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1.
Nature ; 593(7860): 548-552, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33882562

RESUMEN

Global peatlands store more carbon than is naturally present in the atmosphere1,2. However, many peatlands are under pressure from drainage-based agriculture, plantation development and fire, with the equivalent of around 3 per cent of all anthropogenic greenhouse gases emitted from drained peatland3-5. Efforts to curb such emissions are intensifying through the conservation of undrained peatlands and re-wetting of drained systems6. Here we report eddy covariance data for carbon dioxide from 16 locations and static chamber measurements for methane from 41 locations in the UK and Ireland. We combine these with published data from sites across all major peatland biomes. We find that the mean annual effective water table depth (WTDe; that is, the average depth of the aerated peat layer) overrides all other ecosystem- and management-related controls on greenhouse gas fluxes. We estimate that every 10 centimetres of reduction in WTDe could reduce the net warming impact of CO2 and CH4 emissions (100-year global warming potentials) by the equivalent of at least 3 tonnes of CO2 per hectare per year, until WTDe is less than 30 centimetres. Raising water levels further would continue to have a net cooling effect until WTDe is within 10 centimetres of the surface. Our results suggest that greenhouse gas emissions from peatlands drained for agriculture could be greatly reduced without necessarily halting their productive use. Halving WTDe in all drained agricultural peatlands, for example, could reduce emissions by the equivalent of over 1 per cent of global anthropogenic emissions.

2.
Mol Psychiatry ; 28(9): 3688-3697, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37903876

RESUMEN

Psychotic experiences (PEs) occur in 5-10% of the general population and are associated with exposure to childhood trauma and obstetric complications. However, the neurobiological mechanisms underlying these associations are unclear. Using the Avon Longitudinal Study of Parents and Children (ALSPAC), we studied 138 young people aged 20 with PEs (n = 49 suspected, n = 53 definite, n = 36 psychotic disorder) and 275 controls. Voxel-based morphometry assessed whether MRI measures of grey matter volume were associated with (i) PEs, (ii) cumulative childhood psychological trauma (weighted summary score of 6 trauma types), (iii) cumulative pre/peri-natal risk factors for psychosis (weighted summary score of 16 risk factors), and (iv) the interaction between PEs and cumulative trauma or pre/peri-natal risk. PEs were associated with smaller left posterior cingulate (pFWE < 0.001, Z = 4.19) and thalamus volumes (pFWE = 0.006, Z = 3.91). Cumulative pre/perinatal risk was associated with smaller left subgenual cingulate volume (pFWE < 0.001, Z = 4.54). A significant interaction between PEs and cumulative pre/perinatal risk found larger striatum (pFWE = 0.04, Z = 3.89) and smaller right insula volume extending into the supramarginal gyrus and superior temporal gyrus (pFWE = 0.002, Z = 4.79), specifically in those with definite PEs and psychotic disorder. Cumulative childhood trauma was associated with larger left dorsal striatum (pFWE = 0.002, Z = 3.65), right prefrontal cortex (pFWE < 0.001, Z = 4.63) and smaller left insula volume in all participants (pFWE = 0.03, Z = 3.60), and there was no interaction with PEs group. In summary, pre/peri-natal risk factors and childhood psychological trauma impact similar brain pathways, namely smaller insula and larger striatum volumes. The effect of pre/perinatal risk was greatest in those with more severe PEs, whereas effects of trauma were seen in all participants. In conclusion, environmental risk factors affect brain networks implicated in schizophrenia, which may increase an individual's propensity to develop later psychotic disorders.


Asunto(s)
Experiencias Adversas de la Infancia , Trastornos Psicóticos , Esquizofrenia , Niño , Humanos , Adolescente , Estudios Longitudinales , Imagen por Resonancia Magnética , Encéfalo
3.
Anal Chem ; 95(40): 14981-14989, 2023 10 10.
Artículo en Inglés | MEDLINE | ID: mdl-37750823

RESUMEN

The main protease of SARS-CoV-2, 3CLpro, is a dimeric enzyme that is indispensable to viral replication and presents an attractive opportunity for therapeutic intervention. Previous reports regarding the key properties of 3CLpro and its highly similar SARS-CoV homologue conflict dramatically. Values of the dimeric Kd and enzymic kcat/KM differ by 106- and 103-fold, respectively. Establishing a confident benchmark of the intrinsic capabilities of this enzyme is essential for combating the current pandemic as well as potential future outbreaks. Here, we use enzymatic methods to characterize the dimerization and catalytic efficiency of the authentic protease from SARS-CoV-2. Specifically, we use the rigor of Bayesian inference in a Markov Chain Monte Carlo analysis of progress curves to circumvent the limitations of traditional Michaelis-Menten initial rate analysis. We report that SARS-CoV-2 3CLpro forms a dimer at pH 7.5 that has Kd = 16 ± 4 nM and is capable of catalysis with kcat = 9.9 ± 1.5 s-1, KM = 0.23 ± 0.01 mM, and kcat/KM = (4.3 ± 0.7) × 104 M-1 s-1. We also find that enzymatic activity decreases substantially in solutions of high ionic strength, largely as a consequence of impaired dimerization. We conclude that 3CLpro is a more capable catalyst than appreciated previously, which has important implications for the design of antiviral therapeutic agents that target 3CLpro.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , Teorema de Bayes , Cisteína Endopeptidasas , Péptido Hidrolasas , Catálisis , Antivirales
4.
Clin Radiol ; 78(12): 885-894, 2023 12.
Artículo en Inglés | MEDLINE | ID: mdl-37709611

RESUMEN

Anterior mediastinal masses can be difficult to characterise on computed tomography (CT) due to the wide spectrum of normal appearances of thymic tissue as well as the challenge of differentiating between benign and malignant pathologies. Additionally, attenuation of cystic mediastinal lesions can be misinterpreted on CT due to varying attenuation values. Anecdotally, non-vascular magnetic resonance imaging (MRI) of the thorax is underutilised across radiology departments in the UK, but has been shown to improve diagnostic certainty and reduce unnecessary surgical intervention. T2-weighted MRI is useful in confirming the cystic nature of lesions, whereas chemical shift techniques can be utilised to document the presence of macroscopic and intra-cellular fat and thus help distinguish between benign and malignant pathologies. In this review article, we present a practical approach to using MRI for the characterisation of anterior mediastinal lesions based on our clinical experience in a UK district general hospital.


Asunto(s)
Neoplasias del Mediastino , Humanos , Neoplasias del Mediastino/diagnóstico por imagen , Neoplasias del Mediastino/patología , Imagen por Resonancia Magnética/métodos , Timo/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Mediastino/diagnóstico por imagen
5.
Magn Reson Med ; 87(5): 2512-2520, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-34932236

RESUMEN

PURPOSE: The use of high-performance gradient systems (i.e., high gradient strength and/or high slew rate) for human MRI is limited by physiological effects (including the elicitation of magnetophosphenes and peripheral nerve stimulation (PNS)). These effects, in turn, depend on the interaction between time-varying magnetic fields and the body, and thus on the participant's position with respect to the scanner's isocenter. This study investigated the occurrence of magnetophosphenes and PNS when scanning participants on a high-gradient (300 mT/m) system, for different gradient amplitudes, ramp times, and participant positions. METHODS: Using a whole-body 300 mT/m gradient MRI system, a cohort of participants was scanned with the head, heart, and prostate at magnet isocenter and a train of trapezoidal bipolar gradient pulses, with ramp times from 0.88 to 4.20 ms and gradient amplitudes from 60 to 300 mT/m. Reports of magnetophosphenes and incidental reports of PNS were obtained. A questionnaire was used to record any additional subjective effects. RESULTS: Magnetophosphenes were strongly dependent on participant position in the scanner. 87% of participants reported the effect with the heart at isocenter, 33% with the head at isocenter, and only 7% with the prostate at isocenter. PNS was most widely reported by participants for the vertical gradient axis (67% of participants), and was the dominant physiological effect for ramp times below 2 ms. CONCLUSION: This study evaluates the probability of eliciting magnetophosphenes during whole-body imaging using an ultra-strong gradient MRI system. It provides empirical guidance on the use of high-performance gradient systems for whole-body human MRI.


Asunto(s)
Cuerpo Humano , Imagen por Resonancia Magnética , Humanos , Campos Magnéticos , Imagen por Resonancia Magnética/métodos , Masculino , Probabilidad
6.
Eur Cell Mater ; 43: 153-161, 2022 04 21.
Artículo en Inglés | MEDLINE | ID: mdl-35446434

RESUMEN

The Achilles tendon is the strongest tendon in the human body but its mechanical behaviour during failure has been little studied and the basis of its high tensile strength has not been elucidated in detail. In the present study, healthy, human, Achilles tendons were loaded to failure in an anatomically authentic fashion while the local deformation and strains were studied in real time, with very high precision, using digital image correlation (DIC). The values determined for the strength of the Achilles tendon were at the high end of those reported in the literature, consistent with the absence of a pre-existing tendinopathy in the samples, as determined by careful gross inspection and histology. Early in the loading cycle, the proximal region of the tendon accumulated high lateral strains while longitudinal strains remained low. However, immediately before rupture, the mid-substance of the Achilles tendon, its weakest part, started to show high longitudinal strains. These new insights advance the understanding of the mechanical behaviour of tendons as they are stretched to failure.


Asunto(s)
Tendón Calcáneo , Tendinopatía , Fenómenos Biomecánicos , Humanos , Técnicas In Vitro , Rotura
7.
Eur Cell Mater ; 44: 43-55, 2022 08 17.
Artículo en Inglés | MEDLINE | ID: mdl-35976149

RESUMEN

The interphase between tendon and bone consists of a highly specialised tissue called enthesis. Typically, the enthesis is described as a succession of four different zones: tendon, non-mineralised fibrocartilage, mineralised fibrocartilage and bone. However, the microstructure of the entheses, cellular composition and mechanical properties vary depending on their anatomical location. The present study aimed to characterise three of the most relevant sites of enthesis injury in a rat model: the patellar tendon, the Achilles tendon and the supraspinatus enthesis, in terms of biomechanics, histology and genetic expression. The patellar enthesis presented the highest ultimate load and lowest stiffness of the three, while the supraspinatus was the weakest and stiffest. The histological characterisation revealed key differences at the insertion site for each enthesis. The patellar enthesis showed a large cartilaginous area at the tendon-to-bone interphase whilst this interphase was smaller in the supraspinatus entheses samples. Furthermore, the Achilles tendon enthesis displayed a more abrupt transition from tendon to bone. Additionally, each enthesis exhibited a particular and distinct pattern of expression of tenogenic, chondrogenic and osteogenic markers. This study provided valuable insights for a better understanding of the three entheses at relevant anatomical sites. Moreover, the larger cross-sectional area of the patellar enthesis, the strong mechanical properties and the easier surgical access to this location led to the conclusion that the patellar tendon enthesis site could be most suitable for the development of a preclinical model for general enthesis regeneration studies in rats.


Asunto(s)
Tendón Calcáneo , Fibrocartílago , Tendón Calcáneo/patología , Animales , Huesos , Osteogénesis , Ratas , Manguito de los Rotadores
8.
Mol Divers ; 26(1): 73-96, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33385288

RESUMEN

N-furfuryl piperazine ureas disclosed by scientists at GSK Tres Cantos were chosen as antimycobacterial hits from a phenotypic whole-cell screen. Bioisosteric replacement of the furan ring in the GSK Tres Cantos molecules with a phenyl ring led to molecule (I) with an MIC of 1 µM against Mtb H37Rv, low cellular toxicity (HepG2 IC50 ~ 80 µM), good DMPK properties and specificity for Mtb. With the aim of delineating the SAR associated with (I), fifty-five analogs were synthesized and screened against Mtb. The SAR suggests that the piperazine ring, benzyl urea and piperonyl moieties are essential signatures of this series. Active compounds in this series are metabolically stable, have low cellular toxicity and are valuable leads for optimization. Molecular docking suggests these molecules occupy the Q0 site of QcrB like Q203. Bioisosteric replacement of N-furfuryl piperazine-1-carboxamides yielded molecule (I) a novel lead with satisfactory PD, metabolism, and toxicity profiles.


Asunto(s)
Mycobacterium tuberculosis , Antituberculosos/farmacología , Pruebas de Sensibilidad Microbiana , Simulación del Acoplamiento Molecular , Estructura Molecular , Piperazinas/farmacología , Relación Estructura-Actividad , Urea/farmacología
9.
Eur J Appl Physiol ; 122(3): 769-779, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35038023

RESUMEN

PURPOSE: The force-velocity relationship of muscular contraction has been extensively studied. However, previous research has focussed either on isolated muscle or single-joint movements, whereas human movement consists of multi-joint movements (e.g. squatting). Therefore, the purpose of this study was to investigate the force-velocity relationship of isovelocity squatting. METHODS: Fifteen male participants (24 ± 2 years, 79.8 ± 9.1 kg, 177.5 ± 6 cm) performed isovelocity squats on a novel motorised isovelocity device (Kineo Training System) at three concentric (0.25, 0.5, and 0.75 m s-1) and three eccentric velocities (- 0.25, - 0.5, and - 0.75 m s-1). Peak vertical ground reaction forces, that occurred during the isovelocity phase, were collected using dual force plates (2000 Hz) (Kistler, Switzerland). RESULTS: The group mean squat force-velocity profile conformed to the typical in vivo profile, with peak vertical ground reaction forces during eccentric squatting being 9.5 ± 19% greater than isometric (P = 0.037), and occurring between - 0.5 and - 0.75 m s-1. However, large inter-participant variability was identified (0.84-1.62 × isometric force), with some participants being unable to produce eccentric forces greater than isometric. Sub-group analyses could not identify differences between individuals who could/could not produce eccentric forces above isometric, although those who could not tended to be taller. CONCLUSIONS: These finding suggest that variability exists between participants in the ability to generate maximum eccentric forces during squatting, and the magnitude of eccentric increase above isometric cannot be predicted solely based on a concentric assessment. Therefore, an assessment of eccentric capabilities may be required prior to prescribing eccentric-specific resistance training.


Asunto(s)
Extremidad Inferior/fisiología , Contracción Muscular/fisiología , Músculo Esquelético/fisiología , Fenómenos Biomecánicos , Humanos , Masculino , Fuerza Muscular/fisiología , Postura , Adulto Joven
10.
Dis Aquat Organ ; 150: 1-16, 2022 Jul 07.
Artículo en Inglés | MEDLINE | ID: mdl-35796507

RESUMEN

The genera Paramoeba and Neoparamoeba (Amoebozoa, Dactylopodida, Paramoebidae) include well-known opportunistic pathogens associated with fish (N. peruans; amoebic gill disease), lobsters, molluscs and sea urchins, but only rarely with crabs (grey crab disease of blue crabs). Following reports of elevated post-capture mortality in edible crabs Cancer pagurus captured from a site within the English Channel fishery in the UK, a novel disease (amoebic crab disease, ACD) was detected in significant proportions of the catch. We present histopathological, transmission electron microscopy and molecular phylogenetic data, showing that this disease is defined by colonization of haemolymph, connective tissues and fixed phagocytes by amoeboid cells, leading to tissue destruction and presumably death in severely diseased hosts. The pathology was strongly associated with a novel amoeba with a phylogenetic position on 18S rRNA gene trees robustly sister to Janickina pigmentifera (which groups within the current circumscription of Paramoeba/Neoparamoeba), herein described as Janickina feisti n. sp. We provide evidence that J. feisti is associated with ACD in 50% of C. pagurus sampled from the mortality event. A diversity of other paramoebid sequence types, clustering with known radiations of N. pemaquidensis and N. aestuarina and a novel N. aestuarina sequence type, was detected by PCR in most of the crabs investigated, but their detection was much less strongly associated with clinical signs of disease. The discovery of ACD in edible crabs from the UK is discussed relative to published historical health surveys for this species.


Asunto(s)
Amebiasis , Amoeba , Braquiuros , Neoplasias , Amebiasis/veterinaria , Animales , Neoplasias/veterinaria , Filogenia , Reino Unido/epidemiología
11.
Neuroimage ; 225: 117406, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-33045335

RESUMEN

We provide a rich multi-contrast microstructural MRI dataset acquired on an ultra-strong gradient 3T Connectom MRI scanner comprising 5 repeated sets of MRI microstructural contrasts in 6 healthy human participants. The availability of data sets that support comprehensive simultaneous assessment of test-retest reliability of multiple microstructural contrasts (i.e., those derived from advanced diffusion, multi-component relaxometry and quantitative magnetisation transfer MRI) in the same population is extremely limited. This unique dataset is offered to the imaging community as a test-bed resource for conducting specialised analyses that may assist and inform their current and future research. The Microstructural Image Compilation with Repeated Acquisitions (MICRA) dataset includes raw data and computed microstructure maps derived from multi-shell and multi-direction encoded diffusion, multi-component relaxometry and quantitative magnetisation transfer acquisition protocols. Our data demonstrate high reproducibility of several microstructural MRI measures across scan sessions as shown by intra-class correlation coefficients and coefficients of variation. To illustrate a potential use of the MICRA dataset, we computed sample sizes required to provide sufficient statistical power a priori across different white matter pathways and microstructure measures for different statistical comparisons. We also demonstrate whole brain white matter voxel-wise repeatability in several microstructural maps. The MICRA dataset will be of benefit to researchers wishing to conduct similar reliability tests, power estimations or to evaluate the robustness of their own analysis pipelines.


Asunto(s)
Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Adulto , Femenino , Voluntarios Sanos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Adulto Joven
12.
Neuroimage ; 241: 118430, 2021 11 01.
Artículo en Inglés | MEDLINE | ID: mdl-34314848

RESUMEN

PURPOSE: Heating of gradient coils and passive shim components is a common cause of instability in the B0 field, especially when gradient intensive sequences are used. The aim of the study was to set a benchmark for typical drift encountered during MR spectroscopy (MRS) to assess the need for real-time field-frequency locking on MRI scanners by comparing field drift data from a large number of sites. METHOD: A standardized protocol was developed for 80 participating sites using 99 3T MR scanners from 3 major vendors. Phantom water signals were acquired before and after an EPI sequence. The protocol consisted of: minimal preparatory imaging; a short pre-fMRI PRESS; a ten-minute fMRI acquisition; and a long post-fMRI PRESS acquisition. Both pre- and post-fMRI PRESS were non-water suppressed. Real-time frequency stabilization/adjustment was switched off when appropriate. Sixty scanners repeated the protocol for a second dataset. In addition, a three-hour post-fMRI MRS acquisition was performed at one site to observe change of gradient temperature and drift rate. Spectral analysis was performed using MATLAB. Frequency drift in pre-fMRI PRESS data were compared with the first 5:20 minutes and the full 30:00 minutes of data after fMRI. Median (interquartile range) drifts were measured and showed in violin plot. Paired t-tests were performed to compare frequency drift pre- and post-fMRI. A simulated in vivo spectrum was generated using FID-A to visualize the effect of the observed frequency drifts. The simulated spectrum was convolved with the frequency trace for the most extreme cases. Impacts of frequency drifts on NAA and GABA were also simulated as a function of linear drift. Data from the repeated protocol were compared with the corresponding first dataset using Pearson's and intraclass correlation coefficients (ICC). RESULTS: Of the data collected from 99 scanners, 4 were excluded due to various reasons. Thus, data from 95 scanners were ultimately analyzed. For the first 5:20 min (64 transients), median (interquartile range) drift was 0.44 (1.29) Hz before fMRI and 0.83 (1.29) Hz after. This increased to 3.15 (4.02) Hz for the full 30 min (360 transients) run. Average drift rates were 0.29 Hz/min before fMRI and 0.43 Hz/min after. Paired t-tests indicated that drift increased after fMRI, as expected (p < 0.05). Simulated spectra convolved with the frequency drift showed that the intensity of the NAA singlet was reduced by up to 26%, 44 % and 18% for GE, Philips and Siemens scanners after fMRI, respectively. ICCs indicated good agreement between datasets acquired on separate days. The single site long acquisition showed drift rate was reduced to 0.03 Hz/min approximately three hours after fMRI. DISCUSSION: This study analyzed frequency drift data from 95 3T MRI scanners. Median levels of drift were relatively low (5-min average under 1 Hz), but the most extreme cases suffered from higher levels of drift. The extent of drift varied across scanners which both linear and nonlinear drifts were observed.


Asunto(s)
Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Análisis de Datos , Bases de Datos Factuales/normas , Imagen por Resonancia Magnética/normas , Espectroscopía de Resonancia Magnética/normas , Humanos , Imagen por Resonancia Magnética/métodos , Espectroscopía de Resonancia Magnética/métodos
13.
Bioconjug Chem ; 32(1): 82-87, 2021 01 20.
Artículo en Inglés | MEDLINE | ID: mdl-33296182

RESUMEN

Since its conception, the ribonuclease S complex (RNase S) has led to historic discoveries in protein chemistry, enzymology, and related fields. Derived by the proteolytic cleavage of a single peptide bond in bovine pancreatic ribonuclease (RNase A), RNase S serves as a convenient and reliable model system for incorporating unlimited functionality into an enzyme. Applications of the RNase S system in biomedicine and biotechnology have, however, been hindered by two shortcomings: (1) the bovine-derived enzyme could elicit an immune response in humans, and (2) the complex is susceptible to dissociation. Here, we have addressed both limitations in the first semisynthesis of an RNase S conjugate derived from human pancreatic ribonuclease and stabilized by a covalent interfragment cross-link. We anticipate that this strategy will enable unprecedented applications of the "RNase-S" system.


Asunto(s)
Ribonucleasas/biosíntesis , Secuencia de Aminoácidos , Electroforesis en Gel de Poliacrilamida , Humanos , Ribonucleasa Pancreática/metabolismo , Ribonucleasas/química , Espectrometría de Masa por Láser de Matriz Asistida de Ionización Desorción
14.
Glob Chang Biol ; 27(20): 5109-5123, 2021 10.
Artículo en Inglés | MEDLINE | ID: mdl-34165851

RESUMEN

Inland waters play an active role in the global carbon cycle and emit large volumes of the greenhouse gases (GHGs), methane (CH4 ) and carbon dioxide (CO2 ). A considerable body of research has improved emissions estimates from lakes, reservoirs and rivers but recent attention has been drawn to the importance of small, artificial waterbodies as poorly quantified but potentially important emission hotspots. Of particular interest are emissions from drainage ditches and constructed ponds. These waterbody types are prevalent in many landscapes and their cumulative surface areas can be substantial. Furthermore, GHG emissions from constructed waterbodies are anthropogenic in origin and form part of national emissions reporting, whereas emissions from natural waterbodies do not (according to Intergovernmental Panel on Climate Change guidelines). Here, we present GHG data from two complementary studies covering a range of land uses. In the first, we measured emissions from nine ponds and seven ditches over a full year. Annual emissions varied considerably: 0.1-44.3 g CH4  m-2  year-1 and -36-4421 g CO2  m-2  year-1 . In the second, we measured GHG concentrations in 96 ponds and 64 ditches across seven countries, covering subtropical, temperate and sub-arctic biomes. When CH4 emissions were converted to CO2  equivalents, 93% of waterbodies were GHG sources. In both studies, GHGs were positively related to nutrient status (C, N, P), and pond GHG concentrations were highest in smallest waterbodies. Ditch and pond emissions were larger per unit area when compared to equivalent natural systems (streams, natural ponds). We show that GHG emissions from natural systems should not be used as proxies for those from artificial waterbodies, and that artificial waterbodies have the potential to make a substantial but largely unquantified contribution to emissions from the Agriculture, Forestry and Other Land Use sector, and the global carbon cycle.


Asunto(s)
Dióxido de Carbono , Gases de Efecto Invernadero , Dióxido de Carbono/análisis , Efecto Invernadero , Gases de Efecto Invernadero/análisis , Lagos , Metano/análisis , Óxido Nitroso/análisis , Ríos
15.
Eur Cell Mater ; 41: 668-679, 2021 06 10.
Artículo en Inglés | MEDLINE | ID: mdl-34111297

RESUMEN

The present review acknowledges the tremendous impact of Stephan Perren's strain theory, considered with respect to the earlier contributions of Roux and Pauwels. Then, it provides further insight by examining how the concept of reverse dynamisation extended Perren's theory within a modern context. A key factor of this more contemporary theory is that it introduces variable mechanical conditions at different time points during bone healing, opening the possibility of manipulating biology through mechanics to achieve the desired clinical outcome. The discussion focusses on the current state of the art and the most recent advances made towards optimising and accelerating bone regeneration, by actively controlling the mechanical environment as healing progresses. Reverse dynamisation utilises a very specific mechanical manipulation regimen, with conditions initially flexible to encourage and expedite early callus formation. Once callus has formed, the mechanical conditions are intentionally modified to create a rigid environment under which the soft callus is quickly converted to hard callus, bridging the fracture site and leading to a more rapid union. The relevant literature, principally animal studies, was surveyed to provide ample evidence in support of the effectiveness of reverse dynamisation. By providing a modern perspective on Stephan Perren's strain theory, reverse dynamisation perhaps holds the key to tipping the balance in favour of a more rapid and reliable union when treating acute fractures, osteotomies, non-unions and other circumstances where it is necessary to regenerate bone.


Asunto(s)
Regeneración Ósea/fisiología , Huesos/fisiopatología , Curación de Fractura/fisiología , Fracturas Óseas/fisiopatología , Animales , Callo Óseo/fisiopatología , Humanos
16.
Eur Cell Mater ; 41: 345-354, 2021 03 17.
Artículo en Inglés | MEDLINE | ID: mdl-33729540

RESUMEN

Clinical management of delayed healing or non-union of long bone fractures and segmental defects poses a substantial orthopaedic challenge. There are suggestions in the literature that bone healing may be enhanced by inhibiting the activities of T and B lymphocytes, but this remains controversial. To examine this matter in more detail, sub-critical-sized segmental defects were created in the femora of mice and it was assessed whether there might be a benefit from the administration of a Food and Drug Administration (FDA)-approved drug that blocks T cell activation (tacrolimus). Defects were stabilised using an internal plate. In certain groups of animals, 1 mg/kg or 10 mg/kg tacrolimus was delivered locally to the defect site for 3 or 7 d using an implanted osmotic pump with a silicon catheter directing drug delivery into the defect area. Healing was monitored by weekly X-ray and assessed at 12 weeks by mechanical testing, µCT and histology. Radiographic and histological evaluations revealed that 100 % of defects healed well regardless of tacrolimus dosage or duration. A comparison of healed C57BL/6 and Rag1-/- femora by µCT and ex vivo torsion testing showed no differences within mouse strains in terms of bone volume, tissue volume, bone volume/tissue volume ratio, shear modulus, torsional rigidity or torsional stiffness. These data failed to support an important role for tacrolimus in modulating the natural healing of segmental defects under those experimental conditions.


Asunto(s)
Curación de Fractura/efectos de los fármacos , Fracturas Óseas/tratamiento farmacológico , Fracturas Óseas/metabolismo , Proteínas de Homeodominio/metabolismo , Tacrolimus/farmacología , Animales , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Fémur , Masculino , Ratones , Ratones Endogámicos C57BL , Osteotomía/métodos , Linfocitos T/efectos de los fármacos , Linfocitos T/metabolismo , Microtomografía por Rayos X/métodos
17.
Anaesthesia ; 76(5): 639-646, 2021 05.
Artículo en Inglés | MEDLINE | ID: mdl-33512713

RESUMEN

Cardiac surgical patients with anaemia experience increased morbidity and mortality. Iron deficiency is the most common cause of pre-operative anaemia in this group. We designed and implemented the Cardiff Pathway, a pre-assessment and treatment pathway to identify cardiac surgical patients with anaemia and iron deficiency. Patients identified with anaemia and/or iron deficiency (Hb < 130 g.l-1 and ferritin < 100 µg.l-1 ) were offered intravenous iron infusion 20 mg.kg-1 pre-operatively. Treatment success was defined as Hb ≥ 130g.l-1 on the day of surgery. We analysed data from 447 patients: 300 (67%) were not anaemic; 75 (17%) were anaemic and treated with intravenous iron; and 72 (16%) were anaemic and not treated. Haemoglobin concentration increased in successfully treated anaemic patients by a mean (95%CI) of 17 (13-21) g.l-1 and they received a median (IQR [range]) of 0 (0-2 [0-15]) units of blood peri-operatively. Transfusion was avoided in 54% of the successfully treated anaemic patients, which was significantly more than the unsuccessfully treated anaemic (22%, p = 0.005) and untreated anaemic (28%, p = 0.018) patients and similar to non-anaemic patients who received a median (IQR [range] of 0 (0-1 [0-16])) units of blood and, 63% avoided transfusion). Mean (95%CI) Hb fell between pre-assessment and surgery in the untreated anaemic (-2 (0 to -4) g.l-1 ) and non-anaemic groups (-2 (-1 to -3) g.l-1 ). Twenty-one (7%) of the non-anaemic group became newly anaemic waiting for surgery. The Cardiff Pathway reliably identified patients with anaemia and iron deficiency. Anaemic patients who had their Hb restored to normal after treatment required less blood peri-operatively and over half of them required no transfusion at all.


Asunto(s)
Anemia/patología , Hierro/administración & dosificación , Administración Intravenosa , Anciano , Anemia/mortalidad , Anemia/cirugía , Procedimientos Quirúrgicos Electivos , Transfusión de Eritrocitos , Femenino , Hemoglobinas/análisis , Mortalidad Hospitalaria , Humanos , Tiempo de Internación , Masculino , Persona de Mediana Edad , Cuidados Preoperatorios , Resultado del Tratamiento
18.
Public Health ; 194: 4-10, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33836318

RESUMEN

OBJECTIVES: To examine the patterns and influences on repeated emergency department attendance among frail older people with deteriorating health. STUDY DESIGN: Multicentre prospective cohort study (International Access Rights and Empowerment II study) with convergent mixed methods design. METHODS: Eligible patients were aged ≥65 years, with Clinical Frailty Score ≥5, and ≥1 hospital admission or ≥2 acute attendances in the previous 6 months. Questionnaires were administered to participants over 6 months and we extracted clinical data from the medical records. We conducted modified Poisson multivariable regression analysis to identify factors associated with repeated emergency department attendance (≥2 over 6 months) and thematic analysis of qualitative interviews. RESULTS: A total of 90 participants were recruited. The mean age was 84 years, and 63% were women. Of 87 participants, 21 experienced repeated emergency department attendance. Severe and/or overwhelming pain (adjusted prevalence ratio 2.44, 95% confidence interval 1.17-5.11), greater number of comorbidities (1.32, 1.08-1.62), ≥10 community nursing contacts (2.93, 1.31-6.56), and a total of ≥2 weeks spent in hospital during the previous 6 months (2.91, 1.24-6.84) were associated with repeated attendance. From 45 interviews, we identified influences on emergency department attendance: 1. inaccessibility of community healthcare; 2. perceived barriers to community healthcare seeking; 3. perceived benefits of hospital admission; 4. barriers to recovery during previous hospital admission (unsuitable food, inactivity); and 5. poorly coordinated transitions between settings. CONCLUSIONS: We identified missed opportunities to optimise older people's recovery during hospital admission, such as improved food and a timely and coordinated discharge, which may reduce reattendances. Proactive care in the community with systematic assessment of symptoms may be required, particularly for those with multimorbidity.


Asunto(s)
Servicio de Urgencia en Hospital/estadística & datos numéricos , Anciano Frágil/estadística & datos numéricos , Estado de Salud , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Estudios Prospectivos
19.
Community Dent Health ; 38(2): 138-141, 2021 May 28.
Artículo en Inglés | MEDLINE | ID: mdl-33769722

RESUMEN

This paper comments on the Effects of Racism on Oral Health in the United States (US). It provides the background and sets the stage to raise questions about race: how was race defined originally, what exactly is race, and how have racial categories been enumerated? Following this path, the paper broadens the scope of view regarding data attributable to racial categories pointing to social and cultural factors that influence overall health outcomes, particularly those related to oral health. Oral health researchers, advocates, providers, administrators, program planners, and funders, among others rely on data, often compiled by racial categories. We should be aware of potential vagaries that can accompany race-based data, and its interpretation and application, regarding oral health. The paper suggests we should be mindful of other influences that affect documented differences among populations regarding their oral health status.


Asunto(s)
Racismo , Humanos , Salud Bucal , Estados Unidos
20.
N Z Vet J ; 69(5): 274-284, 2021 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-33879036

RESUMEN

AIMS: To explore recommendations that New Zealand veterinarians make for diagnosing and managing bovine viral diarrhoea (BVD) in cattle herds under different clinical scenarios and their opinions towards potential barriers and opportunities for implementing BVD control programmes in New Zealand. METHODS: A cross-sectional survey of registered veterinarians in New Zealand was conducted in 2019. Respondents were asked about the approaches they would use to manage BVD under different clinical scenarios as well as their opinions on national BVD control. A subset of veterinarians completed a more in-depth survey providing additional free-text responses on a range of different BVD topics. Descriptive statistics were provided for all quantitative study variables and the free-text responses were also analysed to generate further insights into veterinarians' perceptions towards BVD management. RESULTS: The cross-sectional survey was completed by 101 of an estimated 870 (11.6%) cattle veterinarians. Thirty-five veterinarians completed the in-depth survey. There was wide variation in the BVD diagnostic testing and vaccination protocols that respondents recommended under different clinical scenarios. Annual bulk milk BVD testing was perceived as a valuable tool for initiating BVD discussions with dairy farmers. Respondents indicated that beef farmers were more difficult to engage in BVD control largely due to the logistical challenges of yarding cattle at the appropriate times to implement interventions, with many farmers only contacting veterinarians after experiencing a BVD outbreak Most respondents (91/101; 90%) believed it was possible to eradicate BVD from New Zealand, but cited lack of farmer awareness and poor compliance with management recommendations as significant barriers. The measure with the most support for inclusion in a compulsory national eradication programme was requiring farmers to declare the status of their animals prior to sale while the least supported measure was requiring farmers to double fence boundaries to prevent nose-to-nose contact with neighbouring stock. Although respondents highlighted the need for farmers and industry to support any national eradication programme in order for it to be successful, there was also recognition that veterinarians could be more pro-active in engaging with farmers particularly in discussions around the economics of BVD. CONCLUSIONS AND CLINICAL RELEVANCE: While the survey respondents appeared to be highly supportive of BVD control, it was perceived that financial and logistical barriers existed that could impede farmer engagement. Further extension efforts may be needed to ensure that veterinarians are presenting clear and consistent recommendations about BVD management to farmers.Abbreviations: BVD: Bovine viral diarrhoea; NAIT: National Animal Identification and Tracing System; PI: Persistently infected.


Asunto(s)
Diarrea Mucosa Bovina Viral , Enfermedades de los Bovinos , Virus de la Diarrea Viral Bovina , Veterinarios , Crianza de Animales Domésticos , Animales , Diarrea Mucosa Bovina Viral/diagnóstico , Diarrea Mucosa Bovina Viral/epidemiología , Diarrea Mucosa Bovina Viral/prevención & control , Bovinos , Estudios Transversales , Diarrea/veterinaria , Humanos , Nueva Zelanda/epidemiología
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