OBJECTIVE
To evaluate the effectiveness of a well‐controlled programme of early detection and treatment of prostate cancer in the population of Tyrol, Austria, where such a programme of early ...detection and treatment was initiated in 1988 and where prostate‐specific antigen (PSA) testing was offered for free to all men aged 45–75 years from 1993.
SUBJECTS AND METHODS
Comparison of prostate cancer mortality rates in Tyrol and the rest of Austria was accomplished through a generalized additive model. A piecewise linear change‐point Poisson regression model was used to compare mortality rates in Tyrol and the rest of Austria. Standardized mortality ratios were calculated with reference to the mortality rates in 1986–1990.
RESULTS
In all, 86.6% of eligible men have been tested at least once since 1993. Cancer deaths in Tyrol in 2005 were 54% (95% confidence interval CI 34–69%) lower than expected compared with 29% (95% CI 22–35%) in the rest of Austria. The decreasing trend in prostate cancer mortality was significantly greater in Tyrol compared with the rest of Austria (P = 0.001). A significant migration to lower stage disease occurred and radical prostatectomy was associated with low morbidity.
CONCLUSIONS
In the Tyrol region where treatment is freely available to all patients, where widespread PSA testing and treatment with curative intent occurs, there was a reduction in prostate cancer mortality rates which was significantly greater than the reduction in the rest of Austria. This reduction in prostate cancer mortality is most probably due to early detection, consequent down‐staging and effective treatment of prostate cancer.
Post-infectious fatigue is a common complication that can lead to decreased physical efficiency, depression, and impaired quality of life. Dysbiosis of the gut microbiota has been proposed as a ...contributing factor, as the gut-brain axis plays an important role in regulating physical and mental health. This pilot study aimed to investigate the severity of fatigue and depression, as well as the quality of life of 70 patients with post-infectious fatigue who received a multi-strain probiotic preparation or placebo in a double-blind, placebo-controlled trial. Patients completed questionnaires to assess their fatigue (fatigue severity scale (FSS)), mood (Beck Depression Inventory II (BDI-II)), and quality of life (short form-36 (SF-36)) at baseline and after 3 and 6 months of treatment. Routine laboratory parameters were also assessed, including immune-mediated changes in tryptophan and phenylalanine metabolism. The intervention was effective in improving fatigue, mood, and quality of life in both the probiotic and placebo groups, with greater improvements seen in the probiotic group. FSS and BDI-II scores declined significantly under treatment with both probiotics and placebo, but patients who received probiotics had significantly lower FSS (
< 0.001) and BDI-II (
< 0.001) scores after 6 months. Quality of life scores improved significantly in patients who received probiotics (
< 0.001), while patients taking a placebo only saw improvements in the "Physical limitation" and "Energy/Fatigue" subcategories. After 6 months neopterin was higher in patients receiving placebo, while no longitudinal changes in interferon-gamma mediated biochemical pathways were observed. These findings suggest that probiotics may be a promising intervention for improving the health of patients with post-infectious fatigue, potentially through modulating the gut-brain axis.
To provide updated estimates on SARS-CoV-2 antibody seroprevalence and average antibody titres for Central Europe.
In repeat cross-sectional investigations (1 May 2022 to 9 March 2023) involving ...28,768 blood donors in the Federal State of Tyrol, Austria (participation rate: 87.0%), we measured Spike receptor-binding domain (RBD) and Nucleocapsid IgG antibodies (37,065 and 12,645 samples), and estimated monthly seroprevalences and geometric mean titres.
Median age of participants was 45.4 years (range 18-70); 43.2% were female. Spike RBD IgG antibody seroprevalence was 96.3% (95% CI: 95.6-96.9%) in May 2022, 97.4% (96.7-98.0%) in December 2022, and 97.9% (96.4-98.8%) in March 2023. Among seropositive participants, geometric mean titres increased from 1400 BAU/mL (95% CI: 1333-1471) in May 2022 to 1821 BAU/mL (1717-1932) in December 2022, and dropped to 1559 BAU/mL (1405-1729) by March 2023. Furthermore, titres differed markedly by vaccination status and history of infection, with being the highest in participants with booster vaccination and prior infection. In autumn 2022, Nucleocapsid IgG antibody seroprevalence ranged from 36.5% (35.0-38.1) in September to 39.2% (37.2-41.2) in December 2022.
Seroprevalence of SARS-CoV-2 antibodies in blood donors from Tyrol, Austria, was remarkably stable from May 2022 to March 2023. In contrast, average Spike RBD IgG antibody titres peaked in December 2022.
Phyllobilins are natural products derived from the degradation of chlorophyll, which proceeds via a common and strictly controlled pathway in higher plants. The resulting tetrapyrrolic ...catabolites—the phyllobilins—are ubiquitous in nature; despite their high abundance, there is still a lack of knowledge about their physiological properties. Phyllobilins are part of human nutrition and were shown to be potent antioxidants accounting with interesting physiological properties. Three different naturally occurring types of phyllobilins—a phylloleucobilin, a dioxobilin-type phylloleucobilin and a phylloxanthobilin (PxB)—were compared regarding potential antioxidative properties in a cell-free and in a cell-based antioxidant activity test system, demonstrating the strongest effect for the PxB. Moreover, the PxB was investigated for its capacity to interfere with immunoregulatory metabolic pathways of tryptophan breakdown in human blood peripheral mononuclear cells. A dose-dependent inhibition of tryptophan catabolism to kynurenine was observed, suggesting a suppressive effect on pathways of cellular immune activation. Although the exact mechanisms of immunomodulatory effects are yet unknown, these prominent bioactivities point towards health-relevant effects, which warrant further mechanistic investigations and the assessment of the in vivo extrapolatability of results. Thus, phyllobilins are a still surprisingly unexplored family of natural products that merit further investigation.
After COVID-19, patients have reported various complaints such as fatigue, neurological symptoms, and insomnia. Immune-mediated changes in amino acid metabolism might contribute to the development of ...these symptoms. Patients who had had acute, PCR-confirmed COVID-19 infection about 60 days earlier were recruited within the scope of the prospective CovILD study. We determined the inflammatory parameters and alterations in tryptophan and phenylalanine metabolism in 142 patients cross-sectionally. Symptom persistence (pain, gastrointestinal symptoms, anosmia, sleep disturbance, and neurological symptoms) and patients' physical levels of functioning were recorded. Symptoms improved in many patients after acute COVID-19 (
= 73, 51.4%). Still, a high percentage of patients had complaints, and women were affected more often. In many patients, ongoing immune activation (as indicated by high neopterin and CRP concentrations) and enhanced tryptophan catabolism were found. A higher phenylalanine to tyrosine ratio (Phe/Tyr) was found in women with a lower level of functioning. Patients who reported improvements in pain had lower Phe/Tyr ratios, while patients with improved gastrointestinal symptoms presented with higher tryptophan and kynurenine values. Our results suggest that women have persistent symptoms after COVID-19 more often than men. In addition, the physical level of functioning and the improvements in certain symptoms appear to be associated with immune-mediated changes in amino acid metabolism.
The flavonoid kaempferol is almost ubiquitously contained in edible and medicinal plants and exerts a broad range of interesting pharmacological activities. Interactions with central inflammatory ...processes can be exploited to treat or attenuate symptoms of disorders associated with chronic immune activation during infections, malignancies, and neurodegenerative or cardiovascular disorders. Many drugs, phytochemicals, and nutritional components target the catabolism of the essential amino acid tryptophan by indoleamine 2,3-dioxygenase 1 (IDO-1) for immunomodulation. We studied the effects of kaempferol by in vitro models with human peripheral blood mononuclear cells (PBMC) and THP-1 derived human myelomonocytic cell lines. Kaempferol suppressed interferon-γ dependent immunometabolic pathways: Formation of the oxidative stress biomarker neopterin and catabolism of tryptophan were inhibited dose-dependently in stimulated cells. In-silico docking studies revealed a potential interaction of kaempferol with the catalytic domain of IDO-1. Kaempferol stimulated nuclear factor kappa B (NF-κB) signaling in lipopolysaccharide (LPS)-treated THP-1 cells, thereby increasing the mRNA expression of interleukin (IL) 1 beta, tumor necrosis factor, and nuclear factor kappa B subunit 1, while IL6 was downregulated. Data suggest that concerted effects of kaempferol on multiple immunologically relevant targets are responsible for its immunomodulatory activity. However, the immunosuppressive effects may be more relevant in a T-cell dominated context.
Antiphospholipid antibodies (aPLs) frequently occur in autoimmune and cardiovascular diseases and correlate with a worse clinical outcome. In the present study, we evaluated the association between ...antiphospholipid antibodies (aPLs), markers of inflammation, disease progression and the presence of an intra-aneurysmal thrombus in abdominal aortic aneurysm (AAA) patients. APLs ELISAs were performed in frozen serum samples of 96 consecutive AAA patients and 48 healthy controls yielding positive test results in 13 patients (13.5%) and 3 controls (6.3%; n.s.). Nine of the 13 aPL-positive AAA patients underwent a second antibody testing >12 weeks apart revealing a positive result in 6 cases. APL-positive patients had increased levels of inflammatory markers compared to aPL-negative patients. Disease progression was defined as an increase of the AAA diameter >0.5 cm/year measured by sonography. Follow-up was performed in 69 patients identifying 41 (59.4%) patients with progressive disease. Performing multipredictor logistic regression analysis adjusting for classical AAA risk factors as confounders, the presence of aPLs at baseline revealed an odds ratio of 9.4 (95% CI 1.0-86.8, p = 0.049) to predict AAA progression. Fifty-five patients underwent a computed tomography in addition to ultrasound assessment indicating intra-aneurysmal thrombus formation in 82.3%. Median thrombus volume was 46.7 cm3 (1.9-377.5). AAA diameter correlated with the size of the intra-aneurysmal thrombus (corrcoeff = 0.721, p<0.001), however neither the presence nor the size of the intra-aneurysmal thrombus were related to the presence of aPLs. In conclusion, the presence of aPLs is associated with elevated levels of inflammatory markers and is an independent predictor of progressive disease in AAA patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The naturally occurring stilbenoid oxyresveratrol was shown to influence inflammatory and metabolic processes. During cellular immune activation, tryptophan breakdown and neopterin formation via the ...enzymes indoleamine 2,3-dioxygenase-1 (IDO-1) and GTP-cyclohydrolase, respectively, are induced. Neopterin and the kynurenine to tryptophan ratio are reliable and pertinent biomarkers of Th1-type immune response and are also used
to monitor effects of active plant ingredients on peripheral blood mononuclear cells (PBMCs). We investigated the effects of oxyresveratrol on the activity of the above-mentioned pathways in mitogen-stimulated human PBMC and in the myelomonocytic cell line THP-1. Oxyresveratrol exerted suppressive effects on tryptophan breakdown in both stimulated cell models. Of note, in PBMC, tryptophan breakdown was induced at lower concentrations (5–20 µM) and suppressed at higher treatment concentrations only. Neopterin formation was decreased dose-dependently in stimulated PBMC. In unstimulated PBMC similar, albeit lesser effects were observed. Data indicate that oxyresveratrol exerts distinct and concentration-dependent effects on different immune cell types. IDO-1 is targeted by oxyresveratrol and its activity can be modulated in both directions. Detailed investigations of the interactions would be interesting to fully explore the activity of this phytocompound.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The small alpine district of East Tyrol (Austria) has an exceptional demographic history. It was contemporaneously inhabited by members of the Romance, the Slavic and the Germanic language groups for ...centuries. Since the Late Middle Ages, however, the population of the principally agrarian-oriented area is solely Germanic speaking. Historic facts about East Tyrol's colonization are rare, but spatial density-distribution analysis based on the etymology of place-names has facilitated accurate spatial mapping of the various language groups' former settlement regions. To test for present-day Y chromosome population substructure, molecular genetic data were compared to the information attained by the linguistic analysis of pasture names. The linguistic data were used for subdividing East Tyrol into two regions of former Romance (A) and Slavic (B) settlement. Samples from 270 East Tyrolean men were genotyped for 17 Y-chromosomal microsatellites (Y-STRs) and 27 single nucleotide polymorphisms (Y-SNPs). Analysis of the probands' surnames revealed no evidence for spatial genetic structuring. Also, spatial autocorrelation analysis did not indicate significant correlation between genetic (Y-STR haplotypes) and geographic distance. Haplogroup R-M17 chromosomes, however, were absent in region A, but constituted one of the most frequent haplogroups in region B. The R-M343 (R1b) clade showed a marked and complementary frequency distribution pattern in these two regions. To further test East Tyrol's modern Y-chromosomal landscape for geographic patterning attributable to the early history of settlement in this alpine area, principal coordinates analysis was performed. The Y-STR haplotypes from region A clearly clustered with those of Romance reference populations and the samples from region B matched best with Germanic speaking reference populations. The combined use of onomastic and molecular genetic data revealed and mapped the marked structuring of the distribution of Y chromosomes in an alpine region that has been culturally homogeneous for centuries.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background
After malaria, babesiosis is the second most common transfusion‐transmitted parasitic disease in the United States. In Europe, one reported transfusion case, concerning Babesia microti, ...occurred in Germany.
Study Design and Methods
Due to the fact that Babesia spp. are present in Tyrolean ticks, the aim of this study is to assess the occurrence of immunoglobulin (Ig)G antibodies against the Babesia divergens complex, including B. divergens and Babesia venatorum (EU1), as well as B. microti by screening a representative collective of 988 blood donors from North and East Tyrol (Austria) with indirect immunofluorescence antibody test. Additionally, we investigated 206 local ixodid ticks for the presence of babesial DNA by polymerase chain reaction.
Results
Seroprevalence data resulted in rates of 2.1% for IgG antibodies against the B. divergens complex and 0.6% against B. microti in Tyrolean blood donors. All sera could be confirmed by independent retesting. Our data indicate that cross‐reactivity is high between B. divergens and B. venatorum and lower than 19.8% between B. divergens and B. microti.
Conclusions
This study shows that Babesia spp. are present in the Tyrols, which blood donors come into serologic contact with, and that we have to consider how to sustain blood product safety concerning this new challenge. Additionally, it is the first description of B. venatorum in the Tyrols, found in one Ixodes ricinus at the Italian border.
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