Progress in pediatrics in 2015: choices in allergy, endocrinology, gastroenterology, genetics, haematology, infectious diseases, neonatology, nephrology, neurology, nutrition, oncology and pulmonology.

This review focuses key advances in different pediatric fields that were published in Italian Journal of Pediatrics and in international journals in 2015. Weaning studies continue to show promise for preventing food allergy. New diagnostic tools are available for identifying the allergic origin of allergic-like symptoms. Advances have been reported in obesity, short stature and autoimmune endocrine disorders. New molecules are offered to reduce weight gain and insulin-resistance in obese children. Regional investigations may provide suggestions for preventing short stature. Epidemiological studies have evidenced the high incidence of Graves' disease and Hashimoto's thyroiditis in patients with Down syndrome. Documentation of novel risk factors for celiac disease are of use to develop strategies for prevention in the population at-risk. Diagnostic criteria for non-celiac gluten sensitivity have been reported. Negative effect on nervous system development of the supernumerary X chromosome in Klinefelter syndrome has emerged. Improvements have been made in understanding rare diseases such as Rubinstein-Taybi syndrome. Eltrombopag is an effective therapy for immune trombocytopenia. Children with sickle-cell anemia are at risk for nocturnal enuresis. Invasive diseases caused by Streptococcus pyogenes are still common despite of vaccination. No difference in frequency of antibiotic prescriptions for acute otitis media between before the publication of the national guideline and after has been found. The importance of timing of iron administration in low birth weight infants, the effect of probiotics for preventing necrotising enterocolitis and perspectives for managing jaundice and cholestasis in neonates have been highlighted. New strategies have been developed to reduce the risk for relapse in nephrotic syndrome including prednisolone during upper respiratory infection. Insights into the pathophysiology of cerebral palsy, arterial ischemic stroke and acute encephalitis may drive advances in treatment. Recommendations on breastfeeding and complementary feeding have been updated. Novel treatments for rhabdomyosarcoma should be considered for paediatric patients. Control of risk factors for bronchiolitis and administration of pavilizumab for preventing respiratory syncytial virus infection may reduce hospitalization. Identification of risk factors for hospitalization in children with wheezing can improve the management of this disease. Deletions or mutations in genes encoding proteins for surfactant function may cause diffuse lung disease.

[Role of vitamin D in allergic diseases: Current research status]. / Die Rolle von Vitamin D bei allergischen Erkrankungen : Eine Standortbestimmung.

BACKGROUND: Recent research has focused on the relationship between vitamin D and allergy development. Results show that on the one hand a vitamin D deficiency can be responsible for the emergence of allergies, however, on the other hand a vitamin-D (over-) substitution was also seen in context with an increased allergy development. OBJECTIVE: This article provides an overview on the current state of research and points at the problematic aspects that accompany the assessment of these studies. RESULTS: The paradoxic effect of vitamin D is currently being explained by epigenetic programming in pregnancy, by too low vitamin-D levels or excessive supplementation in newborns. Very recently, a gender-specific impact of vitamin D is also being discussed. CONCLUSION: For a final assessment of vitamin-D effects on the emergence of allergies, further research is necessary. Due to a high level of heterogeneity among current observational studies regarding central aspects of the discussion, randomised clinical trials are recommended.

Future view and development of immunology: exploring the immunology based on Chinese medicine and culture.

The immunologically mediated disease is a big family which affects many people in the world, since the cures are not yet available for most immune diseases, the patients face a lifetime of illness and treatment. Chinese medicine inspires us to develop new methods for the treatment of immune diseases. Previous researches of immune system have revealed that an immune network exists. The immune system is like a complex highway; if we travel on these highways, we must have a map to avoid travelling in the wrong direction. Drawing the map of immune network will provide new tools for us to look directly at the basis of the immune system.

Photoimmunology.

The discipline that investigates the biologic effects of ultraviolet radiation on the immune system is called photoimmunology. Photoimmunology evolved from an interest in understanding the role of the immune system in skin cancer development and why immunosuppressed organ transplant recipients are at a greatly increased risk for cutaneous neoplasms. In addition to contributing to an understanding of the pathogenesis of nonmelanoma skin cancer, the knowledge acquired about the immunologic effects of ultraviolet radiation exposure has provided an understanding of its role in the pathogenesis of other photodermatologic diseases.

Novel pebbles in the mosaic of autoimmunity.

Almost 25 years ago, the concept of the 'mosaic of autoimmunity' was introduced to the scientific community, and since then this concept has continuously evolved, with new pebbles being added regularly. We are now looking at an era in which the players of autoimmunity have changed names and roles. In this issue of BMC Medicine, several aspects of autoimmunity have been addressed, suggesting that we are now at the forefront of autoimmunity science. Within the environmental factors generating autoimmunity are now included unsuspected molecules such as vitamin D and aluminum. Some adjuvants such as aluminum are recognized as causal factors in the development of the autoimmune response. An entirely new syndrome, the autoimmune/inflammatory syndrome induced by adjuvants (ASIA), has been recently described. This is the new wind blowing within the branches of autoimmunity, adding knowledge to physicians for helping patients with autoimmune disease.

Practical aspects of integrating allergy and pulmonology management into a rhinology practice: the Vanderbilt ASAP experience.

PURPOSE OF REVIEW: In the aftermath of reforms in healthcare laws, there is a focused conversation concerning healthcare delivery with an increasing emphasis on quality, cost containment, improved outcomes and access. Concurrently, providers are experiencing pressure as patient volume escalates yet while funding levels fail to keep pace. Addressing these issues is imperative to the medical practices. In this review, the integration of an allergy and rhinology practice into a center focused on managing chronic airway disease is detailed in the examination of an existing practice. RECENT FINDINGS: In 2010, healthcare spending in the Unites States was nearly US$ 2.6 trillion, 17.9% of the nation's gross domestic product and 10 times 1980 levels. Insurance premiums have increased 113% since 2001 and continue to outpace income gains. Seventy-five percent of spending is attributed to chronic diseases such as stroke, cancer, heart disease, diabetes, Parkinson's disease and Alzheimer's. Airway disease (rhinitis, sinusitis, asthma, chronic obstructive pulmonary disease) is one of the largest chronic disease states. In fact, more patients suffer from airway disease than the aforementioned diseases in total. Any effort to affect costs must include a chronic disease strategy. This review will focus on the nature of the integrated program and its relation to the nature of airway diseases; a detailed description of how it works and why it is different from traditional models. SUMMARY: This integrated model of healthcare will improve the quality of care provided to airway disease patients as well as help contain overall healthcare cost.

Effect of the ethanolic extract from green propolis on production of antibodies after immunization against canine parvovirus (CPV) and canine coronavirus (CCoV) / Efeito do extrato etanólico de própolis verde sobre a produção de anticorpos após imunização contra parvovírus canino (CPV) e coronavírus canino (CCoV)

This study was designed to evaluate whether an ethanolic extract of green propolis (EEP) can interfere with p roduction of specific antibodies after immunization against parvovirus (CPV) and canine coronavirus (CCoV). Mice were vaccinated with CPV and CCoV (0.75, 1.5 and 3 x 106 TCID50) with or without 400 μg/dose of the EEP. Twenty one days after the third dose was measured serum IgG. The co-administration of the EEP significantly enhanced serum specific IgG responses to CPV in animals inoculated with the highest concentration of the antigen, and had no influence on levels of antibodies to CCoV. The results indicate that the EEP has immunomodulatory action closely dependent on the type and concentration of antigen used, being able to increase the levels of antibodies to CPV.

Este estudo foi realizado para avaliar se extrato etanólico de própolis verde (EEP) pode interferir na produção de anticorpos específicos após imunização contra parvovírus (CPV) e coronavírus canino (CCoV). Camundongos foramvacinados com CPV e CCoV (0.75, 1.5 e 3 x 106 TCID50) com ou sem 400 μg/dose de EEP. Vinte e um dias após a terceira dose foi mensurado IgG sérica. A coadministração de EEP aumentou significativamente os níveis de IgG específica para o CPV em animais inoculados com a maior concentração do antígeno, e não teve influência sobre os níveis de anticorpos para CCoV. Os resultados indicam que o EEP tem ação imunomoduladora intimamente dependente do tipo e concentração do antígeno utilizado, sendo capaz de aumentar os níveis de anticorpos contra CPV.

Recent advances in the field of nutritional immunology.

Every 4 years, researchers in the cross-disciplinary field of nutritional immunology convene for a FASEB-sponsored meeting entitled, "Nutritional Immunology: Role in Health and Disease", which was held this summer in Carefree, AZ, USA. The scope of the conference encompassed a diverse list of research topics, including, but not restricted to, obesity and immune dysfunction, nutrient-gene interactions, mucosal immunity and a discussion of future directions for the field. Here, we summarize some of the findings shared at the conference, specifically focusing on obesity, immunological function of dietary components (n-3 polyunsaturated fatty acids and flavanoids), gut immunity and the microbiota, and relevant emerging technologies and databases.

Biomarkers of immunotoxicity for environmental and public health research.

The immune response plays an important role in the pathophysiology of numerous diseases including asthma, autoimmunity and cancer. Application of biomarkers of immunotoxicity in epidemiology studies and human clinical trials can improve our understanding of the mechanisms that underlie the associations between environmental exposures and development of these immune-mediated diseases. Immunological biomarkers currently used in environmental health studies include detection of key components of innate and adaptive immunity (e.g., complement, immunoglobulin and cell subsets) as well as functional responses and activation of key immune cells. The use of high-throughput assays, including flow cytometry, Luminex, and Multi-spot cytokine detection methods can further provide quantitative analysis of immune effects. Due to the complexity and redundancy of the immune response, an integrated assessment of several components of the immune responses is needed. The rapidly expanding field of immunoinformatics will also aid in the synthesis of the vast amount of data being generated. This review discusses and provides examples of how the identification and development of immunological biomarkers for use in studies of environmental exposures and immune-mediated disorders can be achieved.

Novedades Científicas / Scientific novelty

La medicina complementaria y alternativa (MCA) se utiliza, en más de 80% de la población mundial y se esta convirtiendo en un componente en acceso para el sistema de salud de EE.UU. La información sobre las terapias de MCA; representa cada vez más un desafio para los médicos, porque casi el 40% de sus pacientes pueden utilizarla y otro 50% considerar su adquisición, como parte de un régimen alterno, en el cuidado de su salud. La población que utiliza al menos una véz la MCA es de un 70% de la población y el gasto anual alcanza unos $ 34 mil millones. El Informe Nacional sobre Estadísticas de Salud para el año 2007 describe, que el método terapéutico de mayor uso se basó en productos de tipo naturales hasta un 17,7%, sin incluir vitaminas o minerales. Más del 5% de los niños menores de 18 años de edad utilizaron la MCA para condiciones alérgicas como el asma. La cantidad y calidad de ls información disponible y la preocupación acerca de la responsabilidad de su riesgo, representan un reto para la mayoría de los médicos en cualquier país. Desde la creación del Centro Nacional para la Medicina Complementaria y Alternativa se ha producido un enorme aumento en el número de ensayos clínicos en ciencias básicas y terapéuticas basada en la exploración de la MCA. La inmunología clínica, en particular la subespecialidad de enfermedades alérgicas, representa un área fértil por el gran número de terapias MCA que han demostrado afectar el sistema inmune. Recientemente, se han descubierto los posibles mecanismos bioquímicos involucrados en la vía de los inmunomoduladores, suplementos de vitaminas (A, D y E), que parecen afectar la diferenciación de células CD4 y sus subclases Th1 y Th2. Otras investigaciones han demostrado que las hiervas tales como el resveratrol, quercetina y magnolol pueden actuar a nivel de los factores de transcripción como el nuclear-kB y en la señal del transductor y activadose de las vías de transcripción/Janus kinasa

[Cooperation among clinics and practices. Integrated medical care in occupational dermatology]. / Neue Formen der Zusammenarbeit zwischen Praxis und Klinik. Integrierte Versorgung in der Berufsdermatologie.

Preventive measures in occupational dermatology have proven to be very effective in recent years, especially measures of primary and secondary prevention as components of a complex hierarchical prevention concept. For those cases of occupational dermatoses in which these outpatient prevention measures are not successful, interdisciplinary inpatient rehabilitation measures have been developed ("tertiary individual prevention" [TIP]). TIP comprises 3 weeks inpatient treatment including intensive disease-oriented teaching and psychological counseling, followed by outpatient treatment by the local dermatologist. In 2005, a German prospective cohort multicenter study ("Medizinisch-Berufliches Rehabilitationsverfahren Haut--Optimierung und Qualitätssicherung des Heilverfahrens" [ROQ]) started which will further standardize TIP and evaluate long-term success and scientific sustainability in depth. This integrated concept of an inpatient/outpatient disease management reveals remarkable pertinent options for patients with severe occupational dermatoses in all high-risk professions.

Treating autoimmune disease by targeting CD8(+) T suppressor cells.

Current treatments for autoimmune disease are hampered by the non-specificity of immunomodulatory interventions, having to accept broad suppression of immunoresponsiveness with potentially serious side effects, such as infection or malignancy. The development of antigen-specific approaches, downregulating pathogenic immune responses while maintaining protective immunity, would be a major step forward. One possible approach involves the targeting of physiological regulatory mechanisms, such as inhibitory CD8 T cells that are now recognized to fine-tune many aspects of immune responses. CD8 T suppressor (Ts) cells may directly inhibit other T cells or condition antigen-presenting cells in such a way that immune amplification steps are dampened. The promise of CD8 Ts cells lies in their potential to disrupt host-injurious immune responses in a targeted fashion. For therapeutic purposes, such CD8 Ts cells could either be generated in vitro and transferred into the host or their numbers and activity could be modulated by treating the patient with established or novel immunomodulators. Emerging evidence shows that several subsets of CD8 Ts cells exist. While there is still considerable uncertainty about the molecular mechanisms through which CD8 Ts cells can reset immune responses to protect the host, their potential diagnostic and therapeutic use is intriguing and has generated renewed interest.

Prebióticos en las fórmulas para lactantes. ¿Podemos modificar la respuesta inmune? / Prebiotics in infant formulae. Could we modify the immune response?

Introducción: La microflora intestinal de los lactantes amamantados tiene un papel primordial en la función intestinal y en el desarrollo del sistema inmune. Los oligosacáridos presentes en la leche materna estimulan selectivamente el crecimiento de Bifidobacterias y Lactobacilos en el intestino. En los últimos años se han realizado varios intentos para obtener una flora similar en lactantes alimentados con fórmulas infantiles. Una de las posibilidades para obtener este efecto es proporcionar nutrientes selectivos para esta microflora beneficiosa (prebióticos). Objetivo: Realizar una revisión de la evidencia científica disponible sobre la incorporación de prebióticos a los alimentos para lactantes y su posible influencia en la respuesta inmune. Material y métodos: Se realizó un amplia búsqueda bibliográfica con los siguientes términos de búsqueda: "prebióticos OR oligosacáridos OR microflora intestinal AND fórmula infantil AND resultados". Se hizo especial análisis de los estudios clínicos con fórmulas infantiles que incorporaran prebióticos. Resultados: Un prebiótico es una sustancia no absorbible en el intestino delgado y susceptible de fermentación por la flora colónica. El empleo de una mezcla determinada de galactooligosacáridos y fructooligosacáridos en una fórmula infantil aumenta el número de bifidobacterias de una forma dependiente de la dosis (el efecto máximo obtenido a una concentración de 0,8 g/dl) y reduce el número de gérmenes patógenos tanto en lactantes pretérminos como a término cuando se comparaban con lactantes que recibían una fórmula no suplementada. El efecto de los oligosacáridos sobre el metabolismo bacteriano se estudió midiendo la producción de ácidos grasos de cadena corta y el pH fecal. Estudios más recientes han mostrado beneficios clínicos de la incorporación de una mezcla de prebióticos a una fórmula infantil. En primer lugar, se ha visto una disminución en el riesgo de aparición de dermatitis atópica en lactantes de riesgo; en segundo lugar, una reducción en el número de episodios infecciosos, fundamentalmente intestinales e infecciones de vías respiratorias superiores en el primer año de vida. Puede especularse que los prebióticos pueden tener un papel importante en la prevención de la alergia y de las infecciones leves en el lactante (AU)

Introduction: The intestinal microflora of breast-fed infants is an important physiological factor in gut function and the development of the immune system. Human milk oligosaccharides have been shown to selectively stimulate the growth of Bifidobacteria and Lactobacilli in the intestine. In the last few years several attempts have been made to establish the presence of similar microbiota in formula-fed infants. One of the approaches to modify the balance of intestinal microflora is to supply the potentially helpful microbiota with selective nutrients (prebiotics). Goal: To review the current scientific evidence related to the addition of prebiotics to infant feeds and their possible role in the immune function. Material and methods: A bibliographic search with Mesh terms: Prebiotics OR oligosaccharides OR intestinal microflora AND infant formula AND results was performed. Special analysis was done on clinical studies. Results: Prebiotics are substances that are not absorbed through the small intestine and are fermented by colonic bacteria. A prebiotic mixture from galacto-oligosaccharides and fructo-oligosaccharides has been used to mimic the effect of human milk oligosaccharides. It has been demonstrated that such a mixture significantly increases the number of bifidobacteria in a dose-related way (maximum effect at 0.8 g/dl) and reduces the number of pathogens in term as well as in preterm infants when compared with a group of infants fed a non-supplemented formula. The effect of oligosaccharides on bacterial metabolism was studied by measuring short chain fatty acid production and fecal pH. More recent studies have been able to show clinical benefits with the use of a prebiotic mixture in infant formulas. Firstly, it has been shown to decrease the risk of developing atopic dermatitis in high risk infants; secondly a reduced incidence of intestinal as well as upper airway infections in the first year of life. It can be hypothesized that prebiotics might play an important role as a new concept in allergy and infection prevention in infants (AU)

Advances in basic and clinical immunology in 2006.

This article reviews the progress in the field of basic and clinical immunology in 2006, focusing on the articles published in the Journal. The role of Toll-like receptors in the immune response was explored in detail in several articles. The knowledge gained in these investigations is being used to develop strategies that enhance the immunogenicity of vaccines to prevent infectious diseases and to have an immunomodulatory effect on allergic diseases. Other components of the innate immunity reported on were the recognition of allergens with lipid-derived motifs by CD1d-restricted T cells and the role of dendritic cells in the development of an allergic response. More than 120 primary immunodeficiencies were defined at a molecular level, and biological agents such as TNF-alpha antagonists and IFN-alpha were shown to have therapeutic use. New anti-HIV drugs that block cell entry were proven to be effective, thus offering alternative therapies to respond to the development of multidrug-resistant HIV strains. The modern understanding of immunologic concepts is helping to elucidate the mechanisms of defense against viruses, bacteria, and parasites; as a result, strategies to improve management and prevention continue to emerge.

The revolutionary health science of psychoendoneuroimmunology: a new paradigm for understanding health and treating illness.

This paper reviews the social and behavioral factors acting on the brain that influence health, illness, and death. Using data from several areas of research, a new paradigm is proposed for understanding health and illness. This paradigm, psychoendoneuroimmunology (PENI), provides both the concepts and the mechanisms for studying and explaining mind-body relationships. The brain is the body's first line of defense against illness, and the mind is the functioning of the brain. PENI incorporates ideas, belief systems, hopes, and desires as well as biochemistry, physiology, and anatomy. As we change our thoughts, we are changing our brain and thus our biology and our body. Belief systems set a baseline for the brain upon which other variables will act and have their effects.

Immunological research in clinical psychiatry: report on the consensus debate during the 7th Expert Meeting on Psychiatry and Immunology.

There is convincing evidence that cytokines are involved in the physiology and pathophysiology of brain function and interact with different neurotransmitter and neuroendocrine pathways. The possible involvement of the immune system in the neurobiological mechanisms that underlie psychiatric disorders has attracted increasing attention in recent years. Thus in the last decade, numerous clinical studies have demonstrated dysregulated immune functions in patients with psychiatric disorders. Such findings formed the basis of the 7th Expert Meeting on Psychiatry and Immunology in Muenster, Germany, where a consensus symposium was held to consider the strengths and weaknesses of current research in psychoneuroimmunology. Following a general overview of the field, the following topics were discussed: (1) methodological problems in laboratory procedures and recruitment of clinical samples; (2) the importance of pre-clinical research and animal models in psychiatric research; (3) the problem of statistical vs biological relevance. It was concluded that, despite a fruitful proliferation of research activities throughout the last decade, the continuous elaboration of methodological standards including the implementation of hypothesis-driven research represents a task that is likely to prove crucial for the future development of immunology research in clinical psychiatry.