Epstein-Barr virus infection of Langerhans cell precursors as a mechanism of oral epithelial entry, persistence, and reactivation.

Epstein-Barr virus (EBV) is a ubiquitous human herpesvirus associated with many malignant and nonmalignant human diseases. Life-long latent EBV persistence occurs in blood-borne B lymphocytes, while EBV intermittently productively replicates in mucosal epithelia. Although several models have previously been proposed, the mechanism of EBV transition between these two reservoirs of infection has not been determined. In this study, we present the first evidence demonstrating that EBV latently infects a unique subset of blood-borne mononuclear cells that are direct precursors to Langerhans cells and that EBV both latently and productively infects oral epithelium-resident cells that are likely Langerhans cells. These data form the basis of a proposed new model of EBV transition from blood to oral epithelium in which EBV-infected Langerhans cell precursors serve to transport EBV to the oral epithelium as they migrate and differentiate into oral Langerhans cells. This new model contributes fresh insight into the natural history of EBV infection and the pathogenesis of EBV-associated epithelial disease.

Energy harvesting through arterial wall deformation: design considerations for a magneto-hydrodynamic generator

As the complexity of active medical implants increases, the task of embedding a life-long power supply at the time of implantation becomes more challenging. A periodic renewal of the energy source is often required. Human energy harvesting is, therefore, seen as a possible remedy. In this paper, we present a novel idea to harvest energy from the pressure-driven deformation of an artery by the principle of magneto-hydrodynamics. The generator relies on a highly electrically conductive fluid accelerated perpendicularly to a magnetic field by means of an efficient lever arm mechanism. An artery with 10 mm inner diameter is chosen as a potential implantation site and its ability to drive the generator is established. Three analytical models are proposed to investigate the relevant design parameters and to determine the existence of an optimal configuration. The predicted output power reaches 65 μW according to the first two models and 135 μW according to the third model. It is found that the generator, designed as a circular structure encompassing the artery, should not exceed a total volume of 3 cm3.

Fixed and Flexible: Coexistence of Obligate and Facultative Migratory Strategies in a Freshwater Fish

Migration is an important event in many animal life histories, but the degree to which individual animals participate in seasonal migrations often varies within populations. The powerful ecological and evolutionary consequences of such partial migration are now well documented, but the underlying mechanisms are still heavily debated. One potential mechanism of partial migration is between-individual variation in body condition, where animals in poor condition cannot pay the costs of migration and hence adopt a resident strategy. However, underlying intrinsic traits may overrule such environmental influence, dictating individual consistency in migratory patterns. Unfortunately, field tests of individual consistency compared to the importance of individual condition on migratory propensity are rare. Here we analyse 6 years of field data on roach migration, gathered by tagging almost 3000 individual fish and monitoring their seasonal migrations over extended periods of time. Our aims were to provide a field test of the role of condition in wild fish for migratory decisions, and also to assess individual consistency in migratory tendency. Our analyses reveal that (1) migratory strategy, in terms of migration/residency, is highly consistent within individuals over time and (2) there is a positive relationship between condition and the probability of migration, but only in individuals that adopt a migratory strategy at some point during their lives. However, life-long residents do not differ in condition to migrants, hence body condition is only a good predictor of migratory tendency in fish with migratory phenotypes and not a more general determinant of migratory tendency for the population. As resident individuals can achieve very high body condition and still remain resident, we suggest that our data provides some of the first field evidence to show that both facultative and obligate strategies can co-exist within populations of migratory animals.

The Challenge of Preventing Teen Pregnancy in Texas

A reduction in teen pregnancy and subsequent reduction in teen births correlates to myriad improvements in personal (e.g., high school completion, experience of abuse and neglect, etc); social (e.g., number of children in single parent families, life-long poverty, incarceration rates, etc); and economic (e.g., Medicaid costs, decreased tax revenue, etc) outcomes. In 2005, over 73,000 teen girls in Texas age 15-19 became pregnant, a number significantly higher than any other state. Given the severity of the issue the formation of a statewide organization in Texas devoted to addressing the prevention of teen pregnancy is long overdue. The challenge of reducing teen pregnancy is daunting yet there is momentum and a cadre of committed individuals who have formally put together an organization to provide guidance, oversight and a statewide voice of leadership - all things needed to be successful reducing teen pregnancy in Texas. This commentary provides reactions to proposed strategies and to-date lessons learned.

Barry Saltzman and the Theory of Climate

Barry Saltzman was a giant in the fields of meteorology and climate science. A leading figure in the study of weather and climate for over 40 yr, he has frequently been referred to as the "father of modern climate theory." Ahead of his time in many ways, Saltzman made significant contributions to our understanding of the general circulation and spectral energetics budget of the atmosphere, as well as climate change across a wide spectrum of time scales. In his endeavor to develop a unified theory of how the climate system works, lie played a role in the development of energy balance models, statistical dynamical models, and paleoclimate dynamical models. He was a pioneer in developing meteorologically motivated dynamical systems, including the progenitor of Lorenz's famous chaos model. In applying his own dynamical-systems approach to long-term climate change, he recognized the potential for using atmospheric general circulation models in a complimentary way. In 1998, he was awarded the Carl-Gustaf Rossby medal, the highest honor of the American Meteorological Society "for his life-long contributions to the study of the global circulation and the evolution of the earth's climate." In this paper, the authors summarize and place into perspective some of the most significant contributions that Barry Saltzman made during his long and distinguished career. This short review also serves as an introduction to the papers in this special issue of the Journal of Climate dedicated to Barry's memory.

Microsurgical and laser ablation analysis of interactions between the zones and layers of the tomato shoot apical meristern

Plants exhibit life-long organogenic and histogenic activity in a specialised organ, the shoot apical meristem. Leaves and flowers are formed within the ring-shaped peripheral zone, which surrounds the central zone, the site of the stem cells. We have undertaken a series of high-precision laser ablation and microsurgical tissue removal experiments to test the functions of different parts of the tomato meristem, and to reveal their interactions. Ablation of the central zone led to ectopic expression of the WUSCHEL gene at the periphery, followed by the establishment of a new meristem centre. After the ablation of the central zone, organ formation continued without a lag. Thus, the central zone does not participate in organogenesis, except as the ultimate source of founder cells. Microsurgical removal of the external L-1 layer induced periclinal cell divisions and terminal differentiation in the subtending layers. In addition, no organs were initiated in areas devoid of L-1, demonstrating an important role of the L-1 in organogenesis. L-1 ablation had only local effects, an observation that is difficult to reconcile with phyllotaxis theories that invoke physical tension operating within the meristem as a whole. Finally, regeneration of L-1 cells was never observed after ablation. This shows that while the zones of the meristem show a remarkable capacity to regenerate after interference, elimination of the L-1 layer is irreparable and causes terminal differentiation.

Orthodontic retention procedures in Switzerland.

OBJECTIVE To survey retention procedures used in orthodontic practices in Switzerland. MATERIAL AND METHODS A questionnaire previously developed by Renkema et al. (2009) was sent to 223 Swiss orthodontists. The questionnaire comprised six parts, mainly containing multiple-choice questions. Information as to background education of the individual orthodontist, retention in general, frequency of different types of removable or bonded retainers that were used, retention pro- tocol, and the type and size of the wire used for bonded retainers was assessed. RESULTS The overall response rate was 65 percent. Most orthodontists placed a bonded retainer in the upper and lower arch, except when the upper arch was expanded during treatment or when extractions were performed in the upper arch, in which case they placed a combination of fixed and removable retainers. Opinions varied with regard to how many hours the removable retainers should be worn and the duration of the retention phase. As far as bonded retainers were concerned, 87 percent of the orthodontists preferred life-long retention. Ninety-three percent of the orthodontists considered that the development of a guide- line on retention procedures would be useful. CONCLUSIONS The choice of retention procedures is mostly based on orthodontists personal preference. A further research into the long-term effectiveness of individual retention protocols is needed.

A glance on recent progresses in diagnosis and treatment of primary immunodeficiencies

Primary immunodeficiencies (PIDs)* belong to the group of rare diseases which need more awareness by the relevant medical disciplines. Below a review on recent progresses in diagnosis and treatment of PIDs is given. Reducing the regrettable delay in diagnosis of PIDs (worldwide) is possible only when awareness is increased by doctors who may encounter patients with PID. This review shall serve this purpose. Progresses in understanding what the link might be between one genetic defect presenting in various phenotypes or how various gene defects may manifest by very similar PID phenotypes helps building awareness. Knowledge of PID favours early diagnosis, a cornerstone of optimal, sometimes life-long care at justifiable costs. The complexity of PIDs calls for clinical laboratory and clinical diagnostic performed by experts only. Exciting laboratory diagnostic progresses in early diagnosis of the most severe forms of PID are reviewed below. Progresses in curative therapies for PIDs, such as hematopoietic stem cell transplantation and gene therapies, are mentioned in short. About 80% of PID patients suffer from an antibody deficiency syndrome and can profit from non-curative replacement therapies with human immunoglobulin G concentrates. Modes of application, safety and hints for dosing of replacement therapies to reduce frequencies of severe infections are mentioned below. Thanks to the increasing quality of care, patients survive adolescence. A glance is given on the problems of transition to the adult medicine setting.

The care of adults with congenital heart disease across the globe: Current assessment and future perspective

The number of adults with congenital heart disease (CHD) has increased markedly over the past few decades as a result of astounding successes in pediatric cardiac care. Nevertheless, it is now well understood that CHD is not cured but palliated, such that life-long expert care is required to optimize outcomes. All countries in the world that experience improved survival in CHD must face new challenges inherent to the emergence of a growing and aging CHD population with changing needs and medical and psychosocial issues. Founded in 1992, the International Society for Adult Congenital Heart Disease (ISACHD) is the leading global organization of professionals dedicated to pursuing excellence in the care of adults with CHD worldwide. Recognizing the unique and varied issues involved in caring for adults with CHD, ISACHD established a task force to assess the current status of care for adults with CHD across the globe, highlight major challenges and priorities, and provide future direction. The writing committee consisted of experts from North America, South America, Europe, South Asia, East Asia, and Oceania. The committee was divided into subgroups to review key aspects of adult CHD (ACHD) care. Regional representatives were tasked with investigating and reporting on relevant local issues as accurately as possible, within the constraints of available data. The resulting ISACHD position statement addresses changing patterns of worldwide epidemiology, models of care and organization of care, education and training, and the global research landscape in ACHD.

On the Dark Side of Therapies with Immunoglobulin Concentrates: The Adverse Events

Therapy by human immunoglobulin G (IgG) concentrates is a success story ongoing for decades with an ever increasing demand for this plasma product. The success of IgG concentrates on a clinical level is documented by the slowly increasing number of registered indication and the more rapid increase of the off-label uses, a topic dealt with in another contribution to this special issue of Frontiers in Immunology. A part of the success is the adverse event (AE) profile of IgG concentrates which is, even at life-long need for therapy, excellent. Transmission of pathogens in the last decade could be entirely controlled through the antecedent introduction by authorities of a regulatory network and installing quality standards by the plasma fractionation industry. The cornerstone of the regulatory network is current good manufacturing practice. Non-infectious AEs occur rarely and mainly are mild to moderate. However, in recent times, the increase in frequency of hemolytic and thrombotic AEs raised worrying questions on the possible background for these AEs. Below, we review elements of non-infectious AEs, and particularly focus on hemolysis and thrombosis. We discuss how the introduction of plasma fractionation by ion-exchange chromatography and polishing by immunoaffinity chromatographic steps might alter repertoire of specificities and influence AE profiles and efficacy of IgG concentrates.

Collaborative Research in Childhood Cancer Survivorship: The Current Landscape.

Survivors of childhood cancer carry a substantial burden of morbidity and are at increased risk for premature death. Furthermore, clear associations exist between specific therapeutic exposures and the risk for a variety of long-term complications. The entire landscape of health issues encountered for decades after successful completion of treatment is currently being explored in various collaborative research settings. These settings include large population-based or multi-institutional cohorts and single-institution studies. The ascertainment of outcomes has depended on self-reporting, linkage to registries, or clinical assessments. Survivorship research in the cooperative group setting, such as the Children's Oncology Group, has leveraged the clinical trials infrastructure to explore the molecular underpinnings of treatment-related adverse events, and to understand specific complications in the setting of randomized risk-reduction strategies. This review highlights the salient findings from these large collaborative initiatives, emphasizing the need for life-long follow-up of survivors of childhood cancer, and describing the development of several guidelines and efforts toward harmonization. Finally, the review reinforces the need to identify populations at highest risk, facilitating the development of risk prediction models that would allow for targeted interventions across the entire trajectory of survivorship.

Summary of European Association of Urology (EAU) Guidelines on Neuro-Urology

CONTEXT Most patients with neuro-urological disorders require life-long medical care. The European Association of Urology (EAU) regularly updates guidelines for the diagnosis and treatment of these patients. OBJECTIVE To provide a summary of the 2015 updated EAU Guidelines on Neuro-Urology. EVIDENCE ACQUISITION Structured literature searches in several databases were carried out to update the 2014 guidelines. Levels of evidence and grades of recommendation were assigned where possible. EVIDENCE SYNTHESIS Neurological disorders often cause urinary tract, sexual, and bowel dysfunction. Most neuro-urological patients need life-long care for optimal life expectancy and quality of life. Timely diagnosis and treatment are essential to prevent upper and lower urinary tract deterioration. Clinical assessment should be comprehensive and usually includes a urodynamic investigation. The neuro-urological management must be tailored to the needs of the individual patient and may require a multidisciplinary approach. Sexuality and fertility issues should not be ignored. Numerous conservative and noninvasive possibilities of management are available and should be considered before a surgical approach is chosen. Neuro-urological patients require life-long follow-up and particular attention has to be paid to this aspect of management. CONCLUSIONS The current EAU Guidelines on Neuro-Urology provide an up-to-date overview of the available evidence for adequate diagnosis, treatment, and follow-up of neuro-urological patients. PATIENT SUMMARY Patients with a neurological disorder often suffer from urinary tract, sexual, and bowel dysfunction and life-long care is usually necessary. The update of the EAU Guidelines on Neuro-Urology, summarized in this paper, enables caregivers to provide optimal support to neuro-urological patients. Conservative, noninvasive, or minimally invasive approaches are often possible.

Managing Complications of Fillers: Rare and Not-So-Rare.

Fillers belong to the most frequently used beautifying products. They are generally well tolerated, but any one of them may occasionally produce adverse side effects. Adverse effects usually last as long as the filler is in the skin, which means that short-lived fillers have short-term side effects and permanent fillers may induce life-long adverse effects. The main goal is to prevent them, however, this is not always possible. Utmost care has to be given to the prevention of infections and the injection technique has to be perfect. Treatment of adverse effects is often with hyaluronidase or steroid injections and in some cases together with 5-fluorouracil plus allopurinol orally. Histological examination of biopsy specimens often helps to identify the responsible filler allowing a specific treatment to be adapted.

The role of the experience and expression of anger in future cardiovascular profiles in young adolescents

Cardiovascular disease (CVD) is this nation's leading source of morbidity and mortality, with health disparities evident. Despite inconsistencies in the literature, there is a growing body of evidence that links anger and CV reactivity (CVR) to future CVD. Because CVD is a life-long process with beginnings in childhood, and because adolescents experience and express anger frequently, the need to understand the role that anger has in future CV profiles is important. If identifiable patterns are found, nursing interventions can be implemented at the most beneficial point in the lifespan. This study examined data collected as part of The Heartfelt Study (N = 374), which investigated anger in relation to 24-hour ambulatory blood pressure (BP) and CVR in a multi-ethnic (African, Hispanic, and European American) sample of adolescents (Time 1). This investigator conducted a follow-up for all The Heartfelt Study participants, 11 to 13 years old at the beginning of study, still in attendance at the middle school (N = 44) one year later (Time 2) to determine: (1) changes in anger over time were associated with changes in ambulatory CV profiles: systolic (SBP), diastolic (DBP), heart rate (HR), and pulse pressure (PP) over time; and (2) the extent to which CVR, initiated by talking about a recent anger-producing event, related to future ambulatory CV profiles. A mixed-effects regression for repeated measures was used to analyze the data and found that SBP reactivity at Time 1 was significantly (β = 0.2341, t = 5.91, p < 0.0001) associated with ambulatory SBP at Time 2 and PP reactivity at Time 1 was significantly (β = 0.1530, t = 5.70, p < 0.0001) associated with ambulatory PP at Time 2. Changes in anger over time were not associated with changes in ambulatory BP measures over time. Further research on anger and CVR among adolescents over longer periods of time is recommended. ^

Determining acquisition and cessation antecedents to adolescent cigarette smoking for development of intervention strategies

Our national focus and emphasis on the promotion of healthy behavior choices regarding tobacco and other drugs continues to target adolescents. Multiple studies have shown that adolescence is the optimum period for the prevention of substance use initiation as life-long patterns of health behaviors are established during this critical developmental stage. Tobacco use is associated with an increase in morbid and mortal health conditions of which prevalence increases throughout the lifespan. Attention to the antecedents of preventable health conditions aims to modify the risks and identify health promotion factors. Modifying antecedent factors for tobacco initiation in youth and identifying protective factors for successful smoking cessation has major public health implications across the lifespan. Of foremost interest are those risk factors and resultant behaviors that predict a youth's probability of initiating cigarette use and their cessation of cigarette use. Specifically, this dissertation supports previous results identifying intervention variables on the initiation/cessation continuum model especially with the established predictors of smoking (decisional balance and susceptibility) and with more recently identified predictors of smoking (nicotine dependence and withdrawal symptoms) in current and former smokers in a sample of high school students in Austin and Houston, Texas. These results offer insight for the development of appropriate intervention program strategies for our youth. ^