Peroxiredoxin 1 is a member of the ubiquitous peroxiredoxin family of thiol peroxidases that catalyse the reduction of peroxides. In recent years eukaryotic peroxiredoxins have emerged as a critical ...component of cellular redox signalling, particularly in response to alterations in production of hydrogen peroxide. Peroxiredoxins are exquisitely sensitive to oxidation by hydrogen peroxide making them key peroxide sensing enzymes within cells. Evidence gathered over the last decade suggests that in addition to sensing the redox signal, peroxiredoxins have a major role in transducing this signal to downstream signalling proteins, ultimately contributing to regulation of diverse cellular processes including proliferation, differentiation and apoptosis. In this review we present the three current models for the sensing and signal transducing roles of peroxiredoxins, with a specific focus on mammalian peroxiredoxin 1. The evidence for each mechanism is discussed and areas for future work are identified.
•Mammalian Prdx1 is a key mediator of H2O2-induced signalling.•Post-translational modifications of Prdx1 alter its activity.•Evidence supporting three models for Prdx1 function is discussed.
Closing wedge high tibial osteotomy is a common, effective and well-established procedure to treat unicompartment osteoarthrosis of the knee. It is, however, not without its complications. This ...article will discuss some of these complications and present an overview of the current literature. It will examine current thoughts on aetiology, techniques to try to avoid, and methods of treatment of these complications.
Background
There is growing interest in and provision of cadaveric simulation courses for surgical trainees. This is being driven by the need to modernize and improve the efficiency of surgical ...training within the current challenging training climate. The objective of this systematic review is to describe and evaluate the evidence for cadaveric simulation in postgraduate surgical training.
Methods
A PRISMA‐compliant systematic literature review of studies that prospectively evaluated a cadaveric simulation training intervention for surgical trainees was undertaken. All relevant databases and trial registries were searched to January 2019. Methodological rigour was assessed using the widely validated Medical Education Research Quality Index (MERSQI) tool.
Results
A total of 51 studies were included, involving 2002 surgical trainees across 69 cadaveric training interventions. Of these, 22 assessed the impact of the cadaveric training intervention using only subjective measures, five measured impact by change in learner knowledge, and 23 used objective tools to assess change in learner behaviour after training. Only one study assessed patient outcome and demonstrated transfer of skill from the simulated environment to the workplace. Of the included studies, 67 per cent had weak methodology (MERSQI score less than 10·7).
Conclusion
There is an abundance of relatively low‐quality evidence showing that cadaveric simulation induces short‐term skill acquisition as measured by objective means. There is currently a lack of evidence of skill retention, and of transfer of skills following training into the live operating theatre.
Antecedentes
Existe un interés creciente en los cursos de simulación con cadáveres para la formación de residentes en cirugía, así como en aumentar la disponibilidad de dichos cursos. Ello es debido a la necesidad de modernizar y mejorar la eficiencia del entrenamiento en el marco actual del reto que supone la formación quirúrgica. El objetivo de esta revisión sistemática era describir y evaluar la evidencia del uso de la simulación con cadáveres en la formación quirúrgica de posgrado.
Métodos
Siguiendo la normativa PRISMA, se realizó una revisión sistemática de la literatura
de estudios que evaluaban prospectivamente el entrenamiento quirúrgico mediante la simulación con cadáveres. Se realizaron búsquedas en todas las bases de datos relevantes y en registros de ensayos clínicos hasta enero de 2019. Se evaluó el rigor metodológico utilizando la herramienta MERSQI (Medical Education Research Quality Index), ampliamente validada.
Resultados
Se incluyeron 51 estudios, con un total de 2.002 residentes de cirugía y 69 intervenciones de formación con simulación con cadáveres. Del total de dichos estudios, 22 evaluaron el impacto de la cirugía con cadáver utilizando solo medidas subjetivas, 5 midieron el impacto por el cambio en el conocimiento del alumno y 23 utilizaron herramientas objetivas para evaluar el cambio en el comportamiento del alumno después de la formación. Solo un estudio evaluó el resultado en pacientes, demostrando la transferencia de habilidades del entorno simulado al lugar de trabajo. De los estudios incluidos, el 55% tenía una metodología débil (puntuación MERSQI < 10,7).
Conclusión
Existe amplia evidencia, pero de baja calidad, referente a la simulación con cadáveres en la formación quirúrgica, demostrando que esta popular herramienta puede ser útil para adquirir habilidades a corto plazo, tal como indican los resultados derivados de medidas objetivas. Actualmente hay una falta de evidencia basada en estudios longitudinales respecto a la retención de habilidades y de cómo estas se transfieren al quirófano real una vez finalizada la formación. Se requieren futuros ensayos aleatorizados de alta calidad para abordar este punto.
This systematic review of cadaveric simulation for surgical training showed that there is low‐quality evidence of short‐term skill acquisition after training, as measured by objective means. There is a lack of evidence of skill retention longitudinally.
Making a comeback?
Group housing and computerized feeding of preweaned dairy calves is gaining popularity among dairy producers worldwide, yet disease incidence and detection remain a challenge in these systems. The ...aim of this prospective observational cohort study was to describe the relationship between morbidity and feeding behavior around the period of illness detection. Calves were enrolled upon entrance to the group pen on 10 farms in Minnesota (n = 4) and Virginia (n = 6) utilizing group housing and computerized feeding from February until October 2014. Morbidity and mortality events were recorded by the calf caregiver. Farms were visited either every week (Minnesota) or every other week (Virginia) to collect calf enrollment data, feeding behavior data, and health records. Daily average feeding behaviors (drinking speed, mL/min; daily consumption, L/d; rewarded visits to the feeder; and unrewarded visits to the feeder) were described both overall and for sick and healthy calf days. Multivariable mixed models were built to assess the differences in daily average feeding behaviors (drinking speed, daily consumption, rewarded visits, unrewarded visits) between matched sick and healthy calves around the time of an illness event (−10 to 10 d). Final models were controlled for calf age, region (Minnesota and Virginia), group size, disease diagnosis, the random effect of farm, and repeated measurements on calf. A stratified analysis was performed by both day from treatment event and disease diagnosis. We enrolled 1,052 calves representing 43,607 calf days over 9 mo. From these, 176 sick calves had a matched control and were carried forward to the matched pair analysis. Fifty-five percent of sick calves (97/176) were treated for diarrhea, 30% (53/176) were treated for pneumonia, and 15% (26/176) were treated for ill thrift. Sick calves drank 183 ± 27 mL/min (mean ± standard error) more slowly, drank 1.2 ± 0.6 L/d less, and had 3.1 ± 0.7 fewer unrewarded visits than control calves on the first day of treatment. These differences began up to 4 d before the calf was detected as sick, and persisted for 7 to 10 d after treatment. However, changes in feeding behaviors varied by disease diagnosed. Rewarded visits were not associated with morbidity status. The results of this study indicate that sick calves change their feeding behavior before and during an illness event, suggesting that feeding behavior may be a useful tool to detect disease onset.
Despite the widespread use of stream restoration structures to improve fish habitat, few quantitative studies have evaluated their effectiveness. This study uses a meta-analysis approach to test the ...effectiveness of five types of in-stream restoration structures (weirs, deflectors, cover structures, boulder placement, and large woody debris) on both salmonid abundance and physical habitat characteristics. Compilation of data from 211 stream restoration projects showed a significant increase in pool area, average depth, large woody debris, and percent cover, as well as a decrease in riffle area, following the installation of in-stream structures. There was also a significant increase in salmonid density (mean effect size of 0.51, or 167%) and biomass (mean effect size of 0.48, or 162%) following the installation of structures. Large differences were observed between species, with rainbow trout (
Oncorhynchus mykiss
) showing the largest increases in density and biomass. This compilation highlights the potential of in-stream structures to create better habitat for and increase the abundance of salmonids, but the scarcity of long-term monitoring of the effectiveness of in-stream structures is problematic.
Understanding the complex variation in patterns of density‐dependent individual growth and survival across populations is critical to adaptive fisheries management, but the extent to which this ...variation is caused by biological or methodological differences is unclear. Consequently, we conducted a correlational meta‐analysis of published literature to investigate the relative importance of methodological and biological predictors on the shape and strength of density‐dependent individual growth and survival in salmonids. We obtained 160 effect sizes from 75 studies of 12 species conducted between 1977 and 2019 that differed in experimental approach (sensu Ecological Monographs, 54, 187–211; 65 laboratory experiments, 60 observational field studies, and 35 field experiments). The experimental approach was the strongest factor influencing the strength of density dependence across studies: density‐dependent survival was stronger than growth in field observational studies, whereas laboratory experiments detected stronger density‐dependent growth than survival. The difference between density‐dependent growth and survival was minimal in field experiments, and between lotic and lentic habitats. The shape of density dependence (logarithmic, linear, exponential or density‐independent) could be predicted with 66.7% accuracy based solely on the experimental approach and the density gradient (highest/lowest*100) of the study. Overall, the strength and shape of density dependence were primarily influenced by methodological predictors, while biological factors (predator presence, food abundance, and species) had predictable but modest effects. For both empirical studies and adaptive fisheries management, we recommend using field experiments with a density gradient of at least 470% to detect the proper shape of the density‐dependent response, or accounting for potential biases if observational or laboratory studies are conducted.
Susceptibility to a clinically significant drug hypersensitivity syndrome associated with abacavir use seems to have a strong genetic component. We have previously shown that the presence of ...HLA-B*5701 strongly predicts abacavir hypersensitivity and have identified a potential susceptibility locus within a 300-kb region between the MEGT1 and C4A6 loci in the central MHC. We now report the results of fine recombinant genetic mapping in an expanded patient population of 248 consecutive, fully ascertained, abacavir-exposed individuals in the Western Australian HIV Cohort Study, in which 18 cases of definite abacavir hypersensitivity (7.3%) and 230 tolerant controls were identified. Haplotype mapping within patients with allelic markers of the 57.1 ancestral haplotype suggests a susceptibility locus within the 14-kb Hsp70 gene cluster. HLA-B*5701 was present in 94.4% of hypersensitive cases compared with 1.7% of controls (odds ratio, 960; P < 0.00001). A haplotypic nonsynonymous polymorphism of Hsp70-Hom (HspA1L, resulting from the substitution of residue M493T in the peptide-binding subunit) was found in combination with HLA-B*5701 in 94.4% of hypersensitive cases and 0.4% of controls (odds ratio, 3,893; P < 0.00001). Individuals with abacavir hypersensitivity demonstrated increased monocyte tumor necrosis factor expression in response to ex vivo abacavir stimulation, which was abrogated with CD8+T cell depletion. These data indicate that the concurrence of HLA-B*5701 and Hsp70-Hom M493T alleles is necessary for the development of abacavir hypersensitivity, which is likely to be mediated by an HLA-B*5701-restricted immune response to abacavir.
Sea otters in California are commonly infected with
Toxoplasma gondii. A unique Type X strain is responsible for 72% of otter infections, but its prevalence in terrestrial animals and marine ...invertebrates inhabiting the same area was unknown. Between 2000 and 2005, 45 terrestrial carnivores (lions, bobcats, domestic cats and foxes) and 1396 invertebrates (mussels, clams and worms) were screened for
T. gondii using PCR and DNA sequencing to determine the phylogeographic distribution of
T. gondii archetypal I, II, III and Type X genotypes. Marine bivalves have been shown to concentrate
T. gondii oocysts in the laboratory, but a comprehensive survey of wild invertebrates has not been reported. A California mussel from an estuary draining into Monterey Bay was confirmed positive for Type X
T. gondii by multilocus PCR and DNA sequencing at the
B1 and
SAG1 loci. This mussel was collected from nearshore marine waters just after the first significant rainfall event in the fall of 2002. Of 45 carnivores tested at the
B1,
SAG1, and
GRA6 typing loci, 15 had PCR-confirmed
T. gondii infection; 11 possessed alleles consistent with infection by archetypal Type I, II or III strains and 4 possessed alleles consistent with Type X
T. gondii infection. No non-canonical alleles were identified. The four
T. gondii strains with Type X alleles were identified from two mountain lions, a bobcat and a fox residing in coastal watersheds adjacent to sea otter habitat near Monterey Bay and Estero Bay. Confirmation of Type X
T. gondii in coastal-dwelling felids, canids, a marine bivalve and nearshore-dwelling sea otters supports the hypotheses that feline faecal contamination is flowing from land to sea through surface runoff, and that otters can be infected with
T. gondii via consumption of filter-feeding marine invertebrates.
An international team of over forty stratigraphic experts have helped to build the most up-to-date international stratigraphic framework for the Precambrian and Phanerozoic. This successor to A ...Geologic Time Scale 1989 by W. Brian Harland et al. (CUP 0521 387655) begins with an introduction to the theory and methodology behind the construction of the new time scale. The main part of the book is devoted to the scale itself, systematically presenting the standard subdivisions at all levels using a variety of correlation markers. Extensive use is made of isotope geochronology, geomathematics and orbital tuning to produce a standard geologic scale of unprecedented detail and accuracy with a full error analysis. A wallchart summarising the whole time scale, with paleogeographic reconstructions throughout the Phanerozoic, is included in the back of the book. The time scale will be an invaluable reference source for academic and professional researchers and students.
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