Impaired Bone Health in Inflammatory Bowel Disease: A Case-Control Study in 80 Pediatric Patients

Peer reviewe

Further investigation of the role of HLA-DPB1 in adult Hodgkin's disease (HD) suggests an influence on susceptibility to different HD subtypes

It has been suggested in a number of studies that susceptibility to adult Hodgkin's disease (HD) is influenced by the HLA class II region, and specifically by alleles at the HLA-DPB1 locus. Since HD is diagnostically complex, it is not clear whether different HLA-DPB1 alleles confer susceptibility to different HD subtypes. To clarify this we have extended a previous study to type DPB1 alleles in 147 adult HD patients from a single centre. We have analysed patients with nodular sclerosing (NS), mixed cellularity (MC) or lymphocyte predominant (LP) HD, and gender in relation to HLA-DPB1 type, in comparison with 183 adult controls. The results confirmed previously reported associations of DPB1*0301 with HD susceptibility (relative risk (RR) = 1.42; 95% confidence interval (CI) 0.86-2.36) and DPB1*0201 with resistance to HD (RR = 0.49; CI 0.27-0.90). However, analysis by HD subtype and gender showed that *0301-associated susceptibility was confined to females with HD (RR = 2.46; CI 1.02-5.92), and *0201-associated resistance to females with NS-HD (RR = 0.28; CI 0.10-0.79). Susceptibility to NS-HD was also associated in females with *1001 (RR = 11.73; CI 1.32-104.36), and resistance with *1101 (RR = 0.08; CI 0.01-0.65). In contrast, susceptibility to LP-HD was associated in males with *2001 (RR = 32.14; CI 3.17-326.17), and to MC-HD with *3401 (RR = 16.78; CI 2.84-99.17). Comparison of DPB1-encoded polymorphic amino-acid frequencies in patients and controls showed that susceptibility to MC-HD was associated with Leucine at position 35 of DPB1 (RR = 8.85; CI 3.04-25.77), Alanine-55 (RR = 15.17; CI 2.00-115.20) and Valine-84 (RR = 15.94; CI 3.55-71.49). In contrast, Glutamic acid 69 was significantly associated with resistance to MC-HD (RR = 0.14; CI 0.03-0.60). Certain DPB1 alleles and individual DPbeta1 polymorphic amino acid residues may thus affect susceptibility and resistance to specific HD subtypes. This may be through their influence on the binding of peptides derived from an HD-associated infectious agent, and the consequent effect on immune responses to the agent

The Evolution of Compact Binary Star Systems

We review the formation and evolution of compact binary stars consisting of white dwarfs (WDs), neutron stars (NSs), and black holes (BHs). Binary NSs and BHs are thought to be the primary astrophysical sources of gravitational waves (GWs) within the frequency band of ground-based detectors, while compact binaries of WDs are important sources of GWs at lower frequencies to be covered by space interferometers (LISA). Major uncertainties in the current understanding of properties of NSs and BHs most relevant to the GW studies are discussed, including the treatment of the natal kicks which compact stellar remnants acquire during the core collapse of massive stars and the common envelope phase of binary evolution. We discuss the coalescence rates of binary NSs and BHs and prospects for their detections, the formation and evolution of binary WDs and their observational manifestations. Special attention is given to AM CVn-stars -- compact binaries in which the Roche lobe is filled by another WD or a low-mass partially degenerate helium-star, as these stars are thought to be the best LISA verification binary GW sources.Comment: 105 pages, 18 figure

Prepatterning in the Stem Cell Compartment

The mechanism by which an apparently uniform population of cells can generate a heterogeneous population of differentiated derivatives is a fundamental aspect of pluripotent and multipotent stem cell behaviour. One possibility is that the environment and the differentiation cues to which the cells are exposed are not uniform. An alternative, but not mutually exclusive possibility is that the observed heterogeneity arises from the stem cells themselves through the existence of different interconvertible substates that pre-exist before the cells commit to differentiate. We have tested this hypothesis in the case of apparently homogeneous pluripotent human embryonal carcinoma (EC) stem cells, which do not follow a uniform pattern of differentiation when exposed to retinoic acid. Instead, they produce differentiated progeny that include both neuronal and non-neural phenotypes. Our results suggest that pluripotent NTERA2 stem cells oscillate between functionally distinct substates that are primed to select distinct lineages when differentiation is induced

Inflammatory responses to acute exercise during pulmonary rehabilitation in patients with COPD

Objective Pulmonary rehabilitation is a cornerstone treatment in the management of chronic obstructive pulmonary disease (COPD). Acute bouts of exercise can lead to short bursts of inflammation in healthy individuals. However, it is unclear how COPD patients respond to acute bouts of exercise. This study assessed inflammatory responses to exercise in COPD patients at the start (phase 1) and end (phase 2) of pulmonary rehabilitation. Methods Blood samples were collected before and after an acute exercise bout at the start (phase 1, n = 40) and end (phase 2, n = 27) of pulmonary rehabilitation. The primary outcome was change in fibrinogen concentrations. Secondary outcomes were changes in CRP concentrations, total/differential leukocyte counts, markers of neutrophil activation (CD11b, CD62L and CD66b), and neutrophil subsets (mature, suppressive, immature, progenitor). Results Acute exercise (phase 1) did not induce significant changes in fibrinogen (p = 0.242) or CRP (p = 0.476). Total leukocyte count [mean difference (MD), 0.5 ± 1.1 (109 L−1); p = 0.004], neutrophil count [MD, 0.4 ± 0.8 (109 L−1); p < 0.001], and immature neutrophils (MD, 0.6 ± 0.8%; p < 0.001) increased post-exercise. Neutrophil activation markers, CD11b (p = 0.470), CD66b (p = 0.334), and CD62L (p = 0.352) were not significantly altered post-exercise. In comparison to the start of pulmonary rehabilitation (phase 2), acute exercise at the end of pulmonary rehabilitation led to a greater fibrinogen response (MD, 84 mg/dL (95% CI − 14, 182); p = 0.045). Conclusion An acute bout of exercise does not appear to induce significant alterations in the concentrations of inflammatory mediators but can increase white blood cell subsets post-exercise. A greater fibrinogen response to acute exercise is seen at the end of pulmonary rehabilitation when compared to the start. Further research is required to understand the clinical context of these acute inflammatory responses to exercise

Culture Adaptation Alters Transcriptional Hierarchies among Single Human Embryonic Stem Cells Reflecting Altered Patterns of Differentiation

We have used single cell transcriptome analysis to re-examine the substates of early passage, karyotypically Normal, and late passage, karyotypically Abnormal (‘Culture Adapted’) human embryonic stem cells characterized by differential expression of the cell surface marker antigen, SSEA3. The results confirmed that culture adaptation is associated with alterations to the dynamics of the SSEA3(+) and SSEA3(-) substates of these cells, with SSEA3(-) Adapted cells remaining within the stem cell compartment whereas the SSEA3(-) Normal cells appear to have differentiated. However, the single cell data reveal that these substates are characterized by further heterogeneity that changes on culture adaptation. Notably the Adapted population includes cells with a transcriptome substate suggestive of a shift to a more naïve-like phenotype in contrast to the cells of the Normal population. Further, a subset of the Normal SSEA3(+) cells expresses genes typical of endoderm differentiation, despite also expressing the undifferentiated stem cell genes, POU5F1 (OCT4) and NANOG, whereas such apparently lineage-primed cells are absent from the Adapted population. These results suggest that the selective growth advantage gained by genetically variant, culture adapted human embryonic stem cells may derive in part from a changed substate structure that influences their propensity for differentiation

A review on herbal antiasthmatics

In traditional systems of medicine, many plants have been documented to be useful for the treatment of various respiratory disorders including asthma. In the last two decades the use of medicinal plants and natural products has been increased dramatically all over the world. Current synthetic drugs used in pharmacotherapy of asthma are unable to act at all the stages and targets of asthma. However some herbal alternatives employed in asthma are proven to provide symptomatic relief and assist in the inhibition of disease progression also. The herbs have shown interesting results in various target specific biological activities such as bronchodilation, mast cell stabilization, anti-anaphylactic, anti-inflammatory, anti-spasmodic, anti-allergic, immunomodulatory and inhibition of mediators such as leukotrienes, lipoxygenase, cyclooxygenase, platelet activating, phosphodiesterase and cytokine, in the treatment of asthma. This paper is an attempt to classify these pharmacological and clinical findings based on their possible mechanism of action reported. It also signifies the need for development of polyherbal formulations containing various herbs acting at particular sites of the pathophysiological cascade of asthma for prophylaxis as well as for the treatment of asthma