Quantitative real-time PCR in Borrelia persica tick-borne relapsing fever demonstrates correlation with the Jarisch-Herxheimer reaction

European Journal of Clinical Microbiology & Infectious Diseases - The purpose of this study is to explore whether a correlation exists between the bacterial load of Borrelia persica in...     

Alterations of monoamines in specific central autonomic nuclei following immunization in mice

At the peak of an immune response (Day 4 following immunization) in mice, norepinephrine (NE) was selectively decreased in the paraventricular nucleus (PVN) of the hypothalamus. At times before (Day 2) and after (Day 8) the peak immune response, no changes in NE were found in this nucleus. Decreases in NE were not seen in other hypothalamic sites or in the A1 cell group of the medulla, which sends noradrenergic projections to the hypothalamus, suggesting that the effect is selective and regional. Morphometric evaluation of varicosities revealed no alterations in density of catecholamine-containing varicosities in the PVN, further suggesting that the decrease in NE is a metabolic effect and not a loss or redistribution of fibers. NE also was decreased in the hippocampus on Day 2 at the rising phase of the immune response. In addition, alterations in serotonin levels were found in the brain during an immune response. Serotonin was decreased in the hippocampus on Day 2, was decreased in the PVN and supraoptic nucleus on Day 4, and was increased in the nucleus tractus solitarius (NTS) on Day 2. These results support the presence of a functional link from the activated immune system to central autonomic nuclei interconnecting the hypothalamus, the limbic system, and the autonomic nervous system. In view of the role of the PVN in corticotropin-releasing factor secretion and regulation of autonomic outflow, evidence from lesion studies for hippocampal involvement in immune regulation, and a key role for NTS in regulation of autonomic outflow, the present findings reinforce the potential importance of these brain regions in reciprocal communication between the nervous and immune systems.     

Sympathetic innervation of lymph nodes in mice

Noradrenergic innervation of popliteal and mesenteric lymph nodes in mice was examined with fluorescence histochemistry. Dense varicose plexuses entered the nodes with the vasculature in the hilar region and continued with the vasculature into the medullary region. Fine, delicate varicosities and small vascular plexuses continued into the cortical and paracortical regions surrounding the germinal centers; some varicosities ended among lymphocytes. A subcapsular plexus contributed fibers into the cortical and paracortical regions. Chemical measurements revealed the presence of norepinephrine in lymph nodes that was depletable with 6-hydroxydopamine. Depletion of norepinephrine from lymph nodes with this agent resulted in a diminished primary immune response in draining lymph nodes following subcutaneous injection of an antigen in two mouse strains, but had no effect in two other strains. These findings suggest that noradrenergic fibers innervate both the vasculature and parenchymal regions of lymph nodes, and may participate in the modulation of immune responses in these organs.     

Emicizumab treatment and monitoring in a paediatric cohort: real-world data

Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks. Emicizumab levels, activated partial thromboplastin time (aPTT) values, and thrombin generation were measured before and during therapy. Twenty patients experienced zero bleeds. All bleeding was trauma-related, and bleeding risk was positively correlated with the length of emicizumab prophylaxis. Sixteen surgical interventions were performed in 12 patients, with no thrombotic complications or thrombotic microangiopathy. Prolonged aPTT values normalised after emicizumab initiation, correlating with an increase in emicizumab plasma levels. Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants. Emicizumab prophylaxis was safe and well tolerated. As all bleedings were trauma-related, laboratory monitoring could not predict bleeding risk. Our results do not support routine thrombin generation monitoring in children treated by emicizumab, yet further studies are warranted in the context of surgical procedures.     

Reduced vital capacity after methacholine challenge in early childhood--is it due to trapped air or loss of motivation

In a previous study we assessed the feasibility of measuring bronchial-reactivity (BHR) in young asthmatic children by the determination of PC(20)-FEV(1) along with clinical end-of-test criteria during a methacholine challenge test (MCT). The end-point was associated with a significant reduction in both flow and vital capacity values. The findings could be due to the children's loss of motivation, which may preclude use of this test. Alternatively, if it reflects air trapping during airway obstruction, it might reinforce its applicability in preschool age children. OBJECTIVES: To elucidate the mechanism of low vital capacity at PC(20)-FEV(1) in preschool age children. SUBJECTS: Twenty-eight children (3.3-6.9 years) with recurrent respiratory symptoms. METHODS: An MCT was carried out using tripling doses (0.06-13.9 mg/ml) delivered by a dosimeter. Spirometry was measured at baseline and after each inhalation in duplicate sets. Whole body plethysmography was measured at baseline and at end-of-test (defined by clinical criteria) according to the recommendations for older populations. RESULTS: Plethysmography was reliably performed by 20 children before and after MCT. At baseline, lung function was within the healthy range. At end-of-test (PC(20)-FEV(1)=4.02+/-3.47 mg/ml), the spirometry parameters and specific conductance values were markedly reduced in correlation with a significant increase in residual volume and resistance. CONCLUSIONS: The study shows that diminished vital capacity is due to the increase in FRC at end-of-test. Our findings support the use of PC(20)-FEV(1) during BHR in young children and suggest that lung volume measurement by a plethysmograph may be feasible in early childhood. Larger studies should be performed to establish the clinical applicability of PC20-FEV1 determination in the preschool age.     

Structure and implied functions of truncated B-cell receptor mRNAs in early embryo and adult mesenchymal stem cells: Cdelta replaces Cmu in mu heavy chain-deficient mice

Stem cells exhibit a promiscuous gene expression pattern. We show herein that the early embryo and adult MSCs express B-cell receptor component mRNAs. To examine possible bearings of these genes on the expressing cells, we studied immunoglobulin mu chain-deficient mice. Pregnant mu chain-deficient females were found to produce a higher percentage of defective morulae compared with control females. Structure analysis indicated that the mu mRNA species found in embryos and in mesenchyme consist of the constant region of the mu heavy chain that encodes a recombinant 50-kDa protein. In situ hybridization localized the constant mu gene expression to loose mesenchymal tissues within the day-12.5 embryo proper and the yolk sac. In early embryo and in adult mesenchyme from mu-deficient mice, delta replaced mu chain, implying a possible requirement of these alternative molecules for embryo development and mesenchymal functions. Indeed, overexpression of the mesenchymal-truncated mu heavy chain in 293T cells resulted in specific subcellular localization and in G(1) growth arrest. The lack of such occurrence following overexpression of a complete, rearranged form of mu chain suggests that the mesenchymal version of this mRNA may possess unique functions.     

Strengthening Partnerships along the Informatics Innovation Stages and Spaces: Research and Practice Collaboration in Utah

Collaborate, translate, and impact are key concepts describing the roles and purposes of the research Centers of Excellence (COE) in Public Health Informatics (PHI). Rocky Mountain COE integrated these concepts into a framework of PHI Innovation Space and Stage to guide their collaboration between the University of Utah, Intermountain Healthcare, and Utah Department of Health. Seven research projects are introduced that illustrate the framework and demonstrate how to effectively manage multiple innovations among multiple organizations over a five-year period. A COE is more than an aggregation of distinct research projects over a short time period. The people, partnership, shared vision, and mutual understanding and appreciation developed over a long period of time form the core and foundation for ongoing collaborative innovations and its successes.