ABSTRACT
Gene transfer agents (GTAs) are genetic elements derived from ancestral bacteriophages that have become domesticated by the host. GTAs are present in diverse prokaryotic organisms, where they can facilitate horizontal gene transfer under certain conditions. Unlike typical bacteriophages, GTAs do not exhibit any preference for the replication or transfer of the genes encoding them; instead, they exhibit a remarkable capacity to package chromosomal, and sometimes extrachromosomal, DNA into virus-like capsids and disseminate it to neighboring cells. Because GTAs resemble defective prophages, identification of novel GTAs is not trivial. The detection of candidates relies on the genetic similarity to known GTAs, which has been fruitful in α-proteobacterial lineages but challenging in more distant bacteria. Here we consider several fundamental questions: What is the true prevalence of GTAs in prokaryote genomes? Given there are high costs for GTA production, what advantage do GTAs provide to the bacterial host to justify their maintenance? How is the bacterial chromosome recognized and processed for inclusion in GTA particles? This article highlights the challenges in comprehensively understanding GTAs' prevalence, function and DNA packaging method. Going forward, broad study of atypical GTAs and use of ecologically relevant conditions are required to uncover their true impact on bacterial chromosome evolution.
ABSTRACT
Tautomers are one of the many types of isomers, and differences in tautomeric structures confer altered chemical and biological properties. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) ex vivo metabolomics, we investigate, in whole blood, the divergent metabolism of enol and keto forms of indole-3-pyruvate (IPyA), a tautomeric product of aromatic amino acid metabolism. Two new compounds resulting from IPyA metabolism were discovered, 3-(1H-indol-3-yl)-2,3-dioxopropanoic acid or "indole-3-oxopyruvic acid" and glutathionyl-indole pyruvate (GSHIPyA), which were characterized via ultraviolet photodissociation (UVPD) and higher-energy collisional dissociation (HCD). Computational calculations support the hypothesis that GSHIPyA forms specifically through the enol form of IPyA. GSHIPyA is also hypothesized to be tautomeric, and a hydrogen-deuterium exchange-high-resolution tandem mass spectrometry (HDX-HRMS/MS) approach is developed to prove the presence of an enol and keto tautomer. HDX of GSHIPyA labels the keto form with an additional deuterium, relative to the enol form. HRMS/MS of the labeled isomers is employed to leverage the relationship of resolving power scaling inversely with the square root of m/z, for Orbitrap mass analyzers. HRMS/MS yields a smaller-molecular-weight deuterated tautomeric product ion, reducing the analyte ion m/z and thus lowering the resolving power necessary to separate the deuterated keto tautomer product ion from the [13]C product ion.
Subject(s)
Amino Acids, Aromatic , Metabolomics , Isomerism , Metabolomics/methods , Amino Acids, Aromatic/chemistry , Amino Acids, Aromatic/metabolism , Amino Acids, Aromatic/analysis , Chromatography, High Pressure Liquid , Tandem Mass Spectrometry/methods , Hydrogen Deuterium Exchange-Mass Spectrometry , Indoles/chemistry , Indoles/metabolism , HumansABSTRACT
It is well-known in biochemistry that structure confers function, meaning that chemical structural elucidation is critical to truly understanding the function of a given metabolite. Indole-3-pyruvate (IPyA) exists in an equilibrium between the keto and enol tautomeric forms. IPyA is suggested to play a role in immune function; however, determining whether the tautomeric forms function differently can only be studied if an analytical method is capable of distinguishing between the two forms. Herein, we describe the use of UHPLC-HRMS to gain insight into the physical variables that govern IPyA tautomer equilibrium, reactivity, and detection limit. We use hydrogen-deuterium exchange (HDX) to identify enol and keto peaks, and we show that tautomers exhibit a valley of fronting followed by a tailing peak shape (though separation is still attainable) and identical MS/MS spectra. We observed drastically different ratios of keto and enol forms in different solvents, which is an important consideration for in vitro studies. IPyA was found to be highly unstable with accelerated reactivity in peroxides. Through in vitro reactivity studies, IPyA produced a myriad of known and unknown metabolites via nonenzymatic processes, many of which were mapped in vivo via the analysis of human plasma. Finally, we show that vitamin C (ascorbic acid) can slow this reactivity and enable sensitive detection in whole blood.
Subject(s)
Indoles , Indoles/chemistry , Chromatography, High Pressure Liquid , Humans , Tandem Mass Spectrometry , IsomerismABSTRACT
Resorption within cortices of long bones removes excess mass and damaged tissue and increases during periods of reduced mechanical loading. Returning to high-intensity exercise may place bones at risk of failure due to increased porosity caused by bone resorption. We used point-projection X-ray microscopy images of bone slices from highly loaded (metacarpal, tibia) and minimally loaded (rib) bones from 12 racehorses, 6 that died during a period of high-intensity exercise and 6 that had a period of intense exercise followed by at least 35 days of rest prior to death, and measured intracortical canal cross-sectional area (Ca.Ar) and number (N.Ca) to infer remodelling activity across sites and exercise groups. Large canals that are the consequence of bone resorption (Ca.Ar >0.04 mm2 ) were 1.4× to 18.7× greater in number and area in the third metacarpal bone from rested than exercised animals (p = 0.005-0.008), but were similar in number and area in ribs from rested and exercised animals (p = 0.575-0.688). An intermediate relationship was present in the tibia, and when large canals and smaller canals that result from partial bony infilling (Ca.Ar >0.002 mm2 ) were considered together. The mechanostat may override targeted remodelling during periods of high mechanical load by enhancing bone formation, reducing resorption and suppressing turnover. Both systems may work synergistically in rest periods to remove excess and damaged tissue.
Subject(s)
Bone Remodeling , Bone Resorption , Animals , Tibia , Ribs , OsteogenesisABSTRACT
Repeatedly capturing national headlines, excessive law enforcement officer (LEO) use of force in critical incident encounters is one of the most divisive human rights issues in the United States. Valid and reliable measures of potential precursors to LEO excessive use of force, such as aggression, are needed. The Buss-Perry Aggression Questionnaire-short form (BPAQ-SF) is a validated measure of aggression across various populations; however, evaluation of this easily administered measure in high-stress, frontline populations such as LEOs is limited. The primary goal of this study was to evaluate the validity, reliability, and sensitivity to change the BPAQ-SF in a sample of LEOs. A confirmatory factor analysis suggested that the hierarchical solution provides a mixed fit to the data: SBχ²(25.84) = 62.50, p = .0001; comparative fit index = .94, non-normed fit index = .92, root mean square error of approximation = .19 (90% confidence interval = .17-.21), standardized root mean squared residual = .08. The BPAQ-SF demonstrated good internal consistency (α = .84) and test-retest reliability (r = .86), correlations in the expected direction with predictors of and buffers against aggression, and sensitivity to change among LEOs who participated in an intervention targeting aggression. Results support and extend previous findings suggesting that the BPAQ-SF is a valid and reliable measure of aggression among LEOs.
Subject(s)
Aggression , Police , Humans , United States , Psychometrics , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
BACKGROUND: Trichoderma is a diverse genus of fungi that includes several species that possess biotechnological and agricultural applications, including the biocontrol of pathogenic fungi and nematodes. The mitochondrial genome of a putative strain of Trichoderma harzianum called PAR3 was analyzed after isolation from the roots of Scarlet Royal grapevine scion grafted to Freedom rootstock, located in a grapevine vineyard in Parlier, CA, USA. Here, we report the sequencing, comparative assembly, and annotation of the nuclear genome of PAR3 and confirm its identification as a strain of T. harzianum. We subsequently compared the genes found in T. harzianum PAR3 to other known T. harzianum strains. Assembly of Illumina and/or Oxford Nanopore reads by the popular long-read assemblers, Flye and Canu, and the hybrid assemblers, SPAdes and MaSuRCA, was performed and the quality of the resulting assemblies were compared to ascertain which assembler generated the highest quality draft genome assembly. RESULTS: MaSuRCA produced the most complete and high-fidelity assembly yielding a nuclear genome of 40.7 Mb comprised of 112 scaffolds. Subsequent annotation of this assembly produced 12,074 gene models and 210 tRNAs. This included 221 genes that did not have equivalent genes in other T. harzainum strains. Phylogenetic analysis of ITS, rpb2, and tef1a sequences from PAR3 and established Trichoderma spp. showed that all three sequences from PAR3 possessed more than 99% identity to those of Trichoderma harzianum, confirming that PAR3 is an isolate of Trichoderma harzianum. We also found that comparison of gene models between T. harzianum PAR3 and other T. harzianum strains resulted in the identification of significant differences in gene type and number, with 221 unique genes identified in the PAR3 strain. CONCLUSIONS: This study gives insight into the efficacy of several popular assembly platforms for assembly of fungal nuclear genomes, and found that the hybrid assembler, MaSuRCA, was the most effective program for genome assembly. The annotated draft nuclear genome and the identification of genes not found in other T. harzainum strains could be used to investigate the potential applications of T. harzianum PAR3 for biocontrol of grapevine fungal canker pathogens and as source of anti-microbial compounds.
Subject(s)
Hypocreales , Trichoderma , Phylogeny , Trichoderma/genetics , Hypocreales/genetics , Genome, FungalABSTRACT
ABSTRACTPerceived ethnic discrimination (PED) is predictive of chronic pain-related outcomes. Less is known about pathways through which these constructs interact. The goal of this study was to test whether PED was predictive of chronic pain-related outcomes (pain interference, pain intensity, and symptoms related to central sensitization), whether depression mediated the relationship between PED and pain outcomes, and if these relationships were maintained across sex in a sample of racially and ethnically minoritized adults (n = 77). PED significantly predicted pain interference, pain intensity, and symptoms related to central sensitization. Sex accounted for a significant proportion of the variance in pain interference only. Depression explained the relationship between PED and pain interference and pain intensity. Sex moderated the indirect pathway, such that for men, the relationship between PED and pain interference and pain intensity was explained via depression. Depression partially explained the relationship between PED and symptoms related to central sensitization. Sex did not moderate this mediational effect. This study provided a unique contribution to the pain literature by providing a contextual analysis of PED and pain. Addressing and validating experiences of lifetime discrimination may be a clinically relevant tool in the management of chronic pain for of racially and ethnically minoritized adults.
Subject(s)
Chronic Pain , Racism , Adult , Male , Humans , DepressionABSTRACT
Community health workers (CHWs) play a crucial role in improving child health and development in underserved populations. However, CHWs often face challenges in accessing appropriate guidance and materials for their home visits, hindering their ability to deliver accurate and relevant information to families. Extensive searches for existing resources were conducted to search for established field manual guidebooks for CHWs, however, no suitable material was found, highlighting the need for this case study. The exercise aimed to develop a comprehensive field manual guidebook and animated videos to support CHWs in the Amazon of Peru during their home visits. A multidisciplinary team of specialists was assembled to develop the material. The material development process employed a design thinking methodology, incorporating participatory content creation workshops with CHWs and experts in health topics relevant to the Amazon. This approach ensured cultural relevance and sensitivity in conveying information. The team created a list of 38 essential health and early childhood development messages for Amazonian communities. Infographics were designed for each topic, accompanied by easy-to-understand language and images to assist CHWs in conveying information effectively. To provide additional support, seven animated videos were created based on health behavior theory, covering topics such as anemia, healthy diet, diarrhea, breastfeeding, clean water, child-caregiver bond, and early childhood stimulation. The videos were designed for CHWs to share with caregivers during home visits, enhancing information transmission. The resulting guidebook, infographics, and animated videos were presented to CHWs in Loreto, Peru for feedback. Updated versions were printed and distributed to CHWs in seven communities in Loreto.
Subject(s)
Child Health , Community Health Workers , Child, Preschool , Female , Child , Humans , Community Health Workers/education , House Calls , Medically Underserved Area , Breast FeedingABSTRACT
BACKGROUND: There are several approaches to THA, and each has their respective advantages and disadvantages. Previous meta-analysis included non-randomised studies that introduce further heterogeneity and bias to the evidence presented. This meta-analysis aims to present level I evidence by comparing functional outcomes, peri-operative parameters and complications of direct anterior approach (DAA) versus posterior approach (PA) or lateral approach (LA) in THA. PATIENTS AND METHODS: A comprehensive multi-database search (PubMed, OVID Medline, EMBASE) was conducted from date of database inception to 1st December 2020. Data from randomised controlled trials comparing outcomes of DAA versus PA or LA in THA were extracted and analysed. RESULTS: Twenty-four studies comprising 2010 patients were included in this meta-analysis. DAA has a longer operative time (MD = 17.38 min, 95%CI: 12.28, 22.47 min, P < 0.001) but a shorter length of stay compared to PA (MD = - 0.33 days, 95%CI: - 0.55, - 0.11 days, P = 0.003). There was no difference in operative time or length of stay when comparing DAA versus LA. DAA also had significantly better HHS than PA at 6 weeks (MD = 8.00, 95%CI: 5.85, 10.15, P < 0.001) and LA at 12 weeks (MD = 2.23, 95%CI: 0.31, 4.15, P = 0.02). There was no significant difference in risk of neurapraxia for DAA versus LA or in risk of dislocations, periprosthetic fractures or VTE between DAA and PA or DAA and LA. CONCLUSION: The DAA has better early functional outcomes with shorter mean length of stay but was associated with a longer operative time than PA. There was no difference in risk of dislocations, neurapraxias, periprosthetic fractures or VTE between approaches. Based on our results, choice of THA approach should ultimately be guided by surgeon experience, surgeon preference and patient factors. LEVEL OF EVIDENCE I: Meta-analysis of randomised controlled trials.
Subject(s)
Arthroplasty, Replacement, Hip , Joint Dislocations , Periprosthetic Fractures , Venous Thromboembolism , Humans , Arthroplasty, Replacement, Hip/adverse effects , Arthroplasty, Replacement, Hip/methods , Treatment OutcomeABSTRACT
The implication of lipid dysregulation in diseases, toxic exposure outcomes, and inflammation has brought great interest to lipidomic studies. However, lipids have proven to be analytically challenging due to their highly isomeric nature and vast concentration ranges in biological matrices. Therefore, multidimensional techniques such as those integrating liquid chromatography, ion mobility spectrometry, collision-induced dissociation, and mass spectrometry (LC-IMS-CID-MS) have been implemented to separate lipid isomers as well as provide structural information and increased identification confidence. These data sets are however extremely large and complex, resulting in challenges for data processing and annotation. Here, we have overcome these challenges by developing sample-specific multidimensional lipid libraries using the freely available software Skyline. Specifically, the human plasma library developed for this work contains over 500 unique lipids and is combined with adapted Skyline functions such as indexed retention time (iRT) for retention time prediction and IMS drift time filtering for enhanced selectivity. For comparison with other studies, this database was used to annotate LC-IMS-CID-MS data from a NIST SRM 1950 extract. The same workflow was then utilized to assess plasma and bronchoalveolar lavage fluid (BALF) samples from patients with varying degrees of smoke inhalation injury to identify lipid-based patient prognostic and diagnostic markers.
Subject(s)
Lipidomics , Smoke Inhalation Injury , Chromatography, Liquid , Humans , Ion Mobility Spectrometry , LipidsABSTRACT
OBJECTIVE: To identify grey matter alterations in patients suffering new daily persistent headache to enrich the pathophysiological concept of this rare headache disorder characterised by a distinct, clearly remembered onset and its instant chronification. METHOD: Magnetic resonance-based voxel-based and surface-based morphometry was used to investigate 23 patients suffering from new daily persistent headache and 23 age- and gender-matched healthy controls with 1.5 Tesla MRI.Independent statistical analysis was performed at three sites using statistical parametric mapping, as well as FSL(FMRIB Software Library)-based approaches. RESULTS: No grey matter changes were detected using this sophisticated and cross-checked method. CONCLUSION: The absence of structural brain changes in patients with new daily persistent headache contribute to the recent discussion regarding structural alterations in primary headache disorders in general and does not provide evidence for grey matter changes being associated with the pathophysiology of new daily persistent headache. Future research will have to determine the underlying pathophysiological mechanisms of this disorder.
Subject(s)
Brain , Headache Disorders , Brain/diagnostic imaging , Cross-Sectional Studies , Gray Matter/diagnostic imaging , Headache/diagnostic imaging , Headache Disorders/diagnostic imaging , Humans , Magnetic Resonance Imaging/methodsABSTRACT
In March and April 2018, we carried out a survey of myxosporean parasites in coastal fishes collected from Nha Trang Bay in Vietnam's East Sea. Of the 159 fish specimens, 18 fish species were represented, belonging to 10 families. In 8 host species, 7 myxosporean species were found, representing the genera Kudoa and Unicapsula. Two of these species were new to science: Kudoa igori n. sp. from the gallbladder of Longarm mullet Osteomugil cunnesius (Valenciennes, 1836) (prevalence 10%) and Kudoa borimiri n. sp. from skeletal muscles of Longarm mullet and Longfinned mullet Osteomugil perusii (Valenciennes, 1836) (prevalence 30% and 60%, respectively). Vegetative stages were not found. Spores of K. igori n. sp. were small, orbicular to quadrate in apical view, and with four equal valves. In lateral view, spores were shallowly ovoid with a slightly protruding anterior pole. The 4 polar capsules were slightly unequal sizes and were oriented toward the apex of the spore. Dimensions were as follows: spore length 4.56 ± 0.22 (4.18-4.56), thickness 4.42 ± 0.39 (3.55-5.13), width 5.74 ± 0.46 (4.66-6.50), length of biggest polar capsule 1.38 ± 0.14 (1.1-1.65), middle 1.28 ± 0.12 (1.03-1.53), smallest 1.13 ± 0.11 (0.94-1.30), width of biggest polar capsule 1.03 ± 0.14 (0.83-1.4), middle 0.92 ± 0.12 (0.76-1.08), smallest 0.74 ± 0.12 (0.55-0.94). Spores of K. borimiri n. sp. had four equal valves with slightly rounded ends and were quadrate in apical view. In lateral view, spores were broadly deltoid. Four equal-sized polar capsules opened at the apex of the spore. In O. cunnesius, spore dimensions were as follows: length 3.51 ± 0.15 (3.34-3.92), thickness 3.65 ± 0.38 (2.79-4.21), width 4.97 ± 0.37 (4.13-5.97), length of the polar capsules 1.23 ± 0.18 (0.99-1.57), width 0.88 ± 0.07 (0.70-1.00). Overlapping dimensions for K. borimiri n. sp. spores were also found in O. perusii. Other known myxozoan species we encountered were Kudoa thyrsites and Kudoa whippsi, which had not previously been reported from the East Sea and Vietnam. We also encountered Kudoa monodactyli, which had not previously been reported from Nha Trang Bay. In addition, we report 2 additional species, a Kudoa sp. and a Unicapsula sp., that were not attributable to previously described myxozoans and need further investigation to completely characterize.
Subject(s)
Fish Diseases , Myxozoa , Parasitic Diseases, Animal , Smegmamorpha , Animals , Bays , DNA, Ribosomal , Fish Diseases/parasitology , Fishes , Parasitic Diseases, Animal/epidemiology , Parasitic Diseases, Animal/parasitology , Phylogeny , RNA, Ribosomal, 18S , Sequence Analysis, DNA , Spores , VietnamABSTRACT
The prevalence of food allergy (FA) is increasing in some areas of the globe, highlighting the need for better strategies for prevention, diagnosis, and therapy. In the last few decades, we have made great strides in understanding the causes and mechanisms underlying FAs, prompting guideline updates. Earlier guidelines recommended avoidance of common food allergens during pregnancy and lactation and delaying the introduction of allergenic foods in children aged between 1 and 3 years. Recent guidelines for allergy prevention recommend consumption of a healthy and diverse diet without eliminating or increasing the consumption of allergenic foods during pregnancy or breast-feeding. Early introduction of allergenic foods is recommended by most guidelines for allergy prevention after a period of exclusive breast-feedng (6 months [World Health Organization] or 4 months [European Academy of Allergy and Clinical Immunology]). New diagnostics for FA have been developed with varied availability of these tests in different countries. Finally, the first oral immunotherapy drug for FA was approved by the US Food and Drug Administration and European Medicines Agency in 2020. In this review, we will address the global prevalence of FA, our current understanding of the causes of FA, and the latest guidelines for preventing, diagnosing, and treating FA. We will also discuss similarities and differences between FA guidelines.
Subject(s)
Desensitization, Immunologic/methods , Food Hypersensitivity/epidemiology , Allergens/immunology , Animals , Breast Feeding , Child, Preschool , Diet Therapy , Female , Food , Food Hypersensitivity/diagnosis , Food Hypersensitivity/therapy , Humans , Infant , Practice Guidelines as Topic , Pregnancy , PrevalenceABSTRACT
Nordic hamstring curls (NHC) are a commonly used injury intervention method in amateur team sports. Seventeen elite male academy soccer players performed an 8-week low volume NHC programme. Pre-post intervention measures of isokinetic eccentric knee flexor (KF) strength, linear speed, COD performance, hamstring muscle thickness, pennation angle and fascicle length were recorded. No significant main effects were observed for measures of isokinetic KF strength (P ≥ 0.19), linear sprint speed (P ≥ 0.47) or hamstring muscle architecture (P ≥ 0.30). However, significance was noted for improved COD performance (P < 0.01; mean difference, -0.06, p = 0.001, 95% CI = 0.03 to 0.09; d = 0.80), exceeding the minimal detectable difference (MDD = 0.05 s). A low-volume NHC intervention may contribute to significant improvements in COD ability, independent of no significant changes in eccentric KF strength, linear sprint speed or muscle architectural properties in elite youth soccer players.
ABSTRACT
Pseudomonas aeruginosa infection elicits the production of cytotoxic amyloids from lung endothelium, yet molecular mechanisms of host-pathogen interaction that underlie the amyloid production are not well understood. We examined the importance of type III secretion system (T3SS) effectors in the production of cytotoxic amyloids. P aeruginosa possessing a functional T3SS and effectors induced the production and release of cytotoxic amyloids from lung endothelium, including beta amyloid, and tau. T3SS effector intoxication was sufficient to generate cytotoxic amyloid release, yet intoxication with exoenzyme Y (ExoY) alone or together with exoenzymes S and T (ExoS/T/Y) generated the most virulent amyloids. Infection with lab and clinical strains engendered cytotoxic amyloids that were capable of being propagated in endothelial cell culture and passed to naïve cells, indicative of a prion strain. Conversely, T3SS-incompetent P aeruginosa infection produced non-cytotoxic amyloids with antimicrobial properties. These findings provide evidence that (1) endothelial intoxication with ExoY is sufficient to elicit self-propagating amyloid cytotoxins during infection, (2) pulmonary endothelium contributes to innate immunity by generating antimicrobial amyloids in response to bacterial infection, and (3) ExoY contributes to the virulence arsenal of P aeruginosa through the subversion of endothelial amyloid host-defense to promote a lung endothelial-derived cytotoxic proteinopathy.
Subject(s)
Amyloid/chemistry , Anti-Bacterial Agents/pharmacology , Endothelial Cells/drug effects , Lung/drug effects , Prions/pharmacology , Pseudomonas Infections/drug therapy , Pseudomonas aeruginosa/isolation & purification , Animals , Bacterial Proteins/immunology , Cytotoxins/pharmacology , Endothelial Cells/immunology , Endothelial Cells/microbiology , Female , Host-Pathogen Interactions , Humans , Lung/immunology , Lung/microbiology , Male , Pseudomonas Infections/immunology , Pseudomonas Infections/microbiology , Rats , Rats, Inbred F344 , Rats, Sprague-Dawley , Virulence/drug effectsABSTRACT
PURPOSE: The Postural Awareness Scale (PAS) was developed among a sample of German speakers to measure self-reported awareness of body posture. The first aim of this study was to conduct an English translation and cross-cultural adaptation of the PAS. The second aim was to assess psychometric properties of the English version of the PAS. METHODS: Forward and backward translations were conducted. The translated scale was then pretested in a small sample of English-speaking adults (n = 30), followed by cognitive interviews. Finally, consensus of the translated scale was achieved among an expert committee (n = 5), resulting in the Postural Awareness Scale-English Version (PAS-E). Psychometric properties of the PAS-E were investigated among a sample of individuals with chronic pain (n = 301) by evaluating factor structure, reliability, and construct validity. Analyses of variance were conducted to calculate differences in PAS-E scores between specific subgroups (pain conditions, sex, and history of mindfulness practice). Linear regression analyses investigated whether the scores on the PAS-E predicted levels of pain, stress, and mood. RESULTS: The results obtained from an exploratory factor analysis showed a two-factor solution and were supported by a confirmatory factor analysis. The scale demonstrated good internal consistency and satisfactory construct validity. No significant differences related to sex at birth or pain duration were found. CONCLUSION: PAS-E demonstrated good psychometric properties, and therefore, can and should be used both for research and clinical practice.
Subject(s)
Cross-Cultural Comparison , Translations , Adult , Humans , Infant, Newborn , Psychometrics , Reproducibility of Results , Surveys and QuestionnairesABSTRACT
The design of ductile metallic glasses has been a longstanding challenge. Here, we use colloidal synthesis to fabricate nickel-boron metallic glass nanoparticles that exhibit homogeneous deformation at room temperature and moderate strain rates. In situ compression testing is used to characterize the mechanical behavior of 90-260 nm diameter nanoparticles. The force-displacement curves consist of two regimes separated by a slowly propagating shear band in small, 90 nm particles. The propensity for shear banding decreases with increasing particle size, such that large particles are more likely to deform homogeneously through gradual shape change. We relate this behavior to differences in composition and atomic bonding between particles of different size using mass spectroscopy and XPS. We propose that the ductility of the nanoparticles is related to their internal structure, which consists of atomic clusters made of a metalloid core and a metallic shell that are connected to neighboring clusters by metal-metal bonds.
ABSTRACT
BACKGROUND: Although keloids have been empirically treated with steroids and radiation, evidence-based radiation parameters for keloid therapy are lacking. OBJECTIVE: To determine evidence-based radiation parameters for blocking keloid fibroblast proliferation in vitro and apply them to patients. METHODS: The effects of various radiation parameters and steroids on cell proliferation, cell death, and collagen production in keloid explants and fibroblasts were evaluated with standard assays. Effective radiation parameters were then tested on patients. RESULTS: No differences were observed between the effects of 50 and 320 kV radiation or between single and fractionated radiation doses on keloid fibroblasts. A 3 Gy, 50 kV dose inhibited keloid fibroblast proliferation in culture, whereas 9 Gy completely blocked their outgrowth from explants by inducing multiple cell death pathways and reducing collagen levels. Thirteen of 14 keloids treated with a single 8 Gy, 50 kV dose of radiation did not recur, although 4 patients with 6 keloids were lost to follow-up. LIMITATIONS: Seventy-five percent of patients received steroids for pruritus, whereas approximately 25% of patients were lost to follow-up. CONCLUSIONS: A single 8 Gy dose of superficial 50 kV radiation delivered an average of 34 days after keloid excision maybe sufficient to minimize recurrence, including in individuals resistant to steroids. Higher radiation energies, doses, or fractions may be unnecessary for keloid therapy.
Subject(s)
Keloid/radiotherapy , Adult , Aged , Cells, Cultured , Female , Fibroblasts/radiation effects , Humans , Keloid/surgery , Male , Middle Aged , Radiotherapy Dosage , Recurrence , Young AdultABSTRACT
BACKGROUND: Social media is a rich, virtually untapped source of data on the dynamics of intimate partner violence, one that is both global in scale and intimate in detail. OBJECTIVE: The aim of this study is to use machine learning and other computational methods to analyze social media data for the reasons victims give for staying in or leaving abusive relationships. METHODS: Human annotation, part-of-speech tagging, and machine learning predictive models, including support vector machines, were used on a Twitter data set of 8767 #WhyIStayed and #WhyILeft tweets each. RESULTS: Our methods explored whether we can analyze micronarratives that include details about victims, abusers, and other stakeholders, the actions that constitute abuse, and how the stakeholders respond. CONCLUSIONS: Our findings are consistent across various machine learning methods, which correspond to observations in the clinical literature, and affirm the relevance of natural language processing and machine learning for exploring issues of societal importance in social media.
Subject(s)
Internet Use/trends , Intimate Partner Violence/psychology , Machine Learning/standards , Social Media/standards , Female , Humans , Male , Natural Language ProcessingABSTRACT
Self-management education programs (SMEPs) have demonstrated a measurable benefit in enhancing self-efficacy, increasing health knowledge, and improving both health behaviors and physical symptoms associated with underlying conditions in multiple chronic disease populations. Adolescent and young adult (AYA) survivors of childhood cancer, defined as individuals ages 15 to 39 years, are at a high risk for adverse health outcomes due to late complications from previous cancer treatments, knowledge deficits of their risks, and complex socioeconomic challenges associated with transitional periods in their lives. We performed a literature review and environmental scan to systematically survey and interpret relevant SMEPs to identify opportunities for their development specific to the AYA population. Despite evidence existing for the importance of self-management and general educational messages for survivors of childhood cancer, very few evidence-based interventions have been developed for the AYA population. Most SMEPs for cancer survivors are geared towards individuals with cancer in adulthood. Among the limited interventions directed at survivors of childhood cancer, they are focused on individual health behaviors, such as physical exercise, mental health, nutrition, or self-efficacy. Given the ever-growing technological footprint in our daily lives, mobile health (mHealth) applications may be the most efficacious means of delivering self-management education to this specific population. As content is developed through mHealth applications as well as other platforms, they will need to be rigorously evaluated, given their potential to compliment survivor-focused care.