Relationship Between Self-Reported Function, Functional Tests and Biomechanical Parameters in Patients 12 Months After Total Hip Arthroplasty: A Preliminary Cross-Sectional Study

Background/Purpose Several methods are used to evaluate the outcome of total hip arthroplasty (THA), however, their relationship at different time points after surgery is unclear. The purpose of this exploratory study was to investigate correlations between self-report function, performance-based tests (PBTs) and biomechanical parameters in patients 12 months after THA. Methods Eleven patients were included in this preliminary cross-sectional study. Hip disability and Osteoarthritis Outcome Score (HOOS) was completed for self-reported function. As PBTs, the Timed-up-and-Go test (TUG) and 30-Second-Chair-Stand test (30CST) were used. Biomechanical parameters were derived from analyses of hip strength, gait and balance. Potential correlations were calculated using Spearman correlation coefficient r. Results HOOS scores and parameters of PBTs showed moderate to strong correlations (0.3 < r < 0.7). Correlation analysis between HOOS scores and biomechanical parameters revealed moderate to strong correlations for hip strength whereas correlations with gait parameters and balance were rather weak (r < 0.3). Moderate to strong correlations were also found between parameters of hip strength and 30CST. Conclusion For THA outcome assessment 12 months after surgery, our first results indicate that self-report measures or PBTs could be used. Analysis of hip strength also appears to be reflected in HOOS and PBT parameters and may be considered as an adjunct. Given the weak correlations with gait and balance parameters, we suggest that gait analysis and balance testing should be performed in addition to PROMs and PBTs as they may provide supplementary information, especially for THA patients that are at risk for falls

Word Recognition Memory in Adults with Attention-Deficit/Hyperactivity Disorder as Reflected by Event-Related Potentials

Objective: Attention-deficit/hyperactivity disorder (ADHD) is increasingly diagnosed in adults. In this study we address the question whether there are impairments in recognition memory. Methods: In the present study 13 adults diagnosed with ADHD according to DSM-IV and 13 healthy controls were examined with respect to event-related potentials (ERPs) in a visual continuous word recognition paradigm to gain information about recognition memory effects in these patients. Results: The amplitude of one attention-related ERP component, the N1, was significantly increased for the ADHD adults compared with the healthy controls in the occipital electrodes. The ERPs for the second presentation were significantly more positive than the ERPs for the first presentation. This effect did not significantly differ between groups. Conclusion: Neuronal activity related to an early attentional mechanism appears to be enhanced in ADHD patients. Concerning the early or the late part of the old/new effect ADHD patients show no difference which suggests that there are no differences with respect to recollection and familiarity-based recognition processes

Two Mosquito LRR Proteins Function as Complement Control Factors in the TEP1-Mediated Killing of Plasmodium

SummaryPlasmodium development within Anopheles mosquitoes is a vulnerable step in the parasite transmission cycle, and targeting this step represents a promising strategy for malaria control. The thioester-containing complement-like protein TEP1 and two leucine-rich repeat (LRR) proteins, LRIM1 and APL1, have been identified as major mosquito factors that regulate parasite loads. Here, we show that LRIM1 and APL1 are required for binding of TEP1 to parasites. RNAi silencing of the LRR-encoding genes results in deposition of TEP1 on Anopheles tissues, thereby depleting TEP1 from circulation in the hemolymph and impeding its binding to Plasmodium. LRIM1 and APL1 not only stabilize circulating TEP1, they also stabilize each other prior to their interaction with TEP1. Our results indicate that three major antiparasitic factors in mosquitoes jointly function as a complement-like system in parasite killing, and they reveal a role for LRR proteins as complement control factors

PilY1 Promotes Legionella pneumophila Infection of Human Lung Tissue Explants and Contributes to Bacterial Adhesion, Host Cell Invasion, and Twitching Motility

Legionnaires' disease is an acute fibrinopurulent pneumonia. During infection Legionella pneumophila adheres to the alveolar lining and replicates intracellularly within recruited macrophages. Here we provide a sequence and domain composition analysis of the L. pneumophila PilY1 protein, which has a high homology to PilY1 of Pseudomonas aeruginosa. PilY1 proteins of both pathogens contain a von Willebrand factor A (vWFa) and a C-terminal PilY domain. Using cellular fractionation, we assigned the L. pneumophila PilY1 as an outer membrane protein that is only expressed during the transmissive stationary growth phase. PilY1 contributes to infection of human lung tissue explants (HLTEs). A detailed analysis using THP-1 macrophages and A549 lung epithelial cells revealed that this contribution is due to multiple effects depending on host cell type. Deletion of PilY1 resulted in a lower replication rate in THP-1 macrophages but not in A549 cells. Further on, adhesion to THP-1 macrophages and A549 epithelial cells was decreased. Additionally, the invasion into non-phagocytic A549 epithelial cells was drastically reduced when PilY1 was absent. Complementation variants of a PilY1-negative mutant revealed that the C-terminal PilY domain is essential for restoring the wild type phenotype in adhesion, while the putatively mechanosensitive vWFa domain facilitates invasion into non-phagocytic cells. Since PilY1 also promotes twitching motility of L. pneumophila, we discuss the putative contribution of this newly described virulence factor for bacterial dissemination within infected lung tissue

Global Tipping Points Report 2023: Ch1.2: Cryosphere tipping points.

Drastic changes in our planet’s frozen landscapes have occurred over recent decades, from Arctic sea ice decline and thawing of permafrost soils to polar amplification, the retreat of glaciers and ice loss from the ice sheets. In this chapter, we assess multiple lines of evidence for tipping points in the cryosphere – encompassing the ice sheets on Greenland and Antarctica, sea ice, mountain glaciers and permafrost – based on recent observations, palaeorecords, numerical modelling and theoretical understanding. With about 1.2°C of global warming compared to pre-industrial levels, we are getting dangerously close to the temperature thresholds of some major tipping points for the ice sheets of Greenland and West Antarctica. Crossing these would lock in unavoidable long-term global sea level rise of up to 10 metres. There is evidence for localised and regional tipping points for glaciers and permafrost and, while evidence for global-scale tipping dynamics in sea ice, glaciers and permafrost is limited, their decline will continue with unabated global warming. Because of the long response times of these systems, some impacts of crossing potential tipping points will unfold over centuries to millennia. However, with the current trajectory of greenhouse gas (GHG) emissions and subsequent anthropogenic climate change, such largely irreversible changes might already have been triggered. These will cause far-reaching impacts for ecosystems and humans alike, threatening the livelihoods of millions of people, and will become more severe the further global warming progresses

In Situ Dividing and Phagocytosing Retinal Microglia Express Nestin, Vimentin, and NG2 In Vivo

BACKGROUND: Following injury, microglia become activated with subsets expressing nestin as well as other neural markers. Moreover, cerebral microglia can give rise to neurons in vitro. In a previous study, we analysed the proliferation potential and nestin re-expression of retinal macroglial cells such as astrocytes and Müller cells after optic nerve (ON) lesion. However, we were unable to identify the majority of proliferative nestin(+) cells. Thus, the present study evaluates expression of nestin and other neural markers in quiescent and proliferating microglia in naïve retina and following ON transection in adult rats in vivo. METHODOLOGY/PRINCIPAL FINDINGS: For analysis of cell proliferation and cells fates, rats received BrdU injections. Microglia in retinal sections or isolated cells were characterized using immunofluorescence labeling with markers for microglia (e.g., Iba1, CD11b), cell proliferation, and neural cells (e.g., nestin, vimentin, NG2, GFAP, Doublecortin etc.). Cellular analyses were performed using confocal laser scanning microscopy. In the naïve adult rat retina, about 60% of resting ramified microglia expressed nestin. After ON transection, numbers of nestin(+) microglia peaked to a maximum at 7 days, primarily due to in situ cell proliferation of exclusively nestin(+) microglia. After 8 weeks, microglia numbers re-attained control levels, but 20% were still BrdU(+) and nestin(+), although no further local cell proliferation occurred. In addition, nestin(+) microglia co-expressed vimentin and NG2, but not GFAP or neuronal markers. Fourteen days after injury and following retrograde labeling of retinal ganglion cells (RGCs) with Fluorogold (FG), nestin(+)NG2(+) microglia were positive for the dye indicating an active involvement of a proliferating cell population in phagocytosing apoptotic retinal neurons. CONCLUSIONS/SIGNIFICANCE: The current study provides evidence that in adult rat retina, a specific resident population of microglia expresses proteins of immature neural cells that are involved in injury-induced cell proliferation and phagocytosis while transdifferentiation was not observed

Global Tipping Points Report 2023: Ch1.5: Climate tipping point interactions and cascades.

This chapter reviews interactions between climate tipping systems and assesses the potential risk of cascading effects. After a definition of tipping system interactions, we map out the current state of the literature on specific interactions between climate tipping systems that may be important for the overall stability of the climate system. For this, we gather evidence from model simulations, observations and conceptual understanding, as well as archetypal examples of palaeoclimate reconstructions where propagating transitions were potentially at play. This chapter concludes by identifying crucial knowledge gaps in tipping system interactions that should be resolved in order to improve risk assessments of cascading transitions under future climate change scenarios

Climate tipping point interactions and cascades: A review

Climate tipping elements are large-scale subsystems of the Earth that may transgress critical thresholds (tipping points) under ongoing global warming, with substantial impacts on the biosphere and human societies. Frequently studied examples of such tipping elements include the Greenland Ice Sheet, the Atlantic Meridional Overturning Circulation (AMOC), permafrost, monsoon systems, and the Amazon rainforest. While recent scientific efforts have improved our knowledge about individual tipping elements, the interactions between them are less well understood. Also, the potential of individual tipping events to induce additional tipping elsewhere or stabilize other tipping elements is largely unknown. Here, we map out the current state of the literature on the interactions between climate tipping elements and review the influences between them. To do so, we gathered evidence from model simulations, observations, and conceptual understanding, as well as examples of paleoclimate reconstructions where multi-component or spatially propagating transitions were potentially at play. While uncertainties are large, we find indications that many of the interactions between tipping elements are destabilizing. Therefore, we conclude that tipping elements should not only be studied in isolation, but also more emphasis has to be put on potential interactions. This means that tipping cascades cannot be ruled out on centennial to millennial timescales at global warming levels between 1.5 and 2.0 ◦C or on shorter timescales if global warming surpassed 2.0 ◦C. At these higher levels of global warming, tipping cascades may then include fast tipping elements such as the AMOC or the Amazon rainforest. To address crucial knowledge gaps in tipping element interactions, we propose four strategies combining observation-based approaches, Earth system modeling expertise, computational advances, and expert knowledge

Intracellular immune responses of dipteran insects

Vector-borne diseases, transmitted by bloodsucking arthropods, pose worldwide socio-medical and economical problems. Some of the major human infectious diseases, such as malaria, Dengue fever, and yellow fever, are transmitted by mosquitoes. While the majority of pathogens enjoy extracellular life styles in insects, viruses and some endosymbionts are strictly intracellular. Here, we summarize our knowledge on defense reactions against intracellular microorganisms in dipteran insects and discuss the potential of insects as models to study human pathogens

Zinc Metalloprotease ProA from Legionella pneumophila Inhibits the Pro-Inflammatory Host Response by Degradation of Bacterial Flagellin

The environmental bacterium Legionella pneumophila is an intracellular pathogen of various protozoan hosts and able to cause Legionnaires&rsquo; disease, a severe pneumonia in humans. By encoding a wide selection of virulence factors, the infectious agent possesses several strategies to manipulate its host cells and evade immune detection. In the present study, we demonstrate that the L. pneumophila zinc metalloprotease ProA functions as a modulator of flagellin-mediated TLR5 stimulation and subsequent activation of the pro-inflammatory NF-&kappa;B pathway. We found ProA to be capable of directly degrading immunogenic FlaA monomers but not the polymeric form of bacterial flagella. These results indicate a role of the protease in antagonizing immune stimulation, which was further substantiated in HEK-BlueTM hTLR5 Detection assays. Addition of purified proteins, bacterial suspensions of L. pneumophila mutant strains as well as supernatants of human lung tissue explant infection to this reporter cell line demonstrated that ProA specifically decreases the TLR5 response via FlaA degradation. Conclusively, the zinc metalloprotease ProA serves as a powerful regulator of exogenous flagellin and presumably creates an important advantage for L. pneumophila proliferation in mammalian hosts by promoting immune evasion