A combination of laboratory, histopathological and microbiological tests for diagnosis of prosthetic joint infection (PJI) have been strongly recommended. This study aims to characterize the accuracy ...of individual or group tests, such as culture of sonicate fluid, synovial fluid and peri-implant tissue, C-reactive protein (CRP) and histopathology for detection of early, delayed and late PJI.
A prospective study of patients undergoing hip or knee arthroplasty from February 2009 to February 2014 was performed in a Spanish tertiary health care hospital. The diagnostic accuracy of the different methods was evaluated constructing receiver-operating-characteristic (ROC) curve areas.
One hundred thirty consecutive patients were included: 18 (13.8%) early PJI, 35 (27%) delayed PJI and 77 (59.2%) late PJI. For individual parameters, the area under the ROC curve for peri-implant tissue culture was larger for early (0.917) than for delayed (0.829) and late PJI (0.778), p = 0.033. There was a significantly larger difference for ROC area in the synovial fluid culture for delayed (0.803) than for early (0.781) and late infections (0.679), p = 0.039. The comparison of the areas under the ROC curves for the two microbiological tests showed that sonicate fluid was significantly different from peri-implant tissue in delayed (0.951 vs 0.829, p = 0.005) and late PJI (0.901 vs 0.778, p = 0.000). The conjunction of preoperative parameters, synovial fluid culture and CRP, improved the accuracy for late PJI (p = 0.01). The conjunction of histopathology and sonicate fluid culture increased the area under ROC curve of sonication in early (0.917 vs 1.000); p = 0.06 and late cases (0.901 vs 0.999); p < 0.001.
For early PJI, sonicate fluid and peri-implant tissue cultures achieve the same best sensitivity. For delayed and late PJI, sonicate fluid culture is the most sensitive individual diagnostic method. By combining histopathology and peri-implant tissue, all early, 97% of delayed and 94.8% of late cases are diagnosed. The conjunction of histopathology and sonicate fluid culture yields a sensitivity of 100% for all types of infection.
Fragile X syndrome (FXS) is the leading inherited cause of autism and intellectual disability. Aberrant synaptic translation has been implicated in the etiology of FXS, but most lines of research on ...therapeutic strategies have targeted protein synthesis indirectly, far upstream of the translation machinery. We sought to perturb p70 ribosomal S6 kinase 1 (S6K1), a key translation initiation and elongation regulator, in FXS model mice. We found that genetic reduction of S6K1 prevented elevated phosphorylation of translational control molecules, exaggerated protein synthesis, enhanced mGluR-dependent long-term depression (LTD), weight gain, and macro-orchidism in FXS model mice. In addition, S6K1 deletion prevented immature dendritic spine morphology and multiple behavioral phenotypes, including social interaction deficits, impaired novel object recognition, and behavioral inflexibility. Our results support the model that dysregulated protein synthesis is the key causal factor in FXS and that restoration of normal translation can stabilize peripheral and neurological function in FXS.
► Deletion of S6K1 corrected exaggerated protein synthesis in FXS mice ► Deletion of S6K1 corrected plasticity and dendritic spine abnormalities in FXS mice ► Deletion of S6K1 corrected multiple ASD-like behaviors displayed by FXS mice ► Deletion of S6K1 normalized increased weight gain and macro-orchidism in FXS mice
Fragile X syndrome (FXS) results in aberrant synaptic translation. Current therapeutics for FXS have been focused on receptors that indirectly modulate translation. Bhattacharya et al. target a key translation regulator and demonstrate correction of multiple phenotypes associated with FXS.
Background and purpose
Cytomegalovirus (CMV) infection has recently been associated with a lower multiple sclerosis (MS) susceptibility, although it remains controversial whether it has a protective ...role or is merely an epiphenomenon related to westernization and early‐life viral infections. We aimed to evaluate whether CMV serostatus may differ in patients with early MS as compared with patients with non‐early MS, analyzing the putative association of this virus with MS clinical course and humoral immune responses against other herpesviruses.
Methods
Multicentric analysis was undertaken of 310 patients with MS (early MS, disease duration ≤5 years, n = 127) and controls (n = 155), evaluating specific humoral responses to CMV, Epstein–Barr virus and human herpesvirus‐6, as well as T‐cell and natural killer (NK)‐cell immunophenotypes.
Results
Cytomegalovirus seroprevalence in early MS was lower than in non‐early MS or controls (P < 0.01), being independently associated with disease duration (odds ratio, 1.04; 95% confidence interval, 1.01–1.08, P < 0.05). CMV+ patients with MS displayed increased proportions of differentiated T‐cells (CD27−CD28−, CD57+, LILRB1+) and NKG2C+ NK‐cells, which were associated with a lower disability in early MS (P < 0.05). CMV+ patients with early MS had an age‐related decline in serum anti‐EBNA‐1 antibodies (P < 0.01), but no CMV‐related differences in anti‐human herpesvirus‐6 humoral responses.
Conclusions
Low CMV seroprevalence was observed in patients with early MS. Modification of MS risk attributed to CMV might be related to the induction of differentiated T‐cell and NK‐cell subsets and/or modulation of Epstein–Barr virus‐specific immune responses at early stages of the disease.
From the boundary surveys of the 1850s to the ever-expanding fences and highway networks of the twenty-first century, Border Land, Border Water examines the history of the construction projects that ...have shaped the region where the United States and Mexico meet. Tracing the accretion of ports of entry, boundary markers, transportation networks, fences and barriers, surveillance infrastructure, and dams and other river engineering projects, C. J. Alvarez advances a broad chronological narrative that captures the full life cycle of border building. He explains how initial groundbreaking in the nineteenth century transitioned to unbridled faith in the capacity to control the movement of people, goods, and water through the use of physical structures. By the 1960s, however, the built environment of the border began to display increasingly obvious systemic flaws. More often than not, Alvarez shows, federal agencies in both countries responded with more construction—“compensatory building" designed to mitigate unsustainable policies relating to immigration, black markets, and the natural world. Border Land, Border Water reframes our understanding of how the border has come to look and function as it does and is essential to current debates about the future of the US-Mexico divide.
Alveolar echinococcosis (AE) and cystic echinococcosis (CE) are severe helminthic zoonoses. Echinococcus multilocularis (causative agent of AE) is widely distributed in the northern hemisphere where ...it is typically maintained in a wild animal cycle including canids as definitive hosts and rodents as intermediate hosts. The species Echinococcus granulosus, Echinococcus ortleppi, Echinococcus canadensis and Echinococcus intermedius are the causative agents of CE with a worldwide distribution and a highly variable human disease burden in the different endemic areas depending upon human behavioural risk factors, the diversity and ecology of animal host assemblages and the genetic diversity within Echinococcus species which differ in their zoonotic potential and pathogenicity. Both AE and CE are regarded as neglected zoonoses, with a higher overall burden of disease for CE due to its global distribution and high regional prevalence, but a higher pathogenicity and case fatality rate for AE, especially in Asia. Over the past two decades, numerous studies have addressed the epidemiology and distribution of these Echinococcus species worldwide, resulting in better-defined boundaries of the endemic areas. This chapter presents the global distribution of Echinococcus species and human AE and CE in maps and summarizes the global data on host assemblages, transmission, prevalence in animal definitive hosts, incidence in people and molecular epidemiology.
Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the ...pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.
This study assessed the projected near-surface wind speed (SWS) changes and variability over the Iberian Peninsula for the 21st century. Here, we compared Coupled Model Intercomparison Project Phase ...6 global climate models (GCMs) with a higher spatial resolution regional climate model (RCM; ∼20 km), known as WRF-CESM2, which was created by a dynamic downscaling of the Community Earth System Model version 2 (CESM2) using the Weather Research and Forecasting (WRF) model. Our analysis found that the GCMs tended to overestimate observed SWS for 1985-2014, while the higher spatial resolution of the WRF-CESM2 did not improve the accuracy and underestimated the SWS magnitude. GCMs project a decline of SWS under high shared socioeconomic pathways (SSPs) greenhouse concentrations, such as SSP370 and SSP585, while an interdecadal oscillation appears in SSP126 and SSP245 for the end of the century. The WRF-CESM2 under SSP585 predicts the opposite increasing SWS. Our results suggest that 21st-century projections of SWS are uncertain even for regionalized products and should be taken with caution.
Hyaluronic acid (HA) and gelatin (Gel) are major components of the extracellular matrix of different tissues, and thus are largely appealing for the construction of hybrid hydrogels to combine the ...favorable characteristics of each biopolymer, such as the gel adhesiveness of Gel and the better mechanical strength of HA, respectively. However, despite previous studies conducted so far, the relationship between composition and scaffold structure and physico-chemical properties has not been completely and systematically established. In this work, pure and hybrid hydrogels of methacroyl-modified HA (HAMA) and Gel (GelMA) were prepared by UV photopolymerization and an extensive characterization was done to elucidate such correlations. Methacrylation degrees of ca. 40% and 11% for GelMA and HAMA, respectively, were obtained, which allows to improve the hydrogels’ mechanical properties. Hybrid GelMA/HAMA hydrogels were stiffer, with elastic modulus up to ca. 30 kPa, and porous (up to 91%) compared with pure GelMA ones at similar GelMA concentrations thanks to the interaction between HAMA and GelMA chains in the polymeric matrix. The progressive presence of HAMA gave rise to scaffolds with more disorganized, stiffer, and less porous structures owing to the net increase of mass in the hydrogel compositions. HAMA also made hybrid hydrogels more swellable and resistant to collagenase biodegradation. Hence, the suitable choice of polymeric composition allows to regulate the hydrogels´ physical properties to look for the most optimal characteristics required for the intended tissue engineering application.
The past decades have provided valuable information on how animals age in the wild. However, examples of male reproductive senescence are scarce. In particular, few studies have described an ...age-related decline in the expression of conspicuous traits influencing mating success. Red ornaments could be good candidates to detect this decline because their expression may depend on the availability of pigments (carotenoids) related to oxidative stress, the latter frequently linked to senescence. Furthermore, it has been argued that efficient mitochondrial metabolism is key to express red carotenoid-based ornaments, and mitochondrial dysfunction is usually associated with senescence. We studied the age-linked expression of a red carotenoid-based trait: the yellowto-red plumage coloration of male common crossbills (Loxia curvirostra). This coloration has recently been experimentally related to mitochondrial function. Here, we analyzed longitudinal plumage coloration data obtained throughout 28 years in free-living birds. We detected an initial increase in redness during the first 2 years of life and a subsequent decline. The relationship between color and age was unrelated to within-individual body mass variability. As far as we know, this is the first demonstration of an age-related ketocarotenoid-based color decrease detected by simultaneously testing within- and between-individual variability in wild animals.
In this study, we investigated the changes in the origin of moisture for the precipitation associated with tropical cyclones (TCs) after extratropical transition (ET) over the North Atlantic Ocean ...basin from 1980 to 2018. We analyzed the 24 hr before and after the occurrence of ET events. By applying a TC‐centric methodology we found that the moisture uptake (MU) occurred predominantly in the south and southwest sectors within ∼2,000 km of TC center before ET and from the southwest and west sectors after ET. In addition, the development of the cold front and the warm conveyor belt after ET induces changes in the moisture transport pattern. Overall, the secondary circulation of TCs favored the moisture flux inward for TCs precipitation, while the large‐scale baroclinic environment controlled the MU after ET.
Plain Language Summary
Tropical cyclones (TCs) are one of the weather systems that often cause fatalities and strong damage to socioeconomic infrastructures in tropical and subtropical latitudes. During the poleward movement, they can undergo an extratropical transition (ET), experiencing notable changes in their structure, such as the replacement of the warm core with a cold core and an increase in the area of the precipitation pattern. In this study, we investigate the changes in the moisture sources' contribution to the precipitation within the TCs' outer radius before and after ET over the North Atlantic Ocean basin. Our results show that the moisture sources were mainly located in the south and southwest sectors within ∼2,000 km of the TC center before ET and in the southwest and west sector after ET. Additionally, the large‐scale baroclinic environment modulated the moisture transport pattern after ET. These findings contribute to improving our knowledge about the changes in a TC during the ET event.
Key Points
The west North Atlantic Ocean was identified as the main moisture source, accounting for ∼44%–69% of total moisture uptake
The moisture was predominately originated from the south and southwest sectors during PRE‐extratropical transition (ET) and from the southwest‐west during POST‐ET
The large‐scale baroclinic environment controlled the moisture transport for tropical cyclones precipitation after ET
PDF
