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Abstract Clinical examination can be the key to pursuing a diagnosis, even in rare diseases. The “groove sign” is a typical finding in eosinophilic fasciitis and can be elicited by elevation of the arm to allow for venous return with visible “grooving” of the veins due to skin thickening.

Kidney fibrosis is a common manifestation and hallmark of a wide variety of chronic kidney disease (CKD) that appears in different morphological patterns, suggesting distinct pathogenic causes. Broad macroscopically visible scars are the sequelae of severe focal injury and complete parenchymal destruction, reflecting a wound healing response as a consequence of infarction. In the kidney, chronic glomerular injury leads to atrophy of the corresponding tubule, degeneration of this specific nephron, and finally interstitial fibrosis/tubular atrophy (IF/TA). Compared to this glomerulus-induced focal replacement scar, diffuse fibrosis independent of tubular atrophy appears to be a different pathogenic process. Kidney fibrosis appears to develop in a compartment-specific manner, but whether focal and diffuse fibrosis has distinct characteristics associated with other glomerular or tubulointerstitial lesions remains elusive. In the present study, we aimed to analyze renal fibrotic patterns related to renal lesions, which directly contribute to renal fibrogenesis, to unravel fibrotic patterns and manifestations upon damage to distinct renal compartments. Patterns of kidney fibrosis were analyzed in experimental models of CKD and various renal pathologies in correlation with histopathological and ultrastructural findings. After the induction of isolated crescentic glomerulonephritis (GN) in nephrotoxic serum-nephritis (NTN), chronic glomerular damage resulted in predominantly focal fibrosis adjacent to atrophic tubules. By contrast, using unilateral ureteral obstruction (UUO) as a model of primary injury to the tubulointerstitial compartment revealed diffuse fibrosis as the predominant pattern of chronic lesions. Finally, folic acid-induced nephropathy (FAN) as a model of primary tubular injury with consecutive tubular atrophy independent of chronic glomerular damage equally induced predominant focal IF/TA. By analyzing several renal pathologies, our data also suggest that focal and diffuse fibrosis appear to contribute as chronic lesions in the majority of human renal disease, mainly being present in antineutrophil cytoplasmic antibody (ANCA)-associated GN, lupus nephritis, and IgA nephropathy (IgAN). Focal IF/TA correlated with glomerular damage and irreversible injury to nephrons, whereas diffuse fibrosis in ANCA GN was associated explicitly with interstitial inflammation independent of glomerular damage and nephron loss. Ultrastructural analysis of focal IF/TA versus diffuse fibrosis revealed distinct matrix compositions, further supported by different collagen signatures in transcriptome datasets. With regard to long-term renal outcome, only the extent of focal IF/TA correlated with the development of end-stage kidney disease (ESKD) in ANCA GN. In contrast, diffuse kidney fibrosis did not associate with the long-term renal outcome. In conclusion, we here provide evidence that a focal pattern of kidney fibrosis seems to be associated with nephron loss and replacement scarring. In contrast, a diffuse pattern of kidney fibrosis appears to result from primary interstitial inflammation and injury.

Acute kidney injury (AKI) is a common and severe complication of antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) causing progressive chronic kidney disease (CKD), end-stage renal disease (ESRD) or death. Pathogenic ANCAs, in particular proteinase 3 (PR3) and myeloperoxidase (MPO), trigger a deleterious immune response resulting in pauci-immune necrotizing and crescentic glomerulonephritis (GN), a common manifestation of glomerular injury in AAV. However, there is growing evidence that activation of the complement pathway contributes to the pathogenesis and progression of AAV. We here aimed to compare glomerular and tubulointerstitial lesions in ANCA GN and extrarenal manifestation of AAV in association with levels of circulating complement components C3c and C4. Methods: Plasma levels of C3c and C4 in a total number of 53 kidney biopsies with ANCA GN were retrospectively included between 2015 and 2020. Glomerular and tubulointerstitial lesions were evaluated according to established scoring systems for ANCA GN and analogous to the Banff classification. Results: We here show that circulating levels of C3c and C4 in ANCA GN were comparable to the majority of other renal pathologies. Furthermore, hypocomplementemia was only detectable in a minor subset of ANCA GN and not correlated with renal or extrarenal AAV manifestations. However, low levels of circulating C3c correlated with AKI severity in ANCA GN independent of systemic disease activity or extrarenal AAV manifestation. By systematic scoring of glomerular and tubulointerstitial lesions, we provide evidence that low levels of circulating C3c and C4 correlated with vasculitis manifestations to distinct renal compartments in ANCA GN. Conclusions: We here expand our current knowledge about distinct complement components in association with vasculitis manifestations to different renal compartments in ANCA GN. While low levels of C4 correlated with glomerulitis, our observation that low levels of circulating complement component C3c is associated with interstitial vasculitis manifestation reflected by intimal arteritis implicates that C3c contributes to tubulointerstitial injury in ANCA GN.

Telomere length (TL) predicts health and survival across taxa. Variation in TL between individuals is thought to be largely of genetic origin, but telomere inheritance is unusual, because zygotes already express a TL phenotype, the TL of the parental gametes. Offspring TL changes with paternal age in many species including humans, presumably through age-related TL changes in sperm, suggesting an epigenetic inheritance mechanism. However, present evidence is based on cross-sectional analyses, and age at reproduction is confounded with between-father variation in TL. Furthermore, the quantitative importance of epigenetic TL inheritance is unknown. Using longitudinal data of free-living jackdaws Corvus monedula, we show that erythrocyte TL of subsequent offspring decreases with parental age within individual fathers, but not mothers. By cross-fostering eggs, we confirmed the paternal age effect to be independent of paternal age dependent care. Epigenetic inheritance accounted for a minimum of 34% of the variance in offspring TL that was explained by paternal TL. This is a minimum estimate, because it ignores the epigenetic component in paternal TL variation and sperm TL heterogeneity within ejaculates. Our results indicate an important epigenetic component in the heritability of TL with potential consequences for offspring fitness prospects.

IntroductionEarly warning scores (EWS) are being increasingly embedded in hospitals over the world due to their promise to reduce adverse events and improve the outcomes of clinical patients. The aim of this study was to evaluate the clinical use of an automated modified EWS (MEWS) for patients after surgery.MethodsThis study conducted retrospective before-and-after comparative analysis of non-automated and automated MEWS for patients admitted to the surgical high-dependency unit in a tertiary hospital. Operational outcomes included number of recorded assessments of the individual MEWS elements, number of complete MEWS assessments, as well as adherence rate to related protocols. Clinical outcomes included hospital length of stay, in-hospital and 28-day mortality, and ICU readmission rate.ResultsRecordings in the electronic medical record from the control period contained 7929 assessments of MEWS elements and were performed in 320 patients. Recordings from the intervention period contained 8781 assessments of MEWS elements in 273 patients, of which 3418 were performed with the automated EWS system. During the control period, 199 (2.5%) complete MEWS were recorded versus 3991 (45.5%) during intervention period. With the automated MEWS systems, the percentage of missing assessments and the time until the next assessment for patients with a MEWS of ≥2 decreased significantly. The protocol adherence improved from 1.1% during the control period to 25.4% when the automated MEWS system was involved. There were no significant differences in clinical outcomes.ConclusionImplementation of an automated EWS system on a surgical high dependency unit improves the number of complete MEWS assessments, registered vital signs, and adherence to the EWS hospital protocol. However, this positive effect did not translate into a significant decrease in mortality, hospital length of stay, or ICU readmissions. Future research and development on automated EWS systems should focus on data management and technology interoperability.

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Introduction. Physical activity (PA) in preschoolers is vital to protect against obesity but is influenced by different early-life factors. The present study investigated the impact of different preschool programs and selected family factors on preschoolers’ PA in different countries in an explorative way. Methods. The PA of 114 children (age = 5.3 ± 0.65 years) attending different preschool settings in four cities of the trinational Upper Rhine region (Freiburg, Landau/Germany, Basel/Switzerland, and Strasbourg/France) was measured by direct accelerometry. Anthropometrical and family-related data were obtained. Timetables of preschools were analyzed. Results. Comparing the preschool settings, children from Strasbourg and Landau were significantly more passive than children from Basel and Freiburg (P

Hatching asynchrony is a frequent phenomenon in altricial birds and can lead to brood reduction due to sibling competition. There are a number of adaptive hypotheses to explain its occurrence, relating hatching asynchrony to sibling competition and timing of breeding. Incubation prior to clutch completion (early incubation) is the main cause of hatching asynchrony. We used temperature loggers inside the nests of breeding Blue Tits Cyanistes caeruleus to provide a detailed account of female incubation over most of the egg-laying period. We relate this early incubation to the time interval between clutch completion and hatching as well as hatching asynchrony. Our study shows the frequent occurrence of early incubation during the beginning of the laying period, with all females showing more early incubation towards clutch completion. At first, early incubation mostly occurs at night, but as egg laying progresses, it also occurs during the day. However, overall there was more nocturnal than diurnal early incubation. These results were obtained using two different methods for quantifying incubation from temperature profiles, which we compared and cross-validated in this study. Moreover, the amount of early incubation related negatively to the time between clutch completion and first hatching and positively to the extent of hatching asynchrony. While we did not directly investigate the mechanisms driving variation in early incubation, the exceptionally cold March/April period followed by a warm May in our study year may explain the comparatively great amounts of early incubation we observed. We hypothesise that spring temperatures may influence the amount of early incubation, with warmer springs resulting in more early incubation and consequently shorter times from clutch completion until first hatching as well as increased hatching asynchrony. Such a mechanism of adjustment of incubation time and hatching asynchrony may also be important for the adaptation of birds to climate change. [ABSTRACT FROM AUTHOR]