31 research outputs found
Electrical Polarization of Titanium Surfacesfor the Enhancement of Osteoblast Differentiation
Electrical stimulation has been used clinically to promote bone regeneration in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports suggesting its beneficial effects on bone formation. However, the use of electrical stimulation of titanium (Ti) implants to enhance osseointegration is less understood, in part because of the few in vitro models that attempt to represent the in vivo environment. In this article, the design of a new in vitro system that allows direct electrical stimulation of osteoblasts through their Ti substrates without the flow of exogenous currents through the media is presented, and the effect of applied electrical polarization on osteoblast differentiation and local factor production was evaluated. A custom-made polycarbonate tissue culture plate was designed to allow electrical connections directly underneath Ti disks placed inside the wells, which were supplied with electrical polarization ranging from 100 to 500 mV to stimulate MG63 osteoblasts. Our results show that electrical polarization applied directly through Ti substrates on which the cells are growing in the absence of applied electrical currents may increase osteoblast differentiation and local factor production in a voltage-dependent manner. Bioelectromagnetics © 2013 Wiley Periodicals, IncElectrical stimulation has been used clinically to promote bone regeneration in cases of fractures with delayed union or nonunion, with several in vitro and in vivo reports suggesting its beneficial effects on bone formation. However, the use of electrical stimulation of titanium (Ti) implants to enhance osseointegration is less understood, in part because of the few in vitro models that attempt to represent the in vivo environment. In this article, the design of a new in vitro system that allows direct electrical stimulation of osteoblasts through their Ti substrates without the flow of exogenous currents through the media is presented, and the effect of applied electrical polarization on osteoblast differentiation and local factor production was evaluated. A custom-made polycarbonate tissue culture plate was designed to allow electrical connections directly underneath Ti disks placed inside the wells, which were supplied with electrical polarization ranging from 100 to 500 mV to stimulate MG63 osteoblasts. Our results show that electrical polarization applied directly through Ti substrates on which the cells are growing in the absence of applied electrical currents may increase osteoblast differentiation and local factor production in a voltage-dependent manner. Bioelectromagnetics © 2013 Wiley Periodicals, In
Proteomic fingerprint identification of Neotropical hard tick species (Acari: Ixodidae) using a self-curated mass spectra reference library
Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry is an analytical method that detects macromolecules that can be used as biomarkers for taxonomic identification in arthropods. The conventional MALDI approach uses fresh laboratory-reared arthropod specimens to build a reference mass spectra library with high-quality standards required to achieve reliable identification. However, this may not be possible to accomplish in some arthropod groups that are difficult to rear under laboratory conditions, or for which only alcohol preserved samples are available. Here, we generated MALDI mass spectra of highly abundant proteins from the legs of 18 Neotropical species of adult field-collected hard ticks, several of which had not been analyzed by mass spectrometry before. We then used their mass spectra as fingerprints to identify each tick species by applying machine learning and pattern recognition algorithms that combined unsupervised and supervised clustering approaches. Both principal component analysis (PCA) and linear discriminant analysis (LDA) classification algorithms were able to identify spectra from different tick species, with LDA achieving the best performance when applied to field-collected specimens that did have an existing entry in a reference library of arthropod protein spectra. These findings contribute to the growing literature that ascertains mass spectrometry as a rapid and effective method for taxonomic identification of disease vectors, which is the first step to predict and manage arthropod-borne pathogens.
Author Summary Hard ticks (Ixodidae) are external parasites that feed on the blood of almost every species of terrestrial vertebrate on earth, including humans. Due to a complete dependency on blood, both sexes and even immature stages, are capable of transmitting disease agents to their hosts, causing distress and sometimes death. Despite the public health significance of ixodid ticks, accurate species identification remains problematic. Vector species identification is core to developing effective vector control schemes. Herein, we provide the first report of MALDI identification of several species of field-collected Neotropical tick specimens preserved in ethanol for up to four years. Our methodology shows that identification does not depend on a commercial reference library of lab-reared samples, but with the help of machine learning it can rely on a self-curated reference library. In addition, our approach offers greater accuracy and lower cost per sample than conventional and modern identification approaches such as morphology and molecular barcoding.Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry is an analytical method that detects macromolecules that can be used as biomarkers for taxonomic identification in arthropods. The conventional MALDI approach uses fresh laboratory-reared arthropod specimens to build a reference mass spectra library with high-quality standards required to achieve reliable identification. However, this may not be possible to accomplish in some arthropod groups that are difficult to rear under laboratory conditions, or for which only alcohol preserved samples are available. Here, we generated MALDI mass spectra of highly abundant proteins from the legs of 18 Neotropical species of adult field-collected hard ticks, several of which had not been analyzed by mass spectrometry before. We then used their mass spectra as fingerprints to identify each tick species by applying machine learning and pattern recognition algorithms that combined unsupervised and supervised clustering approaches. Both principal component analysis (PCA) and linear discriminant analysis (LDA) classification algorithms were able to identify spectra from different tick species, with LDA achieving the best performance when applied to field-collected specimens that did have an existing entry in a reference library of arthropod protein spectra. These findings contribute to the growing literature that ascertains mass spectrometry as a rapid and effective method for taxonomic identification of disease vectors, which is the first step to predict and manage arthropod-borne pathogens.
Author Summary Hard ticks (Ixodidae) are external parasites that feed on the blood of almost every species of terrestrial vertebrate on earth, including humans. Due to a complete dependency on blood, both sexes and even immature stages, are capable of transmitting disease agents to their hosts, causing distress and sometimes death. Despite the public health significance of ixodid ticks, accurate species identification remains problematic. Vector species identification is core to developing effective vector control schemes. Herein, we provide the first report of MALDI identification of several species of field-collected Neotropical tick specimens preserved in ethanol for up to four years. Our methodology shows that identification does not depend on a commercial reference library of lab-reared samples, but with the help of machine learning it can rely on a self-curated reference library. In addition, our approach offers greater accuracy and lower cost per sample than conventional and modern identification approaches such as morphology and molecular barcoding
Targeting Therapeutics to Bone by Conjugation with Bisphosphonates
Bisphosphonates target and bind avidly to the mineral (hydroxyapatite) found in bone. This targeting ability has been exploited to design and prepare bisphosphonate conjugate prodrugs to deliver a wide variety of drug molecules selectively to bones. It is important that conjugates be stable in the blood stream and that conjugate that is not taken up by bone is eliminated rapidly. The prodrugs should release active drug at a rate appropriate so as to provide efficacy. Radiolabelling is the best method to quantify and evaluate pharmacokinetics, tissue distribution, bone uptake and release of the active drug(s). Recent reports have described bisphosphonate conjugates derived from the antiresorptive drug, alendronic acid and anabolic prostanoid drugs that effectively deliver prostaglandins and prostaglandin EP4 receptor agonists to bone and show enhanced anabolic efficacy and tolerability compared to the drugs alone. These conjugate drugs can be dosed infrequently (weekly or bimonthly) whereas the free drugs must be dosed daily
BOB CAT: a Large-Scale Review and Delphi Consensus for Management of Barrett’s Esophagus With No Dysplasia, Indefinite for, or Low-Grade Dysplasia
OBJECTIVES:
Barrett’s esophagus (BE) is a common premalignant lesion for which surveillance is recommended. This strategy is limited by considerable variations in clinical practice. We conducted an international, multidisciplinary, systematic search and evidence-based review of BE and provided consensus recommendations for clinical use in patients with nondysplastic, indefinite, and low-grade dysplasia (LGD).
METHODS:
We defined the scope, proposed statements, and searched electronic databases, yielding 20,558 publications that were screened, selected online, and formed the evidence base. We used a Delphi consensus process, with an 80% agreement threshold, using GRADE (Grading of Recommendations Assessment, Development and Evaluation) to categorize the quality of evidence and strength of recommendations.
RESULTS:
In total, 80% of respondents agreed with 55 of 127 statements in the final voting rounds. Population endoscopic screening is not recommended and screening should target only very high-risk cases of males aged over 60 years with chronic uncontrolled reflux. A new international definition of BE was agreed upon. For any degree of dysplasia, at least two specialist gastrointestinal (GI) pathologists are required. Risk factors for cancer include male gender, length of BE, and central obesity. Endoscopic resection should be used for visible, nodular areas. Surveillance is not recommended for <5 years of life expectancy. Management strategies for indefinite dysplasia (IND) and LGD were identified, including a de-escalation strategy for lower-risk patients and escalation to intervention with follow-up for higher-risk patients.
CONCLUSIONS:
In this uniquely large consensus process in gastroenterology, we made key clinical recommendations for the escalation/de-escalation of BE in clinical practice. We made strong recommendations for the prioritization of future research
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Neonatal AVPR1a Methylation and In-Utero Exposure to Maternal Smoking.
(1) Introduction: Epigenetic changes have been proposed as a biologic link between in-utero exposure to maternal smoking and health outcomes. Therefore, we examined if in-utero exposure to maternal smoking was associated with infant DNA methylation (DNAm) of cytosine-phosphate-guanine dinucleotides (CpG sites) in the arginine vasopressin receptor 1A AVPR1a gene. The AVPR1a gene encodes a receptor that interacts with the arginine vasopressin hormone and may influence physiological stress regulation, blood pressure, and child development. (2) Methods: Fifty-two infants were included in this cohort study. Multivariable linear models were used to examine the effect of in-utero exposure to maternal smoking on the mean DNAm of CpG sites located at AVPR1a. (3) Results: After adjusting the model for substance use, infants with in-utero exposure to maternal smoking had a reduction in DNAm at AVPR1a CpG sites by -0.02 (95% CI -0.03, -0.01) at one month of age. In conclusion, in-utero exposure to tobacco smoke can lead to differential patterns of DNAm of AVPR1a among infants. Conclusions: Future studies are needed to identify how gene expression in response to early environmental exposures contributes to health outcomes
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A Parental Smoking Cessation Intervention in the Pediatric Emergency Setting: A Randomized Trial
We examined the efficacy of a pediatric emergency visit-based screening, brief intervention, and referral to treatment (SBIRT) condition compared to a control condition (Healthy Habits Control, HHC) to help parental smokers quit smoking. We enrolled 750 parental smokers who presented to the pediatric emergency setting with their child into a two-group randomized controlled clinical trial. SBIRT participants received brief cessation coaching, quitting resources, and up to 12-weeks of nicotine replacement therapy (NRT). HHC participants received healthy lifestyle coaching and resources. The primary outcome was point-prevalence tobacco abstinence at six weeks (T1) and six months (T2). The mean (SD) age of parents was 31.8 (7.7) years, and 86.8% were female, 52.7% were Black, and 64.6% had an income of ≤$15,000. Overall abstinence rates were not statistically significant with 4.2% in both groups at T1 and 12.9% and 8.3% in the SBIRT and HHC groups, respectively, at T2. There were statistically significant differences in SBIRT versus HHC participants on the median (IQR) reduction of daily cigarettes smoked at T1 from baseline (-2 [-5, 0] versus 0 [-4, 0], p = 0.0008),at T2 from baseline (-4 [-9, -1] vs. -2 [-5, 0], p = 0.0006), and on the mean (SD) number of quit attempts at T2 from baseline (1.25 (6.5) vs. 0.02 (4.71), p = 0.02). Self-reported quitting rates were higher in SBIRT parents who received NRT (83.3% vs. 50.9%, p = 0.04). The novel use of the pediatric emergency visit to conduct cessation interventions helped parents quit smoking. The near equivalent abstinence rates in both the SBIRT and HHC groups may be due to underlying parental concern about their child's health. Cessation interventions in this setting may result in adult and pediatric public health benefits.Open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Highly Sensitive Virome Characterization of Aedes aegypti and Culex pipiens Complex from Central Europe and the Caribbean Reveals Potential for Interspecies Viral Transmission
International audienceMosquitoes are the most important vectors for arthropod-borne viral diseases. Mixed viral infections of mosquitoes allow genetic recombination or reassortment of diverse viruses, turning mosquitoes into potential virologic mixing bowls. In this study, we field-collected mosquitoes of different species (Aedes aegypti and Culex pipiens complex), from different geographic locations and environments (central Europe and the Caribbean) for highly sensitive next-generation sequencing-based virome characterization. We found a rich virus community associated with a great diversity of host species. Among those, we detected a large diversity of novel virus sequences that we could predominately assign to circular Rep-encoding single-stranded (CRESS) DNA viruses, including the full-length genome of a yet undescribed Gemykrogvirus species. Moreover, we report for the first time the detection of a potentially zoonotic CRESS-DNA virus (Cyclovirus VN) in mosquito vectors. This study expands the knowledge on virus diversity in medically important mosquito vectors, especially for CRESS-DNA viruses that have previously been shown to easily recombine and jump the species barrier
Healthy families: study protocol for a randomized controlled trial of a screening, brief intervention, and referral to treatment intervention for caregivers to reduce secondhand smoke exposure among pediatric emergency patients
Background: Involuntary exposure to secondhand smoke (SHSe) is an important cause of morbidity in children who present to the pediatric emergency department (PED) and urgent care (UC). SHSe interventions delivered in the PED and UC would benefit both the smoker and child, but there have been no large trials testing the efficacy of such interventions. The Healthy Families program is the first randomized controlled trial to test whether a screening, brief intervention, and referral to treatment (SBIRT) intervention delivered in the PED and UC will be effective in decreasing SHSe in children and increasing cessation in smokers. Methods/design: This trial uses a randomized, two-group design in which caregiver-smokers of children 0-17 years old are recruited from the PED and UC. Eligible caregiver-smokers are randomized to either the: 1) SBIRT Condition with face-to-face, tailored counseling that focuses on the child's illness, the importance of reducing child SHSe, caregiver smoking cessation, and the option to receive nicotine replacement therapy; or 2) Healthy Habits Control Condition which includes face-to-face, tailored attention control "5-2-1-0" counseling that focuses on improving the child's health. Dyadic assessments are conducted in-person at baseline, and via email, phone, or in-person at 6-weeks and 6-months. The primary outcomes are biochemically-verified, 7-day point prevalence and prolonged smoking abstinence. Secondary outcomes are cigarettes smoked per week, 24 h quit attempts, and biochemically validated child SHSe at each time point. The costs of this intervention will also be analyzed. Discussion: This study will test an innovative, multilevel intervention designed to reduce child SHSe and increase smoking cessation in caregivers. If effective and routinely used, this SBIRT model could reach at least one million smokers a year in the U.S., resulting in significant reductions in caregivers' tobacco use, SHSe-related pediatric illness, and healthcare costs in this population of children.National Institutes of Health, National Institute for Child Health and Human Development [R01HD083354]open access journalThis item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]
Proteomic fingerprinting of neotropical hard tick species (Acari : Ixodidae) using a selfcurated mass spectra reference library
Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry is an analytical method that detects macromolecules that can be used for proteomic fingerprinting and taxonomic identification in arthropods. The conventional MALDI approach uses fresh laboratory-reared arthropod specimens to build a reference mass spectra library with high quality standards required to achieve reliable identification. However, this may not be possible to accomplish in some arthropod groups that are difficult to rear under laboratory conditions, or for which only alcohol preserved samples are available. Here, we generated MALDI mass spectra of highly abundant proteins from the legs of 18 Neotropical species of adult field-collected hard ticks, several of which had not been analyzed by mass spectrometry before. We then used their mass spectra as fingerprints to identify each tick species by applying machine learning and pattern recognition algorithms that combined unsupervised and supervised clustering approaches. Both Principal Component Analysis (PCA) and Linear Discriminant Analysis (LDA) classification algorithms were able to identify spectra from different tick species, with LDA achieving the best performance when applied to field-collected specimens that did have an existing entry in a reference library of arthropod protein spectra. These findings contribute to the growing literature that ascertains mass spectrometry as a rapid and effective method to complement other well-established techniques for taxonomic identification of disease vectors, which is the first step to predict and manage arthropod-borne pathogens.</p