The Contribution of Neighborhood Characteristics to Psychological Symptom Severity in a Cohort of Injured Black Men.

BACKGROUND: Traumatic injury is not evenly distributed by race and class in the USA. Black men are marginalized in the society, often reside in disadvantaged neighborhoods, and are at higher risk for injury mortality and ongoing physical and psychological problems following injury. Post-traumatic stress disorder (PTSD) and depressive symptom severity are among several problematic and disabling conditions faced by injury survivors. While much research has examined individual factors that lead to increased post-injury psychological symptom severity, the contribution of the social and physical environment has been relatively understudied. OBJECTIVE: To examine the contribution of neighborhood characteristics to PTSD and depressive symptom severity in Black men following traumatic injury. DESIGN: Prospective cohort study. Participant data were linked via GIS to neighborhood characteristics (constructs established by factor analysis) to spatially model factors associated with increased post-injury psychological symptom severity using a GEE regression analysis, adjusting for injury mechanism and severity, age, and insurance. PARTICIPANTS: Four hundred fifty-one adult Black males hospitalized for traumatic injury. RESULTS: The 4 constructs were neighborhood disconnectedness, concentrated disadvantage/deprivation, crime/violence/vacancy, and race/ethnicity. High depressive and PTSD symptom severity was reported by 36.8% and 30.4% of participants, respectively. Higher PTSD symptom severity was associated with crime/violence/vacancy, and higher depressive symptom severity was associated with neighborhood disconnectedness. PTSD and depressive symptom severity were associated with intentional injury mechanisms and Medicaid/no insurance. Higher injury severity was associated with depressive symptoms. CONCLUSION: Neighborhood characteristics are associated with psychological symptom severity after injury.

Low-Risk Essential Thrombocythemia: A Comprehensive Review.

Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by a persistently elevated platelet count in the absence of a secondary cause. The clinical consequences of uncontrolled thrombocytosis can include both thrombosis and hemorrhage. Patients with features conferring a "high risk" of vascular events benefit from reduction of the platelet count through cytoreductive therapy. The management of patients who lack such high-risk features has until recently been less well defined, but it is now apparent that many require minimal or even no intervention. In this review, we discuss the diagnostic pathway for younger patients with unexplained thrombocytosis, including screening molecular investigations, the role of bone marrow biopsy, and investigations in those patients negative for the classic myeloproliferative neoplasm driver mutations (JAK2, CALR, MPL). We discuss conventional and novel risk stratification methods in essential thrombocythemia and how these can be best applied in clinical practice, particularly in the era of more comprehensive genomic testing. The treatment approach for "low risk" patients is discussed including antiplatelets and the options for cytoreductive therapy, if indicated, together with areas of clinical need for future study.

Animal Models and Alternatives in Vaginal Research: a Comparative Review.

While developments in gynecologic health research continue advancing, relatively few groups specifically focus on vaginal tissue research for areas like wound healing, device development, and/or drug toxicity. Currently, there is no standardized animal or tissue model that mimics the full complexity of the human vagina. Certain practical factors such as appropriate size and anatomy, costs, and tissue environment vary across species and moreover fail to emulate all aspects of the human vagina. Thus, investigators are tasked with compromising specific properties of the vaginal environment as it relates to human physiology to suit their particular scientific question. Our review aims to facilitate the appropriate selection of a model aptly addressing a particular study by discussing pertinent vaginal characteristics of conventional animal and tissue models. In this review, we first cover common laboratory animals studied in vaginal research-mouse, rat, rabbit, minipig, and sheep-as well as human, with respect to the estrus cycle and related hormones, basic reproductive anatomy, the composition of vaginal layers, developmental epithelial origin, and microflora. In light of these relevant comparative metrics, we discuss potential selection criteria for choosing an appropriate animal vaginal model. Finally, we allude to the exciting prospects of increasing biomimicry for in vitro applications to provide a framework for investigators to model, interpret, and predict human vaginal health.

Reactive Oxygen Species Rewires Metabolic Activity in Acute Myeloid Leukemia.

Acute myeloid leukemia (AML) is a heterogeneous disease with poor clinical outcomes. We have previously shown that constitutive activation of NADPH oxidase 2 (NOX2), resulting in over-production of reactive oxygen species (ROS), occurs in over 60% of AML patients. We have also shown that increased ROS production promotes increased glucose uptake and proliferation in AML cells, mediated by changes in carbohydrate metabolism. Given that carbohydrate, lipid, and protein metabolisms are all intricately interconnected, we aimed to examine the effect of cellular ROS levels on these pathways and establish further evidence that ROS rewires metabolism in AML. We carried out metabolomic profiling of AML cell lines in which NOX2-derived ROS production was inhibited and conversely in cells treated with exogenous H2O2. We report significant ROS-specific metabolic alterations in sphingolipid metabolism, fatty acid oxidation, purine metabolism, amino acid homeostasis and glycolysis. These data provide further evidence of ROS directed metabolic changes in AML and the potential for metabolic targeting as novel therapeutic arm to combat this disease.

The feasibility and acceptability of mobile health monitoring for real-time assessment of traumatic injury outcomes.

BACKGROUND: Traumatic injuries are a health event that can begin a trajectory towards chronic health and social challenges. Mobile technology-based prevention and treatment interventions have been used to monitor and transform outcomes across a myriad of health conditions, but their potential in long-term injury recovery is unexplored. The goal of this pilot study was to assess the acceptability and feasibility of mobile health monitoring for long-term outcomes in a population of trauma patients with known barriers to health and social care after injury. METHODS: We re-recruited 25 individuals, 12-36 months after acute hospitalization, from a recently concluded study of psychological outcomes in seriously injured Black men in Philadelphia, Pennsylvania. This mixed- methods pilot study was conducted in three phases: (I) qualitative interviews and development of a pilot monitoring platform; (II) a 3-month feasibility trial of mobile monitoring of patient-reported outcomes and biometric data using a wrist-worn commercial fitness monitor (n=18); (III) post-implementation qualitative interviews. RESULTS: Analysis of data from pre-implementation interviews indicated that the majority of participants used smartphones as a primary means of communicating with their social network and to access the internet. The 90-day pilot trial of mobile monitoring indicated participants' preference text-delivered communication and survey elicitation. Response rates for 12 automated surveys ranged from 84-92%. Twenty-four hours a day adherence to optional biometric monitoring was generally lower than 50% but ranged widely indicating both very low adherence and very high adherence. Four of 25 participants, 2 who had opted for Fitbit monitoring, were lost to follow-up at the end of the 90-day pilot trial. In post-implementation assessments, participants endorsed the acceptability of mobile monitoring highlighting the benefit of its convenience and flexibility over in-person outcome monitoring. Participants also perceived its potential benefit in long-term engagement with health and social services to assist with the challenges they faced when attempting to achieve physical, psychological, social, and financial recovery after hospitalization. These findings were reinforced through qualitative interviews which highlighted, in addition to acceptability, the perceived value of self-monitoring through the use of wearable devices to track health data like physical activity and sleep. CONCLUSIONS: This study indicates the feasibility and acceptability of mobile health monitoring used to examine long-term injury sequalae. Future research may leverage this novel strategy, refining its application to address current limitations in the reliability and accuracy of commercially available wearable technology, relative costs and benefits of different mobile data collection strategies, integration within current clinical paradigms and generalizability across injured populations and socio-ecological environments.

Comparative Analysis of Fiber Alignment Methods in Electrospinning.

Fabrication of anisotropic materials is highly desirable in designing biomaterials and tissue engineered constructs. Electrospinning has been broadly adopted due to its versatility in producing non-woven fibrous meshes with tunable fiber diameters (from 10 nanometers to 10 microns), microarchitectures, and construct geometries. A myriad of approaches have been utilized to control fiber alignment of electrospun materials to achieve complex microarchitectures, improve mechanical properties, and provide topographical cellular cues. This review provides a comparative analysis of the techniques developed to generate fiber alignment in electrospun materials. A description of the underlying mechanisms that drive fiber alignment, setup variations for each technique, and the resulting impact on the aligned microarchitecture is provided. A critical analysis of the advantages and limitations of each approach is provided to guide researchers in method selection. Finally, future perspectives of advanced electrospinning methodologies are discussed in terms of developing a scalable method with precise control of microarchitecture.

Reactive Oxygen Species Drive Proliferation in Acute Myeloid Leukemia via the Glycolytic Regulator PFKFB3.

Acute myeloid leukemia (AML) is a heterogeneous clonal disorder with a poor clinical outcome. Previously, we showed that overproduction of reactive oxygen species (ROS), arising from constitutive activation of NOX2 oxidase, occurs in >60% of patients with AML and that ROS production promotes proliferation of AML cells. We show here that the process most significantly affected by ROS overproduction is glycolysis. Whole metabolome analysis of 20 human primary AML showed that blasts generating high levels of ROS have increased glucose uptake and correspondingly increased glucose metabolism. In support of this, exogenous ROS increased glucose consumption while inhibition of NOX2 oxidase decreased glucose consumption. Mechanistically, ROS promoted uncoupling protein 2 (UCP2) protein expression and phosphorylation of AMPK, upregulating the expression of a key regulatory glycolytic enzyme, 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase (PFKFB3). Overexpression of PFKFB3 promoted glucose uptake and cell proliferation, whereas downregulation of PFKFB3 strongly suppressed leukemia growth both in vitro and in vivo in the NSG model. These experiments provide direct evidence that oxidase-derived ROS promotes the growth of leukemia cells via the glycolytic regulator PFKFB3. Targeting PFKFB3 may therefore present a new mode of therapy for this disease with a poor outcome. SIGNIFICANCE: These findings show that ROS generated by NOX2 in AML cells promotes glycolysis by activating PFKFB3 and suggest PFKFB3 as a novel therapeutic target in AML.

AgriSeqDB: an online RNA-Seq database for functional studies of agriculturally relevant plant species.

BACKGROUND: The genome-wide expression profile of genes in different tissues/cell types and developmental stages is a vital component of many functional genomic studies. Transcriptome data obtained by RNA-sequencing (RNA-Seq) is often deposited in public databases that are made available via data portals. Data visualization is one of the first steps in assessment and hypothesis generation. However, these databases do not typically include visualization tools and establishing one is not trivial for users who are not computational experts. This, as well as the various formats in which data is commonly deposited, makes the processes of data access, sharing and utility more difficult. Our goal was to provide a simple and user-friendly repository that meets these needs for data-sets from major agricultural crops. DESCRIPTION: AgriSeqDB ( https://expression.latrobe.edu.au/agriseqdb ) is a database for viewing, analysing and interpreting developmental and tissue/cell-specific transcriptome data from several species, including major agricultural crops such as wheat, rice, maize, barley and tomato. The disparate manner in which public transcriptome data is often warehoused and the challenge of visualizing raw data are both major hurdles to data reuse. The popular eFP browser does an excellent job of presenting transcriptome data in an easily interpretable view, but previous implementation has been mostly on a case-by-case basis. Here we present an integrated visualisation database of transcriptome data-sets from six species that did not previously have public-facing visualisations. We combine the eFP browser, for gene-by-gene investigation, with the Degust browser, which enables visualisation of all transcripts across multiple samples. The two visualisation interfaces launch from the same point, enabling users to easily switch between analysis modes. The tools allow users, even those without bioinformatics expertise, to mine into data-sets and understand the behaviour of transcripts of interest across samples and time. We have also incorporated an additional graphic download option to simplify incorporation into presentations or publications. CONCLUSION: Powered by eFP and Degust browsers, AgriSeqDB is a quick and easy-to-use platform for data analysis and visualization in five crops and Arabidopsis. Furthermore, it provides a tool that makes it easy for researchers to share their data-sets, promoting research collaborations and data-set reuse.

Comparative analysis of the predicted secretomes of Rosaceae scab pathogens Venturia inaequalis and V. pirina reveals expanded effector families and putative determinants of host range.

BACKGROUND: Fungal plant pathogens belonging to the genus Venturia cause damaging scab diseases of members of the Rosaceae. In terms of economic impact, the most important of these are V. inaequalis, which infects apple, and V. pirina, which is a pathogen of European pear. Given that Venturia fungi colonise the sub-cuticular space without penetrating plant cells, it is assumed that effectors that contribute to virulence and determination of host range will be secreted into this plant-pathogen interface. Thus the predicted secretomes of a range of isolates of Venturia with distinct host-ranges were interrogated to reveal putative proteins involved in virulence and pathogenicity. RESULTS: Genomes of Venturia pirina (one European pear scab isolate) and Venturia inaequalis (three apple scab, and one loquat scab, isolates) were sequenced and the predicted secretomes of each isolate identified. RNA-Seq was conducted on the apple-specific V. inaequalis isolate Vi1 (in vitro and infected apple leaves) to highlight virulence and pathogenicity components of the secretome. Genes encoding over 600 small secreted proteins (candidate effectors) were identified, most of which are novel to Venturia, with expansion of putative effector families a feature of the genus. Numerous genes with similarity to Leptosphaeria maculans AvrLm6 and the Verticillium spp. Ave1 were identified. Candidates for avirulence effectors with cognate resistance genes involved in race-cultivar specificity were identified, as were putative proteins involved in host-species determination. Candidate effectors were found, on average, to be in regions of relatively low gene-density and in closer proximity to repeats (e.g. transposable elements), compared with core eukaryotic genes. CONCLUSIONS: Comparative secretomics has revealed candidate effectors from Venturia fungal plant pathogens that attack pome fruit. Effectors that are putative determinants of host range were identified; both those that may be involved in race-cultivar and host-species specificity. Since many of the effector candidates are in close proximity to repetitive sequences this may point to a possible mechanism for the effector gene family expansion observed and a route to diversification via transposition and repeat-induced point mutation.

Structural homology guided alignment of cysteine rich proteins.

BACKGROUND: Cysteine rich protein families are notoriously difficult to align due to low sequence identity and frequent insertions and deletions. RESULTS: Here we present an alignment method that ensures homologous cysteines align by assigning a unique 10 amino acid barcode to those identified as structurally homologous by the DALI webserver. The free inter-cysteine regions of the barcoded sequences can then be aligned using any standard algorithm. Finally the barcodes are replaced with the original columns to yield an alignment which requires the minimum of manual refinement. CONCLUSIONS: Using structural homology information to constrain sequence alignments allows the alignment of highly divergent, repetitive sequences that are poorly dealt with by existing algorithms. Tools are provided to perform this method online using the CysBar web-tool (http://CysBar.science.latrobe.edu.au) and offline (python script available from http://github.com/ts404/CysBar).

The complete mitochondrial genome of Haliotis laevigata (Gastropoda: Haliotidae) using MiSeq and HiSeq sequencing.

The mitochondrial genome of greenlip abalone, Haliotis laevigata, is reported. MiSeq and HiSeq sequencing of one individual was assembled to yield a single 16,545 bp contig. The sequence shares 92% identity to the H. rubra mitochondrial genome (a closely related species that hybridize with H. laevigata in the wild). The sequence will be useful for determining the maternal contribution to hybrid populations, for investigating population structure and stock-enhancement effectiveness.

Metachronous myxofibrosarcoma and osteosarcoma: case report and review of the literature.

The occurrence of multiple primary sarcomas in one individual is very uncommon and the development of osteosarcoma as a second tumor following a soft tissue sarcoma is extremely rare. We report a case of a 62-year-old man who developed 2 histologically distinct sarcomas: a soft tissue myxofibrosarcoma and vertebral osteosarcoma. This unusual case highlights the critical role of careful histopathological evaluation in distinguishing synchronous or metachronous neoplasia from metastatic tumor. To the best of the authors' knowledge, this is the first reported case of metachronous soft tissue myxofibrosarcoma and osteosarcoma.

Empirical demonstration of environmental sensing in catalytic RNA: evolution of interpretive behavior at the origins of life.

BACKGROUND: The origins of life on the Earth required chemical entities to interact with their environments in ways that could respond to natural selection. The concept of interpretation, where biotic entities use signs in their environment as proxy for the existence of other items of selective value in their environment, has been proposed on theoretical grounds to be relevant to the origins and early evolution of life. However this concept has not been demonstrated empirically. RESULTS: Here, we present data that certain catalytic RNA sequences have properties that would enable interpretation of divalent cation levels in their environment. By assaying the responsiveness of two variants of the Tetrahymena ribozyme to the Ca(2+) ion as a sign for the more catalytically useful Mg(2+) ion, we show an empirical proof-of-principle that interpretation can be an evolvable trait in RNA, often suggested as a model system for early life. In particular we demonstrate that in vitro, the wild-type version of the Tetrahymena ribozyme is not interpretive, in that it cannot use Ca(2+) as a sign for Mg(2+). Yet a variant of this sequence containing five mutations that alter its ability to utilize the Ca(2+) ion engenders a strong interpretive characteristic in this RNA. CONCLUSIONS: We have shown that RNA molecules in a test tube can meet the minimum criteria for the evolution of interpretive behaviour in regards to their responses to divalent metal ion concentrations in their environment. Interpretation in RNA molecules provides a property entirely dependent on natural physico-chemical interactions, but capable of shaping the evolutionary trajectory of macromolecules, especially in the earliest stages of life's history.

A neurophysiological basis for the coordination between hand and foot movement.

Hand and foot movements are made more reliably when both limbs move in the same direction at the same time (isodirectional) compared with when they are made in opposite directions (anisodirectional). We hypothesized that M1 intracortical facilitation may subserve hand-foot coordination and reveal correlates that explain the preference for hand-foot movements to be performed in an isodirectional pattern. To test our hypothesis we investigated behavioral kinematics of hand-foot coordination (experiment 1) and neurophysiological measures of corticomotor excitability and intracortical facilitation (experiment 2) in 17 healthy young adults. As expected, coordination became unstable in the anisodirectional pattern but not the isodirectional pattern, as confirmed in measures of wrist and ankle relative phase error and stability (both P < 0.001). Short-latency paired-pulse TMS was used to elicit motor evoked potentials (MEPs) and produce short-latency intracortical facilitation (sICF) in right extensor carpi radialis (ECR) and flexor carpi radialis (FCR) in the presence and absence of right ankle plantarflexion/dorsiflexion (P < 0.015). An isodirectional preference was confirmed by facilitation of FCR MEPs and TMS-induced wrist flexion during ankle plantarflexion (both P < 0.025) but no evidence of modulation of any particular "I wave" during foot movement compared with rest. A novel finding was the association between loss of stability of the anisodirectional pattern (experiment 1) and the modulation of corticomotor excitability in support of the isodirectional pattern (experiment 2) (P < 0.05). The preference for isodirectional hand-foot movements appears not to depend on M1 intracortical facilitation.

Magnet induced perforated appendicitis and ileo-caecal fistula formation.

Foreign body ingestion is a common paediatric problem. In the majority of cases spontaneous passage occurs. Magnet ingestion is rare and solitary magnet ingestion usually does not cause any complications. A number of gastrointestinal complications have been reported, such as fistula formation, perforation and volvulus following multiple magnet ingestion. We review magnet ingestion and describe the first case in the literature of magnet induced perforated appendicitis with an associated ileo-caecal fistula.