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1.
BMC Health Serv Res ; 24(1): 444, 2024 Apr 09.
Article in English | MEDLINE | ID: mdl-38594665

ABSTRACT

BACKGROUND: Only one out of every ten Nigerian adults with hypertension has their blood pressure controlled. Health worker training is essential to improve hypertension diagnosis and treatment. In-person training has limitations that mobile, on-demand training might address. This pilot study evaluated a self-paced, case-based, mobile-optimized online training to diagnose and manage hypertension for Nigerian health workers. METHODS: Twelve hypertension training modules were developed, based on World Health Organization and Nigerian guidelines. After review by local academic and government partners, the course was piloted by Nigerian health workers at government-owned primary health centers. Primary care physician, nurse, and community health worker participants completed the course on their own smartphones. Before and after the course, hypertension knowledge was evaluated with multiple-choice questions. Learners provided feedback by responding to questions on a Likert scale. RESULTS: Out of 748 users who sampled the course, 574 enrolled, of whom 431 (75%) completed the course. The average pre-test score of completers was 65.4%, which increased to 78.2% on the post-test (P < 0.001, paired t-test). Health workers who were not part of existing hypertension control programs had lower pre-test scores and larger score gains. Most participants (96.1%) agreed that the training was applicable to their work, and nearly all (99.8%) agreed that they enjoyed the training. CONCLUSIONS: An on-demand mobile digital hypertension training increases knowledge of hypertension management among Nigerian health workers. If offered at scale, such courses can be a tool to build health workforce capacity through initial and refresher training on current clinical guidelines in hypertension and other chronic diseases in Nigeria as well as other countries.


Subject(s)
Hypertension , Adult , Humans , Pilot Projects , Nigeria , Hypertension/diagnosis , Hypertension/therapy , Community Health Workers/education , Primary Health Care
2.
BMC Musculoskelet Disord ; 25(1): 144, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38360606

ABSTRACT

BACKGROUND: Investigation of the association between leg axis alignment and biochemical MRI in young professional soccer players in order to identify a potential influence of the leg axis on cartilage regions at risk. METHODS: Sixteen professional soccer players (21 ± 3 years) underwent static and dynamic leg axis analysis via radiation free DIERS formetric 4 D as well as 3-T MRI examination of both knees. Quantitative T2* mapping of the knee cartilage was performed and T2* values were evaluated as 144 regions of interest. Subgroup analysis was performed in players with severe varus alignment (> 6°). RESULTS: Analysis of the leg axis geometry revealed a mean static alignment of 6.6° ± 2.5 varus and a mean dynamic alignment of 5.1° ± 2.6 varus. Quantitative T2* mapping showed significantly increased T2* values in the superficial cartilage layer compared to the deeper region (p < 0.001) as well as a significant increase in relaxation times in the femoral cartilage from anterior to intermediate to posterior (p < 0.001). Combination of both methods revealed a significant correlation for the degree of varus alignment and the femoral, posterior, deep region of the medial knee compartment (r = 0.4; p = 0.03). If severe varus alignment was present this region showed a significant increase in relaxation time compared to players with a less pronounced leg axis deviation (p = 0.003). CONCLUSION: This study demonstrates that varus alignment in young soccer players is associated with elevated T2* relaxation times in the deep cartilage layer of the medial, posterior, femoral compartment and might therefore be a contributing factor in the early pathogenesis of manifest cartilage lesions. Therefore, these findings should be considered in the development of preventive training programs.


Subject(s)
Cartilage, Articular , Soccer , Humans , Leg , Cartilage, Articular/diagnostic imaging , Cartilage, Articular/pathology , Knee Joint/diagnostic imaging , Knee Joint/pathology , Magnetic Resonance Imaging/methods
3.
Eur J Appl Physiol ; 123(10): 2203-2212, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37247005

ABSTRACT

PURPOSE: The use of electrical stimulation to assess voluntary activation of muscle/s is a popular method employed in numerous exercise science and health research settings. This Delphi study aimed to collate expert opinion and provide recommendations for best practice when using electrical stimulation during maximal voluntary contractions. METHODS: A two-round Delphi study was undertaken with 30 experts who completed a 62-item questionnaire (Round 1) comprising of open- and closed-ended questions. Consensus was assumed if ≥ 70% of experts selected the same response; such questions were removed from the subsequent Round 2 questionnaire. Responses were also removed if they failed to meet a 15% threshold. Open-ended questions were analysed and converted into closed-ended questions for Round 2. It was assumed there was no clear consensus if a question failed to achieve a ≥ 70% response in Round 2. RESULTS: A total of 16 out of 62 (25.8%) items reached consensus. Experts agreed that electrical stimulation provides a valid assessment of voluntary activation in specific circumstances, such as during maximal contraction, and this stimulation can be applied at either the muscle or the nerve. Experts recommended using doublet stimuli, self-adhesive electrodes, a familiarisation session, real-time visual or verbal feedback during the contraction, a minimum current increase of + 20% to ensure supramaximal stimulation, and manually triggering stimuli. CONCLUSION: The results of this Delphi consensus study can help researchers make informed decisions when considering technical parameters when designing studies involving electrical stimulation for the assessment of voluntary activation.


Subject(s)
Muscles , Humans , Delphi Technique , Consensus , Surveys and Questionnaires , Electric Stimulation
4.
MMWR Morb Mortal Wkly Rep ; 71(17): 592-596, 2022 Apr 29.
Article in English | MEDLINE | ID: mdl-35482557

ABSTRACT

On August 29, 2021, the United States government oversaw the emergent establishment of Operation Allies Welcome (OAW), led by the U.S. Department of Homeland Security (DHS) and implemented by the U.S. Department of Defense (DoD) and U.S. Department of State (DoS), to safely resettle U.S. citizens and Afghan nationals from Afghanistan to the United States. Evacuees were temporarily housed at several overseas locations in Europe and Asia* before being transported via military and charter flights through two U.S. international airports, and onward to eight U.S. military bases,† with hotel A used for isolation and quarantine of persons with or exposed to certain infectious diseases.§ On August 30, CDC issued an Epi-X notice encouraging public health officials to maintain vigilance for measles among Afghan evacuees because of an ongoing measles outbreak in Afghanistan (25,988 clinical cases reported nationwide during January-November 2021) (1) and low routine measles vaccination coverage (66% and 43% for the first and second doses, respectively, in 2020) (2).


Subject(s)
Communicable Diseases , Measles , Communicable Diseases/epidemiology , Disease Outbreaks/prevention & control , Humans , Measles/epidemiology , Measles/prevention & control , Public Health , United States/epidemiology , Vaccination
5.
BMC Public Health ; 22(1): 551, 2022 03 21.
Article in English | MEDLINE | ID: mdl-35313834

ABSTRACT

BACKGROUND: Health workers (HWs) in Africa face challenges accessing and learning from existing online training opportunities. To address these challenges, we developed a modular, self-paced, mobile-ready and work-relevant online course covering foundational infection prevention and control (IPC) concepts. Here, we evaluate the first pilot of this course, conducted with HWs in Nigeria. METHODS: We used a learner-centered design and prototyping process to create a new approach to delivering online training for HWs. The resulting course comprised 10 self-paced modules optimized for use on mobile devices. Modules presented IPC vignettes in which learning was driven by short assessment questions with feedback. Learners were recruited by distributing a link to the training through Nigeria-based email lists, WhatsApp groups and similar networks of HWs, managers and allied professionals. The course was open to learners for 8 weeks. We tracked question responses and time on task with platform analytics and assessed learning gains with pre- and post-testing. Significance was evaluated with the Wilcoxon signed-rank test, and effect size was calculated using Cohen's d. RESULTS: Three hundred seventy-two learners, with roles across the health system, enrolled in the training; 59% completed all 10 modules and earned a certificate. Baseline knowledge of foundational IPC concepts was low, as measured by pre-test scores (29%). Post-test scores were significantly higher at 54% (effect size 1.22, 95% confidence interval 1.00-1.44). Learning gains were significant both among learners with low pre-test scores and among those who scored higher on the pre-test. We used the Net Promoter Score (NPS), a common user experience metric, to evaluate the training. The NPS was + 62, which is slightly higher than published scores of other self-paced online learning experiences. CONCLUSIONS: High completion rates, significant learning gains and positive feedback indicate that self-paced, mobile-ready training that emphasizes short, low-stakes assessment questions can be an effective, scalable way to train HWs who choose to enroll. Low pre-test scores suggest that there are gaps in IPC knowledge among this learner population.


Subject(s)
Education, Distance , Health Personnel , Health Personnel/education , Health Workforce , Humans , Infection Control , Nigeria
6.
J Genet Couns ; 29(6): 1151-1158, 2020 12.
Article in English | MEDLINE | ID: mdl-32196829

ABSTRACT

Neurofibromatosis type 1 (NF1) is a genetic condition characterized by various cutaneous, neurological and psychological manifestations. The present study examined whether parental knowledge of NF1 is associated with a parent's NF1 status, affected or unaffected, and exposure to genetic counseling. Parents of children with NF1 were invited to complete an online survey answering true or false and multiple-choice questions to evaluate their overall knowledge of NF1. The study included 274 respondents, of which NF1 knowledge scores were significantly higher for unaffected parents (p < .001), and for parents who reported previously meeting with a genetic counselor (p < .001). Items pertaining to NF1-related cancer were least likely to be answered correctly. The results of the current study revealed lower overall NF1 knowledge in affected parents and knowledge gaps identifying areas where focused NF1 education may be beneficial.


Subject(s)
Genetic Counseling/psychology , Neurofibromatosis 1/psychology , Parents/psychology , Child , Female , Humans , Male , Surveys and Questionnaires
7.
BMC Med Educ ; 19(1): 189, 2019 Jun 06.
Article in English | MEDLINE | ID: mdl-31170974

ABSTRACT

BACKGROUND: Whether medical education research (MER) is primarily conducted in wealthy countries (in the "Realm of the Rich") is the subject of an ongoing debate. Previous studies of the geography of MER publication output have relied upon proprietary databases, have not compared MER with other fields of study, and have not studied the relationship between authorship geography and topics of study. This study was designed to evaluate the geographic distribution of MER authorship and to relate this to the topics studied in MER. METHODS: Authors' countries of affiliation were identified from PubMed records by parsing and cleaning the text of affiliations and submitting them to the google maps geocoding API. The geography of publication output in MER was compared to other fields using the chi-square goodness-of-fit test. Country income classifications and medical subject heading (MeSH) terms were used to evaluate the topical contributions of countries at different income levels, and simulation was used to compute significance of MeSH term enrichment in MER papers from low income and lower middle income countries. RESULTS: The vast majority of MER papers were contributed by authors based in high income countries. The top four countries were the United States, the United Kingdom, Canada, and Australia, with listed author affiliations in 80% of all MER papers. This percentage was greater in MER than in several other categories, including Biological Science Disciplines (48%), Medicine (69%) and Education (74%), which is a parent category of MER. Authors from low income countries contributed significantly to the topical diversity of MER. MeSH terms associated with government, community health, and health delivery were enriched in papers from low income countries, while terms associated with specialty and clinical training, technology in teaching, and professional obligations (such as workload, burnout, and empathy) were enriched in papers from high income countries. CONCLUSIONS: Geographic disparities in publication output are greater in MER than in any other field examined. The historical origins of MER in North America might explain disproportionate publication output by authors from this region. This study suggests that the MER field benefits from research contributed by authors from low income countries, and also points to potential gaps in MER (and medical education as a whole) in the developing world.


Subject(s)
Education, Medical , Research , Bibliometrics , Developed Countries/statistics & numerical data , Developing Countries/statistics & numerical data , Education, Medical/methods , Geography , Humans , Research/statistics & numerical data
8.
Scand J Med Sci Sports ; 28(2): 658-666, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28544170

ABSTRACT

We examined the effects of a 12-week program of Nordic hamstring exercises (NHE), administered before or after football training, upon eccentric hamstring strength, muscle activity, and architectural adaptations. Amateur soccer players were randomized into three groups. The control group (CON; n=11) undertook core stability exercises, whereas a periodized NHE program was delivered either before (NHEBEF ; n=10) or after (NHEAFT ; n=14) biweekly training sessions. Outcome measures included peak torque and concomitant normalized peak surface electromyography signals (sEMG) of the biceps femoris (BF) and medial hamstring (MH) muscles during knee flexor maximal eccentric contractions, performed at 30°·s-1 . Ultrasonography was used to determine BF muscle thickness, muscle fiber pennation angle, and fascicle length. Performing the NHE derived likely moderate peak torque increases in both NHEBEF (+11.9%; 90% confidence interval: 3.6%-20.9%) and NHEAFT (+11.6%; 2.6%-21.5%) vs CON. Maximum sEMG increases were moderately greater in the BF of both NHE training groups vs CON. There were likely moderate increases in BF muscle thickness (+0.17 cm; 0.05-0.29 cm) and likely small pennation angle increases (+1.03°; -0.08° to 2.14°) in NHEAFT vs CON and NHEBEF . BF fascicle length increases were likely greater in NHEBEF (+1.58 cm; 0.48-2.68 cm; small effect) vs CON and NHEAFT . A 12-week eccentric hamstring strengthening program increased strength and sEMG to a similar magnitude irrespective of its scheduling relative to the football training session. However, architectural adaptations to support the strength gains differed according to the timing of the injury prevention program.


Subject(s)
Athletic Injuries/prevention & control , Hamstring Muscles/injuries , Physical Conditioning, Human , Soccer/injuries , Adult , Electromyography , Humans , Male , Muscle Strength , Resistance Training , Torque , Young Adult
9.
Scand J Med Sci Sports ; 28(10): 2216-2225, 2018 Oct.
Article in English | MEDLINE | ID: mdl-29797592

ABSTRACT

Scheduling eccentric-based injury prevention programs (IPP) during the common 6-day micro-cycle in soccer is challenged by recovery and tapering phases. This study profiled muscle damage, neuromuscular performance, and perceptual responses to a lower limb eccentric-based IPP administered 1 (MD+1) vs 3 days (MD+3) postmatch. A total of 18 semi-professional players were monitored daily during 3 in-season 6-day micro-cycles, including weekly competitive fixtures. Capillary creatine kinase concentration (CK), posterior lower limb isometric peak force (PF), counter-movement jump (CMJ) performance, and muscle soreness were assessed 24 hours prior to match-day (baseline), and every 24 hours up to 120 hours postmatch. The IPP consisted of lunges, single stiff leg dead-lifts, single leg-squats, and Nordic hamstring exercises. Performing the IPP on MD+1 attenuated the decline in CK normally observed following match play (CON: 142%; MD+3: 166%; small differences). When IPP was delivered on MD+3, CK was higher vs CON and MD+1 trials on both MD+4 (MD+3: 260%; CON: 146%; MD+1: 151%; moderate differences) and MD+5 (MD+3: 209%; CON: 125%; MD+1: 127%; small differences). Soreness ratings were not exacerbated when the IPP was delivered on MD+1, but when prescribed on MD+3, hamstring soreness ratings remained higher on MD+4 and MD+5 (small differences). No between-trial differences were observed for PF and CMJ. Administering the IPP in the middle of the micro-cycle (MD+3) increased measures of muscle damage and soreness, which remained elevated on the day prior to the next match (MD+5). Accordingly, IPP should be scheduled early in the micro-cycle, to avoid compromising preparation for the following match.


Subject(s)
Athletic Injuries/prevention & control , Exercise Therapy , Lower Extremity/injuries , Soccer/injuries , Time Factors , Adult , Creatine Kinase/blood , Cross-Over Studies , Humans , Lower Extremity/physiology , Muscle Strength , Muscle, Skeletal/injuries , Muscle, Skeletal/physiology , Myalgia , Young Adult
10.
Immunol Rev ; 253(1): 237-52, 2013 May.
Article in English | MEDLINE | ID: mdl-23550650

ABSTRACT

Studies of the regulation of gene expression historically focused on transcription. However, during stress and apoptosis, profound gene expression changes occur more rapidly and globally than is possible by regulating transcription. Posttranscriptional changes in mRNA processing and translation in response to diverse stresses shut down most protein translation to conserve energy and lead to rapid remodeling of the proteome to promote repair. Pre-mRNA splicing and mRNA stability are fundamentally altered under some stress conditions. Stress pathways coordinate a cytoprotective repair response, while simultaneously initiating signaling that can ultimately trigger cell death. How the cell mediates the decision between repair and apoptosis is largely not understood. In some stresses, microRNAs may tip the balance. Here, we review what is known about posttranscriptional gene regulation during stress, focusing on what is still unknown and how new technologies might be used to understand what changes are most physiologically important in different forms of stress and death.


Subject(s)
MicroRNAs/immunology , RNA Interference , Stress, Physiological , Animals , Apoptosis/genetics , Apoptosis/immunology , Cytoprotection/genetics , Gene Expression Regulation/genetics , Gene Expression Regulation/immunology , Homeostasis , Humans , RNA Interference/immunology , Signal Transduction/genetics , Signal Transduction/immunology
11.
Clin Exp Immunol ; 185(3): 372-81, 2016 09.
Article in English | MEDLINE | ID: mdl-27218304

ABSTRACT

Recently, there has been considerable interest in using 4-methylumbelliferone (4-MU) to inhibit hyaluronan (HA) synthesis in mouse models of cancer, autoimmunity and a variety of other inflammatory disorders where HA has been implicated in disease pathogenesis. In order to facilitate future studies in this area, we have examined the dosing, treatment route, treatment duration and metabolism of 4-MU in both C57BL/6 and BALB/c mice. Mice fed chow containing 5% 4-MU, a dose calculated to deliver 250 mg/mouse/day, initially lose substantial weight but typically resume normal weight gain after 1 week. It also takes up to a week to see a reduction in serum HA in these animals, indicating that at least a 1-week loading period on the drug is required for most protocols. At steady state, more than 90% of the drug is present in plasma as the glucuronidated metabolite 4-methylumbelliferyl glucuronide (4-MUG), with the sulphated metabolite, 4-methylumbelliferyl sulphate (4-MUS) comprising most of the remainder. Chow containing 5% but not 0·65% 4-MU was effective at preventing disease in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis, as well as in the DORmO mouse model of autoimmune diabetes. While oral 4-MU was effective at preventing EAE, daily intraperitoneal injections of 4-MU were not. Factors potentially affecting 4-MU uptake and plasma concentrations in mice include its taste, short half-life and low bioavailability. These studies provide a practical resource for implementing oral 4-MU treatment protocols in mice.


Subject(s)
Encephalomyelitis, Autoimmune, Experimental/drug therapy , Hyaluronic Acid/antagonists & inhibitors , Hyaluronic Acid/biosynthesis , Hymecromone/administration & dosage , Hymecromone/pharmacokinetics , Administration, Oral , Animals , Biological Availability , Disease Models, Animal , Encephalomyelitis, Autoimmune, Experimental/chemically induced , Encephalomyelitis, Autoimmune, Experimental/immunology , Encephalomyelitis, Autoimmune, Experimental/prevention & control , Half-Life , Hyaluronic Acid/blood , Hymecromone/blood , Hymecromone/metabolism , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL
12.
Analyst ; 141(1): 191-8, 2016 Jan 07.
Article in English | MEDLINE | ID: mdl-26596622

ABSTRACT

Blood evidence is frequently encountered at the scene of violent crimes and can provide valuable intelligence in the forensic investigation of serious offences. Because many of the current enhancement methods used by crime scene investigators are presumptive, the visualisation of blood is not always reliable nor does it bear additional information. In the work presented here, two methods employing a shotgun bottom up proteomic approach for the detection of blood are reported; the developed protocols employ both an in solution digestion method and a recently proposed procedure involving immobilization of trypsin on hydrophobin Vmh2 coated MALDI sample plate. The methods are complementary as whilst one yields more identifiable proteins (as biomolecular signatures), the other is extremely rapid (5 minutes). Additionally, data demonstrate the opportunity to discriminate blood provenance even when two different blood sources are present in a mixture. This approach is also suitable for old bloodstains which had been previously chemically enhanced, as experiments conducted on a 9-year-old bloodstain deposited on a ceramic tile demonstrate.


Subject(s)
Blood , Forensic Medicine/methods , Proteomics/methods , Amino Acid Sequence , Animals , Blood Stains , Child , Horses , Humans , Proteolysis , Reproducibility of Results , Time Factors
13.
J Immunol ; 192(11): 5390-7, 2014 Jun 01.
Article in English | MEDLINE | ID: mdl-24771851

ABSTRACT

Killer lymphocyte granzyme (Gzm) serine proteases induce apoptosis of pathogen-infected cells and tumor cells. Many known Gzm substrates are nucleic acid binding proteins, and the Gzms accumulate in the target cell nucleus by an unknown mechanism. In this study, we show that human Gzms bind to DNA and RNA with nanomolar affinity. Gzms cleave their substrates most efficiently when both are bound to nucleic acids. RNase treatment of cell lysates reduces Gzm cleavage of RNA binding protein targets, whereas adding RNA to recombinant RNA binding protein substrates increases in vitro cleavage. Binding to nucleic acids also influences Gzm trafficking within target cells. Preincubation with competitor DNA and DNase treatment both reduce Gzm nuclear localization. The Gzms are closely related to neutrophil proteases, including neutrophil elastase (NE) and cathepsin G. During neutrophil activation, NE translocates to the nucleus to initiate DNA extrusion into neutrophil extracellular traps, which bind NE and cathepsin G. These myeloid cell proteases, but not digestive serine proteases, also bind DNA strongly and localize to nuclei and neutrophil extracellular traps in a DNA-dependent manner. Thus, high-affinity nucleic acid binding is a conserved and functionally important property specific to leukocyte serine proteases. Furthermore, nucleic acid binding provides an elegant and simple mechanism to confer specificity of these proteases for cleavage of nucleic acid binding protein substrates that play essential roles in cellular gene expression and cell proliferation.


Subject(s)
Cell Nucleus/immunology , DNA-Binding Proteins/immunology , DNA/immunology , Granzymes/immunology , Neutrophils/immunology , Proteolysis , RNA-Binding Proteins/immunology , RNA/immunology , Active Transport, Cell Nucleus/genetics , Active Transport, Cell Nucleus/immunology , Cell Nucleus/enzymology , Cell Nucleus/genetics , DNA/genetics , DNA/metabolism , DNA-Binding Proteins/genetics , DNA-Binding Proteins/metabolism , Female , Granzymes/genetics , Granzymes/metabolism , HEK293 Cells , Humans , Male , Neutrophils/cytology , Neutrophils/enzymology , RNA/genetics , RNA/metabolism , RNA-Binding Proteins/genetics , RNA-Binding Proteins/metabolism
14.
Eur J Cancer Care (Engl) ; 25(5): 784-94, 2016 Sep.
Article in English | MEDLINE | ID: mdl-26593858

ABSTRACT

The primary aim of this study was to evaluate the benefits of resistance training (RT) on quality of life (QOL) and fatigue in breast cancer survivors as an adjunct to usual care. We recruited 39 women who had survived breast cancer [mean age (y) 51.9 ± 8.8; time since diagnosis (m) 11.6 ± 13.2]. Primary outcomes were fatigue as assessed by the Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT) scale and QOL as assessed by the Functional Assessment of Cancer Therapy - General (FACT-G) scale. ANCOVA was used to assess the change in the primary outcomes while controlling for baseline values, with effect sizes (ES) displayed as partial Eta squared. The experimental group received supervised RT 3 days per week in a university clinic for 16 weeks. Perceptions of fatigue improved significantly in the RT group compared to controls [mean (SD) 6.7 (7.5) points vs. 1.5 (3.7) points], (P = 0.006, ES = 0.20) as did QOL [6.9 (8.5) points vs. 1.6 (4.4) points], (P = 0.015, ES = 0.16). We demonstrated both statistically and clinically important improvements in fatigue and QOL in response to RT in breast cancer survivors.


Subject(s)
Breast Neoplasms/complications , Fatigue/prevention & control , Resistance Training/methods , Survivors , Adolescent , Adult , Aged , Breast Neoplasms/physiopathology , Fatigue/physiopathology , Female , Humans , Middle Aged , Muscle Strength , Muscle, Skeletal/physiology , Sedentary Behavior , Young Adult
15.
Nano Lett ; 15(4): 2555-61, 2015 Apr 08.
Article in English | MEDLINE | ID: mdl-25774924

ABSTRACT

Graphene is a promising flexible, highly transparent, and elementally abundant electrode for organic electronics. Typical methods utilized to transfer large-area films of graphene synthesized by chemical vapor deposition on metal catalysts are not compatible with organic thin-films, limiting the integration of graphene into organic optoelectronic devices. This article describes a graphene transfer process onto chemically sensitive organic semiconductor thin-films. The process incorporates an elastomeric stamp with a fluorinated polymer release layer that can be removed, post-transfer, via a fluorinated solvent; neither fluorinated material adversely affects the organic semiconductor materials. We used Raman spectroscopy, atomic force microscopy, and scanning electron microscopy to show that chemical vapor deposition graphene can be successfully transferred without inducing defects in the graphene film. To demonstrate our transfer method's compatibility with organic semiconductors, we fabricate three classes of organic thin-film devices: graphene field effect transistors without additional cleaning processes, transparent organic light-emitting diodes, and transparent small-molecule organic photovoltaic devices. These experiments demonstrate the potential of hybrid graphene/organic devices in which graphene is deposited directly onto underlying organic thin-film structures.


Subject(s)
Fluorine/chemistry , Graphite/chemistry , Microelectrodes , Molecular Imprinting/methods , Nanoparticles/chemistry , Organic Chemicals/chemistry , Electric Conductivity , Equipment Design , Equipment Failure Analysis , Materials Testing , Membranes, Artificial , Nanoparticles/ultrastructure , Particle Size
16.
Osteoarthritis Cartilage ; 23(3): 405-13, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25454370

ABSTRACT

OBJECTIVE: Recent developments in optical clearing and microscopy technology have enabled the imaging of intact tissues at the millimeter scale to characterize cells via fluorescence labeling. While these techniques have facilitated the three-dimensional (3D) cellular characterization within brain and heart, study of dense connective tissues of the musculoskeletal system have been largely unexplored. Here, we quantify how optical clearing impacted the cell and tissue morphology of collagen-, proteoglycan-, and mineral-rich cartilage and bone from the articulating knee joint. METHODS: Water-based fructose solutions were used for optical clearing of bovine osteochondral tissues, followed by imaging with transmission and confocal microscopy. To confirm preservation of tissue structure during the clearing process, samples were mechanically tested in unconfined compression and visualized by cryo-SEM. RESULTS: Optical clearing enhanced light transmission through cartilage, but not subchondral bone regions. Fluorescent staining and immunolabeling was preserved through sample preparations, enabling imaging to cartilage depths five times deeper than previously reported, limited only by the working distance of the microscope objective. Chondrocyte volume remained unchanged in response to, and upon the reversal, of clearing. Equilibrium modulus increased in cleared samples, and was attributed to exchange of interstitial fluid with the more viscous fructose solution, but returned to control levels upon unclearing. In addition, cryo-SEM-based analysis of cartilage showed no ultrastructural changes. CONCLUSION: We anticipate large-scale microscopy of diverse connective tissues will enable the study of intact, 3D interfaces (e.g., osteochondral) and cellular connectivity as a function of development, disease, and regeneration, which have been previously hindered by specimen opacity.


Subject(s)
Bone and Bones/anatomy & histology , Cartilage, Articular/anatomy & histology , Chondrocytes/ultrastructure , Histological Techniques/methods , Stifle/anatomy & histology , Animals , Bone and Bones/ultrastructure , Cartilage, Articular/ultrastructure , Cattle , Collagen , Fructose , Immunohistochemistry , Microscopy, Confocal , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Proteoglycans , Solutions , Stifle/ultrastructure
17.
Proc Natl Acad Sci U S A ; 109(22): 8688-93, 2012 May 29.
Article in English | MEDLINE | ID: mdl-22589304

ABSTRACT

During immune-mediated death, death-inducing granzyme (Gzm) proteases concentrate in the nucleus of cells targeted for immune elimination, suggesting that nuclear processes are important targets. Here we used differential 2D proteomics of GzmA-treated nuclei to identify potential GzmA substrates. Of 44 candidates, 33 were RNA-binding proteins important in posttranscriptional RNA processing, including 14 heterogeneous nuclear ribonucleoproteins (hnRNP). Multiple hnRNPs were degraded in cells undergoing GzmA-, GzmB-, or caspase-mediated death. GzmA and caspase activation impaired nuclear export of newly synthesized RNA and disrupted pre-mRNA splicing. Expressing GzmA-resistant hnRNP A1 inhibited GzmA-mediated cell death and rescued pre-mRNA splicing, suggesting that hnRNP A1 is an important GzmA substrate. Cellular stresses are known to inhibit initiation of cap-dependent translation. Disrupting pre-mRNA processing should block further new protein synthesis and promote death by interfering with pathways induced to protect cells from death.


Subject(s)
Apoptosis , Cell Nucleus/metabolism , Granzymes/metabolism , RNA Precursors/metabolism , RNA Processing, Post-Transcriptional , Cell Line , Cell Line, Transformed , Cell Nucleus/genetics , Cytotoxicity, Immunologic , Electrophoresis, Gel, Two-Dimensional , Gene Expression , Granzymes/genetics , HeLa Cells , Heterogeneous Nuclear Ribonucleoprotein A1 , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/genetics , Heterogeneous-Nuclear Ribonucleoprotein Group A-B/metabolism , Heterogeneous-Nuclear Ribonucleoproteins/genetics , Heterogeneous-Nuclear Ribonucleoproteins/metabolism , Humans , Immunoblotting , Jurkat Cells , K562 Cells , Mass Spectrometry , Microscopy, Fluorescence , Proteome/genetics , Proteome/metabolism , Proteomics/methods , RNA Precursors/genetics , Reverse Transcriptase Polymerase Chain Reaction , Substrate Specificity
18.
PLoS Genet ; 7(11): e1002363, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22102825

ABSTRACT

A simple biochemical method to isolate mRNAs pulled down with a transfected, biotinylated microRNA was used to identify direct target genes of miR-34a, a tumor suppressor gene. The method reidentified most of the known miR-34a regulated genes expressed in K562 and HCT116 cancer cell lines. Transcripts for 982 genes were enriched in the pull-down with miR-34a in both cell lines. Despite this large number, validation experiments suggested that ~90% of the genes identified in both cell lines can be directly regulated by miR-34a. Thus miR-34a is capable of regulating hundreds of genes. The transcripts pulled down with miR-34a were highly enriched for their roles in growth factor signaling and cell cycle progression. These genes form a dense network of interacting gene products that regulate multiple signal transduction pathways that orchestrate the proliferative response to external growth stimuli. Multiple candidate miR-34a-regulated genes participate in RAS-RAF-MAPK signaling. Ectopic miR-34a expression reduced basal ERK and AKT phosphorylation and enhanced sensitivity to serum growth factor withdrawal, while cells genetically deficient in miR-34a were less sensitive. Fourteen new direct targets of miR-34a were experimentally validated, including genes that participate in growth factor signaling (ARAF and PIK3R2) as well as genes that regulate cell cycle progression at various phases of the cell cycle (cyclins D3 and G2, MCM2 and MCM5, PLK1 and SMAD4). Thus miR-34a tempers the proliferative and pro-survival effect of growth factor stimulation by interfering with growth factor signal transduction and downstream pathways required for cell division.


Subject(s)
Genes, Tumor Suppressor , Intercellular Signaling Peptides and Proteins/genetics , Intercellular Signaling Peptides and Proteins/metabolism , MicroRNAs/genetics , Signal Transduction/genetics , Cell Cycle Proteins/genetics , Cell Cycle Proteins/metabolism , Cell Division/genetics , Cell Proliferation , Gene Expression Regulation , Gene Regulatory Networks/genetics , HCT116 Cells , HeLa Cells , Humans , K562 Cells , MAP Kinase Signaling System , Oligonucleotide Array Sequence Analysis , Oncogene Protein v-akt/genetics , Oncogene Protein v-akt/metabolism , Phosphorylation , RNA, Messenger/genetics
19.
Environ Monit Assess ; 186(12): 8527-40, 2014 Dec.
Article in English | MEDLINE | ID: mdl-25179944

ABSTRACT

Managing to support coral reef resilience as the climate changes requires strategic and responsive actions that reduce anthropogenic stress. Managers can only target and tailor these actions if they regularly receive information on system condition and impact severity. In large coral reef areas like the Great Barrier Reef Marine Park (GBRMP), acquiring condition and impact data with good spatial and temporal coverage requires using a large network of observers. Here, we describe the result of ~10 years of evolving and refining participatory monitoring programs used in the GBR that have rangers, tourism operators and members of the public as observers. Participants complete Reef Health and Impact Surveys (RHIS) using a protocol that meets coral reef managers' needs for up-to-date information on the following: benthic community composition, reef condition and impacts including coral diseases, damage, predation and the presence of rubbish. Training programs ensure that the information gathered is sufficiently precise to inform management decisions. Participants regularly report because the demands of the survey methodology have been matched to their time availability. Undertaking the RHIS protocol we describe involves three ~20 min surveys at each site. Participants enter data into an online data management system that can create reports for managers and participants within minutes of data being submitted. Since 2009, 211 participants have completed a total of more than 10,415 surveys at more than 625 different reefs. The two-way exchange of information between managers and participants increases the capacity to manage reefs adaptively, meets education and outreach objectives and can increase stewardship. The general approach used and the survey methodology are both sufficiently adaptable to be used in all reef regions.


Subject(s)
Coral Reefs , Environmental Monitoring/methods , Animals , Anthozoa , Australia , Climate Change , Conservation of Natural Resources/methods , Data Collection
20.
Opt Express ; 21(4): 4411-23, 2013 Feb 25.
Article in English | MEDLINE | ID: mdl-23481975

ABSTRACT

Photonic crystal spectrometers possess significant size and cost advantages over traditional grating-based spectrometers. In a previous work [Pervez, et al, Opt. Express 18, 8277 (2010)] we demonstrated a proof of this concept by implementing a 9-element array photonic crystal spectrometer with a resolution of 20 nm. Here we demonstrate a photonic crystal spectrometer with improved performance. The dependence of the spectral recovery resolution on the number of photonic crystal arrays and the width of the response function from each photonic crystal is investigated. A mathematical treatment, regularization based on known information of the spectrum, is utilized in order to stabilize the spectral estimation inverse problem and achieve improved spectral recovery. Colorimetry applications, the measurement of CIE 1931 chromaticities and the color rendering index, are demonstrated with the improved spectrometer.


Subject(s)
Colorimetry/instrumentation , Refractometry/instrumentation , Spectrum Analysis/instrumentation , Equipment Design , Equipment Failure Analysis
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