Publications by authors named "Amy Holmes"

35 Publications

Comparison of neonatal outcomes with use of a soybean oil-based injectable lipid emulsion vs a 4-oil emulsion product.

Am J Health Syst Pharm 2021 01;78(3):210-215

Department of Pharmacy, Novant Health Hemby Children's Hospital, Charlotte, NC.

Purpose: Results of a study comparing the safety and efficacy outcomes with use of a soybean oil-based injectable lipid emulsion (SO-ILE) vs a 4-oil alternative product in a neonatal population are presented.

Methods: In an institutional review board-approved, multicenter retrospective review, the medical records of 328 patients who were born at a gestational age of ≤34 weeks, had a birth weight of 500 to 2,000 g, were admitted to one of 2 neonatal intensive care units (NICUs) within a large health system, and received at least 7 days of a parenteral nutrition containing either lipid emulsion product were reviewed: 151 (46%) had received SO-ILE and 177 (54%) had received SMOFlipid (Fresenius Kabi). The primary outcome of the study was a composite of development of cholestasis and development of hypertriglyceridemia. Secondary outcomes included total duration of cholestasis treatment with ursodiol and change in body weight from initiation to completion of lipid emulsion treatment.

Results: The primary outcome of development of cholestasis or hypertriglyceridemia occurred in 14.6% of patients in the SO-ILE group and 18.1% of patients in the SMOFlipid group (P = 0.393). There were no statistically significant differences between the groups in total days of ursodiol treatment or average body weight change during the course of lipid emulsion treatment.

Conclusion: In preterm neonates weighing 500 to 2,000 g, use of SMOFlipid did not significantly reduce the incidence of cholestasis or hypertriglyceridemia relative to the incidence with use of SO-ILE. Further research to validate these results is needed.
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http://dx.doi.org/10.1093/ajhp/zxaa377DOI Listing
January 2021

In situ spectroscopic identification of the six types of asbestos.

J Hazard Mater 2021 Feb 12;403:123951. Epub 2020 Sep 12.

School of Chemical and Physical Sciences, Keele University, Keele ST5 5BG, United Kingdom.

Exposure to asbestos fibres is related to a number of severe lung diseases, and therefore, rapid, accurate and reliable in situ or on-site asbestos detection in real-life samples is of considerable importance. This work presents a comprehensive investigation of all six types of asbestos by mid-infrared ATR-FTIR, NIR spectroscopy and Raman microspectroscopy. Our studies demonstrate that for practical applications, NIR spectroscopy is potentially the most powerful method for asbestos identification in materials utilised by the construction industry. By focusing on the narrow spectral region, 7300-7000 cm (~1370-1430 nm, overtones of O‒H vibrations), which is highly specific to these materials, and optimising the sensitivity and resolution of the instrumentation, we have been able to discriminate and identify each of the six types of asbestos with the level of detection significantly better than 1 wt%. Furthermore, straightforward computational analysis has allowed for automated objective evaluation of the spectroscopic data.
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http://dx.doi.org/10.1016/j.jhazmat.2020.123951DOI Listing
February 2021

The Influence of the Food and Drug Administration Pregnancy and Lactation Labeling Rule on Drug Information Resources.

Ann Pharmacother 2021 Apr 4;55(4):459-465. Epub 2020 Sep 4.

Auburn University Harrison School of Pharmacy, Meridian, MS, USA.

Background: Drug information resources are commonly used by health-care providers answering pregnancy-related medication questions. In 2015, the United States Food and Drug Administration approved a new pregnancy and lactation medication labeling content and format, removing the pregnancy category, and using a narrative. Despite labeling requirements changing, it is unknown if drug information resources updated monographs to reflect these changes.

Objective: The primary objective was to evaluate if commonly used drug information resources provide pregnancy information listed similar to the requirements of the Pregnancy and Lactation Labeling Rule (PLLR). Secondary analyses included evaluating the references and inclusion of the pregnancy category rating.

Methods: Pregnancy recommendations for 23 medications were evaluated in 9 drug information resources (Clinical Pharmacology, , Epocrates®, First Databank, LexiComp® Online, LexiComp® Online Pregnancy & Lactation, In-Depth, Medi-Span®, Micromedex®, and Multum®). The number of references per drug monograph and most recent reference publication year was obtained.

Results: LexiComp® Online Pregnancy & Lactation, In-Depth mimics the new PLLR structure and consistently had the highest number of and most recent references when the medication was included. was the next most similar in content with the PLLR and second in most references per monograph; however, the most recent reference was the textbook publication year.

Conclusion And Relevance: LexiComp® Online Pregnancy & Lactation, In-Depth and provided pregnancy information in a format most similar to the PLLR. However, several drug information resources contained pregnancy categories ratings that were to be removed from medication labeling per the PLLR.
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http://dx.doi.org/10.1177/1060028020956658DOI Listing
April 2021

Implementing a Clinic-Based Telehealth Support Service (FamilyStrong) for Family Caregivers of Individuals with Grade IV Brain Tumors.

J Palliat Med 2021 Mar 24;24(3):347-353. Epub 2020 Jul 24.

Center for Palliative and Supportive Care, School of Medicine, University of Alabama at Birmingham (UAB), Birmingham, Alabama, USA.

Nearly 3 million U.S. family caregivers support someone with cancer. However, oncology clinic-based service lines that proactively screen, assess, and support cancer caregivers are nearly nonexistent. To examine first-year experiences of a nurse-led clinic-based telehealth support service (FamilyStrong) for family caregivers of patients with recently diagnosed grade IV brain tumors. This is a retrospective evaluation of operational outcomes from initial implementation of the FamilyStrong Service, developed in partnership with Caregiver and Bereavement Support Services at the University of Alabama at Birmingham (UAB) and the UAB Center for Palliative and Supportive Care. From August 2018 to December 2019, 53 family caregivers were proactively identified and enrolled by a palliative care nurse, working approximately one day/week, who performed monthly caregiver distress thermometer screenings by phone and provided emotional, educational, problem-solving, and referral support. Enrolled family caregivers were a mean age of 53.5 years and mostly female (62.3%), full- or part-time employed (67.9%), and the patient's spouse/partner (79.3%). Caregivers provided support 6.7 days/week for 11.2 hours/day. The palliative care nurse performed 235 distress screenings and provided support that included 68 documented instances of emotional, problem-solving, and educational support, 41 nurse-facilitated communications with the neuro-oncology team about patient issues, and 24 referrals to UAB and community services (e.g., counseling). The most common problems caregivers wanted assistance with included: managing their relative's health condition and symptoms (51%), coordinating care/services (21%), and planning for the future/advance care planning (17%). The FamilyStrong Program is among the first "real world" oncology clinic-based formal support services for advance cancer family caregivers.
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http://dx.doi.org/10.1089/jpm.2020.0178DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7894044PMC
March 2021

Disposition and measured toxicity of zinc oxide nanoparticles and zinc ions against keratinocytes in cell culture and viable human epidermis.

Nanotoxicology 2020 03 31;14(2):263-274. Epub 2020 Jan 31.

School of Pharmacy and Medical Sciences, The University of South Australia, Adelaide, Australia.

Suspensions of the UV filter, zinc oxide nanoparticles (ZnO NP), are widely used in sunscreen products. This paper compared the relative disposition and local cytotoxicity of ZnO NP, and zinc ions formed on its dissolution, against keratinocyte cultures and in the human epidermis () after application of suspensions of ZnO NP. HaCaT keratinocyte cytotoxicities were found to be related to labile intra-cellular zinc but also total zinc and extra-cellular concentrations in cell culture media and to a degree ameliorated by the presence of a zinc chelating agent. Secondly, the zinc species were then dosed onto exposed viable human epidermis and it was found that an increase in labile zinc level correlated with a shift in the metabolic state of the viable epidermis. This study highlights that excised viable skin acts as a more relevant model for determining cutaneous toxicity over keratinocyte monolayers .
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http://dx.doi.org/10.1080/17435390.2019.1692382DOI Listing
March 2020

Noninvasive in vivo human multiphoton microscopy: a key method in proving nanoparticulate zinc oxide sunscreen safety.

J Biomed Opt 2020 01;25(1):1-19

Diamantina Institute, The Univ. of Queensland, Australia.

We describe the contribution of our multiphoton microscopy (MPM) studies over the last ten years with DermaInspect (JenLab, Germany), a CE-certified medical tomograph based on detection of fluorescent biomolecules, to the assessment of possible penetration of nanoparticulate zinc oxide in sunscreen through human skin. At the time we started our work, there was a strong movement for the precautionary principle to be applied to the use of nanoparticles in consumer products due to a lack of knowledge. The combined application of different MPM modalities, including spectral imaging, fluorescence lifetime imaging, second harmonic fluorescence generation, and phosphorescence microscopy, has provided overwhelming evidence that nanoparticle zinc oxide particles do not penetrate human skin when applied to various skin types with a range of methods of topical sunscreen application. MPM has also been used to study the viable epidermal morphology and redox state in supporting the safe use of topical zinc oxide nanoparticles. The impact of this work is emphasized by the recent proposed rule by the United States FDA on Sunscreen Drug Products for Over-the-Counter Human Use, which listed only zinc oxide and titanium dioxide of the currently marketed products to be generally recognized as safe and effective.
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http://dx.doi.org/10.1117/1.JBO.25.1.014509DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7008509PMC
January 2020

High Direct Bilirubin Associated With Levoffoxacin Use in a Neonate.

J Pediatr Pharmacol Ther 2020 Jan-Feb;25(1):64-67

Limited data exist regarding the use of fluoroquinolones in the neonatal population. Levofloxacin has some utility in this population because it is one of a very limited number of antibiotics with activity against Stenotrophomonas maltophilia. We describe the successful treatment of S maltophilia tracheitis in a premature neonate using levofloxacin 10 mg/kg every 24 hours and the subsequent unexpected sharp rise in the direct bilirubin. This case illustrates a previously unrecognized adverse drug effect associated with levofloxacin use in neonates.
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http://dx.doi.org/10.5863/1551-6776-25.1.64DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6938287PMC
January 2020

Multiparameter toxicity screening on a chip: Effects of UV radiation and titanium dioxide nanoparticles on HaCaT cells.

Biomicrofluidics 2019 Jul 27;13(4):044112. Epub 2019 Aug 27.

Future Industries Institute, University of South Australia, Mawson Lakes Campus, Mawson Lakes Boulevard, Mawson Lakes, SA 5095, Australia.

Microfluidic screening is gaining attention as an efficient method for evaluating nanomaterial toxicity. Here, we consider a multiparameter treatment where nanomaterials interact with cells in the presence of a secondary exposure (UV radiation). The microfluidic device contains channels that permit immobilization of HaCaT cells (human skin cell line), delivery of titanium dioxide nanoparticles (TNPs), and exposure to a known dose of UV radiation. The effect of single-parameter exposures (UV or TNP) was first studied as a benchmark, and then multiparameter toxicity (UV and TNP) at different concentrations was explored. The results demonstrate a concentration-dependent protective effect of TNP when exposed to UV irradiation.
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http://dx.doi.org/10.1063/1.5113729DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6932853PMC
July 2019

Hypothermia in an Adolescent Due to Probable Drug-Drug Interaction Involving Clobazam.

J Pediatr Pharmacol Ther 2019 Mar-Apr;24(2):156-159

We report on a 16-year-old female who developed hypothermia as a result of a drug-drug interaction that produced supratherapeutic serum concentrations of clobazam. Although clobazam and its active metabolite (-desmethylclobazam) are metabolized by cytochrome 2C19 (CYP2C19), literature suggests that clobazam-associated drug interactions involving this isoenzyme are not clinically relevant because of its wide therapeutic index. This report describes clobazam-associated hypothermia due to supratherapeutic serum concentrations of clobazam that resulted from the combination of 2 CYP2C19 inhibitors.
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http://dx.doi.org/10.5863/1551-6776-24.2.156DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6478366PMC
April 2019

The natural history of vascular and other complications in patients treated with nilotinib for chronic myeloid leukemia.

Blood Adv 2019 04;3(7):1084-1091

Department of Clinical Haematology, Austin Hospital, Melbourne, Australia.

Although second-generation tyrosine kinase inhibitors (TKIs) show superiority in achieving deep molecular responses in chronic myeloid leukemia in chronic phase (CML-CP) compared with imatinib, the differing adverse effect (AE) profiles need consideration when deciding the best drug for individual patients. Long-term data from randomized trials of nilotinib demonstrate an increased risk of vascular AEs (VAEs) compared with other TKIs, although the natural history of these events in response to dose modifications or cessation has not been fully characterized. We retrospectively reviewed the incidence of nilotinib-associated AEs in 220 patients with CML-CP at 17 Australian institutions. Overall, AEs of any grade were reported in 95 patients (43%) and prompted nilotinib cessation in 46 (21%). VAEs occurred in 26 patients (12%), with an incidence of 4.1 events per 100 patient-years. Multivariate analysis identified age ( = .022) and dyslipidemia ( = .007) as independent variables for their development. There was 1 fatal first VAE, whereas the remaining patients either continued nilotinib (14 patients) or stopped it immediately (11 patients). Recurrent VAEs were associated with ongoing therapy in 7 of 14 who continued (with 2 fatal VAEs) vs 1 of 11 who discontinued ( = .04). Nineteen of the 23 evaluable patients surviving a VAE ultimately stopped nilotinib, of whom 14 received an alternative TKI. Dose reduction or cessation because of VAEs did not adversely affect maintenance of major molecular response. These findings demonstrate that in contrast to other AEs, VAEs are ideally managed with nilotinib cessation because of the increased risk of additional events with its ongoing use.
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http://dx.doi.org/10.1182/bloodadvances.2018028035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457217PMC
April 2019

Evaluation of Lactation Compatibility Reference Recommendations.

Ann Pharmacother 2019 09 24;53(9):899-904. Epub 2019 Mar 24.

4 Avita Pharmacy, Salisbury, NC, USA.

Multiple resources aid the interprofessional health care team when recommending medications for lactating patients. Varying degrees of breastfeeding compatibility and safety are recommended in different resources. New Food and Drug Administration labeling for lactation is being phased in to provide more consistent language in safety recommendations. The objective of this study is to evaluate lactation recommendations for select medications from different drug information resources to determine the compatibility recommendations for lactating patients. The breastfeeding recommendations for 19 medications were analyzed in 10 drug information resources. Each drug was reviewed in each resource and the published recommendations evaluated. and LactMed had the most medications listed as compatible with breastfeeding, with Lexicomp Online, , and Epocrates following. LactMed stands out from the group with an average of 15.1 references per medication and number of references ranging from 0 to 58. Date ranges of references used by select resources varied. References to support recommendations ranged from 1979 to 2018 for the select resources. Variation continues to exist across resources with regard to recommendations for medication safety in lactation. LactMed represents the most up-to-date and comprehensive review of literature in this review. When making decisions regarding medication use during lactation, health care professionals should consider reviewing data behind the recommendations and consulting multiple resources.
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http://dx.doi.org/10.1177/1060028019839389DOI Listing
September 2019

Optical Characterization of Zinc Pyrithione.

Photochem Photobiol 2019 09 22;95(5):1142-1150. Epub 2019 Apr 22.

School of Pharmacy and Medical Sciences, University of South Australia and Basil Hetzel Institute for Translational Health Research, Adelaide, SA, Australia.

Zinc pyrithione is ubiquitous in commercial products particularly antidandruff shampoos. For the efficacy of zinc pyrithione therapeutic cleansers to be assessed accurately, the distribution of particles on the scalp needs to be visualized. Currently, no technique is available which provides the chemical specificity and sensitivity required. Here, we report application of fluorescence-lifetime imaging microscopy (FLIM) for high-contrast mapping of zinc pyrithione distribution on the scalp. Characterization of the zinc pyrithione emission by using both one-photon excitation at five specific wavelengths and two-photon excitation in the range of 740-820 nm revealed its FLIM fingerprint-a characteristic short average time-weighted emission lifetime of Τ = 250 ps. Bandpass-filtering FLIM signals at Τ enabled an efficient discrimination between the zinc pyrithione and major endogenous skin species in comparison with that of the conventional reflectance confocal microscopy. Our findings provide means for in vivo high-sensitivity assaying and high-contrast imaging of zinc pyrithione in biological systems.
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http://dx.doi.org/10.1111/php.13100DOI Listing
September 2019

Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment.

Eur J Pharm Biopharm 2019 Jun 13;139:33-43. Epub 2019 Feb 13.

Division of Advanced Materials and Healthcare Technologies, School of Pharmacy, The University of Nottingham, NG7 2RD, UK. Electronic address:

Basal cell carcinoma (BCC) is the most common skin cancer in humans. Topical treatment with imiquimod provides a non-invasive, self-administered treatment with relatively low treatment cost. Despite displaying excellent efficacy, imiquimod is only licensed by the FDA for superficial BCC. The current work employed HPLC and ToF-SIMS analysis to provide a novel assessment of imiquimod permeation from Aldara™ cream in skin depth and lateral distribution. Using Aldara™ cream and in vitro Franz cell studies with subsequent HPLC analysis, it is apparent that most of the topically applied imiquimod cream is left on the skin surface with more than 80% of the drug being recovered from skin wash. In addition, ToF-SIMS chemical imaging of recovered tape stripped skin samples illustrated significant detection of imiquimod signal over the entire skin area for the upper tape strips, whereas the deeper strips show large portions of the skin area without detected imiquimod. Given the limited permeation depth and non-uniform permeation observed at tape strips 6-18 when applied as a topical imiquimod cream, a permeation enhancement strategy utilising a skin pre-treatment with a microneedle device was investigated as a method to improve intradermal delivery. The recovered amount of imiquimod in tape strips and remaining skin determined by HPLC was approximately three times higher when Aldara™ was applied on microneedle pre-treated skin relative to intact skin. The ToF-SIMS ion images of the tape strips and cross-sections illustrated the existence of imiquimod in the microchannels which then laterally diffuses to peripheral epidermal strata. The current work demonstrates the first known attempt to enhance intradermal delivery of imiquimod using a microneedle device as well as underscoring the complementary role of ToF-SIMS analysis in chemically mapping imiquimod permeation into the skin with high sensitivity.
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http://dx.doi.org/10.1016/j.ejpb.2019.02.006DOI Listing
June 2019

Antimicrobial efficacy and mechanism of action of poly(amidoamine) (PAMAM) dendrimers against opportunistic pathogens.

Int J Antimicrob Agents 2019 Apr 30;53(4):500-507. Epub 2018 Dec 30.

School of Pharmacy, Keele University, Keele, Staffordshire ST5 5BG, UK. Electronic address:

The aim of this study was to investigate a range of poly(amidoamine) (PAMAM) dendrimer generations against Gram-positive and Gram-negative skin pathogens and to determine any differences in antimicrobial potency for different generations, characterising how differences in physicochemical properties influence antimicrobial efficacy. A range of tests were carried out, including viable count assays to determine half maximal inhibitory concentration (IC) values for each dendrimer, membrane integrity studies and an inner membrane permeabilisation assay. This is supported by scanning electron microscopy imaging of the interactions observed between dendrimers and bacteria. The results of this study indicate that the antimicrobial efficacy of native PAMAM dendrimers is dependent on generation, concentration and terminal functionalities, for example, the concentration at 50% growth inhibition (MIC) (µg/mL), against Staphylococcus aureus was between 26.77 for the G2-PAMAM-NH dendrimer and 2.881 for the G5-PAMAM-NH dendrimer. There was a strong correlation between membrane disruption and the determined biocidal activity, making it a key contributing mechanism of action. This study demonstrates that selection of the type of PAMAM dendrimer is important as their inherent antimicrobial efficacy varies according to their individual physicochemical properties. This understanding may pave the way for the development of enhanced dendrimer-based antimicrobial formulations and drug-delivery systems.
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http://dx.doi.org/10.1016/j.ijantimicag.2018.12.012DOI Listing
April 2019

Support for the Safe Use of Zinc Oxide Nanoparticle Sunscreens: Lack of Skin Penetration or Cellular Toxicity after Repeated Application in Volunteers.

J Invest Dermatol 2019 02 15;139(2):308-315. Epub 2018 Nov 15.

Therapeutics Research Centre, The University of Queensland Diamantina Institute, Translational Research Institute, Brisbane, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Sansom Institute, City East Campus, Adelaide, Australia. Electronic address:

Zinc oxide is a widely used broad-spectrum sunscreen, but concerns have been raised about the safety of its nanoparticle (NP) form. We studied the safety of repeated application of agglomerated zinc oxide (ZnO) NPs applied to human volunteers over 5 days by assessing the skin penetration of intact ZnO-NPs and zinc ions and measuring local skin toxicity. Multiphoton tomography with fluorescence lifetime imaging microscopy was used to directly visualize ZnO-NP skin penetration and viable epidermal metabolic changes in human volunteers. The fate of ZnO-NPs was also characterized in excised human skin in vitro. ZnO-NPs accumulated on the skin surface and within the skin furrows but did not enter or cause cellular toxicity in the viable epidermis. Zinc ion concentrations in the viable epidermis of excised human skin were slightly elevated. In conclusion, repeated application of ZnO-NPs to the skin, as used in global sunscreen products, appears to be safe, with no evidence of ZnO-NP penetration into the viable epidermis nor toxicity in the underlying viable epidermis. It was associated with the release and penetration of zinc ions into the skin, but this did not appear to cause local toxicity.
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http://dx.doi.org/10.1016/j.jid.2018.08.024DOI Listing
February 2019

Position Paper: Pharmacists and Childhood Vaccines.

J Pediatr Pharmacol Ther 2018 Jul-Aug;23(4):343-346

Vaccination rates of children in the United States remain below the target coverage levels identified in the Healthy People 2020 objectives. Given the success of pharmacists in providing adult vaccinations and the accessibility of pharmacists to the public, expanding pharmacists' authority to vaccinate children may improve vaccination rates of children, particularly in key disease states. This article serves as a Position Statement of the Pediatric Pharmacy Advocacy Group (PPAG), who supports the expansion of pharmacists' authority to vaccinate children. PPAG also believes that increased use of state vaccination registries by pharmacists will help improve communication and documentation of vaccines between providers. PPAG also recommends that continued education and maintaining current knowledge of vaccines and vaccine schedules are vital for pharmacist immunizers. Finally, PPAG believes that pharmacists should be advocates for childhood vaccinations.
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http://dx.doi.org/10.5863/1551-6776-23.4.343DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117813PMC
September 2018

In-field collection and preservation of decomposing human tissues to facilitate rapid purification and STR typing.

Forensic Sci Int Genet 2018 09 25;36:124-129. Epub 2018 Jun 25.

Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, TX 77340, United States. Electronic address:

Short tandem repeats (STR) are currently the gold standard in human identification for forensic casework purposes, and successful STR typing is dependent on sufficient quantity and quality DNA. In the aftermath of a mass disaster and some forensic cases, human remains are recovered for identification in various stages of decomposition, and ideally these remains are transported to a refrigerated facility in order to halt the decomposition process and preserve the integrity of DNA within the tissue. However, in situations where refrigeration is not available (e.g., after a mass disaster or in rural forensic casework), remains continue to be exposed to environmental insults after collection, causing further DNA damage and degradation. Therefore, successful STR typing is dependent on the time of collection and preservation of the DNA sample. This study aims to test two simple in-field collection and preservation methods for decomposing human tissues that are subsequently stored at room temperature for up to six months either in a tissue preservative solution (modified TENT buffer) or on an FTA Elute Card. In addition, these collection and preservation methods were tested for their ability to facilitate more direct and faster processing of DNA from preserved tissues or DNA leached into the surrounding TENT preservative solution for STR typing. Pre-PCR methods tested in this study include a quick lysis of FTA Elute Cards, silica-based purification (QIAquick), enzyme-based extractions (PDQeX), and simple dilution of liquid preservative. The traditional DNA analysis pipeline, which includes DNA extraction and quantification, will be compared to an alternate direct PCR method, thereby allowing the elimination of these two time-consuming and costly steps. The results indicate that modified TENT preservative and FTA Elute Cards both preserved DNA from relatively fresh tissue for up to six months at room temperature. However, mostly partial profiles were produced from decomposed tissues (day 6 - day 14 in this study) when stored for up to six months compared to when tissues were processed immediately following collection. Overall, the modified TENT preservative produced higher DNA concentrations and more successful STR results than FTA Elute Cards. In addition, a rapid DNA extraction platform (PDQeX) generated the most successful STR typing results from the decomposed tissues stored in TENT for up to six months at room temperature. The direct PCR method used in this study generated comparable STR results to the traditional DNA analysis approach, warranting further investigation of direct PCR methods for forensic casework type samples.
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http://dx.doi.org/10.1016/j.fsigen.2018.06.015DOI Listing
September 2018

Demonstration of the lack of cytotoxicity of unmodified and folic acid modified graphene oxide quantum dots, and their application to fluorescence lifetime imaging of HaCaT cells.

Mikrochim Acta 2018 01 24;185(2):128. Epub 2018 Jan 24.

The MacDiarmid Institute for Advanced Materials and Nanotechnology, School of Chemical and Physical Science, Victoria University of Wellington, PO Box 600, Wellington, 6140, New Zealand.

The authors describe the synthesis of water-soluble and fluorescent graphene oxide quantum dots via acid exfoliation of graphite nanoparticles. The resultant graphene oxide quantum dots (GoQDs) were then modified with folic acid. Folic acid receptors are overexpressed in cancer cells and hence can bind to functionalized graphene oxide quantum dots. On excitation at 305 nm, the GoQDs display green fluorescence with a peak wavelength at ~520 nm. The modified GoQDs are non-toxic to macrophage cells even after prolonged exposure and high concentrations. Fluorescence lifetime imaging and multiphoton microscopy was used (in combination) to image HeCaT cells exposed to GoQDs, resulting in a superior method for bioimaging. Graphical abstract Schematic representation of graphene oxide quantum dots, folic acid modified graphene oxide quantum dots (red), and the use of fluorescence lifetime to discriminate against green auto-fluorescence of HeCaT cells.
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http://dx.doi.org/10.1007/s00604-018-2679-8DOI Listing
January 2018

Imaging the penetration and distribution of zinc and zinc species after topical application of zinc pyrithione to human skin.

Toxicol Appl Pharmacol 2018 03 20;343:40-47. Epub 2018 Feb 20.

The University of South Australia, School of Pharmacy and Medical Sciences, Adelaide, Australia; The University of Queensland, Therapeutics Research Centre, Brisbane, Australia. Electronic address:

Zinc pyrithione is an active component incorporated in an extensive range of topically applied commercial products that are used worldwide. Despite its prevalence, no published study has investigated the penetration of zinc from the zinc pyrithione complex into human skin. Zinc is crucial for healthy skin function however an elevated concentration of labile zinc is toxic outside a narrow concentration range. Synchrotron X-ray fluorescence microscopy in conjunction with X-ray absorption near edge structure spectroscopy was used to map the deposition of zinc, quantitate the amount of zinc within the skin and to identify a change in the chemical form of zinc after application. This study has demonstrated a ~3.8 fold increase in zinc concentration within the viable epidermis (VE) after 24 h topical application of zinc pyrithione that increased significantly by ~250 fold after 48 h when compared to control skin. Confocal microscopy using a labile zinc specific dye, ZinPyr-1, showed that zinc pyrithione disrupted the skin cells zinc homeostasis and significantly increased the intracellular zinc concentration leading to cell toxicity. Overall, this study demonstrates that topical application of zinc pyrithione formulations leads to an increase in zinc penetration in human skin, consequently, raising concerns for potential localised toxicity to occur.
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http://dx.doi.org/10.1016/j.taap.2018.02.012DOI Listing
March 2018

The incidence and natural history of dasatinib complications in the treatment of chronic myeloid leukemia.

Blood Adv 2017 May 15;1(13):802-811. Epub 2017 May 15.

Austin Hospital, Melbourne, Australia.

Dasatinib has shown superiority over imatinib in achieving molecular responses (MRs) in chronic phase chronic myeloid leukemia but with a different toxicity profile, which may impact its overall benefit. Reported toxicities include pleural effusions and pulmonary hypertension, and although the incidence of these events is well described, response to therapy and impact of dose modifications on toxicity has not been comprehensively characterized in a real-world setting. We retrospectively reviewed the incidence of dasatinib adverse events in 212 chronic phase chronic myeloid leukemia patients at 17 Australian institutions. Adverse events were reported in 116 patients (55%), most commonly pleural effusions (53 patients, 25%), which was the predominant cause of permanent drug cessation. Age and dose were risk factors for pleural effusion ( < .01 and .047, respectively). Recurrence rates were higher in those who remained on 100 mg compared with those who dose reduced ( = .041); however, recurrence still occurred at 50 mg. Patients who developed pleural effusions were more likely to have achieved MR4.5 after 6 months of dasatinib than those without effusions ( = .008). Pulmonary hypertension occurred in 5% of patients, frequently in association with pleural effusion, and was reversible upon dasatinib cessation in 6 of 7 patients. Dose reductions and temporary cessations had minimal impact on MR rates. Our observations suggest that by using the lowest effective dose in older patients to minimize the effusion risk, dose modification for cytopenias, and care with concomitant antiplatelet therapy, the necessity for permanent dasatinib cessation due to toxicity is likely to be minimal in immunologically competent patients.
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http://dx.doi.org/10.1182/bloodadvances.2016003889DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5727806PMC
May 2017

Evaluation of four commercial quantitative real-time PCR kits with inhibited and degraded samples.

Int J Legal Med 2018 May 24;132(3):691-701. Epub 2017 Nov 24.

Department of Forensic Science, College of Criminal Justice, Sam Houston State University, Huntsville, TX, 77340, USA.

DNA quantification is a vital step in forensic DNA analysis to determine the optimal input amount for DNA typing. A quantitative real-time polymerase chain reaction (qPCR) assay that can predict DNA degradation or inhibitors present in the sample prior to DNA amplification could aid forensic laboratories in creating a more streamlined and efficient workflow. This study compares the results from four commercial qPCR kits: (1) Investigator® Quantiplex® Pro Kit, (2) Quantifiler® Trio DNA Quantification Kit, (3) PowerQuant® System, and (4) InnoQuant® HY with high molecular weight DNA, low template samples, degraded samples, and DNA spiked with various inhibitors.The results of this study indicate that all kits were comparable in accurately predicting quantities of high quality DNA down to the sub-picogram level. However, the InnoQuant(R) HY kit showed the highest precision across the DNA concentration range tested in this study. In addition, all kits performed similarly with low concentrations of forensically relevant PCR inhibitors. However, in general, the Investigator® Quantiplex® Pro Kit was the most tolerant kit to inhibitors and provided the most accurate quantification results with higher concentrations of inhibitors (except with salt). PowerQuant® and InnoQuant® HY were the most sensitive to inhibitors, but they did indicate significant levels of PCR inhibition. When quantifying degraded samples, each kit provided different degradation indices (DI), with Investigator® Quantiplex® Pro indicating the largest DI and Quantifiler® Trio indicating the smallest DI. When the qPCR kits were paired with their respective STR kit to genotype highly degraded samples, the Investigator® 24plex QS and GlobalFiler® kits generated more complete profiles when the small target concentrations were used for calculating input amount.
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http://dx.doi.org/10.1007/s00414-017-1745-9DOI Listing
May 2018

Changes in Neonatal Mineral Administration and Contaminant Exposure due to Sodium Phosphate Shortage.

Am J Perinatol 2017 12 13;34(14):1451-1457. Epub 2017 Jul 13.

Department of Pharmacy, Novant Health Forsyth Medical Center, Winston-Salem, North Carolina.

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http://dx.doi.org/10.1055/s-0037-1604041DOI Listing
December 2017

Breastfeeding Considerations for Mothers of Infants with Neonatal Abstinence Syndrome.

Pharmacotherapy 2017 Jul 22;37(7):861-869. Epub 2017 Jun 22.

Wake Forest Baptist Medical Center, Winston Salem, North Carolina.

Breastfeeding offers many benefits to both mother and baby. Breastfeeding is generally recommended for mothers of infants with neonatal abstinence syndrome (NAS) unless some associated risk outweighs the benefits. Evidence indicates that infants with NAS who receive human milk require less pharmacologic treatment and have shorter hospital lengths of stay. Perhaps the greatest barrier to breastfeeding for women with opioid dependence is the inaccurate and inconsistent information they receive from different sources, including health care professionals. The American Congress of Obstetricians and Gynecologists, American Academy of Pediatrics, and Academy of Breastfeeding Medicine (ABM) have published statements that support breastfeeding infants with NAS. The ABM has a dedicated protocol to guide clinicians in deciding which mothers should and which mothers should not breastfeed their infants. In this review, studies evaluating the effects of breastfeeding, professional organizations' protocols and recommendations regarding breastfeeding, and barriers to breastfeeding infants with NAS are discussed, as well as the dangers of illicit drug exposure and avoiding rebound NAS in a breastfed infant. Clinicians can play an important role in in identifying, supporting, counseling, and advocating for mothers who wish to breastfeed their infant with NAS.
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http://dx.doi.org/10.1002/phar.1944DOI Listing
July 2017

Neonatal Herpes Simplex Viral Infections and Acyclovir: An Update.

J Pediatr Pharmacol Ther 2017 Mar-Apr;22(2):88-93

Neonatal herpes simplex virus (HSV) infections have high morbidity and mortality rates. Optimization of treatment and prevention strategies are imperative to improve the care and outcomes of neonates infected with HSV. Management of HSV includes reducing neonatal transmission, treating acute infections, and limiting adverse neurodevelopmental outcomes and future cutaneous outbreaks after acute infections. Transmission risk may be affected by route of delivery and maternal suppressive therapy. Neonatal HSV infections are divided into 3 categories: localized skin, eyes, or mouth; localized central nervous system; or disseminated infections. Parenteral acyclovir, the pharmacologic agent of choice, is used when treating each type of infection. However, dosage strategies and durations of therapy may vary based on disease state severity, presentation, and patient characteristics. Oral acyclovir may be used as suppressive therapy after acute treatment completion in specific neonatal populations, reducing long-term adverse neurodevelopmental outcomes and future skin eruptions. The mortality rate remains high even with treatment.
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http://dx.doi.org/10.5863/1551-6776-22.2.88DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5410863PMC
May 2017

Novel Mutations Resulting in a Moderate to Severe Phenotypic Manifestation of Hemophilia A in a Female.

J Pediatr Hematol Oncol 2017 10;39(7):e403-e405

*College of Medicine, Biology and Environment, Australian National University †The Canberra Hospital, Canberra, ACT, Australia.

Hemophilia A is an X-linked, recessive disorder resulting from mutations in the f8 gene. Here we report the rare case of a female compound heterozygote with mild factor VIII deficiency (fVIII:C 9%) and moderate phenotype. On investigation she was confirmed to have normal Von Willebrand factor studies with a 46XY genotype. Further genetic testing revealed 3 mutations in the f8 gene: 1 novel missense mutation (c.6142T>G), 1 novel in-frame deletion (c.1281_1292del), and another missense mutation of unclear significance (c.3780C>G). Both parents had normal coagulation profiles; however, the 2 novel mutations were present in the patient's mother and the known missense mutation was present in her father. This unusual case demonstrates the utility in genetic analysis for f8 gene mutational analysis and suggests a compound effect of the 3 identified mutations as a cause for factor deficiency.
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http://dx.doi.org/10.1097/MPH.0000000000000832DOI Listing
October 2017

Dendrimer pre-treatment enhances the skin permeation of chlorhexidine digluconate: Characterisation by in vitro percutaneous absorption studies and Time-of-Flight Secondary Ion Mass Spectrometry.

Eur J Pharm Sci 2017 Jun 29;104:90-101. Epub 2017 Mar 29.

School of Pharmacy, Keele University, Keele, Staffordshire ST5 5BG, UK. Electronic address:

Skin penetration and localisation of chlorhexidine digluconate (CHG) within the skin have been investigated in order to better understand and optimise the delivery using a nano polymeric delivery system of this topically-applied antimicrobial drug. Franz-type diffusion cell studies using in vitro porcine skin and tape stripping procedures were coupled with Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS) to visualise the skin during various treatments with CHG and polyamidoamine dendrimers (PAMAM). Pre-treatment of the skin with PAMAM dendrimers significantly increased the amount and depth of permeation of CHG into the skin in vitro. The effect observed was not concentration dependant in the range 0.5-10mM PAMAM. This could be important in terms of the efficiency of treatment of bacterial infection in the skin. It appears that the mechanism of enhancement is due to the PAMAM dendrimer disrupting skin barrier lipid conformation or by occluding the skin surface. Franz-type diffusion cell experiments are complimented by the detailed visualisation offered by the semi-quantitative ToF-SIMS method which provides excellent benefits in terms of sensitivity and fragment ion specificity. This allows a more accurate depth profile of chlorhexidine permeation within the skin to be obtained and potentially affords the opportunity to map the co-localisation of permeants with skin structures, thus providing a greater ability to characterise skin absorption and to understand the mechanism of permeation, providing opportunities for new and more effective therapies.
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http://dx.doi.org/10.1016/j.ejps.2017.03.034DOI Listing
June 2017

Varying the morphology of silver nanoparticles results in differential toxicity against micro-organisms, HaCaT keratinocytes and affects skin deposition.

Nanotoxicology 2016 12 5;10(10):1503-1514. Epub 2016 Oct 5.

a School of Pharmacy and Medical Sciences, The University of South Australia , Adelaide , Australia.

The use of silver nanoparticles (Ag NPs) within the healthcare sector and consumer products is rapidly increasing. There are now a range of diverse-shaped Ag NPs that are commercially available and many of the products containing nanosilver are topically applied to human skin. Currently, there is limited data on the extent to which the antimicrobial efficacy and cytotoxicity of Ag NPs is related to their shape and how the shape of the Ag NPs affects their distribution in both intact and burn wounded human skin after topical application. In this study, we related the relative Ag NP cytotoxicity to potential skin pathogens and HaCaT keratinocytes in vitro with the shape of the Ag NPs. We employed multiphoton fluorescence lifetime imaging to map the distribution of the native and unlabeled Ag NPs after topical application to both intact and burn wounded human skin using the localized surface plasmon resonance signal of the Ag NPs. Truncated plate shaped Ag NPs led to the highest cytotoxicity against both bacteria (IC ranges from 31.25 to 125 μg/mL depending on the bacterial species) and HaCaT keratinocytes (IC 78.65 μg/mL [95%CI 63.88, 96.83]) thus both with similar orders of magnitude. All Ag NPs were less cytotoxic than solutions of silver nitrate (IC of 7.85 μg/mL [95%CI 1.49, 14.69]). Plate-shaped Ag NPs displayed the highest substantivity within the superficial layers of the stratum corneum when topically applied to intact skin and the highest deposition into the wound bed when applied to burned ex vivo human skin relative to other Ag NP shapes.
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http://dx.doi.org/10.1080/17435390.2016.1236993DOI Listing
December 2016

First Golden Hour of Life: A Quality Improvement Initiative.

Adv Neonatal Care 2016 Aug;16(4):264-72

Wake Forest University School of Medicine, Winston-Salem, North Carolina (Drs Lambeth and Rojas); Novant Health Forsyth Medical Center, Winston-Salem, North Carolina (Drs Lambeth, Rojas, and Holmes); and Duke University School of Nursing and School of Medicine, Durham, North Carolina (Dr Dail).

Background: Very low birth-weight (<1500 g) infants are vulnerable to their environment during the first hour after birth. We designed an evidence-based golden hour protocol (GHP) with a goal to stabilize and perform admission procedures within 1 hour of birth at a level IIIB neonatal intensive care unit (NICU).

Purpose: The aim of this quality improvement project was to ascertain whether an evidence-based GHP would improve care efficiency and short-term outcomes.

Methods: Rapid cycles of change using Plan Do Study Act were utilized to document progress and gain knowledge during the quality improvement project. Measures were plotted with statistical process control methods (SPC), which analyzed improvement over time.

Results: Both admission temperature and glucose-level means were within reference range throughout the project and predicted a stable process. We observed significantly decreased time to initiation of intravenous fluids and antibiotics. An upward trend of surfactant administration within the first 2 hours of life was also observed.

Implications For Practice: The use of a GHP provided an organized approach to admission procedures and care. By using a checklist and recording intervention times, NICU caregivers were more aware of time management for each intervention and were able to decrease time to initiation of intravenous fluids and antibiotics.

Implications For Research: Future research should focus on establishing normal blood pressure ranges and safe pain management during the "golden hour" and beyond. Future quality improvement should focus on improving subsequent temperature and blood glucose levels after admission umbilical artery and venous catheter placement.
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http://dx.doi.org/10.1097/ANC.0000000000000306DOI Listing
August 2016

Effect of flexing and massage on in vivo human skin penetration and toxicity of zinc oxide nanoparticles.

Nanomedicine (Lond) 2016 05 22;11(10):1193-205. Epub 2016 Apr 22.

Therapeutics Research Centre, School of Medicine, The University of Queensland, Translational Research Institute, Woolloongabba, QLD, Australia.

Aim: We assessed the effects of flexing and massage on human skin penetration and toxicity of topically applied coated and uncoated zinc oxide nanoparticles (˜75 nm) in vivo.

Materials & Methods: Noninvasive multiphoton tomography with fluorescence lifetime imaging was used to evaluate the penetration of nanoparticles through the skin barrier and cellular apoptosis in the viable epidermis.

Results: All nanoparticles applied to skin with flexing and massage were retained in the stratum corneum or skin furrows. No significant penetration into the viable epidermis was seen and no cellular toxicity was detected.

Conclusion: Exposure of normal in vivo human skin to these nanoparticles under common in-use conditions of flexing or massage is not associated with significant adverse events.
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http://dx.doi.org/10.2217/nnm-2016-0010DOI Listing
May 2016

Relative Penetration of Zinc Oxide and Zinc Ions into Human Skin after Application of Different Zinc Oxide Formulations.

ACS Nano 2016 Feb 21;10(2):1810-9. Epub 2016 Jan 21.

School of Pharmacy and Medical Sciences, The University of South Australia , Adelaide, Australia , 5000.

Zinc oxide (ZnO) is frequently used in commercial sunscreen formulations to deliver their broad range of UV protection properties. Concern has been raised about the extent to which these ZnO particles (both micronized and nanoparticulate) penetrate the skin and their resultant toxicity. This work has explored the human epidermal skin penetration of zinc oxide and its labile zinc ion dissolution product that may potentially be formed after application of ZnO nanoparticles to human epidermis. Three ZnO nanoparticle formulations were used: a suspension in the oil, capric caprylic triglycerides (CCT), the base formulation commonly used in commercially available sunscreen products; an aqueous ZnO suspension at pH 6, similar to the natural skin surface pH; and an aqueous ZnO suspension at pH 9, a pH at which ZnO is stable and there is minimal pH-induced impairment of epidermal integrity. In each case, the ZnO in the formulations did not penetrate into the intact viable epidermis for any of the formulations but was associated with an enhanced increase in zinc ion fluorescence signal in both the stratum corneum and the viable epidermis. The highest labile zinc fluorescence was found for the ZnO suspension at pH 6. It is concluded that, while topically applied ZnO does not penetrate into the viable epidermis, these applications are associated with hydrolysis of ZnO on the skin surface, leading to an increase in zinc ion levels in the stratum corneum, thence in the viable epidermis and subsequently in the systemic circulation and the urine.
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http://dx.doi.org/10.1021/acsnano.5b04148DOI Listing
February 2016