搜索结果：Translational pediatrics

Neuroblastoma is a childhood tumor in which MYC oncogenes are commonly activated to drive tumor progression. Survival for children with high-risk neuroblastoma remains poor despite treatment that incorporates high-dose chemotherapy, stem cell support, surgery, radiation therapy and immunotherapy. More effective and less toxic treatments are sought and one approach under clinical development involves re-purposing the anti-protozoan drug difluoromethylornithine (DFMO; Eflornithine) as a neuroblastoma therapeutic. DFMO is an irreversible inhibitor of ornithine decarboxylase (Odc), a MYC target gene, bona fide oncogene, and the rate-limiting enzyme in polyamine synthesis. DFMO is approved for the treatment of Trypanosoma brucei gambiense encephalitis ("African sleeping sickness") since polyamines are essential for the proliferation of these protozoa. However, polyamines are also critical for mammalian cell proliferation and the finding that MYC coordinately regulates all aspects of polyamine metabolism suggests polyamines may be required to support cancer promotion by MYC. Pre-emptive blockade of polyamine synthesis is sufficient to block tumor initiation in an otherwise fully penetrant transgenic mouse model of neuroblastoma driven by MYCN, underscoring the necessity of polyamines in this process. Moreover, polyamine depletion regimens exert potent anti-tumor activity in pre-clinical models of established neuroblastoma as well, in combination with numerous chemotherapeutic agents and even in tumors with unfavorable genetic features such as MYCN, ALK or TP53 mutation. This has led to the testing of DFMO in clinical trials for children with neuroblastoma. Current trial designs include testing lower dose DFMO alone (2,000 mg/m(2)/day) starting at the completion of standard therapy, or higher doses combined with chemotherapy (up to 9,000 mg/m(2)/day) for patients with relapsed disease that has progressed. In this review we will discuss important considerations for the future design of DFMO-based clinical trials for neuroblastoma, focusing on the need to better define the principal mechanisms of anti-tumor activity for polyamine depletion regimens. Putative DFMO activities that are both cancer cell intrinsic (targeting the principal oncogenic driver, MYC) and cancer cell extrinsic (altering the tumor microenvironment to support anti-tumor immunity) will be discussed. Understanding the mechanisms of DFMO activity are critical in determining how it might be best leveraged in upcoming clinical trials. This mechanistic approach also provides a platform by which iterative pre-clinical testing using translational tumor models may complement our clinical approaches.

Changes in medicine domestically and globally are transforming primary care in the United States. Many have suggested that primary care is in crisis or at least at a crossroads in the United States. The Annals of Internal Medicine recently devoted much of one issue to this topic.1 Primary care for children and adolescents, however, was not addressed specifically. This article focuses on pediatrics and identifies potential roles and new models for primary care pediatrics. The Institute of Medicine has defined primary care as “the provision of integrated, accessible health care services by clinicians who are accountable for addressing a large majority of personal health care needs, developing a sustained partnership with patients, and practicing in the context of family and community.”2 Starfield3 has defined 4 attributes of primary care including first-contact care, longitudinality, comprehensiveness, and coordination. September 11, 2001, the anthrax scare, and emerging threats such as severe acute respiratory syndrome (SARS) have brought a new focus on the importance of individual-level contacts in addressing population-level threats. Before these world events, however, primary care pediatrics was already grappling with its identity and responding to significant changes in medical systems, science, and family needs. The pace and scope of these changes are such that primary care pediatricians of the future will not be performing the same role as today.Historically, American medicine has tended to be reactive rather than proactive in defining its roles in society. However, dynamic change demands collective reflection; it is time to be proactive in assessing the needs of patients, exploring potential roles as health care providers, and developing the mechanisms to redefine the primary care pediatrician of the future.Projecting future trends requires reflection on the history of the profession of preventive pediatrics. In the 1800s, few physicians in the United States routinely treated children; mothers were responsible for treating pediatric illnesses at home. Influential physicians sought to address the needs of this underserved population of children. Some credit social feminism and women physicians such as Elizabeth Blackwell, who established infant hospitals in the 1850s, and S. Josephine Baker, who on a wide scale implemented maternal education on health issues by nurses and established a network of infant welfare stations that included physical examinations and anticipatory guidance.4 Others recognize Nathan Straus, who in the late 1890s initiated a free-milk program and child-weighing stations seeking to combat mortality from diarrheal disease and monitor child health.5 Primary care pediatrics in the United States originated with a strong emphasis on prevention, public health, and advocacy. The advent of vaccines and toxoids in the 1930s and antimicrobials in the 1940s and 1950s expanded the role of primary care. Since then, the history and physical examination, a variety of other screening tests, and numerous immunizations have been added to the repertoire of the primary care pediatrician.In the 1970s, psychosocial issues were termed the “new morbidity.”6 Attention to these psychosocial issues affecting child and adolescent health have further expanded the role of pediatricians in prevention through screening and anticipatory guidance on behavioral issues. The American Academy of Pediatrics published “The Pediatrician and the ‘New Morbidity’”7 in 1993 and “The New Morbidity Revisited: A Renewed Commitment to the Psychosocial Aspects of Pediatric Care”8 in 2001. Although this new morbidity is not particularly new, the breadth of pediatric primary care has broadened, with the provider increasingly called on to address an array of social problems during the 15-minute office visit. As the range of preventive roles has widened, pediatricians have become increasingly grounded in public health efforts and population-level goals, even as individual-level contacts have remained the central focus of health care delivery.Evolution in the role of the primary care pediatrician has occurred in concert with the changing organization and financing of health services. Although current changes seem especially tumultuous and difficult to negotiate, it has been almost 2 decades since Green9 noted that organizational and funding changes, despite their regressive character, offered an opportunity to promote a “new prevention.” That opportunity continues to exist.As with a historical perspective, understanding the role of primary care pediatricians in other countries can offer a broader view of pediatric primary care in the United States. In fact, the United States is among a minority of countries that utilize highly trained pediatricians as providers of first-contact care and well-child care.4 In Canada and Britain, primary care of children is largely provided by general practitioners and public health units, with pediatrician involvement concentrated in more complicated cases and hospital-based care. In many nonindustrialized countries, first-contact care typically is provided by public health workers, with pediatricians providing specialized Western medical care in combination with traditional medical modalities.The United States is unique also in integrating well care and acute care into the primary care system (although such integration is far more complete for affluent Americans than for the poor). The concept of the medical home led by a pediatrician that provides primary, secondary, and tertiary preventive care has been endorsed by the American Academy of Pediatrics.10,11 In many other countries, preventive services are offered by public health workers in a setting separate from those dedicated to illness care. The growth of pediatric nurse practitioners and other primary care providers may begin a trend in which US primary care pediatrics will become a “specialty” similar to international models.Internationally, many view the United States as already having a specialty orientation with underdevelopment of a primary care health system.12,13 Although many look abroad when discussing models of health care financing and the appropriate balance between private and public sector involvement, Starfield reflects that “little of the debate centers on the value of the systems as reflected by indicators of health that are amenable by medical care.”13 Starfield compared 10 Western industrialized nations on their extent of primary health service, health indicators (eg, infant mortality, life expectancy, and death rates), and satisfaction in relation to overall costs of the health system. Primary health services correlated with better health and public satisfaction in 9 of the 10 countries. In the cross-national comparison, the United States ranked low in the extent of primary health service, health indicators, and public satisfaction. Within the US, states with more primary care physicians had better health indicators.14 International, national, and individual patient studies have shown that continuity of relationships and primary care improve health.In “Crossing the Quality Chasm: A New Health System for the 21st Century,” the Institute of Medicine states that “the American health care delivery system is in need of fundamental change…the frustration levels of both patients and clinicians have probably never been higher.”15 Whether this is a sober or alarmist assessment is debatable, but it highlights the need to create a vision for the future of primary care pediatrics. Such reflection begins with acknowledgment of a few clear trends. One is the rise of nonpediatrician providers. Currently, general pediatricians provide the bulk of primary health care to children. Data from the National Ambulatory Medical Care Survey show that >60% of office visits to primary care physicians are to general pediatricians, with remaining visits to family practitioners, general practitioners, or other providers,16 and this percentage has increased in the last 20 years.17 A growing number of pediatric nurse practitioners and other nonphysician providers has begun working alongside primary care pediatricians. There are ∼10000 pediatric nurse practitioners in the United States,18 with the majority involved in the delivery of primary care services. More than 60% of the 6700 members of the National Association of Pediatric Nurse Associates and Practitioners work in urban areas with populations of >100000, increasing access for many poor, underserved families.19 Telephone pediatrics once provided by primary care pediatricians is increasingly provided by nurse call systems.Many managed care plans initially were reluctant to use midlevel professionals such as pediatric nurse providers or child health associates (pediatric physician assistants) to provide pediatric primary care services because of a concern that these practitioners would be perceived as providing inferior care.20 However, it has been shown that they can meet the majority of children’s primary care needs as currently conceived, and it is likely that there will be an increasing reliance on midlevel providers.21–24 Pediatricians Pizzo and Lovejoy have asserted that “. . . routine well child care and some aspects of acute care management in otherwise healthy children should be increasingly delivered by the nurse clinician and family practitioner who are working in collaboration with the pediatric generalist.”25A second trend is the increasing bureaucratization of health care. It was hoped that managed care would promote the status of the primary care provider by allowing them to control the coordination and referral of patients. Instead, the role of the “gatekeeper” has become mired in paperwork and bureaucracy and viewed negatively by patients. The rise of managed care and capitation has challenged the productivity and financial management of outpatient pediatrics. Malpractice insurance costs have risen dramatically. Increasing numbers of primary care pediatricians are dissatisfied,26 and some are opting out of managed care or out of medicine altogether because of increased stress and financial concerns. Some have predicted a tiering of providers with the rich using non-managed care providers and those unable to afford it staying in managed care.27A third trend on the inpatient side is the growth of hospitalist systems in pediatrics. In many locales, hospitalists have replaced primary care pediatricians on the general inpatient ward. In 1996 the term “hospitalist” was coined to describe physicians primarily dedicated to care of hospitalized patients.28 Eight years later the movement has grown dramatically. Although it has been argued that the cost29 and efficiency of inpatient care can be improved with full-time hospitalists without harmful effects on quality or patient satisfaction,28 there are challenges to continuity of care, the doctor-patient relationship, financial reimbursement,30,31 and communication among multiple providers, institutions, and systems.A fourth trend related to the hospitalist trend is growing specialization.32 The numbers of primary care pediatricians who regularly attend deliveries and are involved in the care of critically ill newborns are declining. With the rise of neonatology as a specialty, this role has diminished. Some pediatric specialists have been performing primary care services or have defined specialty areas that were previously in the domain of primary care (eg, neonatology, adolescent medicine, and developmental-behavioral pediatrics). Faced with a growing list of primary care needs (eg, new morbidities), some primary care pediatricians perceive less time to handle complicated medical issues and to interface with subspecialists. Growing financial pressures have sometimes pitted generalists and specialists against each other despite a shared goal of quality child health.Challenges to primary care pediatrics are many. However, amid challenges and crises there are opportunities. What are the core values of the primary care pediatrician, and are they salient today? What is the niche for the primary care pediatrician of the future? Some present and future niches may include the following.A central tenet of primary care is the long-term, trusting relationship between patient and provider. Americans want this continuity. In a survey of patients, 94% valued having a primary care physician who knew all their medical problems; most wanted initial care for common problems to come from their primary physician.33 Another study found that 92% of US patients valued continuity with a doctor, compared with 71% of patients from the United Kingdom.34 Unfortunately, there is much evidence that the quality of primary care relationships has eroded over the years.35,36Considerable research demonstrates that characteristics of primary care are linked to health outcomes. Patient trust in the physician and physician knowledge of the patient increase the likelihood of patient adherence to a physician’s advice and are correlated with satisfaction and improved health status.37 A continuous relationship with a primary care health provider has been linked to a wide range of positive outcomes: higher trust between patient and physician,34 improved chronic disease management,38 fewer hospitalizations and emergency department visits,39,40 healthy behaviors,41 and fewer lawsuits.42–44 In pediatrics, continuity has been associated with timely immunization,45 parent report of higher quality of care,46 and better care coordination.47Primary care pediatricians of the future will continue to carry the banner of continuity, although the and of may With the rise of hospitalist systems, in continuity during will be a Primary care providers will need to new mechanisms to communication among care members and communication for systems and for the integrating and for integration of health services in the in including the of the are having a on understanding of disease and the of the medical system. In the that is not a of pediatrics system (eg, and but is the of and a for understanding disease and as the list of and prevention and care will a of in medical led by primary care providers. are likely to be in or pediatricians may be central in in and disease into primary care a of in medical It is not the of physical characteristics to in a or disease through of a It the of each individual in to for disease or for preventive In this child health providers will need to a new to primary care, with emphasis on and also will need to be and on new knowledge in Some emphasis include and communication and change to of a and The will also new and new tests, new even on a The primary care provider will be on the and some of these new to primary care providers and on new knowledge and its to need to be It is that can the and the new role of primary care physicians as Primary care providers this and the knowledge and to address to children that are at new to and with children who are at in the psychosocial or physical may emphasis on the need to address that including health and social mortality of children and in the United related to health, and other psychosocial issues are at the of the the health and disease prevention for the the need to address these new with primary care access and primary care providers a central child health needs in the context of the family and requires assessment of needs from the of the and addressing to care and new requires that the pediatric office but address child health in the context of family and and with child care and other has suggested that well-child care should to care, the focus from children in a family to of children in a This requires a to and communication to an expanded of health care. systems of care the office with integration of health, and social services is to address the health and well of adolescents, and and pediatricians have been of public health Primary care pediatricians have a history of involvement in public health and to health in areas of and The of September 11, 2001, the anthrax scare, and emerging threats such as acute respiratory syndrome have brought a new focus on the importance of this Although the and of September on health systems is to be primary care providers were into the role of health and an role in the public health As first-contact providers, primary care pediatricians were the for need for and to to children and With new health and other emerging threats to public health, a strong primary care system to public health efforts is more than of the future will be increasingly Growing in the may in increased and Some have even suggested that physicians in the future will have a role as patients less medical advice and and problems with the of accessible or New is likely to not the of communication but also the and quality of between the and has the of medicine in the and with which is and has communication among patients, and other In have provided for education and for patients in and underserved The and have an of and to physicians and their patients. The education of primary care clinicians include in the of health care, and issues in of and the potential and problems in on to and use medical In physicians with of and have the communication to health in for children and is likely to in the This may include nurse practitioners, physician social workers, health providers, physical and other child health The of care more and health The Institute of Medicine that a in the health care system is the to new and new of to patients and to each the primary care pediatrician may be the of an as suggested by the American Academy of the role of the pediatrician may to be one of many with the growing of and medicine, the pediatrician may not be the provider of Primary care physicians may be one health among other valued health from other As the is likely to not to other health but to include collaboration and partnership with providers of services and of roles and in models and are to address family health chronic have come to a of the primary care pediatricians have on a role in care for patients with chronic Although primary care pediatricians have and will continue to the more common chronic illnesses of pediatricians also will care for more and chronic In pediatrics, the growing number of of previously requires coordination with other health and role of chronic care requires knowledge and in the management of and an to care. American Academy of Pediatrics Health and of Care for With Health Care 4 of care access to and services and systems with the and and for improved individual This coordination in multiple with Primary care practitioners be in for the patient in the multiple systems, (eg, from to home to to and pediatrician to addressing family health multiple medical communication and collaboration with and family and child Primary care pediatricians will need to with new for and new models of US health care system is among a minority of nations with highly specialized physicians providing well care. In many other countries, pediatricians are for illness care and provide care. In the United however, many primary care pediatricians are in the of providing care, especially with the growth of the hospitalist It is also that using hospitalists may in more of care, and there are that hospitalist systems may create between primary care physicians and The will be to this and the core values of primary care inpatient and outpatient A is the and of hospital-based by outpatient primary care research on the of hospitalists and on patient is future roles study of health care quality and systems and their on patient is The of a and highly trained of primary care and health services research is to and improve the quality of care. The and areas of of of of and of are an appropriate for the of to further primary care. of new knowledge has been the research of integration studies between from or and new models of care. of and to the and of these and research that knowledge and from to and to is including study of to this in the importance of the of be This communication and of new knowledge to patients, and the of Pediatric report future roles of the pediatrician, and this article on some of a of that roles for pediatricians of the The child and adolescent health needs in the context of the family and changes in the health care system organization and and in and psychosocial As child health the central role of primary care pediatricians is to address the child and adolescent health needs in the context of the family and Primary care core values include quality care, continuity of care, and and care in a medical home. Primary care pediatricians continue to promote these values as new systems of care are and of present and future primary care are in for new roles in primary care requires a In the be a niche be and the be to In pediatrics, patient and a Increasing public the importance of primary care and the expanded roles of providers are an studies have found that not psychosocial because they not it is in the of the primary care pediatrician or they not that providers are parent of the role of the pediatrician may pediatricians to and more and improve health outcomes. The roles are not to be but are to and new roles to current and future pediatricians be to new roles into on the of screening and behavioral and system is pediatrician using a social have suggested that physician or in and their that their efforts may a were most in their and responding to needs are not new but will be even more in an of and will need to core in and on for as research from to is education be in integrating from the to to to in issue of a pediatric that the primary care provider should address or more to address a medical or psychosocial issue of Primary care practitioners are increasingly to more patients and for and on a list of and social and have termed this health in which providers are on a working to in With time and increasing financial new models are to address the issues children and New models and the of primary care into the with other education and may include of implemented by pediatricians or their (eg, and expanded of care (eg, well-child or increasing the of services (eg, is for the and of models such as health centers for physical and health, home management for children with health needs, or other integrating multiple services and dedicated to the welfare of adolescents, and future needs and the and to address these than a in The for Pediatric that many In developing the profession never of the that pediatrics is a and an for the poor, for children and their is a large the is and pediatricians have time to be Although in this in the values and and pediatrics into the is by the to Health National for Health and Health the many and who to the in this

Translational research is expanding and has become a focus of National Research funding agencies, touted as the primary avenue to improve health care practice. The use of human tissues for research on disease etiology is a pillar of translational research, particularly with innovations in research technologies to investigate the building blocks of disease. In pediatrics, translational research using human tissues has been hindered by the many practical and ethical considerations associated with tissue procurement from children and also by a limited population base for study, by the increasing complexities in conducting clinical research, and by a lack of dedicated child-health research funding. Given these obstacles, pediatric translational research can be enhanced by developing strategic and efficient biobanks that will provide scientists with quality tissue specimens to render accurate and reproducible research results. Indeed, tissue sampling and biobanking within pediatric academic settings has potential to impact child health by promoting bidirectional interaction between clinicians and scientists, helping to maximize research productivity, and providing a competitive edge for attracting and maintaining high-quality personnel. The authors of this review outline key issues and practical solutions to optimize pediatric tissue sampling and biobanking for translational research, activities that will ultimately reduce the burden of childhood disease.

Translational research often involves tissue sampling and analysis. Blood is by far the most common tissue collected. Due to the many difficulties encountered with blood procurement from children, it is imperative to maximize the quality and stability of the collected samples to optimize research results. Collected blood can remain whole or be fractionated into serum, plasma, or cell concentrates such as red blood cells, leukocytes, or platelets. Serum and plasma can be used for analyte studies, including proteins, lipids, and small molecules, and as a source of cell-free nucleic acids. Cell concentrates are used in functional studies, flow cytometry, culture experiments, or as a source for cellular nucleic acids. Before initiating studies on blood, a thorough evaluation of practices that may influence analyte and/or cellular integrity is required. Thus, it is imperative that child health researchers working with human blood are aware of how experimental results can be altered by blood sampling methods, times to processing, container tubes, presence or absence of additives, shipping and storage variables, and freeze-thaw cycles. The authors of this review, in an effort to encourage and optimize translational research using blood from pediatric patients, outline best practices for blood collection, processing, shipment, and storage.

The role of flexible bronchoscopy and bronchoalveolar lavage (BAL) for the care of children with airway and pulmonary diseases is well established, with collected BAL fluid most often used clinically for microbiologic pathogen identification and cellular analyses. More recently, powerful analytic research methods have been used to investigate BAL samples to better understand the pathophysiological basis of pediatric respiratory disease. Investigations have focused on the cellular components contained in BAL fluid, such as macrophages, lymphocytes, neutrophils, eosinophils, and mast cells, as well as the noncellular components such as serum molecules, inflammatory proteins, and surfactant. Molecular techniques are frequently used to investigate BAL fluid for the presence of infectious pathologies and for cellular gene expression. Recent advances in proteomics allow identification of multiple protein expression patterns linked to specific respiratory diseases, whereas newer analytic techniques allow for investigations on surfactant quantification and function. These translational research studies on BAL fluid have aided our understanding of pulmonary inflammation and the injury/repair responses in children. We review the ethics and practices for the execution of BAL in children for translational research purposes, with an emphasis on the optimal handling and processing of BAL samples.

Solid tissues are critical for child-health research. Specimens are commonly obtained at the time of biopsy/surgery or postmortem. Research tissues can also be obtained at the time of organ retrieval for donation or from tissue that would otherwise have been discarded. Navigating the ethics of solid tissue collection from children is challenging, and optimal handling practices are imperative to maximize tissue quality. Fresh biopsy/surgical specimens can be affected by a variety of factors, including age, gender, BMI, relative humidity, freeze/thaw steps, and tissue fixation solutions. Postmortem tissues are also vulnerable to agonal factors, body storage temperature, and postmortem intervals. Nonoptimal tissue handling practices result in nucleotide degradation, decreased protein stability, artificial posttranslational protein modifications, and altered lipid concentrations. Tissue pH and tryptophan levels are 2 methods to judge the quality of solid tissue collected for research purposes; however, the RNA integrity number, together with analyses of housekeeping genes, is the new standard. A comprehensive clinical data set accompanying all tissue samples is imperative. In this review, we examined: the ethical standards relating to solid tissue procurement from children; potential sources of solid tissues; optimal practices for solid tissue processing, handling, and storage; and reliable markers of solid tissue quality.

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BACKGROUND: The National Institutes of Health (NIH) Roadmap places special emphasis on "bench-to-bedside" research, or the "translation" of basic science research into practical clinical applications. The Clinical and Translational Science Awards (CTSA) Consortium is one example of the large investments being made to develop a national infrastructure to support translational science, which involves reducing regulatory burdens, launching new educational initiatives, and forming partnerships between academia and industry. However, while numerous definitions have been suggested for translational science, including the qualitative T1-T4 classification, a consensus has not yet been reached. This makes it challenging to tract the impact of these major policy changes. METHODS: In this study, we use a bibliometric approach to map PubMed articles onto a graph, called the Triangle of Biomedicine. The corners of the triangle represent research related to animals, cells and molecules, and humans; and, the position of a publication on the graph is based on its topics, as determined by its Medical Subject Headings (MeSH). We define translation as movement of a collection of articles, or the articles that cite those articles, towards the human corner. RESULTS: The Triangle of Biomedicine provides a quantitative way of determining if an individual scientist, research organization, funding agency, or scientific field is producing results that are relevant to clinical medicine. We validate our technique using examples that have been previously described in the literature and by comparing it to prior methods of measuring translational science. CONCLUSIONS: The Triangle of Biomedicine is a novel way to identify translational science and track changes over time. This is important to policy makers in evaluating the impact of the large investments being made to accelerate translation. The Triangle of Biomedicine also provides a simple visual way of depicting this impact, which can be far more powerful than numbers alone.

Importance: Based on the new 2017 blood pressure guidelines, the prevalence of high blood pressure (BP) among adults has increased from 32% to 46%. Based on new norms and diagnostic thresholds that better align with adult definitions, new clinical practice guidelines were also published for children. The American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children replace the 2004 fourth report from the National Heart, Lung, and Blood Institute. Objectives: To assess the consequences of the American Academy of Pediatrics clinical practice guidelines for the management of elevated BP in children on the prevalence and severity of elevated BP among children and to characterize risk factors for children with new-onset hypertension or a worsening in clinical stage ("reclassified upward"). Design, Setting, and Participants: This study applied both sets of guidelines to classify BP in 15 647 generally healthy, low-risk children aged 5 to 18 years from National Health and Nutrition Examination Surveys (from January 1, 1999, to December 31, 2014). In the case-control portion of the study, children whose BP was reclassified upward (cases) were matched for sex, age, and height with controls with normal BP. Anthropometric and laboratory risk factors were compared, and age- and sex-specific z scores for weight, waist circumference, and body mass index were calculated. Blood pressure was measured by auscultation by trained personnel. After the child rested quietly for 5 minutes, 3 to 4 consecutive BP readings were recorded. Main Outcomes and Measures: Blood pressure percentiles and clinical classification based on either the 2017 American Academy of Pediatrics guidelines or the 2004 National Heart, Lung, and Blood Institute report. Results: Among the 15 647 children in the study (7799 girls and 7848 boys; mean [SD] age, 13.4 [2.8] years), based on the American Academy of Pediatrics guidelines, the estimated (weighted) population prevalence of elevated BP increased from 11.8% (95% CI, 11.1%-13.0%) to 14.2% (95% CI, 13.4%-15.0%). Overall, 905 of 15 584 children (5.8%) had newly diagnosed hypertension (n = 381) or a worsening in clinical stage (n = 524), which represents a substantial increase in disease burden for the health care system. Children whose BP was reclassified upward were more likely to be overweight or obese, with higher z scores for weight, waist circumference, and body mass index. The prevalence of abnormal laboratory test results was also increased, with adverse lipid profiles and increased hemoglobin A1c levels (prediabetes). Conclusions and Relevance: Clustering of cardiovascular risk factors in otherwise healthy US children suggests that those whose BP was reclassified represent a high-risk population whose cardiovascular risk may previously have been underestimated.

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Physician-scientists and scientists in all the health professions are vital members of the U.S. biomedical workforce, but their numbers at academic health centers are declining. Mentorship has been identified as a key component in retention of faculty members at academic health centers. Effective mentoring may promote the retention of clinician-scientists in the biomedical workforce. The authors describe a holistic institutional mentoring program to support junior faculty members engaged in clinical and translational science at the University of Utah. The clinical and translational scholars (CATS) program leverages the resources of the institution, including the Center for Clinical and Translational Science, to augment departmental resources to support junior faculty investigators and uses a multilevel mentoring matrix that includes self, senior, scientific, peer, and staff mentorship. Begun in the Department of Pediatrics, the program was expanded in 2013 to include all departments in the school of medicine and the health sciences. During the two-year program, scholars learn management essentials and have leadership training designed to develop principal investigators. Of the 86 program participants since fiscal year 2008, 92% have received extramural awards, 99% remain in academic medicine, and 95% remain at the University of Utah. The CATS program has also been associated with increased inclusion of women and underrepresented minorities in the institutional research enterprise. The CATS program manifests institutional collaboration and coordination of resources, which have benefited faculty members and the institution. The model can be applied to other academic health centers to support and sustain the biomedical workforce.

Metabolomics is one of the latest omics technologies that has been applied successfully in many areas of life sciences. Despite being relatively new, a plethora of publications over the years have exploited the opportunities provided through this data and question driven approach. Most importantly, metabolomics studies have produced great breakthroughs in biomarker discovery, identification of novel metabolites and more detailed characterisation of biological pathways in many organisms. However, translation of the research outcomes into clinical tests and user-friendly interfaces has been hindered due to many factors, some of which have been outlined hereafter. This position paper is the summary of discussion on translational metabolomics undertaken during a peer session of the Australian and New Zealand Metabolomics Conference (ANZMET 2018) held in Auckland, New Zealand. Here, we discuss some of the key areas in translational metabolomics including existing challenges and suggested solutions, as well as how to expand the clinical and industrial application of metabolomics. In addition, we share our perspective on how full translational capability of metabolomics research can be explored.

Translation of genomic discoveries into patient care is slowly becoming a reality in developed economies around the world. In contrast, low- and middle-income countries (LMIC) have participated minimally in genomic research for several reasons including the lack of coherent national policies, the limited number of well-trained genomic scientists, poor research infrastructure, and local economic and cultural challenges. Recent initiatives such as the Human Heredity and Health in Africa (H3Africa), the Qatar Genome Project, and the Mexico National Institute of Genomic Medicine (INMEGEN) that aim to address these problems through capacity building and empowerment of local researchers have sparked a paradigm shift. In this short communication, we describe experiences of small-scale medical genetics and translational genomic research programs in LMIC. The lessons drawn from these programs drive home the importance of addressing resource, policy, and sociocultural dynamics to realize the promise of precision medicine driven by genomic science globally. By echoing lessons from a bench-to-community translational genomic research, we advocate that large-scale genomic research projects can be successfully linked with health care programs. To harness the benefits of genomics-led health care, LMIC governments should begin to develop national genomics policies that will address human and technology capacity development within the context of their national economic and sociocultural uniqueness. These policies should encourage international collaboration and promote the link between the public health program and genomics researchers. Finally, we highlight the potential catalytic roles of the global community to foster translational genomics in LMIC.

In the treatment of pediatric diseases, mass-produced dosage forms are often not suitable for children. Commercially available medicines are commonly manipulated and mixed with food by caregivers at home, or extemporaneous medications are routinely compounded in the hospital pharmacies to treat hospitalized children. Despite considerable efforts by regulatory agencies, the pediatric population is still exposed to questionable and potentially harmful practices. When designing medicines for children, the ability to fine-tune the dosage while ensuring the safety of the ingredients is of paramount importance. For these purposes solid formulations may represent a valid alternative to liquid formulations for their simpler formula and more stability, and, to overcome the problem of swelling ability, mini-tablets could be a practicable option. This review deals with the different approaches that may be applied to develop mini-tablets intended for pediatrics with a focus on the safety of excipients. Alongside the conventional method of compression, 3D printing appeared particularly appealing, as it allows to reduce the number of ingredients and to avoid both the mixing of powders and intermediate steps such as granulation. Therefore, this technique could be well adaptable to the daily galenic preparations of a hospital pharmacy, thus leading to a reduction of the common practice of off-label preparations.

THIS ARTICLE EXPLORES THE CONVERGENCE OF TWO FIELDS, WHICH HAVE SIMILAR THEORETICAL ORIGINS: a clinical field originally known as sensory integration and a branch of neuroscience that conducts research in an area also called sensory integration. Clinically, the term was used to identify a pattern of dysfunction in children and adults, as well as a related theory, assessment, and treatment method for children who have atypical responses to ordinary sensory stimulation. Currently the term for the disorder is sensory processing disorder (SPD). In neuroscience, the term sensory integration refers to converging information in the brain from one or more sensory domains. A recent subspecialty in neuroscience labeled multisensory integration (MSI) refers to the neural process that occurs when sensory input from two or more different sensory modalities converge. Understanding the specific meanings of the term sensory integration intended by the clinical and neuroscience fields and the term MSI in neuroscience is critical. A translational research approach would improve exploration of crucial research questions in both the basic science and clinical science. Refinement of the conceptual model of the disorder and the related treatment approach would help prioritize which specific hypotheses should be studied in both the clinical and neuroscience fields. The issue is how we can facilitate a translational approach between researchers in the two fields. Multidisciplinary, collaborative studies would increase knowledge of brain function and could make a significant contribution to alleviating the impairments of individuals with SPD and their families.