Health Research, School of Pharmacy and Life Sciences, Robert Gordon University, Sir Ian Wood Building, Aberdeen AB10 7GJ, UK.

Emerging evidence suggests that G protein coupled receptor 55 (GPR55) may influence adrenoceptor function/activity in the cardiovascular system. Whether this reflects direct interaction (dimerization) between receptors or signalling crosstalk has not been investigated. This study explored the interaction between GPR55 and the alpha 1A-adrenoceptor (α-AR) in the cardiovascular system and the potential to influence function/signalling activities. GPR55 and α-AR mediated changes in both cardiac and vascular function was assessed in male wild-type (WT) and GPR55 homozygous knockout (GPR55) mice by pressure volume loop analysis and isolated vessel myography, respectively. Dimerization of GPR55 with the α-AR was examined in transfected Chinese hamster ovary-K1 (CHO-K1) cells via Bioluminescence Resonance Energy Transfer (BRET). GPR55 and α-AR mediated signalling (extracellular signal-regulated kinase 1/2 (ERK1/2) phosphorylation) was investigated in neonatal rat ventricular cardiomyocytes using AlphaScreen proximity assays. GPR55 mice exhibited both enhanced pressor and inotropic responses to A61603 (α-AR agonist), while in isolated vessels, A61603 induced vasoconstriction was attenuated by a GPR55-dependent mechanism. Conversely, GPR55-mediated vasorelaxation was not altered by pharmacological blockade of α-ARs with tamsulosin. While cellular studies demonstrated that GPR55 and α-AR failed to dimerize, pharmacological blockade of GPR55 altered α-AR mediated signalling and reduced ERK1/2 phosphorylation. Taken together, this study provides evidence that GPR55 and α-AR do not dimerize to form heteromers, but do interact at the signalling level to modulate the function of α-AR in the cardiovascular system.
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http://dx.doi.org/10.1016/j.bcp.2021.114560DOI Listing
May 2021

Alarming Cargo: The Role of Exosomes in Trauma-Induced Inflammation.

Biomolecules 2021 Mar 31;11(4). Epub 2021 Mar 31.

USU Walter Reed Surgery, Uniformed Services University, Bethesda, MD 20814, USA.

Severe polytraumatic injury initiates a robust immune response. Broad immune dysfunction in patients with such injuries has been well-documented; however, early biomarkers of immune dysfunction post-injury, which are critical for comprehensive intervention and can predict the clinical course of patients, have not been reported. Current circulating markers such as IL-6 and IL-10 are broad, non-specific, and lag behind the clinical course of patients. General blockade of the inflammatory response is detrimental to patients, as a certain degree of regulated inflammation is critical and necessary following trauma. Exosomes, small membrane-bound extracellular vesicles, found in a variety of biofluids, carry within them a complex functional cargo, comprised of coding and non-coding RNAs, proteins, and metabolites. Composition of circulating exosomal cargo is modulated by changes in the intra- and extracellular microenvironment, thereby serving as a homeostasis sensor. With its extensively documented involvement in immune regulation in multiple pathologies, study of exosomal cargo in polytrauma patients can provide critical insights on trauma-specific, temporal immune dysregulation, with tremendous potential to serve as unique biomarkers and therapeutic targets for timely and precise intervention.
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http://dx.doi.org/10.3390/biom11040522DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8065643PMC
March 2021

Comparative effects of viral-transport-medium heat inactivation upon downstream SARS-CoV-2 detection in patient samples.

J Med Microbiol 2021 Mar 18;70(3). Epub 2021 Mar 18.

Division of Cancer and Stem Cells, Biodiscovery Institute, School of Medicine, University of Nottingham, Nottingham, NG7 2RD, UK.

The COVID-19 pandemic, which began in 2020 is testing economic resilience and surge capacity of healthcare providers worldwide. At the time of writing, positive detection of the SARS-CoV-2 virus remains the only method for diagnosing COVID-19 infection. Rapid upscaling of national SARS-CoV-2 genome testing presented challenges: (1) Unpredictable supply chains of reagents and kits for virus inactivation, RNA extraction and PCR-detection of viral genomes. (2) Rapid time to result of <24 h is required in order to facilitate timely infection control measures. Extraction-free sample processing would impact commercially available SARS-CoV-2 genome detection methods. We evaluated whether alternative commercially available kits provided sensitivity and accuracy of SARS-CoV-2 genome detection comparable to those used by regional National Healthcare Services (NHS). We tested several detection methods and tested whether detection was altered by heat inactivation, an approach for rapid one-step viral inactivation and RNA extraction without chemicals or kits. Using purified RNA, we found the CerTest VIASURE kit to be comparable to the Altona RealStar system currently in use, and further showed that both diagnostic kits performed similarly in the BioRad CFX96 and Roche LightCycler 480 II machines. Additionally, both kits were comparable to a third alternative using a combination of Quantabio qScript one-step Quantitative Reverse Transcription Polymerase Chain Reaction (qRT-PCR) mix and Centre for Disease Control and Prevention (CDC)-accredited N1 and N2 primer/probes when looking specifically at borderline samples. Importantly, when using the kits in an extraction-free protocol, following heat inactivation, we saw differing results, with the combined Quantabio-CDC assay showing superior accuracy and sensitivity. In particular, detection using the CDC N2 probe following the extraction-free protocol was highly correlated to results generated with the same probe following RNA extraction and reported clinically (=127; R=0.9259). Our results demonstrate that sample treatment can greatly affect the downstream performance of SARS-CoV-2 diagnostic kits, with varying impact depending on the kit. We also showed that one-step heat-inactivation methods could reduce time from swab receipt to outcome of test result. Combined, these findings present alternatives to the protocols in use and can serve to alleviate any arising supply-chain issues at different points in the workflow, whilst accelerating testing, and reducing cost and environmental impact.
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http://dx.doi.org/10.1099/jmm.0.001301DOI Listing
March 2021

High Frequency Spectral Ultrasound Imaging Detects Early Heterotopic Ossification in Rodents.

Stem Cells Dev 2021 May 19;30(9):473-484. Epub 2021 Apr 19.

Department of Surgery, University of Texas Southwestern Medical Center, Dallas, Texas, USA.

Heterotopic ossification (HO) is a devastating condition in which ectopic bone forms inappropriately in soft tissues following traumatic injuries and orthopedic surgeries as a result of aberrant mesenchymal progenitor cell (MPC) differentiation. HO leads to chronic pain, decreased range of motion, and an overall decrease in quality of life. While several treatments have shown promise in animal models, all must be given during early stages of formation. Methods for early determination of whether and where endochondral ossification/soft tissue mineralization (HO anlagen) develop are lacking. At-risk patients are not identified sufficiently early in the process of MPC differentiation and soft tissue endochondral ossification for potential treatments to be effective. Hence, a critical need exists to develop technologies capable of detecting HO anlagen soon after trauma, when treatments are most effective. In this study, we investigate high frequency spectral ultrasound imaging (SUSI) as a noninvasive strategy to identify HO anlagen at early time points after injury. We show that by determining quantitative parameters based on tissue organization and structure, SUSI identifies HO anlagen as early as 1-week postinjury in a mouse model of burn/tenotomy and 3 days postinjury in a rat model of blast/amputation. We analyze single cell RNA sequencing profiles of the MPCs responsible for HO formation and show that the early tissue changes detected by SUSI match chondrogenic and osteogenic gene expression in this population. SUSI identifies sites of soft tissue endochondral ossification at early stages of HO formation so that effective intervention can be targeted when and where it is needed following trauma-induced injury. Furthermore, we characterize the chondrogenic to osteogenic transition that occurs in the MPCs during HO formation and correlate gene expression to SUSI detection of the HO anlagen.
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http://dx.doi.org/10.1089/scd.2021.0011DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8106252PMC
May 2021

Trimethoprim-induced drug reaction with eosinophilia and systemic symptoms (DRESS) associated with reactivation of human herpes virus-6 (HHV-6) leading to acute liver failure.

Clin Case Rep 2020 Dec 9;8(12):2568-2573. Epub 2020 Aug 9.

Liver Intensive Therapy Unit (LITU) King's College Hospital London UK.

Drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome can have insidious symptoms which may lead to acute liver failure and death. Prompt recognition, stopping offending drug, and initiating corticosteroid are the mainstay of treatment. Early involvement of a specialist liver unit is vital.
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http://dx.doi.org/10.1002/ccr3.3218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7752394PMC
December 2020

Surgical Elbow Dislocation Approach to the Distal Humerus for Apparent Capitellar and Lateral Condyle Fractures in Adults.

J Orthop Trauma 2021 03;35(3):e77-e81

Department of Orthopaedic Surgery, R Adams Cowley Shock Trauma Center, University of Maryland, Baltimore, MD.

Objectives: Access to fractures of the distal humeral capitellum, trochlea, and lateral condyle is difficult through traditional approaches due to limited anterior articular exposure for direct reduction and fixation. The purpose of this study is to evaluate the relative articular exposure of a surgical dislocation (SD) approach to the distal humerus compared with olecranon osteotomy (OO).

Methods: Eight paired elbows from 4 cadavers underwent either SD or OO approach. Methylene blue staining demarcated visualized articular surface before disarticulation of the elbows. The main outcome measures were average visualized total distal humeral articular surface and anterior and posterior surface, and capitellar surface relative to the total surfaces was compared for each surgical approach using unpaired parametric t-tests.

Results: Intraclass correlation between raters was 0.995. The median exposed articular surface for SD and OO approaches was 90.0% and 62.8%, respectively. The overall exposure was significantly greater for the dislocation technique (P = 0.0003). With respect to specific regions of the distal humeral articular surface, SD allowed significantly greater visualization of the anterior surface (95.9% vs. 48.9%, P < 0.0001) and capitellum (100% vs. 40.4%, P < 0.0001).

Conclusion: The surgical elbow dislocation approach to the distal humerus permits near total exposure of the anterior articular surface and the entire capitellum. Our data support this approach for anterior articular fractures of the distal humerus, to include those fractures that extend to the medial surface of the trochlea.
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http://dx.doi.org/10.1097/BOT.0000000000001923DOI Listing
March 2021

Evidence on Physical Activity and the Prevention of Frailty and Sarcopenia Among Older People: A Systematic Review to Inform the World Health Organization Physical Activity Guidelines.

J Phys Act Health 2020 Aug 11:1-12. Epub 2020 Aug 11.

Background: Frailty and sarcopenia are common age-related conditions associated with adverse outcomes. Physical activity has been identified as a potential preventive strategy for both frailty and sarcopenia. The authors aimed to investigate the association between physical activity and prevention of frailty and sarcopenia in people aged 65 years and older.

Methods: The authors searched for systematic reviews (January 2008 to November 2019) and individual studies (January 2010 to March 2020) in PubMed. Eligible studies were randomized controlled trials and longitudinal studies that investigated the effect of physical activity on frailty and/or sarcopenia in people aged 65 years and older. The Grading of Recommendations Assessment, Development and Evaluation approach was used to rate certainty of evidence.

Results: Meta-analysis showed that physical activity probably prevents frailty (4 studies; frailty score pooled standardized mean difference, 0.24; 95% confidence interval, 0.04-0.43; P = .017, I2 = 57%, moderate certainty evidence). Only one trial investigated physical activity for sarcopenia prevention and did not provide conclusive evidence (risk ratio 1.08; 95% confidence interval, 0.10-12.19). Five observational studies showed positive associations between physical activity and frailty or sarcopenia prevention.

Conclusions: Physical activity probably prevents frailty among people aged 65 years and older. The impact of physical activity on the prevention of sarcopenia remains unknown, but observational studies indicate the preventive role of physical activity.
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http://dx.doi.org/10.1123/jpah.2020-0323DOI Listing
August 2020

Development of Gene-Targeted Polypyridyl Triplex-Forming Oligonucleotide Hybrids.

Chembiochem 2020 12 24;21(24):3563-3574. Epub 2020 Sep 24.

School of Chemical Sciences and National Institute for Cellular Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland.

In the field of nucleic acid therapy there is major interest in the development of libraries of DNA-reactive small molecules which are tethered to vectors that recognize and bind specific genes. This approach mimics enzymatic gene editors, such as ZFNs, TALENs and CRISPR-Cas, but overcomes the limitations imposed by the delivery of a large protein endonuclease which is required for DNA cleavage. Here, we introduce a chemistry-based DNA-cleavage system comprising an artificial metallo-nuclease (AMN) that oxidatively cuts DNA, and a triplex-forming oligonucleotide (TFO) that sequence-specifically recognises duplex DNA. The AMN-TFO hybrids coordinate Cu ions to form chimeric catalytic complexes that are programmable - based on the TFO sequence employed - to bind and cut specific DNA sequences. Use of the alkyne-azide cycloaddition click reaction allows scalable and high-throughput generation of hybrid libraries that can be tuned for specific reactivity and gene-of-interest knockout. As a first approach, we demonstrate targeted cleavage of purine-rich sequences, optimisation of the hybrid system to enhance stability, and discrimination between target and off-target sequences. Our results highlight the potential of this approach where the cutting unit, which mimics the endonuclease cleavage machinery, is directly bound to a TFO guide by click chemistry.
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http://dx.doi.org/10.1002/cbic.202000408DOI Listing
December 2020

Frailty and Nutrition Risk Screening in Home-Delivered Meal Clients.

J Nutr Gerontol Geriatr 2020 Apr-Jun;39(2):114-130. Epub 2020 Feb 3.

School of Health Sciences, Eastern Michigan University, Ypsilanti, MI, USA.

Community service providers, such as Meals on Wheels (MOW) programs, help older adults remain in their homes despite advanced care needs. The purpose of this study was to determine if a frailty index (FI) could be calculated from self-reported health, function, and nutrition information already collected by MOW providers to provide additional information for care planning and risk stratification. Data from 258 MOW clients at one provider were used to calculate the FI from 40 possible health and age-related variables collected during routine health assessments. The average FI was 0.29 ± 0.13(SD), range 0.05-0.68. Frailty was categorized as non-frail, vulnerable, frail, and most frail; nutrition risk increased incrementally with these categories; however, they appear to assess risk from differing angles and etiologies. The addition of the FI can provide a more holistic picture of MOW client health than nutrition risk alone and the FI can be calculated from routinely-collected data.
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http://dx.doi.org/10.1080/21551197.2020.1719258DOI Listing
August 2020

Osseointegrated prostheses for the rehabilitation of amputees (OPRA): results and clinical perspective.

Expert Rev Med Devices 2020 Jan 13;17(1):17-25. Epub 2020 Jan 13.

USU-Walter Reed Department of Surgery, Walter Reed National Military Medical Center, Bethesda, MD, USA.

: Patients who undergo extremity amputation have historically used socket prosthetics to ambulate and perform daily functions; however, these prosthetics can be limited by poor terminal control and wear issues. In patients who have difficulty wearing their prostheses or with upper extremity amputations, osseointegrated implants may offer better function and quality of life. The Osseointegrated Prostheses for the Rehabilitation of Amputees (OPRA) was the first such device to become commercially available. Clinical trials have demonstrated benefit in patient gait, prosthetic use, and overall well-being, and new implants may be applied for various amputation levels.: The OPRA, the most studied osseointegrated prosthetic stem, is reviewed, presenting indications, surgical procedure, complications, and results of clinical studies.: Osseointegration for amputees is an expanding field that has the potential to enhance rehabilitative potential. The OPRA implant is an effective device with a long life-span and low complication profile.
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http://dx.doi.org/10.1080/17434440.2020.1704623DOI Listing
January 2020

l-α-Lysophosphatidylinositol (LPI) aggravates myocardial ischemia/reperfusion injury via a GPR55/ROCK-dependent pathway.

Pharmacol Res Perspect 2019 06 24;7(3):e00487. Epub 2019 May 24.

Cardiometabolic Health Research School of Pharmacy & Life Sciences Robert Gordon University Aberdeen Scotland UK.

The phospholipid l-α-lysophosphatidylinositol (LPI), an endogenous ligand for GPR55, is elevated in patients with acute coronary syndrome, and a GPR55 antagonist cannabidiol (CBD) reduces experimental ischemia/reperfusion (I/R) injury. While LPI activates multiple signaling pathways, little is known about which ones are important in cardiomyocytes. In this study we explored whether activation of the Rho kinase/ROCK/p38 MAPK pathway is responsible for LPI-induced extension of I/R injury. Using a high-throughput screening method (dynamic mass redistribution; DMR), mouse- and human-induced pluripotent stem cell (iPSC) cardiomyocytes exposed to LPI were shown to exhibit a rapid, sustained, and concentration-dependent (1 nmol L-30 μmol L) cellular response. Y-27632 (ROCK inhibitor; 10 & 50 μmol L) and CBD (1 μmol L) both abolished the DMR response to LPI (10 μmol L). In murine iPSC cardiomyocytes, LPI-induced ROCK and p38 MAPK phosphorylation, both of which were prevented by Y-27632 and CBD, but did not induce JNK activation or cleavage of caspase-3. In hearts isolated from wild type (WT) mice subjected to 30 minutes global I/R, LPI (10 μmol L) administered via the coronary circulation increased infarct size when applied prior to ischemia onset, but not when given at the time of reperfusion. The exacerbation of tissue injury by LPI was not seen in hearts from GPR55 mice or in the presence of Y-27632, confirming that injury is mediated via the GPR55/ROCK/p38 MAPK pathway. These findings suggest that raised levels of LPI in the vicinity of a developing infarct may worsen the outcome of AMI.
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http://dx.doi.org/10.1002/prp2.487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6533556PMC
June 2019

Patient-rated physician empathy and patient satisfaction during pain clinic consultations.

Ir J Med Sci 2019 Nov 27;188(4):1379-1384. Epub 2019 Mar 27.

Graduate Entry Medical School, University of Limerick, Limerick, Ireland.

Background: Little is known about the influence of patient-perceived healthcare provider empathy on patient satisfaction in the setting of a hospital pain clinic consultation. The objective of this research was to examine the relationship between patient-rated physician empathy and patient satisfaction after a single new pain clinic consultation.

Methods: After institutional ethics committee approval, a sample of 140 adult patients completed a two-page questionnaire, directly after a pain clinic consultation. This included a brief sociodemographic questionnaire, the Consultation and Relational Empathy (CARE) measure and an overall satisfaction rating.

Results: The sample, N = 140 patients, was balanced for gender and 80% of participants ranged in age from 30 to 70. Of these patients, 80.7% had been living with chronic pain between 1 and 5 years. The data were deemed to be non-parametric and a Spearman's ranked order correlation analysis yielded a strong positive correlation between patient-rated physician empathy and patient consultation satisfaction.

Conclusion: Patient-rated physician empathy was strongly correlated with patient satisfaction in a pain clinic consultation. Patient satisfaction plays a significant role in adherence to treatment and contributes to a positive working patient-physician therapeutic relationship. This research supports the growing body of research citing the importance of investing in, promoting and developing educational programs for physicians and medical trainees to enhance empathic communication skills within the clinical setting.
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http://dx.doi.org/10.1007/s11845-019-01999-5DOI Listing
November 2019

Acute dietary zinc deficiency in rats exacerbates myocardial ischaemia-reperfusion injury through depletion of glutathione.

Br J Nutr 2019 05 22;121(9):961-973. Epub 2019 Feb 22.

1Centre for Cardiometabolic Health Research,School of Pharmacy and Life Sciences,Robert Gordon University,AberdeenAB10 7GJ,UK.

Zn plays an important role in maintaining the anti-oxidant status within the heart and helps to counter the acute redox stress that occurs during myocardial ischaemia and reperfusion. Individuals with low Zn levels are at greater risk of developing an acute myocardial infarction; however, the impact of this on the extent of myocardial injury is unknown. The present study aimed to compare the effects of dietary Zn depletion with in vitro removal of Zn (N,N,N',N'-tetrakis(2-pyridinylmethyl)-1,2-ethanediamine (TPEN)) on the outcome of acute myocardial infarction and vascular function. Male Sprague-Dawley rats were fed either a Zn-adequate (35 mg Zn/kg diet) or Zn-deficient (<1 mg Zn/kg diet) diet for 2 weeks before heart isolation. Perfused hearts were subjected to a 30 min ischaemia/2 h reperfusion (I/R) protocol, during which time ventricular arrhythmias were recorded and after which infarct size was measured, along with markers of anti-oxidant status. In separate experiments, hearts were challenged with the Zn chelator TPEN (10 µm) before ischaemia onset. Both dietary and TPEN-induced Zn depletion significantly extended infarct size; dietary Zn depletion was associated with reduced total cardiac glutathione (GSH) levels, while TPEN decreased cardiac superoxide dismutase 1 levels. TPEN, but not dietary Zn depletion, also suppressed ventricular arrhythmias and depressed vascular responses to nitric oxide. These findings demonstrate that both modes of Zn depletion worsen the outcome from I/R but through different mechanisms. Dietary Zn deficiency, resulting in reduced cardiac GSH, is the most appropriate model for determining the role of endogenous Zn in I/R injury.
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http://dx.doi.org/10.1017/S0007114519000230DOI Listing
May 2019

Periocular rash.

BMJ 2018 Dec 21;363:k5098. Epub 2018 Dec 21.

King's College Hospital, London, UK.

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http://dx.doi.org/10.1136/bmj.k5098DOI Listing
December 2018

Fluorogenic thiazole orange TOTFO probes stabilise parallel DNA triplexes at pH 7 and above.

Chem Sci 2018 Oct 1;9(39):7681-7687. Epub 2018 Aug 1.

Department of Chemistry , University of Oxford , Oxford , OX1 3TA , UK . Email:

The instability of DNA triplexes particularly at neutral pH and above severely limits their applications. Here, we demonstrate that the introduction of a thiazole orange (TO) intercalator onto a thymine nucleobase in triplex forming oligonucleotides (TFOs) resolves this problem. The stabilising effects are additive; multiple TO units produce nanomolar duplex binding and triplex stability can surpass that of the underlying duplex. In one example, a TFO containing three TO units increased the triplex melting temperature at pH 7 by a remarkable 50 °C relative to the unmodified triplex. Notably, TO intercalation promotes TFO binding to target sequences other than pure polypurine tracts by the use of 5-(1-propynyl)cytosine (pC) against C:G inversions. By overcoming the instability of triplexes across a broad range of pH and sequence contexts, these very simple 'TOTFO' probes could expand triplex applications into many areas including diagnostics and cell imaging.
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http://dx.doi.org/10.1039/c8sc02418aDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6182420PMC
October 2018

Influence of Built Environment Quality and Social Capital on Mental Health of Residents of Assisted Living Communities in Louisville, Kentucky.

Gerontol Geriatr Med 2018 Jan-Dec;4:2333721418795900. Epub 2018 Aug 24.

University of Louisville, KY, USA.

Prior research has shown social capital and built environment quality are associated with overall health status and the incidence of mental illness. This study explores the relationship between social capital, built environment, and quality of life specifically for assisted living residents, currently a gap in the literature. A total of 76 assisted living residents were interviewed for the study using researcher-administered questionnaires. In addition, site audits were conducted to quantitatively evaluate the built environment surrounding 12 assisted living communities in the Louisville Metro region. There was a moderate, positive correlation between social capital and mental health, = .473, < .001. Built environment quality for the neighborhood immediately surrounding the assisted living community was not significantly correlated with quality of life for assisted living residents. Other population characteristics, including demographic characteristics, self-rated health status, and instrumental activities of daily living were not significantly predictive of mental health scores. This study demonstrates that social capital is associated with happiness and self-rated quality of life. Specifically, increased social capital is associated with increased mental well-being for older adults residing in assisted living communities, with social capital explaining about 20% of the variation in quality of life scores.
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http://dx.doi.org/10.1177/2333721418795900DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6109847PMC
August 2018

GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.

FASEB J 2019 01 27;33(1):1299-1312. Epub 2018 Aug 27.

Division of Cell Signalling and Immunology, Sir James Black Centre, School of Life Sciences, University of Dundee, Dundee, United Kingdom.

Emerging evidence indicates that G-protein coupled receptor 55 (GPR55), a nonclassic receptor of the endocannabinoid system that is activated by L-α-lysophosphatidylinositol and various cannabinoid ligands, may regulate endocrine function and energy metabolism. We examined how GPR55 deficiency and modulation affects insulin signaling in skeletal muscle, adipose tissue, and liver alongside expression analysis of proteins implicated in insulin action and energy metabolism. We show that GPR55-null mice display decreased insulin sensitivity in these tissues, as evidenced by reduced phosphorylation of PKB/Akt and its downstream targets, concomitant with increased adiposity and reduced physical activity relative to wild-type counterparts. Impaired tissue insulin sensitivity coincided with reduced insulin receptor substrate-1 abundance in skeletal muscle, whereas in liver and epididymal fat it was associated with increased expression of the 3-phosphoinoistide lipid phosphatase, phosphatase and tensin homolog. In contrast, GPR55 activation enhanced insulin signaling in cultured skeletal muscle cells, adipocytes, and hepatocytes; this response was negated by receptor antagonists and GPR55 gene silencing in L6 myotubes. Sustained GPR55 antagonism in 3T3-L1 adipocytes enhanced expression of proteins implicated in lipogenesis and promoted triglyceride accumulation. Our findings identify GPR55 as a positive regulator of insulin action and adipogenesis and as a potential therapeutic target for countering obesity-induced metabolic dysfunction and insulin resistance.-Lipina, C., Walsh, S. K., Mitchell, S. E., Speakman, J. R., Wainwright, C. L., Hundal, H. S. GPR55 deficiency is associated with increased adiposity and impaired insulin signaling in peripheral metabolic tissues.
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http://dx.doi.org/10.1096/fj.201800171RDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6355063PMC
January 2019

Severe cutaneous adverse reactions syndromes and prescribing autonomy.

Br J Dermatol 2018 08;179(2):242-243

King's College Hospital NHS Foundation Trust, London, SE5 9RS, U.K.

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http://dx.doi.org/10.1111/bjd.16790DOI Listing
August 2018

The executioner's shadow: Coerced sterilization and the creation of "Latin" eugenics in Chile.

Authors:
Sarah Walsh

Hist Sci 2018 Apr 1:73275318755533. Epub 2018 Apr 1.

The Colour of Labour: The Racialized Lives of Migrants, European Research Council Project AdG 2015 - 695573, Universidade de Lisboa, Portugal.

Scholars such as Nancy Leys Stepan, Alexandra Minna Stern, Marius Turda and Aaron Gillette have all argued that the rejection of coerced sterilization was a defining feature of "Latin" eugenic theory and practice. These studies highlight the influence of neo-Lamarckism in this development not only in Latin America but also in parts of Europe in the first half of the twentieth century. This article builds upon this historiographical framework to examine an often-neglected site of Latin American eugenic knowledge production: Chile. By focusing on Chilean eugenicists' understandings of environment and coerced sterilization, this article argues that there was no uniquely Latin objection to the practice initially. In fact, Chilean eugenicists echoed concerns of eugenicists from a variety of locations, both "mainstream" and Latin, who felt that sterilization was not the most effective way to ensure the eugenic improvement of national populations. Instead, the article contends that it was not until the implementation of the 1933 German racial purity laws, which included coerced sterilization legislation, that Chilean eugenicists began to define their objections to the practice as explicitly Latin. Using a variety of medical texts which appeared in popular periodicals as well as professional journals, this article reveals the complexity of eugenic thought and practice in Chile in the early twentieth century.
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http://dx.doi.org/10.1177/0073275318755533DOI Listing
April 2018

Public Opinions Regarding Advanced Dental Hygiene Practitioners in a High-Need State.

J Dent Hyg 2016 Oct;90(5):269-274

The new Advanced Dental Hygiene Practitioner (ADHP) profession is expected to increase access to oral health care for the general population, particularly in rural and underserved areas. In order for this strategy to be successful, the public must feel comfortable with the care provided by ADHPs and seek out their services, yet consumer receptivity has been overlooked in the literature. The current study explores comfort with ADHPs for one high-need state: Kentucky. Consumer receptivity to the ADHP was assessed using a large, random sample telephone survey. As a point of comparison, respondents were first asked about their comfort with care provided by two other advanced practice clinicians already licensed in the state: advanced practice registered nurses (APRN) and physician assistants (PA). After hearing a brief description of the profession, nearly 3 in 4 Kentucky adults said they would be somewhat (35.4%) or very (38.2%) comfortable seeing an ADHP for routine dental care. The total proportion of Kentucky adults who were comfortable seeking care from an ADHP (73.6%) was slightly less than the proportion indicating comfort seeing an APRN (79.7%) or PA (81.3%). Overall, this study demonstrates that adults are receptive to new models of care delivery and report high levels of comfort with ADHPs. Consumer concerns are unlikely to be a barrier to expanded licensure for dental hygienists in high-need areas like Kentucky.
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October 2016

Feasibility and Acceptability of a Web Site to Promote Survivorship Care in Survivors of Hodgkin Disease.

JCO Clin Cancer Inform 2017 11;1:1-10

Meghan L. Underhill, Fangxin Hong, Kim Sprunck-Harrild, Sarah K. Walsh, Donna L. Berry, and Ann Partridge, Dana-Farber Cancer Institute; Richard Boyajian, Brigham and Women's Hospital Boston, MA; and Tarsha Jones, Florida Atlantic University, Boca Raton, FL.

Purpose: Evaluate rates of enrollment, completion, and patient-reported acceptability of an educational survivorship-care Web site for survivors of Hodgkin disease (HD).

Patients And Methods: The study was a mixed-method evaluation design. Eligible participants were adults who had completed treatment of a primary diagnosis of HD ≥ 2 years before enrollment. Patients were recruited through postal mail and telephone and were asked to review a Web site, complete an adapted version of the Acceptability E-scale (total score of 24 or greater indicates acceptability), and respond to a structured telephone or e-mail interview to discuss experiences with the Web site.

Results: Of 259 potentially eligible participants identified by medical record review, 124 survivors had confirmed contact with study staff and were invited to participate; 63 people (50.8%; 90% CI, 43% to 59%) enrolled; 37 participants (58.7%) were men. The median age at time of enrollment was 51.0 years (range, 29.3 to 80.0 years), and the median time since completion of treatment of HD was 14.9 years (range, 3 to 38.75 years). Overall, 82.5% of those enrolled viewed all Web site content. Forty-eight participants completed the acceptability survey, which resulted in a mean acceptability score of 26.5 (standard deviation, 3.5). The majority of enrollees (67%) completed a follow-up interview.

Conclusion: Overall, HD survivor participants viewed the content and reviewed it favorably. A Web-based intervention is a promising way to provide survivors of HD with information about how to manage the long-term and late effects from cancer and treatment, and provide trusted survivorship resources.
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http://dx.doi.org/10.1200/CCI.17.00012DOI Listing
November 2017

Developing a Novel Model to Improve Research and care for Cancer Survivors: a Feasibility Study.

J Cancer Educ 2019 04;34(2):229-233

Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA, 02215, USA.

Despite a growing number of clinical trials and supportive care programs for cancer survivors, recruitment of patients for these opportunities during the survivorship phase of care is challenging. We piloted a novel process to systematically educate patients about available research studies and supportive care programs as part of a survivorship care visit. Between 3/2015 and 8/2015, patients seen in the Adult Survivorship Program who had not previously received a treatment summary and survivorship care plan (TS/SCP) were provided with one accompanied by a list of survivorship research studies and care programs tailored to their diagnosis. Survivorship providers discussed the opportunities and recorded whether the patient was interested in relevant studies and placed referrals to study staff. Following the visit, we tracked study enrollment and surveyed patients about their experience. Fifty of 56 (89%) pilot participants completed the survey. Almost all (98%) reported that the TS/SCP visit and document helped with knowledge of research opportunities and supportive care interventions. Following receipt of the TS/SCP, 44% were interested in at least one study and in further follow-up with research staff. Of the 30 survivors eligible for at least one study, 6 (20%) have enrolled in at least one study to date. This pilot program demonstrates that the systematic sharing of available clinical studies and supportive care programming as part of a survivorship care plan visit is feasible and well received by cancer survivors and may facilitate and enhance accrual to clinical trials in the survivorship phase of care.
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http://dx.doi.org/10.1007/s13187-017-1291-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5910291PMC
April 2019

A review of the musculoskeletal manifestations of sarcoidosis.

Rheumatology (Oxford) 2018 05;57(5):777-783

Academic Department of Rheumatology, King's College London, London, UK.

Sarcoidosis is a systemic disease of unknown aetiology that is characterized by granulomatous inflammation that can develop in almost any organ system. Musculoskeletal manifestations are seen in up to one-third of patients, ranging from arthralgia through to widespread destructive bone lesions. Inflammatory tendon lesions and periarticular swelling are more common than true joint synovitis. Despite advances in our understanding of the pathophysiology of the disease, diagnosis remains challenging. Definitive diagnosis, irrespective of organ site involvement, hinges on histological confirmation of non-caseating granuloma combined with an appropriate clinical syndrome. Musculoskeletal involvement usually develops early in the disease course. Imaging modalities, particularly fluorodeoxyglucose PET, are helpful in delineating the extent of involvement and measuring disease activity. Bone involvement may only become apparent following isotope imaging. Corticosteroids remain the cornerstone of treatment. MTX is the steroid-sparing agent of choice unless there is renal involvement. Biologic therapies are sometimes used in severe disease, although the evidence base for efficacy is inconsistent.
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http://dx.doi.org/10.1093/rheumatology/kex317DOI Listing
May 2018

Improving the comfort of nurses caring for stroke patients at the end of life.

Int J Palliat Nurs 2017 May;23(5):248-254

Associate Professor, Division of Palliative Care, Department of Medicine, University of Ottawa, The Ottawa Hospital, Ottawa, Ontario, Canada.

Background: End-of-life care of stroke patients is an important aspect of stroke care. It has been previously reported that nurses express discomfort caring for patients at the end of life or caring for patients who have suffered severe strokes. Nurses at our centre expressed similar discomfort.

Aim: To improve the comfort of nurses caring for patients at the end of life after stroke.

Design: Nurses were asked to rate their comfort with treating patients at the end of life using the Stroke End-of-Life Care Comfort Scale before and after attending an education session. The education sessions included the presentation of a checklist for suggested orders for end-of-life care.

Setting/participants: The project was conducted with the neurosciences nurses at a tertiary care hospital. 54 out of a possible 122 nurses attended an education session.

Results: There was a significant improvement in the Stroke End-of-Life Care Comfort Scale score (p=0.00004) 3-4 weeks after the education session compared to the score before the session.

Conclusions: The combination of focused education sessions and an order checklist can significantly improve the comfort of nurses caring for patients at the end-of-life after stroke.
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http://dx.doi.org/10.12968/ijpn.2017.23.5.248DOI Listing
May 2017

Comparative effectiveness of guided weight loss and physical activity monitoring for weight loss and metabolic risks: A pilot study.

Prev Med Rep 2017 Jun 25;6:271-277. Epub 2017 Mar 25.

Iowa State University, Department of Kinesiology, USA.

Many consumer-based physical activity monitors (PAMs) are available but it is not clear how to use them to most effectively promote weight loss. The purpose of this pilot study was to compare the effectiveness of a personal PAM, a guided weight loss program (GWL), and the combination of these approaches on weight loss and metabolic risk. Participants completed the study in two cohorts: Fall 2010 and Spring 2011. A sample of 72 obese individuals in the Ames, IA area were randomized to one of 3 conditions: 1) (GWL, N = 31), 2) PAM, N = 29, or 3) a combination group (PAM + GWL, N = 29). Weight and metabolic syndrome score (MetS), computed from waist circumference (WC), BMI, blood pressure (BP), and lipids were assessed at baseline and following an 8-week intervention. Weight was also assessed four months later. Two-way (Group × Time) ANOVAs examined intervention effects and maintenance. Effect sizes were used to compare magnitude of improvements among groups. During the intervention, all groups demonstrated significant improvements in weight and MetS (mean weight loss = 4.16 kg,  < 0.001). Mean weight continued to decline modestly during follow-up, with average weight loss of 4.82 kg from baseline ( < 0.01). There were no group differences for weight loss but the PAM + GWL group had significantly larger changes in MetS score ( = 0.06-0.77). The use of PAM resulted in significant improvements in weight and MetS that were maintained across a four-month follow-up. Evidence suggests that the addition of GWL contributed to enhanced metabolic outcomes.
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http://dx.doi.org/10.1016/j.pmedr.2017.03.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5385579PMC
June 2017

Oncofertility: Fertile Ground for Conflict Between Patient Autonomy and Medical Values.

Oncologist 2017 07 13;22(7):860-863. Epub 2017 Apr 13.

Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA

Oncofertility is a unique, multidisciplinary field that serves to bridge the gap between available fertility resources and the special reproductive needs of cancer patients. Oncofertility is a growing field due to the increasing number of survivors, development of new oncologic therapies, extension of duration of therapies, and development and refinement of reproductive therapies. While the technologies and demand for services expand, clinicians need to be appropriately prepared for dealing with various clinical scenarios that may require ethical deliberation. Three real cases are presented in which the patient wishes to pursue reproductive assistance, but her decision is met with hesitance or uncertainty by her care team. Discussion of these clinical scenarios highlights ethical implications of oncofertility practice and serves to highlight the need for the establishment of multidisciplinary care teams and guidelines to support both clinicians and patients.

Implications For Practice: The growing field of oncofertility is ripe for conflict between patient autonomy and medical values due to the nature of cancer and associated threat on an individual's health and survival, as well as the personal significance of childbearing. Cases are presented and ethical implications are discussed to further explore the inherent difficulties in oncofertility practice and guide clinicians in similar situations. Developing guidelines and establishing multidisciplinary teams to facilitate oncofertility discussions and care, as well as training of clinical team members, may improve patient safety, well-being, and satisfaction within the context of fertility decision making, care, and outcomes.
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http://dx.doi.org/10.1634/theoncologist.2016-0373DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5507640PMC
July 2017

Impact of an Intervention Designed to Reduce Sexual Health Risk Behaviors of African American Adolescents: Results of a Randomized Controlled Trial.

Am J Public Health 2016 Sep;106(S1):S78-S84

All of the authors are with The Policy & Research Group, New Orleans, LA.

Objectives: To replicate an evidence-based HIV risk reduction program and assess its impact on 2 behavioral outcomes-inconsistency of condom use and frequency of sex-6 months after the program.

Methods: The study was an individual-level randomized controlled trial in which we randomly assigned 850 youths (aged 14-18 years) to 1 of 2 conditions. The treatment (Becoming a Responsible Teen) is a group-level sociocognitive and skills training sexual education course; the control is a general health intervention that includes the same initial informational component as the treatment. Participants were recruited over 3 summers (2012-2014) from a summer employment program in New Orleans, Louisiana, that serves primarily African American adolescents.

Results: Six months after program exposure, we found no statistically significant difference between treatment and control group members' self-reported inconsistency of condom use or frequency of sex (P > .05).

Conclusions: Although previous evidence has indicated that this particular program can be effective, this study's findings indicate that it was not effective in this setting with this specific population. Results should provide an incentive to learn why the intervention works in some cases and what conditions are necessary for causal impacts.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5049459PMC
http://dx.doi.org/10.2105/AJPH.2016.303291DOI Listing
September 2016