Relative quantitative analysis of amyloid plaque burden in Alzheimer’s disease (AD) patients can be reported as standardized uptake value ratio (SUVR) from positron emission tomography (PET). Here, ...the SUVR is the ratio of the mean amyloid radioligand retention in a composite (COMP) neocortical volume of interest (VOI) to that in a reference VOI, such as the cerebellum, brainstem (BST)/pons, or white matter (WM). Some longitudinal PET investigations show that the rate of amyloid accumulation to follow-up has an inverted U relationship with baseline amyloid SUVR relative to cerebellar or brainstem/pons reference VOIs. The corresponding association with SUVR relative to WM is unknown. To test the possible benefits of WM normalization, we analyzed
18
F-AV45 PET data from 404 subjects in the AD Neuroimaging Initiative (ADNI) database at baseline and 2-year follow-up (144 cognitively normal controls, 225 patients with mild cognitive impairment, and 35 AD patients). Reference regions included subcortical WM as well as conventional cerebellar gray matter (CBL), and BST. We tested associations between each subject’s inter-session change (∆) of SUVR and their baseline SUVR by applying linear, logarithmic, and quadratic regression analyses. Unscaled standardized uptake values (SUVs) were correlated between VOIs at baseline and follow-up, and within VOIs in the longitudinal run. The association between ∆SUVR and baseline SUVR relative to WM reference was best described by an inverted U-shaped function. Correlation analyses demonstrated a high regional and temporal correlation between COMP and WM VOI SUVs. For WM normalization, we confirm that the rate of amyloid accumulation over time follows an inverted U-shaped function of baseline amyloid burden. Reference region selection, however, has substantial effects on SUVR results. This reflects the extent of covariance between SUVs in the COMP VOI and those in the various reference VOIs. We speculate that PET labeling of amyloid deposition within target regions is partially confounded by effects of longitudinal changes of cerebral blood flow (CBF) on tracer delivery. Indeed, CBF may be the leading factor influencing longitudinal SUV changes. We suggest that SUVR relative to WM may be more robust to changes in CBF, and thus fitter for sensitive detection of amyloid accumulation in intervention studies.
The integration of three-dimensional (3D) cameras into clinical practice for pre-operative planning and post-operative monitoring of rhinoplasties remains controversial. However, this technology ...offers the advantage of capturing the 3D surface without exposing patients to potentially harmful radiation. Continuous assessment allows the follow-up of swelling patterns, cartilage alignment, and bone remodeling. The primary objective of our study was to quantify changes in nasal structure before and after rhinoplasty by using 3D photography. Our study cohort consisted of 29 patients who underwent open structural rhinoplasty. We used the Artec Space Spider camera to acquire a total of 103 3D images. We collected pre-operative and at least two or three post-operative follow-up scans, which were taken one, three, and six months after surgery. We evaluated paired scans that included various time intervals to improve our understanding of swelling behavior and to ensure an objective analysis of changes. Eleven specific anatomical landmarks were identified for measurement. Two independent raters determined the distances between these landmarks over time. The calculation of intraclass correlation coefficients showed low inter-rater variability. Statistically significant changes over time (p < 0.05) were observed for various anatomical landmarks, including soft tissue nasion, soft tissue orbitale right, soft tissue maxillofrontale left, soft tissue maxillofrontale right, nasal bridge, and nasal break point. Conversely, no significant changes (p > 0.05) were observed in the measurements of soft tissue orbitale left, pronasale, subnasale, alare right, or alare left. A visual assessment was conducted using surface distance maps. The results indicate that the complete decrease in swelling takes at least 6 months or even longer. Additionally, 3D photography can provide an objectively comparable analysis of the face and external contours. Furthermore, it allows for a comparison of external contours and therefore pre- and post-operative differences.
Background
Studies show that proallergic TH2 cells decrease after successful allergen‐specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to ...exhaustion due to chronic T‐cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergen exposure during AIT in mice and two independent patient cohorts.
Methods
OVA‐sensitized C57BL/6J mice were challenged and treated with OVA, and the development of exhaustion in local and systemic TH2 cells was analyzed. In patients, the expression of exhaustion‐associated surface markers on TH2 cells was evaluated using flow cytometry in a cross‐sectional grass pollen allergy cohort with and without AIT. The treatment effect was further studied in PBMC collected from a prospective long‐term AIT cohort.
Results
The exhaustion‐associated surface markers CTLA‐4 and PD‐1 were significantly upregulated on TH2 cells upon OVA aerosol exposure in OVA‐allergic compared to non‐allergic mice. CTLA‐4 and PD‐1 decreased after AIT, in particular on the surface of local lung TH2 cells. Similarly, CTLA‐4 and PD‐1 expression was enhanced on TH2 cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discovered a late‐differentiated TH2 population expressing both markers that decreased during up‐dosing but persisted long term during the maintenance phase.
Conclusions
This study shows that allergen exposure promotes CTLA‐4 and PD‐1 expression on TH2 cells and that the dynamic change in frequencies of exhausted TH2 cells exhibits a differential pattern during the up‐dosing versus the maintenance phases of AIT.
This study shows that TH2 cells upregulate the exhaustion‐associated surface markers CTLA‐4 and PD‐1 upon in vivo allergen exposure in OVA‐sensitized mice and grass pollen‐allergic patients. This upregulation is reduced after AIT, in particular in TH2 cells from local mouse lungs and AR patients with concurrent asthma. The transcriptome of allergic mouse lungs shows enhanced expression of both markers.
Abbreviations: AAI, allergic airway inflammation; AIT, allergen‐specific immunotherapy; AR, allergic rhinitis; Baz1a, bromodomain adjacent to zinc finger domain 1A; CTLA‐4, cytotoxic T‐lymphocyte‐associated antigen‐4; Egr2, early growth response 2; Hif1a, hypoxia inducible factor 1 subunit alpha; Icos, inducible T cell costimulator; OVA, ovalbumin; PD‐1, program death protein‐1; Pdcd1, programmed cell death 1; Pilra, paired immunoglobin like type 2 receptor alpha; Tnfsf, TNF superfamily member; Tnfrsf, TNF receptor superfamily member; Tshz2, teashirt zinc finger homeobox 2
Studies show that proallergic T
2-cells decrease after successful allergen-specific immunotherapy (AIT). It is likely that iatrogenic administration of allergens drives these cells to exhaustion due ...to chronic T cell receptor stimulation. This study aimed to investigate the exhaustion of T cells in connection with allergenexposure during AIT in mice and two independent patient cohorts.
OVA-sensitized C57BL/6J mice were challenged and treated with OVA, and the development of exhaustion inlocal and systemic T
2-cells was analyzed.In patients, the expression of exhaustion-associated surface markers on T
2-cells was evaluated using flow cytometry in a cross-sectional grass pollen allergy cohort with and without AIT.The treatment effect was further studied in PBMC collected from a prospective long-termAIT cohort.
The exhaustion-associated surface markers CTLA-4 and PD-1 were significantly upregulated on T
2-cells upon OVA aerosol exposure in OVA-allergic compared to non-allergic mice. CTLA-4 and PD-1decreased after AIT, in particular on the surface oflocal lung T
2-cells. Similarly, CTLA-4 and PD-1 expression were enhanced on T
2-cells from patients with allergic rhinitis with an even stronger effect in those with concomitant asthma. Using an unbiased Louvain clustering analysis, we discoveredalate-differentiated T
2 population expressing both markers that decreased during up-dosing but persisted long-term during the maintenance phase.
This study shows that allergen exposure promotes CTLA-4 and PD-1 expression onT
2-cells, andthat the dynamic change in frequencies of exhausted T
2-cells exhibits a differential pattern during the up-dosing versus the maintenance phases of AIT.
Sensing of the intestinal microbiota by the host immune system is important to induce protective immune responses. Hence, modification of the gut microbiota might be able to prevent or treat ...allergies, mediated by proinflammatory Th2 immune responses. The aim was to investigate the ex vivo immunomodulatory effects of the synbiotics Pollagen® and Kallergen®, containing the probiotic bacterial strains
Lactobacillus
,
Lacticaseibacillus
and
Bifidobacterium
, in the context of grass pollen allergy. Peripheral blood mononuclear cells (PBMCs) from grass pollen–allergic patients and healthy controls were stimulated with grass pollen extract (GPE) and synbiotics and Gata3 expression and cytokine secretion analyzed. Monocyte-derived dendritic cells (MoDCs) cells were matured in the presence of GPE and synbiotics, co-cultured with autologous naïve T cells and maturation markers and cytokine secretion analyzed. GPE stimulation of PBMCs from grass pollen–allergic patients resulted in a significant higher production of the Th2 cytokines IL-4, IL-5, IL-9 and IL-13 compared to healthy controls. Gata3
+
CD4
+
T cell induction was independent of the allergic status. The synbiotics promoted IL-10 and IFN-γ secretion and downregulated the GPE-induced Th2-like phenotype. Co-culturing naïve T cells with MoDCs, matured in the presence of GPE and synbiotics, shifted the GPE-induced Th2 cytokine release towards Th1-Th17-promoting conditions in allergic subjects. The investigated synbiotics are effective in downregulating the GPE-induced Th2 immune response in PBMCs from grass pollen–allergic patients as well as in autologous MoDC-T cell stimulation assays. In addition to increased IL-10 release, the data indicates a shift from a Th2- to a more Th1- and Th17-like phenotype.
Occupational rhinitis Kotz, Sebastian; Pechtold, Lisa; Jörres, Rudolf A ...
Allergologie select,
2021, Letnik:
5, Številka:
1
Journal Article
Odprti dostop
Occupational rhinitis (OR) has so far received little attention even though it shares common pathophysiological features and trigger factors and is closely associated with occupational asthma (OA). ...Work-related exposure to certain substances, such as animal dander, is considered to be the main factor for the development of OR. The new EAACI definition of OR stresses the causal relationship between workplace exposure and onset of rhinitis symptoms as opposed to previous definitions that mainly focused on a temporal relationship between workplace exposure and occurrence of nasal symptoms. Also, it has been suggested to use the term "work-related rhinitis" for classifying the different forms of rhinitis associated with the workplace. These forms can be subdivided into allergic or non-allergic OR, which is due to causes and conditions related to a particular work environment, as well as work-exacerbated rhinitis, which is defined as a pre-existing rhinitis exacerbated by exposure at the workplace. Even though taking a detailed patient history is especially important when it comes to diagnosing OR, the gold standard for confirming the diagnosis is nasal provocation testing. Best possible symptomatic relief and prevention of development of OA constitute the main therapeutic objectives in OR. Treatment options consist of total avoidance of trigger substances (main goal), reduction of exposure to certain substances, and pharmacotherapy. Furthermore, it is important to note that allergic OR is an occupational disease in Germany (Berufskrankheit No 4301) and needs to be reported to health authorities.
Es ist ein großes Jubiläum: 2015 feiert die Nikolaikirche Leipzig ihr 850-jähriges Bestehen. Die Nikolaikirche ist dem heiligen Nikolaus geweiht, dem Schutzpatron der Kaufleute. Die Entstehung der ...Kirche ist eng mit der Verleihung des Stadtrechts an Leipzig durch Markgraf Otto von Meißen verbunden. Mit Einführung der Reformation 1539 wurde St. Nikolai zu einer Hauptkirche Leipzigs. Die Geschichte dieser nicht nur stadtgeschichtlich bedeutsamen Kirche ist unmittelbar mit der Geschichte der Universitätsbibliothek Leipzig (UBL) verknüpft: 1930 kam die Bibliothek der Nikolaikirche als Depositum an die UBL, wo sie sich noch heute befindet. Der Bestand umfasst über 3.000 Bände.
Es ist ein großes Jubiläum: 2015 feiert die Nikolaikirche Leipzig ihr 850-jähriges Bestehen. Die Nikolaikirche ist dem heiligen Nikolaus geweiht, dem Schutzpatron der Kaufleute. Die Entstehung der ...Kirche ist eng mit der Verleihung des Stadtrechts an Leipzig durch Markgraf Otto von Meißen verbunden. Mit Einführung der Reformation 1539 wurde St. Nikolai zu einer Hauptkirche Leipzigs. Die Geschichte dieser nicht nur stadtgeschichtlich bedeutsamen Kirche ist unmittelbar mit der Geschichte der Universitätsbibliothek Leipzig (UBL) verknüpft: 1930 kam die Bibliothek der Nikolaikirche als Depositum an die UBL, wo sie sich noch heute befindet. Der Bestand umfasst über 3.000 Bände.
Von Anfang an Zukunft Götze, Astrid; Link, Daniela; Kötz, Sebastian ... Dissertation
Odprti dostop
Ende Mai wurde das Messezentrum Nürnberg zum Mittelpunkt der deutschsprachigen Bibliotheksszene und ein Pilgerort vieler Bibliothekarinnen und Bibliothekare. Der diesjährige Bibliothekartag stand ...unter dem Motto „Von Anfang an Zukunft“ und zählte 3.815 Teilnehmerinnen und Teilnehmer, die sich bei 250 Veranstaltungen – darunter 389 Vorträge, Podiumsdiskussionen und Workshops – vier Tage lang intensiv mit den Herausforderungen und Zukunftsperspektiven der Bibliothekslandschaft auseinandersetzten.
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