Miracle-dz/UniFAR-FTUs huggingface dataset:
Posttreatment Hepatitis B Surface Antigen Seroreversion: The Bane of Combination Therapy in Chronic Hepatitis B?

actually similar to that reported in Peg-IFN phase III registration trial (3.4% [12/356]). Moreover, it is interesting that the rate of HBeAg seroconversion is significantly higher in TDF þ Peg-IFN group than that in Peg-IFN monotherapy group (23.1% vs 12.3%) at week 48, but the rates between the 2 groups were comparable at week 72 (25.0% vs 24.5%), indicating that the combination therapy might “speed up” but not improve HBeAg seroconversion. Similarly, it is also possible that the combination therapy just speed up HBsAg clearance in the short term. Long-term follow-up studies in HBeAg-positive and -negative patients treated with Peg-IFN showed that 11% and 8.7% could achieve HBsAg loss during long-term off-treatment followup, respectively. Therefore, based on the results of current trial, whether the short-term benefit of TDF þ Peg IFN strategy on HBsAg clearance can be translated into longterm benefit remains unknown; long-term follow-up is warranted to clarify this important issue. On the other hand, it should be mentioned that HBsAg clearance is indeed an ideal endpoint that we all dream of and make great effort to realize; however, wedo have to admit that HBsAg clearance is still rare by using current available drugs, although different strategies have been tried to improve HBsAg clearance. What is more important is that sustained suppression of viral replication was demonstrated clearly to be related to the improvement of survival for chronic hepatitis B patients, where HBsAg clearance is not required. Until now, almost all the patients could achieve undetectable HBV DNA level after long-term entecavir or TDF treatment. Thus, it is more realistic to keep viral replication under control for more patients rather than seekHBsAgclearance for fewpatients.We will pursue HBsAg clearance with the advent of novel drugs with new targets and newmechanisms, just like the successful story of chronic hepatitis C.
More about Asthma in PAI

Asthma occurs throughout life but often starts at an early age. In a Canadian study of lifetime risk of asthma, one in five individuals was diagnosed during childhood (1). Not all children who wheeze during childhood will have asthma later in life. For pediatricians, some problematic issues emerge. Wheezing with viral infections is one of the most common causes of visits to the emergency room and also for some children the first sign of what will develop into chronic asthma (2). We now know that structural changes of bronchial tissue can be found in young children and that allergic disease combined with viral wheeze (3), particularly rhinovirus infections may increase the risk of chronic asthma. However, so far we have failed in finding preventive measures against asthma, allergic, or non-allergic. The search for the mechanisms of early bronchial inflammation and sensitization is therefore one of the most important tasks for pediatricians. Likewise, the development of a rhinovirus vaccine could change the disease patterns and possibly prevent not only viral wheeze but also – or at least postpone – the development of asthma. These are speculations and wishful thinking but still not completely out of the blue. Another important issue is the fact that we have not managed to find pharmacologic treatment strategies that are efficacious for the bronchial obstruction and inflammation caused by the viral infections, although reports on treatment with antileukotrienes are mixed as illustrated by Peng et al. (4). In this issue, we have collected papers reporting on a wide set of questions concerning asthma in children. We have reports on early risk factors due to infections, early structural changes in the airways due to or predisposing for early asthma (2, 3, 5). The issue of severe asthma which affects a small proportion of children with asthma is also discussed (6). These children, although few, require extensive health care. Polysensitization, comorbidity, and/or cross-reactivity toward cats, dogs, and other mammalian animals are prevalent in this group (7) and are associated with more severe allergic disease. Refined diagnostic tools may be useful to assess their allergic pattern (8). These papers and other interesting asthma related topics are highlighted in this issue. The intention of the Editorial Board of PAI is to strengthen the area of research on pediatric asthma in the future.
Laser photobiomodulation of gene expression and release of growth factors and cytokines from cells in culture: a review of human and animal studies.

AIM The aim of this paper was to review experimental studies of laser irradiation of human and animal cells in culture to assess the photobiomodulatory effects of such irradiation on gene expression and release of growth factors and CYTOKINES. BACKGROUND Previous studies have reported that the release of certain growth factors and cytokines by various types of cells can be modulated by laser irradiation. A review of recent studies may provide further insight into the clinical effects brought about by laser irradiation of cells and tissues, including changes in inflammation and cellular proliferation. METHODS A systematic review was completed of original research papers investigating the effects of laser phototherapy on gene expression and release of these mediators from human and animal cells in culture (January 2002 to September 2009). Relevant papers were retrieved primarily from PubMed and Medline databases. The search terms were "growth factors", "cytokines", "laser therapy", "laser irradiation", "laser phototherapy," and "phototherapy". RESULTS A total of 17 relevant papers were included in the review, comprising studies on a variety of cell types. Considerable variation occurred in research design, methodology, and irradiation parameters employed, limiting comparison of research findings between studies. Results demonstrated that laser irradiation at green, red, or infrared wavelengths at a range of dosage parameters can cause significant changes in the cellular gene expression and release of these mediators, and that such effects depend upon wavelength and radiant exposure. CONCLUSION Findings from the reviewed studies clearly demonstrate the ability of laser irradiation to modulate gene expression and the release of growth factors and cytokines from cells in culture. Further work is indicated at the clinical level to elucidate the putative clinical relevance of these cellular-level effects.
Comments on: ‘Anaphylaxis caused by in‐season switchover of sublingual immunotherapy formulation’

adverse reactions, including anaphylaxis, in association with tablet sublingual immunotherapy and advise caution when undertaking in-seasonal initiation or switchover of immunotherapy. Initiation or switchover of immunotherapy should always take place under direct medical supervision in a facility prepared to treat anaphylaxis. Kuang-Chih Hsiao & Joanne Smart Epworth HealthCare Richmond, Richmond; Murdoch Childrens Research Institute; Royal Children’s Hospital, Melbourne, Vic. , Australia E-mail: kuangchih.hsiao@mcri.edu. au DOI:10.1111/pai.12268
Prescription patterns of inhaled corticosteroids for preschool children – A Norwegian register study

Although guidelines for treatment of wheeze and asthma in preschool children are available, symptoms are overlapping and it may be difficult to decide which children should be given inhaled corticosteroids (ICS). Previous studies suggest an inappropriate prescription pattern of ICS in this age group. We studied time trends of ICS use in preschool children in Norway during 2004–2013 by age, gender and physician specialty, and the persistence of ICS use during preschool years.
Session 3: Joint Nutrition Society and Irish Nutrition and Dietetic Institute Symposium on ‘Nutrition and autoimmune disease’ PUFA, inflammatory processes and rheumatoid arthritis

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease manifested by swollen and painful joints, bone erosion and functional impairment. The joint lesions are characterised by infiltration of T lymphocytes, macrophages and B lymphocytes into the synovium and by synovial inflammation involving eicosanoids, cytokines and matrix metalloproteinases. In relation to inflammatory processes, the main fatty acids of interest are the n-6 PUFA arachidonic acid, which is the precursor of inflammatory eicosanoids such as PGE2 and leukotriene B4, and the n-3 PUFA EPA and DHA, which are found in oily fish and fish oils. Eicosanoids derived from the n-6 PUFA arachidonic acid play a role in RA, and the efficacy of non-steroidal anti-inflammatory drugs in RA indicates the importance of pro-inflammatory cyclooxygenase pathway products of arachidonic acid in the pathophysiology of the disease. EPA and DHA inhibit arachidonic acid metabolism to inflammatory eicosanoids. EPA also gives rise to eicosanoid mediators that are less inflammatory than those produced from arachidonic acid and both EPA and DHA give rise to resolvins that are anti-inflammatory and inflammation resolving. In addition to modifying the lipid mediator profile, n-3 PUFA exert effects on other aspects of immunity relevant to RA such as antigen presentation, T-cell reactivity and inflammatory cytokine production. Fish oil has been shown to slow the development of arthritis in an animal model and to reduce disease severity. Randomised clinical trials have demonstrated a range of clinical benefits in patients with RA that include reducing pain, duration of morning stiffness and use of non-steroidal anti-inflammatory drugs.
Early childhood growth patterns and school‐age respiratory resistance, fractional exhaled nitric oxide and asthma

Greater infant weight gain is associated with lower lung function and increased risk of childhood asthma. The role of early childhood peak growth patterns is unclear. We assessed the associations of individually derived early childhood peak growth patterns with respiratory resistance, fractional exhaled nitric oxide, wheezing patterns, and asthma until school‐age.
Conference on ‘ Over-and undernutrition : challenges and approaches ’ Symposium on ‘ Geographical and geological influences on nutrition ’ Factors controlling the distribution of selenium in the environment and their impact on health and nutrition

Se is essential to human and animal health but can be toxic in excess. An interest in its geochemistry has developed alongside a greater understanding of its function in a number of health conditions. Geology exerts a strong control on the Se status of the surface environment; low-Se rock-types (0.05–0.09 mg Se/kg) make up the majority of rocks occurring at the Earth’s surface, which in turn account for the generally low levels of Se in most soils. However, there are exceptions such as associations with sulfide mineralisation and in some types of sedimentary rocks (e.g. black shales) in which contents of Se can be much higher. Baseline geochemical data now enable a comparison to be made between environmental and human Se status, although a direct link is only likely to be seen if the population is dependent on the local environment for sustenance. This situation is demonstrated with an example from the work of the British Geological Survey in the Se-deficiency belt of China. The recent fall in the daily dietary Se intake in the UK is discussed in the context of human Se status and declining use of North American wheat in bread making. Generally, US wheat has ten times more Se than UK wheat, attributed to the fact that soils from the wheat-growing belt of America are more enriched in Se to a similar order of magnitude. In agriculture effective biofortification of crops with Se-rich fertilisers must be demonstrably safe to the environment and monitored appropriately and baseline geochemical data will enable this process to be done with confidence.
The present status of glutamine

Clinical glutamine supplements are a curious phenomenon, being more akin to bicarbonate to correct acidosis than to antibiotics to cure infection. The amino acid glutamine, a central compound in amino acid and intermediary metabolism, is made and consumed in large amounts by the body each day. Although supplements will not correct a “nutritional deficiency” of glutamine, nevertheless, the particular metabolic features of the intestine, skeletal muscle, and cells of the immune system suggest that they have a dependency on the metabolism of this amino acid. Animal studies suggest that glutamine supplements can reverse the atrophy of the small intestine that occurs during total parenteral nutrition. Similarly, improvements in the immune function of injured animals have been noted. Several clinical studies have also demonstrated positive effects on clinical outcome and patient well-being.
Converging Reflections on Music Therapy With Children and Adolescents: A Collaborative Seminar on Diverse Areas of Music Therapy Practice and Research

Normal 0 21 false false false MicrosoftInternetExplorer4 Four music therapists working at the Grieg Academy Music Therapy Research Centre (GAMUT) in Bergen, Norway, collaborated in providing a seminar at a national conference called “Barn og deres andre” [Children and their others] in November 2012. The four therapists were educated in different music therapy training courses in four different countries, and have worked and carried out research in distinctly different areas of music therapy practice: pediatric traumatic brain injury, children with autism, and children and adolescents in child welfare. Significantly, their experience of creating a collaborative seminar led to an awareness of each other’s work and also a process of identifying shared perspectives about music therapy with children and adolescents. This report on the symposium presents the three seminar papers and documents the journey of a team-building process within the music therapy discipline.
Challenges assessing clinical endpoints in early Huntington disease

The basic aim of this study was to evaluate the current accepted standard clinical endpoint for the earliest‐studied HD participants likely to be recruited into clinical trials. As the advent of genetic testing for HD, it is possible to identify gene carriers before the diagnosis of disease, which opens up the possibility of clinical trials of disease‐modifying treatments in clinically asymptomatic persons. Current accepted standard clinical endpoints were examined as part of a multinational, 32‐site, longitudinal, observational study of 786 research participants currently in the HD prodrome (gene‐positive but not clinically diagnosed). Clinical signs and symptoms were used to prospectively predict functional loss as assessed by current accepted standard endpoints over 8 years of follow‐up. Functional capacity measures were not sensitive for HD in the prodrome; over 88% scored at ceiling. Prospective evaluation revealed that the first functional loss was in their accustomed work. In a survival analysis, motor, cognitive, and psychiatric measures were all predictors of job change. To our knowledge, this is the first prospective study ever conducted on the emergence of functional loss secondary to brain disease. We conclude that future clinical trials designed for very early disease will require the development of new and more sensitive measures of real‐life function. © 2010 Movement Disorder Society
Variables Antropométricas y Rendimiento Físico en Estudiantes Universitarios de Educación Física

La estructura corporal del estudiante universitario de Educacion Fisica cobra vital importancia debido a que sera relevante en sus logros en las asignaturas que impliquen esfuerzo fisico. Consistente con esto, es deseable contar con datos de las caracteristicas morfoestructurales basadas en el somatotipo y la composicion corporal de los estudiantes de ambos sexos que ingresan a estudiar a esta carrera, cotejados con pruebas fisicas. Se estudiaron 32 hombres y 18 mujeres, en edades entre 17 y 25 anos, de la carrera de Educacion Fisica, de la Pontificia Universidad Catolica de Valparaiso, Chile. Se aplicaron los metodos de Composicion Corporal de Deborah Kerr y de Somatotipo de Heath-Carter, y se correlaciono con las pruebas fisicas de: carrera de 2400 m de George ­ Fisher, salto vertical con pies juntos, biceps en traccion vertical, prueba de abdominales y 50 m de velocidad. Los datos indican que el grupo masculino con un mayor porcentaje de masa grasa realizan la prueba de 50 m de velocidad en un mayor tiempo (r= 0,57) e inversamente, quienes tienen menor masa grasa, realizaron mayor cantidad de repeticiones en la prueba de barra (r=-0,55), en el grupo femenino se encuentra una correlacion media entre la masa muscular y la prueba de 50 m, r=0,52. Sin embargo, no existen correlaciones suficientes entre la masa muscular y las pruebas de rendimiento, en las que se esperaba que la cantidad de masa muscular influyera sobre las pruebas que dependen de este componente. Las variables antropometricas del grupo universitario evaluado, no se correlacionan de manera significativa con el rendimiento fisico, puesto que el nivel de entrenamiento es bajo, lo que determina el nivel de rendimiento, a diferencia de lo que ocurre con deportistas.
Oligoclonal bands in cerebrospinal fluid in patients with Tourette's syndrome

Since a postinfectious or autoimmune etiology is suggested to be involved in the pathogenesis of Tourette's syndrome (TS), we investigated oligoclonal bands (OB) of immunoglobulin G (IgG) in cerebrospinal fluid (CSF), indicating a humoral immune response in the central nervous system. CSF examinations including isoelectric focusing to analyze the presence of OB were performed in 21 TS patients [17 men/4 women, mean age = 29 ± 12 (SD) years]. Isoelectric focusing showed the presence of positive OB in 6, borderline bands in 2, and serum and CSF bands (“mirrored pattern”) in another 2 patients. Clinical data did not correlate with CSF findings. Thus, 38% (8 of 21) of our patients exhibited pathological CSF bands. Since none of them suffered from another disease known to be associated with OB, our results suggest an association with the pathogenesis of TS itself and point to an involvement of immunological mechanisms in TS pathology. © 2010 Movement Disorder Society.
HBV DNA Integration and Clonal Hepatocyte Expansion in Chronic Hepatitis B Patients Considered Immune Tolerant.

BACKGROUND & AIMS Chronic infection with hepatitis B virus (HBV) progresses through different phases. The first, called the immune-tolerant phase, has been associated with a lack of disease activity. We examined HBV-DNA integration, clonal hepatocyte expansion, HBV antigen expression, and HBV-specific immune responses in patients in the immune-tolerant phase to assess whether this designation is appropriate or if there is evidence of disease activity. METHODS We studied HBV-DNA integration, clonal hepatocyte expansion, and expression of hepatitis B surface antigen and core antigen in liver tissues from 26 patients with chronic HBV infection (ages, 14-39 y); 9 patients were positive for hepatitis B e antigen (HBeAg) in the immune-tolerant phase and were matched for age with 10 HBeAg-positive patients with active disease and 7 HBeAg-negative patients with active disease. Peripheral blood samples were collected and HBV-specific T cells were quantified for each group. RESULTS Detection of HBV antigens differed among groups. However, unexpectedly high numbers of HBV-DNA integrations, randomly distributed among chromosomes, were detected in all groups. Clonal hepatocyte expansion in patients considered immune tolerant also was greater than expected, potentially in response to hepatocyte turnover mediated by HBV-specific T cells, which were detected in peripheral blood cells from patients in all phases of infection. CONCLUSIONS We measured HBV-specific T cells, HBV-DNA integration, and clonal hepatocyte expansion in different disease phases of young patients with chronic hepatitis B, with emphasis on the so-called immune-tolerant phase. A high level of HBV-DNA integration and clonal hepatocyte expansion in patients considered immune tolerant indicated that hepatocarcinogenesis could be underway-even in patients with early stage chronic HBV infection. Our findings do not support the concepts that this phase is devoid of markers of disease progression or that an immune response has not been initiated. We propose that this early phase be called a high-replication, low-inflammation stage. The timing of therapeutic interventions to minimize further genetic damage to the hepatocyte population should be reconsidered.
Downregulated Cardiac Annexin VI mRNA and Protein Levels in Chronically Fibrillating Human Atria

Objectives: We compared the expression and distribution of atrial annexin VI between patients with atrial fibrillation (AF) or sinus rhythm (SR). Methods: Atrial appendages were obtained during cardiac surgery from 20 patients with chronic AF and 34 matched controls in SR. The expression and distribution of annexin VI were analyzed using semiquantitative RT-PCR, Western blotting and immunoconfocal microscopy. Results: In the AF group, compared to SR, the mRNA was reduced to <35% and the protein to <50% in amount (for each atrium, all p < 0.01). Immunoconfocal microscopy confirmed the downregulation of annexin VI protein in AF and demonstrated the colocalization of annexin VI with both Na+/Ca2+ exchangers and L-type Ca2+ channels in the sarcolemma, but not with ryanodine receptors in the sarcoplasmic reticulum. Conclusions: Atrial annexin VI, spatially colocalized with both Na+/Ca2+ exchangers and L-type Ca2+ channels in the myocyte membrane, is downregulated during chronic AF.
MUTUAL TOLERANCE OF DONOR AND HOST LYMPHO-RETICULAR CELLS IN LASTING TOLERANCE

Evidence is presented indicating that in mice with long lasting tolerance the lympho-reticular cells of donor origin, as weil as those of host origin, develop a toierant state. Homologous disease does not develop in sublethally irradiated (A x C3H) F/sub 1/ recipients upon injection of ceIIs from donors made tolerant at birth by intravenous injection of spleen cells taken from A strain donors. Lymphoid cells from C3H strain mice rendered tolerant to A strain tissues protect against fatal irradiation and do not produce late deaths due to homologous disease. The protection afforded against lethal irradiation in the F/sub 1/ hybrid by cells from one parert strain tolerant to the cells of the other parert strain is comparable to the protection provided by cells from isologous Fi hybrid donors. These observations provide additional evidence that adult cells, just as embryonic cells or cells from neonatal animals, can develop immunologic tolerance.
ApoE genotype: from geographic distribution to function and responsiveness to dietary factors

ApoE is a key protein in lipid metabolism with three major isoforms. ApoE allele frequencies show non-random global distribution especially in Europe with high apoE ε3 frequency in the Mediterranean area, whereas the apoE ε4 genotype is enriched in Northern Europe. The apoE ε4 genotype is one of the most important genetic risk factors for age-dependent chronic diseases, including CVD and Alzheimer's disease (AD). The apoE polymorphism has been shown to impact on blood lipids, biomarkers of oxidative stress and chronic inflammation, which all may contribute to the isoform-dependent disease risk. Studies in mice and human subjects indicate that the apoE ε3 but not the apoE ε4 genotype may significantly benefit from dietary flavonoids (e.g. quercetin) and n-3 fatty acids. Metabolism of lipid soluble vitamins E and D is likewise differentially affected by the apoE genotype. Epidemiological and experimental evidence suggest a better vitamin D status in apoE ε4 than ε3 subjects indicating a certain advantage of ε4 over ε3. The present review aims at evaluation of current data available on interactions between apoE polymorphism and dietary responsiveness to flavonoids, fat soluble vitamins and n-3 fatty acids. Likewise, distinct geographic distribution and chronic disease risk of the different apoE isoforms are addressed.