Translational Gap Research Articles

The Management of Irritable Bowel Syndrome: The Viewpoint of Italian General Practitioners in Activity and in Training

Background: Guidelines on Irritable Bowel Syndrome (IBS) are usually developed by specialists, with a possible translational gap in primary care. Aims: To evaluate the knowledge of IBS of Italian General Practitioners (GPs) and the difference compared to doctors in Training for General Practice (ITGPs). Methods: A questionnaire was completed by 170 GPs and 64 ITGPs. Results: The Rome Criteria and Bristol Scale are more familiar to ITGPs than GPs. The most frequently used diagnostic symptoms are abdominal pain, bowel movement frequency and bloating. GPs and ITGPs think that bloating and abdominal discomfort should be introduced into the definition of IBS. Intestinal motility disorders and psychological factors are considered to be the most probable cause of IBS. GPs report more frequently than ITGPs that the patient's request and difficulties in managing the disorder are reasons for a gastroenterological referral. Conclusions: There is still a gap between the indications provided by the experts and clinical practice, and this seems greater on the part of GPs than ITGPs. Abdominal pain and bowel frequency changes are considered the main symptoms for diagnosing IBS, but most GPs and ITGPs would like to include bloating among the diagnostic criteria. It would be highly desirable to develop commonly shared guidelines between gastroenterologists and GPs.

The Delivery Challenge of Genome Editing in Human Epithelia.

Despite exciting advances in gene editing, their clinical translation is still hampered by the lack of delivery systems that can encapsulate and deliver gene editing tools like CRISPR-Cas9 or prime editors to the target side. This is particularly challenging in human epithelia, such as the skin and the lung; the latter of which being a mucosal surface that is covered by a mucus layer. In this perspective, the design and biological assessment of delivery systems for gene editing tools like CRISPR in skin and mucosal surfaces are discussed. The current state-of-the-art, current knowledge, and translational gaps, and guide toward improved translation are highlighted.

Studying human nociceptors: from fundamentals to clinic.

Chronic pain affects one in five of the general population and is the third most important cause of disability-adjusted life-years globally. Unfortunately, treatment remains inadequate due to poor efficacy and tolerability. There has been a failure in translating promising preclinical drug targets into clinic use. This reflects challenges across the whole drug development pathway, from preclinical models to trial design. Nociceptors remain an attractive therapeutic target: their sensitization makes an important contribution to many chronic pain states, they are located outside the blood–brain barrier, and they are relatively specific. The past decade has seen significant advances in the techniques available to study human nociceptors, including: the use of corneal confocal microscopy and biopsy samples to observe nociceptor morphology, the culture of human nociceptors (either from surgical or post-mortem tissue or using human induced pluripotent stem cell derived nociceptors), the application of high throughput technologies such as transcriptomics, the in vitro and in vivo electrophysiological characterization through microneurography, and the correlation with pain percepts provided by quantitative sensory testing. Genome editing in human induced pluripotent stem cell-derived nociceptors enables the interrogation of the causal role of genes in the regulation of nociceptor function. Both human and rodent nociceptors are more heterogeneous at a molecular level than previously appreciated, and while we find that there are broad similarities between human and rodent nociceptors there are also important differences involving ion channel function, expression, and cellular excitability. These technological advances have emphasized the maladaptive plastic changes occurring in human nociceptors following injury that contribute to chronic pain. Studying human nociceptors has revealed new therapeutic targets for the suppression of chronic pain and enhanced repair. Cellular models of human nociceptors have enabled the screening of small molecule and gene therapy approaches on nociceptor function, and in some cases have enabled correlation with clinical outcomes. Undoubtedly, challenges remain. Many of these techniques are difficult to implement at scale, current induced pluripotent stem cell differentiation protocols do not generate the full diversity of nociceptor populations, and we still have a relatively poor understanding of inter-individual variation in nociceptors due to factors such as age, sex, or ethnicity. We hope our ability to directly investigate human nociceptors will not only aid our understanding of the fundamental neurobiology underlying acute and chronic pain but also help bridge the translational gap.

Foundational concepts in the biology of bacterial keratitis

Bacterial infections of the cornea, or bacterial keratitis (BK), are notorious for causing rapidly fulminant disease and permanent vision loss, even among treated patients. In the last sixty years, dramatic upward trajectories in the frequency of BK have been observed internationally, driven in large part by the commercialization of hydrogel contact lenses in the late 1960s. Despite this worsening burden of disease, current evidence-based therapies for BK – including broad-spectrum topical antibiotics and, if indicated, topical corticosteroids – fail to salvage vision in a substantial proportion of affected patients. Amid growing concerns of rapidly diminishing antibiotic utility, there has been renewed interest in urgently needed novel treatments that may improve clinical outcomes on an individual and public health level. Bridging the translational gap in the care of BK requires the identification of new therapeutic targets and rational treatment design, but neither of these aims can be achieved without understanding the complex biological processes that determine how bacterial corneal infections arise, progress, and resolve. In this chapter, we synthesize the current wealth of human and animal experimental data that now inform our understanding of basic BK pathophysiology, in context with modern concepts in ocular immunology and microbiology. By identifying the key molecular determinants of clinical disease, we explore how novel treatments can be developed and translated into routine patient care.

Translating across Languages and Cultures: A Study of Culture-Specific Terms in Bhattarai’s Muglan

The article aims to explore and categorize culture-specific terms (CSTs) in Bhattarai’s novel Muglan, investigate and analyze the strategies applied in the translated version, assess the strategies for plausibility and evaluate gaps in translation. The data for the study were collected from Nepali and English versions of the novel. The basic technique for collecting data was the observation, which was done by using a checklist. The selection of the 220 cultural terms from the novel was done by applying a purposive sampling procedure. They were investigated in terms of five categories and seven strategies. The major finding of the research was that the terms, categorized into five types, employed seven strategies. The most frequent strategy was the translation by cultural substitution, followed by loan word (plus explanation), neutral word and general word. The subsequent strategies were translation by paraphrase (related words), paraphrase (unrelated words) and omission. Moreover, not specific but different reasons were found in the selection and use of the strategies. Finally, the study found that cultural references necessitate the use of appropriate strategies for transferring them across languages.

Lessons on integrated knowledge translation through algorithm's utilization in homecare services: a multiple case study.

Integrated knowledge translation (IKT) is an increasingly recommended collaborative approach to minimize knowledge translation gap. Still, few studies have documented the impact of IKT to optimize knowledge uptake in healthcare settings. An IKT-based clinical algorithm (Algo) was deployed in Quebec (Canada) homecare services to support skill mix for selecting bathing equipment for community-dwelling adults. The objective of this study was to document the characteristics related to Algo's IKT process. A multiple-case study with a nested concurrent mixed design was conducted in provincial homecare services. Based on Knott and Wildavsky's seven-stage classification and the integrated-Promoting Action on Research Implementation in Health Services model, Innovation, Recipients, and Context, characteristics related to Algo's levels of utilization were documented. Quantitative (electronic questionnaire) and qualitative (semistructured interviews and focus groups) data were collected for each case (i.e., homecare service). Descriptive statistics and thematic analysis were performed to describe each case through a mixed methods matrix, for intra/intercase analyses. Knowledge translation characteristics of five Algo's levels of utilization were documented: reception, cognition, reference, effort, and impact. Innovation characteristics (e.g., underlying knowledge) were found to facilitate its dissemination and its use. However, the Recipients (e.g., unclear mechanisms to implement change) and Context (e.g., organizational mandates nonaligned with skill mix) characteristics hampered its application through intermediate and advanced levels of utilization. The knowledge translation analysis of Algo allowed for documenting the IKT-based benefits in terms of utilization in healthcare settings. Although an IKT approach appears to be a strong facilitator for initiating the implementation process, additional characteristics should be considered for promoting and sustaining its use on local, organizational, and external levels of context. Facilitation strategies should document the administrative benefits related to Algo's utilization and contextualize it according to homecare services' characteristics.

Migrant health and language barriers: Uncovering macro level influences on the implementation of trained interpreters in healthcare settings

There is a knowledge translation gap between policies promoting equitable access to healthcare and person-centred care, and the use of untrained interpreters in cross-cultural consultations leading to disparities in health outcomes. An 11 member inter-sectoral working group met at four workshops to discuss and agree on levers and barriers to the provision of trained interpreters in healthcare settings in Ireland. The process was informed by Participatory Learning and Action (PLA) research to support inter-stakeholder dialogue and learning. Normalisation Process Theory (NPT) was used as a conceptual framework to analyse levers and barriers. The NPT analysis explored sense-making, engagement and enactment and found challenges with sense-making and engagement in senior level service planners, managers and governmental offices. This had negative impacts on other key actors, including healthcare providers, medical students and interpreters. This also meant that the enactment of interpreted consultations in practice settings was replete with barriers, most notably a lack of resources, training and supportive organisational structures. The emergent action plan focused on improving sense-making and engagement through inter-sectoral awareness raising, designed to stimulate a series of complementary levers for implementation. Combining PLA and NPT provided new insights into macro level influences on implementation work at the level of a national healthcare system. The approaches used in this study are applicable in other fields.

Structure, Dynamics, and Ligand Recognition of Human-Specific CHRFAM7A (Dupα7) Nicotinic Receptor Linked to Neuropsychiatric Disorders.

Cholinergic α7 nicotinic receptors encoded by the CHRNA7 gene are ligand-gated ion channels directly related to memory and immunomodulation. Exons 5–7 in CHRNA7 can be duplicated and fused to exons A-E of FAR7a, resulting in a hybrid gene known as CHRFAM7A, unique to humans. Its product, denoted herein as Dupα7, is a truncated subunit where the N-terminal 146 residues of the ligand binding domain of the α7 receptor have been replaced by 27 residues from FAM7. Dupα7 negatively affects the functioning of α7 receptors associated with neurological disorders, including Alzheimer’s diseases and schizophrenia. However, the stoichiometry for the α7 nicotinic receptor containing dupα7 monomers remains unknown. In this work, we developed computational models of all possible combinations of wild-type α7 and dupα7 pentamers and evaluated their stability via atomistic molecular dynamics and coarse-grain simulations. We assessed the effect of dupα7 subunits on the Ca2+ conductance using free energy calculations. We showed that receptors comprising of four or more dupα7 subunits are not stable enough to constitute a functional ion channel. We also showed that models with dupα7/α7 interfaces are more stable and are less detrimental for the ion conductance in comparison to dupα7/dupα7 interfaces. Based on these models, we used protein–protein docking to evaluate how such interfaces would interact with an antagonist, α-bungarotoxin, and amyloid Aβ42. Our findings show that the optimal stoichiometry of dupα7/α7 functional pentamers should be no more than three dupα7 monomers, in favour of a dupα7/α7 interface in comparison to a homodimer dupα7/dupα7 interface. We also showed that receptors bearing dupα7 subunits are less sensitive to Aβ42 effects, which may shed light on the translational gap reported for strategies focused on nicotinic receptors in ‘Alzheimer’s disease research.

Prognostic models for knee osteoarthritis: a protocol for systematic review, critical appraisal, and meta-analysis

BackgroundOsteoarthritis is the most common degenerative joint disease. It is associated with significant socioeconomic burden and poor quality of life, mainly due to knee osteoarthritis (KOA), and related total knee arthroplasty (TKA). Since early detection method and disease-modifying drug is lacking, the key of KOA treatment is shifting to disease prevention and progression slowing. The prognostic prediction models are called for to guide clinical decision-making. The aim of our review is to identify and characterize reported multivariable prognostic models for KOA about three clinical concerns: (1) the risk of developing KOA in the general population, (2) the risk of receiving TKA in KOA patients, and (3) the outcome of TKA in KOA patients who plan to receive TKA.MethodsThe electronic datasets (PubMed, Embase, the Cochrane Library, Web of Science, Scopus, SportDiscus, and CINAHL) and gray literature sources (OpenGrey, British Library Inside, ProQuest Dissertations & Theses Global, and BIOSIS preview) will be searched from their inception onwards. Title and abstract screening and full-text review will be accomplished by two independent reviewers. The multivariable prognostic models that concern on (1) the risk of developing KOA in the general population, (2) the risk of receiving TKA in KOA patients, and (3) the outcome of TKA in KOA patients who plan to receive TKA will be included. Data extraction instrument and critical appraisal instrument will be developed before formal assessment and will be modified during a training phase in advance. Study reporting transparency, methodological quality, and risk of bias will be assessed according to the TRIPOD statement, CHARMS checklist, and PROBAST tool, respectively. Prognostic prediction models will be summarized qualitatively. Quantitative metrics on the predictive performance of these models will be synthesized with meta-analyses if appropriate.DiscussionOur systematic review will collate evidence from prognostic prediction models that can be used through the whole process of KOA. The review may identify models which are capable of allowing personalized preventative and therapeutic interventions to be precisely targeted at those individuals who are at the highest risk. To accomplish the prediction models to cross the translational gaps between an exploratory research method and a valued addition to precision medicine workflows, research recommendations relating to model development, validation, or impact assessment will be made.Systematic review registrationPROSPERO CRD42020203543

Human surrogate models of central sensitization: A critical review and practical guide.

BackgroundAs in other fields of medicine, development of new medications for management of neuropathic pain has been difficult since preclinical rodent models do not necessarily translate to the clinics. Aside from ongoing pain with burning or shock‐like qualities, neuropathic pain is often characterized by pain hypersensitivity (hyperalgesia and allodynia), most often towards mechanical stimuli, reflecting sensitization of neural transmission.Data treatmentWe therefore performed a systematic literature review (PubMed‐Medline, Cochrane, WoS, ClinicalTrials) and semi‐quantitative meta‐analysis of human pain models that aim to induce central sensitization, and generate hyperalgesia surrounding a real or simulated injury.ResultsFrom an initial set of 1569 reports, we identified and analysed 269 studies using more than a dozen human models of sensitization. Five of these models (intradermal or topical capsaicin, low‐ or high‐frequency electrical stimulation, thermode‐induced heat‐injury) were found to reliably induce secondary hyperalgesia to pinprick and have been implemented in multiple laboratories. The ability of these models to induce dynamic mechanical allodynia was however substantially lower. The proportion of subjects who developed hypersensitivity was rarely provided, giving rise to significant reporting bias. In four of these models pharmacological profiles allowed to verify similarity to some clinical conditions, and therefore may inform basic research for new drug development.ConclusionsWhile there is no single “optimal” model of central sensitization, the range of validated and easy‐to‐use procedures in humans should be able to inform preclinical researchers on helpful potential biomarkers, thereby narrowing the translation gap between basic and clinical data.SignificanceBeing able to mimic aspects of pathological pain directly in humans has a huge potential to understand pathophysiology and provide animal research with translatable biomarkers for drug development. One group of human surrogate models has proven to have excellent predictive validity: they respond to clinically active medications and do not respond to clinically inactive medications, including some that worked in animals but failed in the clinics. They should therefore inform basic research for new drug development.

Microglia in Aging and Alzheimer's Disease: A Comparative Species Review.

Microglia are the primary immune cells of the central nervous system that help nourish and support neurons, clear debris, and respond to foreign stimuli. Greatly impacted by their environment, microglia go through rapid changes in cell shape, gene expression, and functional behavior during states of infection, trauma, and neurodegeneration. Aging also has a profound effect on microglia, leading to chronic inflammation and an increase in the brain’s susceptibility to neurodegenerative processes that occur in Alzheimer’s disease. Despite the scientific community’s growing knowledge in the field of neuroinflammation, the overall success rate of drug treatment for age-related and neurodegenerative diseases remains incredibly low. Potential reasons for the lack of translation from animal models to the clinic include the use of a single species model, an assumption of similarity in humans, and ignoring contradictory data or information from other species. To aid in the selection of validated and predictive animal models and to bridge the translational gap, this review evaluates similarities and differences among species in microglial activation and density, morphology and phenotype, cytokine expression, phagocytosis, and production of oxidative species in aging and Alzheimer’s disease.

A narrative review of in utero gene therapy: advances, challenges, and future considerations.

The field of in utero gene therapy (IUGT) represents a crossroad of technologic advancements and medical ethical boundaries. Several strategies have been developed for IUGT focusing on either modifying endogenous genes, replacing missing genes, or modifying gene transcription products. The list of candidate diseases such as hemoglobinopathies, cystic fibrosis, lysosomal storage disorders continues to grow with new strategies being developed as our understanding of their respective underlying molecular pathogenesis increases. Treatment in utero has several distinct advantages to postnatal treatment. Biologic and physiologic phenomena enable the delivery of a higher effective dose, generation of immune tolerance, and the prevention of phenotypic onset for genetic diseases. Therapeutic technology for IUGT including CRISPR-Cas9 systems, zinc finger nucleases (ZFN), and peptide nucleic acids (PNAs) has already shown promise in animal models and early postnatal clinical trials. While the ability to detect fetal diagnoses has dramatically improved with developments in ultrasound and next-generation sequencing, treatment options remain experimental, with several translational gaps remaining prior to implementation in the clinical realm. Complicating this issue, the potential diseases targeted by this approach are often debilitating and would otherwise prove fatal if not treated in some manner. The leap from small animals to large animals, and subsequently, to humans will require further vigorous testing of safety and efficacy.

A novel swine model of the acute respiratory distress syndrome using clinically relevant injury exposures.

To date, existing animal models of the acute respiratory distress syndrome (ARDS) have failed to translate preclinical discoveries into effective pharmacotherapy or diagnostic biomarkers. To address this translational gap, we developed a high‐fidelity swine model of ARDS utilizing clinically relevant lung injury exposures. Fourteen male swine were anesthetized, mechanically ventilated, and surgically instrumented for hemodynamic monitoring, blood, and tissue sampling. Animals were allocated to one of three groups: (1) Indirect lung injury only: animals were inoculated by direct injection of Escherichia coli into the kidney parenchyma, provoking systemic inflammation and distributive shock physiology; (2) Direct lung injury only: animals received volutrauma, hyperoxia, and bronchoscope‐delivered gastric particles; (3) Combined indirect and direct lung injury: animals were administered both above‐described indirect and direct lung injury exposures. Animals were monitored for up to 12 h, with serial collection of physiologic data, blood samples, and radiographic imaging. Lung tissue was acquired postmortem for pathological examination. In contrast to indirect lung injury only and direct lung injury only groups, animals in the combined indirect and direct lung injury group exhibited all of the physiological, radiographic, and histopathologic hallmarks of human ARDS: impaired gas exchange (mean PaO2/FiO2 ratio 124.8 ± 63.8), diffuse bilateral opacities on chest radiographs, and extensive pathologic evidence of diffuse alveolar damage. Our novel porcine model of ARDS, built on clinically relevant lung injury exposures, faithfully recapitulates the physiologic, radiographic, and histopathologic features of human ARDS and fills a crucial gap in the translational study of human lung injury.

Bringing the Lab to the Field: Tracking Movement and Phenotyping Stress in Wild Rats

Rodents are used ubiquitously in stress biology research. However, inbred populations housed under laboratory conditions are meant to control for, not model, complex interactions between development, genetics, and environmental uncertainty. Alternatively, studying stress pathophysiology in wild Norway rats (Rattus norvegicus) offers an opportunity to “bring the lab to the field” and close the translational gap that exists between our understanding of stress-induced disorders in laboratory rodents and our ability to treat them in humans. To achieve this, a new approach for tracking and phenotyping wild rats in New York City has been realized.

Natural and synthetic antioxidants targeting cardiac oxidative stress and redox signaling in cardiometabolic diseases

Cardiometabolic diseases (CMDs) are metabolic diseases (e.g., obesity, diabetes, atherosclerosis, rare genetic metabolic diseases, etc.) associated with cardiac pathologies. Pathophysiology of most CMDs involves increased production of reactive oxygen species and impaired antioxidant defense systems, resulting in cardiac oxidative stress (OxS). To alleviate OxS, various antioxidants have been investigated in several diseases with conflicting results. Here we review the effect of CMDs on cardiac redox homeostasis, the role of OxS in cardiac pathologies, as well as experimental and clinical data on the therapeutic potential of natural antioxidants (including resveratrol, quercetin, curcumin, vitamins A, C, and E, coenzyme Q10, etc.), synthetic antioxidants (including N-acetylcysteine, SOD mimetics, mitoTEMPO, SkQ1, etc.), and promoters of antioxidant enzymes in CMDs. As no antioxidant indicated for the prevention and/or treatment of CMDs has reached the market despite the large number of preclinical and clinical studies, a sizeable translational gap is evident in this field. Thus, we also highlight potential underlying factors that may contribute to the failure of translation of antioxidant therapies in CMDs.

Exploring translational gaps between basic scientists, clinical researchers, clinicians, and consumers: Proceedings and recommendations arising from the 2020 mine the gap online workshop

ObjectiveTo provide a summary of the translational gaps in musculoskeletal research as identified in the Mine the Gap workshop and propose possible solutions. MethodsThe Mine the Gap online workshop was hosted on October 14th and 15th, 2020. Five international panels, each comprised of a clinician, clinical researcher and basic scientist, presented gaps and proposed solutions for the themes of biomechanics, pain, biological measurements, phenotypes and imaging. This was followed by an interactive panel discussion with consumer insights. ResultsA number of translational gaps and proposed solutions across each of the five themes were identified. A consumer panel provided constructive feedback highlighting the need for improved resources, communication and shared decision making, and treatment individualisation. ConclusionThis brief report provides a greater understanding of the diverse work and gaps relevant to fundamental/discovery scientists, clinical researchers and clinicians working across the musculoskeletal field. The numerous translational gaps highlight the need to improve communication and collaboration across the musculoskeletal field.

Thrombospondin-1 CD47 Signalling: From Mechanisms to Medicine.

Recent advances provide evidence that the cellular signalling pathway comprising the ligand-receptor duo of thrombospondin-1 (TSP1) and CD47 is involved in mediating a range of diseases affecting renal, vascular, and metabolic function, as well as cancer. In several instances, research has barely progressed past pre-clinical animal models of disease and early phase 1 clinical trials, while for cancers, anti-CD47 therapy has emerged from phase 2 clinical trials in humans as a crucial adjuvant therapeutic agent. This has important implications for interventions that seek to capitalize on targeting this pathway in diseases where TSP1 and/or CD47 play a role. Despite substantial progress made in our understanding of this pathway in malignant and cardiovascular disease, knowledge and translational gaps remain regarding the role of this pathway in kidney and metabolic diseases, limiting identification of putative drug targets and development of effective treatments. This review considers recent advances reported in the field of TSP1-CD47 signalling, focusing on several aspects including enzymatic production, receptor function, interacting partners, localization of signalling, matrix-cellular and cell-to-cell cross talk. The potential impact that these newly described mechanisms have on health, with a particular focus on renal and metabolic disease, is also discussed.

Meet me halfway: Are in vitro 3D cancer models on the way to replace in vivo models for nanomedicine development?

The complexity and diversity of the biochemical processes that occur during tumorigenesis and metastasis are frequently over-simplified in the traditional in vitro cell cultures. Two-dimensional cultures limit researchers' experimental observations and frequently give rise to misleading and contradictory results. Therefore, in order to overcome the limitations of in vitro studies and bridge the translational gap to in vivo applications, 3D models of cancer were developed in the last decades. The three dimensions of the tumor, including its cellular and extracellular microenvironment, are recreated by combining co-cultures of cancer and stromal cells in 3D hydrogel-based growth factors-inclusive scaffolds. More complex 3D cultures, containing functional blood vasculature, can integrate in the system external stimuli (e.g. oxygen and nutrient deprivation, cytokines, growth factors) along with drugs, or other therapeutic compounds. In this scenario, cell signaling pathways, metastatic cascade steps, cell differentiation and self-renewal, tumor-microenvironment interactions, and precision and personalized medicine, are among the wide range of biological applications that can be studied. Here, we discuss a broad variety of strategies exploited by scientists to create in vitro 3D cancer models that resemble as much as possible the biology and patho-physiology of in vivo tumors and predict faithfully the treatment outcome.

Selected Articles from This Issue

While many cancer risk prediction models have been developed, very few have been externally validated, and almost none are used routinely in clinical practice beyond identification of family risk. To address the gap in translation to practice, Rosner and colleagues simplified a summary of breast cancer risk factors, added mammographic breast density, and a 77 SNP polygenic risk score to predict 10-year risk of breast cancer. This simplified model performed well in external validation in the Mayo Mammography Health Study (AUC=0.687). Adding simplified questionnaire data and polygenic risk each improved performance over mammographic breast density and age. This approach can be easily implemented in routine mammography screening clinics.Identification and management of cancer patients' financial concerns is essential as cancer care costs rise. McLouth and colleagues aimed to describe the prevalence of financial screening, sources of financial navigation services, and availability of cancer-specific financial navigators within the National Cancer Institute's Community Oncology Research Program (NCORP). Most NCORP community oncology practice group. had a financial screening process. Practice groups reported multiple potential sources of financial navigation services, but cancer-specific financial navigators were available at only half of the practice groups. Critically, fewer NCORP practice groups serving a higher proportion of racial and ethnic minority patients screened for financial concerns and had a designated financial navigator for cancer patients. Results highlight several opportunities to improve identification of cancer patients who may be vulnerable to financial hardship and to increase services to address financial hardship in community cancer care.Observational studies suggest that men engaged in high levels of physical activity have lower risk of clinically significant prostate cancer. To investigate potential mechanisms, Pernar and colleagues evaluated molecular differences in prostate tissue in men with prostate cancer according to physical activity level. The authors identified several biological pathways that were altered between men with different levels of vigorous physical activity in adjacent normal prostate tissue, such as cancer- and immune-related pathways. These results help illuminate how physical activity may influence the prostate tissue in men with prostate cancer.Inflammation and insulin resistance/hyperinsulinemia are important pathways in hepatocarcinogenesis. Diet and lifestyle behaviors modulate inflammation and insulin response and may thus be crucial modifiable factors in primary prevention for hepatocellular carcinoma (HCC). In a cohort study that followed 119,316 US adults for 25.6 years, participants who consumed diet or had lifestyle behaviors with higher inflammatory and insulinemic potential had higher of developing HCC. These findings by Yang and colleagues suggest that inflammation and insulin resistance/hyperinsulinemia may partly underline the influence of diet and other lifestyle on HCC development, and interventions to reduce the adverse effect of pro-inflammatory and hyper-insulinemic lifestyle may reduce HCC risk.

Assessing the Arabic Translation of Selected Walt Disney Bedtime Stories (2014): A Pragma-Stylistic Approach

Every translation process should be guided by “a communicative purpose of the source text which is supposed to be fulfilled in the target text” (Nord, 2006, p.44). This paper seeks to examine the role of the pragmatic analysis in assessing the quality of the translation process by formulating a tripartite model. This model combines the pragmatic analysis and two functional translation models, which are Nord (1997) and House (2015) to tackle the translation quality assessment. Specifically, this paper assesses the Arabic translation of one bedtime short stories selected from children’s Disney book, 365 Bedtime Stories (2014). The researcher applies a pragma-stylistic framework along with two functional translation models to measure the quality assessment of the target texts and minimize the gap between the two cultures in the source and the target texts of children's literature. Consequently, the study provides further suggestions for the translation gaps and errors which are found in the translated target texts by applying Baker's (2011) and Van Coillie's (2006) strategies. This paper tests the validity of the proposed model to perform a pragma-stylistic model that helps in the translation quality assessment to classify the translation errors and offer solutions that can be used in any children’s literature.