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1.
Microbiol Resour Announc ; 12(11): e0049923, 2023 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-37905902

RESUMO

Lactobacillus fermentum remains as potential probiotic bacterium that enhances immunological response, produces antimicrobials, acts as food preservative, and lowers blood cholesterol level. We report the draft genome of Lactobacillus fermentum S2 consisting of 1.97 Mb genome size, 52.27% G + C content, 3 rRNA genes, 51 tRNA genes, and 2,004 protein-coding sequences.

2.
J Org Chem ; 88(17): 12677-12697, 2023 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-37608565

RESUMO

A systematic study is undertaken to investigate the less explored endo-trig radical cyclization in activated olefin-appended epoxides using Cp2TiCl. The radical generated by the Ti(III)-promoted reductive opening of the epoxy ring promptly underwent endo-trig cyclization, giving access to differently 1,3-disubstituted six- and seven-membered carbocycles in good yields and diastereoselectivity. This protocol was successfully employed in the construction of 5,7- and 6,7-fused bicyclic frameworks entailing a de novo synthesis of (±)-isoclavukerin A belonging to tri-nor-guaiane class of sesquiterpene natural products in eight simple steps from commercially available starting materials. Besides the Ti(III)-mediated reaction serving as a key step in the synthesis, a sequential [2,3]-sigmatropic rearrangement/syn-elimination of an allyl sulfenate intermediate successfully rendered the highly constrained diene moiety in the hydroazulene core of the target molecule.

3.
Life (Basel) ; 13(6)2023 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-37374160

RESUMO

Bone mechanics is well understood at every length scale except the nano-level. We aimed to investigate the relationship between bone nanoscale and tissue-level mechanics experimentally. We tested two hypotheses: (1) nanoscale strains were lower in hip fracture patients versus controls, and (2) nanoscale mineral and fibril strains were inversely correlated with aging and fracture. A cross-sectional sample of trabecular bone sections was prepared from the proximal femora of two human donor groups (aged 44-94 years): an aging non-fracture control group (n = 17) and a hip-fracture group (n = 20). Tissue, fibril, and mineral strain were measured simultaneously using synchrotron X-ray diffraction during tensile load to failure, then compared between groups using unpaired t-tests and correlated with age using Pearson's correlation. Controls exhibited significantly greater peak tissue, mineral, and fibril strains than the hip fracture (all p < 0.05). Age was associated with a decrease in peak tissue (p = 0.099) and mineral (p = 0.004) strain, but not fibril strain (p = 0.260). Overall, hip fracture and aging were associated with changes in the nanoscale strain that are reflected at the tissue level. Data must be interpreted within the limitations of the observational cross-sectional study design, so we propose two new hypotheses on the importance of nanomechanics. (1) Hip fracture risk is increased by low tissue strain, which can be caused by low collagen or mineral strain. (2) Age-related loss of tissue strain is dependent on the loss of mineral but not fibril strain. Novel insights into bone nano- and tissue-level mechanics could provide a platform for the development of bone health diagnostics and interventions based on failure mechanisms from the nanoscale up.

4.
J Pharm Biomed Anal ; 226: 115254, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36701879

RESUMO

The evaluation of joint disease using synovial fluid is an emerging field of metabolic profiling. The analysis is challenged by multiple macromolecules which can obscure the small molecule chemistry. The use of protein precipitation and extraction has been evaluated previously, but not in synovial fluid. We systematically review the published NMR spectroscopy methods of synovial fluid analysis and investigated the efficacy of three different protein precipitation techniques: methanol, acetonitrile and trichloroacetic acid. The trichloroacetic wash removed the most protein. However, metabolite recoveries were universally very poor. Acetonitrile liquid/liquid extraction gave metabolite gains from four unknown compounds with spectral peaks at δ = 1.91 ppm, 3.64 ppm, 3.95 ppm & 4.05 ppm. The metabolite recoveries for acetonitrile were between 1.5 and 7 times higher than the methanol method, across all classes of metabolite. The methanol method was more effective in removing protein as reported by the free GAG undefined peak (44 % vs 125 %). However, qualitative evaluation showed that acetonitrile and methanol provided good restoration of the spectra to baseline. The methanol extraction has issues of a gelatinous substrate in the samples. All metabolite recoveries had a CV of > 15 %. A recommendation of acetonitrile liquid/liquid extraction was made for human synovial fluid (HSF) analysis. This is due to consistency, effective protein precipitation, recovery of metabolites and additional compounds not previously visible.


Assuntos
Metanol , Líquido Sinovial , Humanos , Líquido Sinovial/química , Líquido Sinovial/metabolismo , Metanol/química , Espectroscopia de Ressonância Magnética/métodos , Extração Líquido-Líquido , Acetonitrilas/metabolismo
5.
J Mech Behav Biomed Mater ; 136: 105468, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36244325

RESUMO

The bone quality of patients undergoing hip replacement surgery is poorly predicted by radiographs alone. With better bone quality information available to a surgeon, the operation can be performed more safely. The aim of this study was to investigate whether ultrasound signals of cortical bone at peripheral sites such as the tibia and radius can be used to predict the compressive mechanical properties of cortical bone at the femoral neck. We recruited 19 patients undergoing elective hip arthroplasty and assessed the radius and tibia of these patients with the Azalée guided wave ultrasound to estimate the porosity and thickness of the cortex. Excess bone tissues were collected from the femoral neck and the compressive mechanical properties of the cortex were characterised under a mechanical loading rig to determine stiffness, ultimate strength, and density. The correlations between the ultrasound measurements and mechanical properties were analysed using linear regression, Pearson correlation statistics, and multiple regression analysis. Cortical mechanical properties were weakly to moderately correlated with the ultrasound measurements at various sites (R2 = 0.00-0.36). The significant correlations found were not consistent across all 4 peripheral measurement sites. Additionally, weak to moderate ability of the ultrasound to predict mechanical properties at the neck of femur with multiple regression analysis was found (R2 = 0.00-0.48). Again, this was inconsistent across the different anatomical sites. Overall, the results demonstrate the need for ultrasound scans to be collected directly from clinically relevant sites such as the femoral neck due to the inconsistency of mechanical properties across various sites.


Assuntos
Artroplastia de Quadril , Colo do Fêmur , Humanos , Colo do Fêmur/diagnóstico por imagem , Fêmur/diagnóstico por imagem , Fêmur/cirurgia , Osso Cortical , Radiografia , Densidade Óssea
6.
Ir J Med Sci ; 191(3): 1005-1012, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34184207

RESUMO

INTRODUCTION: COVID-19 has been recognized as the unprecedented global health crisis in modern times. The purpose of this study was to assess the impact of COVID-19 on treatment of neck of femur fractures (NOFF) against the current guidelines and meeting best practice key performance indicators (KPIs) according to the National Hip Fracture Database (NHFD) in two large central London hospitals. MATERIALS AND METHODS: A multi-center, longitudinal, retrospective, observational study of NOFF patients was performed for the first 'golden' month following the lockdown measures introduced in mid-March 2020. This was compared to the same time period in 2019. RESULTS: A total of 78 cases were observed. NOFFs accounted for 11% more of all acute referrals during the COVID era. There were fewer overall breaches in KPIs in time to theatre in 2020 and also for those awaiting an orthogeriatric review. Time to discharge from the trust during the pandemic was improved by 54% (p < 0.00001) but patients were 51% less likely to return to their usual residence (p = 0.007). The odds ratio was significantly higher for consultant surgeon-led operations and consultant orthogeriatric-led review in the post-COVID era. There was no significant difference in using aerosol-generating anaesthetic procedures or immortality rates between both years. CONCLUSION: The impact of COVID-19 pandemic has not adversely affected the KPIs for the treatment of NOFF patients with significant improvement in numerous care domains. These findings may represent the efforts to ensure that these vulnerable patients are treated promptly to minimize their risks from the coronavirus.


Assuntos
COVID-19 , Fraturas do Quadril , Ortopedia , Idoso , COVID-19/epidemiologia , Controle de Doenças Transmissíveis , Tosse , Fraturas do Quadril/epidemiologia , Fraturas do Quadril/cirurgia , Humanos , Londres/epidemiologia , Pandemias , Estudos Retrospectivos
7.
Arch Microbiol ; 204(1): 36, 2021 Dec 20.
Artigo em Inglês | MEDLINE | ID: mdl-34927211

RESUMO

The rhizospheric microbiome is capable of changing the physio-chemical properties of its own micro-environment and found to be indispensable in the overall health of the hostplant. The interplay between the rhizospheric environment and the microbiota residing therein tune the physiology of the associated plant. In this study, we have determined how the soil properties and the host-plant remains as an important parameter for microbial community dynamics in the rhizosphere of rice and peanut. In addition to check the physio-chemical parameters of the rhizospheric soil, we have also prepared the metagenomic DNA from each rhizospheric soil followed by high-throughput sequencing and sequence analysis to predict the OTUs that represents the community structure. The alpha-diversity of the bacterial community in the RRN sample was highest, while the lowest was in PRS sample. Actinobacteria is the most predominant phylum in PRN, PRS and RRN, whereas Acidobacteria in RRS. We found a clear shift in bacterial community over the rice and peanut rhizosphere and also over these host-rhizospheres from normal and high saline region. The rhizospheric bacterial community composition found to be affected by the close-by environmental factors. Thus, the rhizospheric bacterial community structure is related to both the adjoining soil characters and the type of the hosts.


Assuntos
Oryza , Arachis , Metagenômica , Salinidade , Solo
8.
Int J Biol Macromol ; 193(Pt B): 1379-1390, 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34774593

RESUMO

Lymphatic filariasis and its associated health hazards have taken enormous tolls especially in the tropical and sub-tropical countries round the globe. Our present work contemplates the immunomodulatory role of filarial Thioredoxin reductase (TrxR) for the survival of the parasite inside the human host. For this, the protein TrxR was purified from the filarial parasite Setaria cervi and further substantiated through specific anti-TrxR antibody raised in mice. Both commercially available anti-TrxR antibody and laboratory raised antibody produced a single band with a molecular mass of ~80 kDa on western blot. The protein is optimally active at pH 7.0 and at temperature 37 °C. This protein contains both alpha helix and beta pleated sheet with selenocysteine at its active site. The Km was found to be 2.75 ± 0.49 mM. TrxR was found to downregulate lipopolysaccharide (LPS)-induced inflammation in macrophages due to inhibition of TLR4-NF-κB pathway. The result was further supported by the downregulation of inflammasome pathway and activation of alternatively activated macrophages upon TrxR treatment. Hence this study projects insights into the importance of filarial TrxR in host-parasite interface as well as it illustrates novel therapeutic strategy towards anti-filarial drug development.


Assuntos
Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Macrófagos/metabolismo , Tiorredoxina Dissulfeto Redutase/metabolismo , Tiorredoxina Dissulfeto Redutase/farmacologia , Animais , Linhagem Celular , Regulação para Baixo/efeitos dos fármacos , Proteínas de Helminto/metabolismo , Inflamação/induzido quimicamente , Lipopolissacarídeos/farmacologia , Camundongos , NF-kappa B/metabolismo , Conformação Proteica em alfa-Hélice/efeitos dos fármacos , Conformação Proteica em Folha beta/efeitos dos fármacos , Células RAW 264.7 , Setaria (Nematoide)/efeitos dos fármacos , Receptor 4 Toll-Like/metabolismo
9.
Bone Jt Open ; 2(10): 886-892, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34693724

RESUMO

AIMS: As the world continues to fight successive waves of COVID-19 variants, we have seen worldwide infections surpass 100 million. London, UK, has been severely affected throughout the pandemic, and the resulting impact on the NHS has been profound. The aim of this study is to evaluate the impact of COVID-19 on theatre productivity across London's four major trauma centres (MTCs), and to assess how the changes to normal protocols and working patterns impacted trauma theatre efficiency. METHODS: This was a collaborative study across London's MTCs. A two-month period was selected from 5 March to 5 May 2020. The same two-month period in 2019 was used to provide baseline data for comparison. Demographic information was collected, as well as surgical speciality, procedure, time to surgery, type of anaesthesia, and various time points throughout the patient journey to theatre. RESULTS: In total, 1,243 theatre visits were analyzed as part of the study. Of these, 834 patients presented in 2019 and 409 in 2020. Fewer open reduction and internal fixations were performed in 2020 (33.5% vs 38.2%), and there was an increase in the number of orthoplastic cases in 2020 (8.3% vs 2.2%), both statistically significant results (p < 0.000). There was a statistically significant increase in median time from 2019 to 2020, between sending for a patient and their arrival to the anaesthetic room (29 vs 35 minutes; p = 0.000). Median time between arrival in the anaesthetic room and commencement of anaesthetic increased (7 to 9 minutes; p = 0.104). CONCLUSION: Changes in working practices necessitated by COVID-19 led to modest delays to all aspects of theatre use, and consequently theatre efficiency. However, the reality is that the major concerns of impact of service did not occur to the levels that were expected. Cite this article: Bone Jt Open 2021;2(10):886-892.

10.
EFORT Open Rev ; 6(7): 539-544, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34377545

RESUMO

BACKGROUND: Slipped capital femoral epiphysis (SCFE) results in alterations to femoral head anatomy, predisposing patients to degenerative hip disease at a young age. Total hip arthroplasty (THA) is performed to relieve symptoms and improve function. However, it can be associated with a variable outcomes and little evidence exists on the functional outcomes, complications and revision rate following such procedures. PURPOSE: The aim of this systematic review is to determine the safety and effectiveness of performing hip arthroplasty in patients with degenerative hips secondary to SCFE. METHODOLOGY: A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A literature review was conducted of MEDLINE and Embase. Both single-arm and comparative studies were included. The outcomes of interest were functional scores, post-operative complications and revision rate. RESULTS: Six studies fit the inclusion criteria. Of these, five were retrospective single-arm studies and one was a retrospective comparative study based on registry data.All studies reported significant improvement in hip function and quality of life after THA. An overall revision rate of 11.9% was reported, occurring at a mean of 6.5 years (0.75-18.7 years).THA in patients after SCFE leads to improved functional outcomes that are comparable to patients receiving THA for osteoarthritis. The revision rate appears to be higher than is reported in patients undergoing THA for osteoarthritis at mid-term follow-up. Further prospective comparative studies are needed to evaluate the efficacy of the treatment in more detail. Cite this article: EFORT Open Rev 2021;6:539-544. DOI: 10.1302/2058-5241.6.200038.

11.
Am J Sports Med ; 49(9): 2341-2350, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34166100

RESUMO

BACKGROUND: All-inside meniscal repair is an increasingly common technique for the surgical treatment of meniscal tears. There are currently no standardized techniques for training residents in this procedure. Cognitive task analysis (CTA) is a method of analyzing and standardizing key steps in a procedure that allows training to be conducted in a validated and reproducible manner. PURPOSE: (1) To design a digital CTA teaching tool for a standardized all-inside meniscal repair. (2) To evaluate whether CTA-trained residents would perform better in a meniscal repair task compared with a control group who underwent traditional apprenticeship methods of training. STUDY DESIGN: Controlled laboratory study. METHODS: Three expert knee surgeons were interviewed using a modified Delphi method to generate a consensus among the ideal technical steps, cognitive decision points, and common errors and solutions for an all-inside meniscal repair. This written information was then combined with visual and audio components and integrated onto a digital platform to create the Imperial College London/University College London Meniscus Repair Cognitive Task Analysis (IUMeRCTA) tool. Eighteen novice residents were randomized into an intervention group (digital CTA tool) and control group (equipment instruction manual). Both groups performed an all-inside meniscal repair on high-fidelity, phantom knee models and were assessed by expert surgeons, blinded to the interventions, using a validated global rating scale (GRS). After a power calculation, median GRS scores were compared between groups using the Mann-Whitney U test; significance was set at P < .05. RESULTS: For the IUMeRCTA tool design, the procedure was divided into 55 steps across 9 phases: (1) preoperative planning, (2) theater and patient setup, (3) portal placement, (4) meniscal examination, (5) tear reduction, (6) suture planning, (7) suture insertion, (8) repair completion, and (9) postoperative care and rehabilitation. For the trial, the intervention group (mean ± SD GRS, 32 ± 2.9) performed significantly better than did the control group (GRS, 24 ± 3.3; P < .001). CONCLUSION: This is the first CTA tool to demonstrate objective benefits in training novices to perform an arthroscopic all-inside meniscal repair. CLINICAL RELEVANCE: The IUMeRCTA tool is an easily accessible and effective adjunct to traditional teaching that enhances learning the all-inside meniscal repair for novice surgeons.


Assuntos
Menisco , Cirurgiões , Artroscopia , Cognição , Humanos , Londres , Meniscos Tibiais/cirurgia , Técnicas de Sutura , Universidades
12.
Injury ; 52(11): 3420-3426, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33745697

RESUMO

INTRODUCTION: Working time regulations, senior led service delivery and increasing complexity of surgical technology has led to significant strains in surgical training. Additionally, the current COVID-19 pandemic has placed substantial limitations on surgical training worldwide. Contact free, remote, web-based, validated learning tools which are easily accessible and allows repeated, sustained practice are the need of the hour. Cognitive Task Analysis (CTA) have been used extensively to train pilots and military personnel and has shown excellent early results within orthopaedic training. We designed a femoral nailing CTA tool which showed objective benefits in the enhancement of cognitive knowledge in medical students. The aim of this study was to evaluate the effectiveness of this CTA tool to enhance practical skills in orthopaedic trainees in a real time interactive simulation setting (Distributed Interactive Simulation (DIS)). METHODS: This was a double blinded, randomized controlled trial. 14 junior orthopaedic residents who met the inclusion criteria were recruited in the study. They were randomized into two equal groups. The intervention group were given the CTA learning tool, the control group were given a standard operative technique manual used for antegrade femoral intramedullary nailing. The participants were assessed on a high-fidelity phantom femur model with actual femoral nailing instruments in a simulation mobile operating theatre where the candidate had a simulation patient, an acting anesthetist and a scrub nurse (DIS). They were assessed using the modified Objective Structured Assessment of Technical Skills (OSATS) rating scale which has been validated for orthopaedic trauma. RESULTS: The median OSATS score in the intervention group was 49 (±4.93, range 39-55) compared to 17 in the control group (±14.98, range 12-51). The median improvement was by 32 points (p = 0.02). The ICC between the two raters was 0.977. CONCLUSIONS: This study has demonstrated objective benefits of a novel femoral nailing CTA tool in the enhancement of practical skills for junior trainees in the DIS setting. This adds to the growing evidence supporting the use of CTA in orthopaedic training. This tool can be accessed remotely, is contact free and allows repeated sustained practice which is key in simulation training.


Assuntos
COVID-19 , Fixação Intramedular de Fraturas , Treinamento por Simulação , Competência Clínica , Cognição , Fêmur , Humanos , Pandemias , SARS-CoV-2
13.
J Pharm Biomed Anal ; 197: 113942, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33607503

RESUMO

The impact of metabolism upon the altered pathology of joint disease is rapidly becoming recognized as an important area of study. Synovial joint fluid is an attractive and representative biofluid of joint disease. A systemic review revealed little evidence of the metabolic stability of synovial joint fluid collection, handling or storage, despite recent reports characterizing the metabolic phenotype in joint disease. We aim to report the changes in small molecule detection within human synovial fluid (HSF) using nuclear magnetic resonance (NMR) spectroscopy at varying storage temperatures, durations and conditions. HSF was harvested by arthrocentesis from patients with isolated monoarthropathy or undergoing joint replacement (n = 30). Short-term storage (0-12 h, 4°C & 18°C) and the effect of repeated freeze-thaw cycles (-80°C to 18°C) was assessed. Long-term storage was evaluated by early (-80°C, <21days) and late analysis (-80°C, 10-12 months). 1D NMR spectroscopy experiments, NOESYGPPR1D and CPMG identified metabolites and semi-quantification was performed. Samples demonstrated broad stability to freeze-thaw cycling and refrigeration of <4 h. Short-term room temperature or refrigerated storage showed significant variation in 2-ketoisovalerate, valine, dimethylamine, succinate, 2-hydroxybutyrate, and acetaminophen glucuronide. Lipid and macromolecule detection was variable. Long-term storage demonstrated significant changes in: acetate, acetoacetate, creatine, N,N-dimethylglycine, dimethylsulfone, 3-hydroxybutyrate and succinate. Changeable metabolites during short-term storage appeared to be energy-synthesis intermediates. Most metabolites were stable for the first four hours at room temperature or refrigeration, with notable exceptions. We therefore recommend that HSF samples should be kept refrigerated for no more than 4 hours prior to freezing at -80°C. Furthermore, storage of HSF samples for 10-12 months before analysis can affect the detection of selected metabolites.


Assuntos
Manejo de Espécimes , Líquido Sinovial , Congelamento , Humanos , Espectroscopia de Ressonância Magnética , Metabolômica , Temperatura
14.
Bone Joint Res ; 10(1): 85-95, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33502243

RESUMO

AIMS: The diagnosis of joint infections is an inexact science using combinations of blood inflammatory markers and microscopy, culture, and sensitivity of synovial fluid (SF). There is potential for small molecule metabolites in infected SF to act as infection markers that could improve accuracy and speed of detection. The objective of this study was to use nuclear magnetic resonance (NMR) spectroscopy to identify small molecule differences between infected and noninfected human SF. METHODS: In all, 16 SF samples (eight infected native and prosthetic joints plus eight noninfected joints requiring arthroplasty for end-stage osteoarthritis) were collected from patients. NMR spectroscopy was used to analyze the metabolites present in each sample. Principal component analysis and univariate statistical analysis were undertaken to investigate metabolic differences between the two groups. RESULTS: A total of 16 metabolites were found in significantly different concentrations between the groups. Three were in higher relative concentrations (lipids, cholesterol, and N-acetylated molecules) and 13 in lower relative concentrations in the infected group (citrate, glycine, glycosaminoglycans, creatinine, histidine, lysine, formate, glucose, proline, valine, dimethylsulfone, mannose, and glutamine). CONCLUSION: Metabolites found in significantly greater concentrations in the infected cohort are markers of inflammation and infection. They play a role in lipid metabolism and the inflammatory response. Those found in significantly reduced concentrations were involved in carbohydrate metabolism, nucleoside metabolism, the glutamate metabolic pathway, increased oxidative stress in the diseased state, and reduced articular cartilage breakdown. This is the first study to demonstrate differences in the metabolic profile of infected and noninfected human SF, using a noninfected matched cohort, and may represent putative biomarkers that form the basis of new diagnostic tests for infected SF. Cite this article: Bone Joint Res 2021;10(1):85-95.

15.
Virology ; 552: 107-111, 2021 01 02.
Artigo em Inglês | MEDLINE | ID: mdl-33130382

RESUMO

Nisin, a food-grade antimicrobial peptide produced by lactic acid bacteria has been examined for its probable interaction with the human ACE2 (hACE2) receptor, the site where spike protein of SARS-CoV-2 binds. Among the eight nisin variants examined, nisin H, nisin Z, nisin U and nisin A showed a significant binding affinity towards hACE2, higher than that of the RBD (receptor binding domain) of the SARS-CoV-2 spike protein. The molecular interaction of nisin with hACE2 was investigated by homology modeling and docking studies. Further, binding efficiency of the most potent nisin H was evaluated through the interaction of hACE2:nisin H complex with RBD (receptor-binding domain) of SARS-CoV-2 and that of hACE2:RBD complex with nisin H. Here, nisin H acted as a potential competitor of RBD to access the hACE2 receptor. The study unravels for the first time that a globally used food preservative, nisin has the potential to bind to hACE2.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , Nisina/metabolismo , Receptores Virais/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Sequência de Aminoácidos , Enzima de Conversão de Angiotensina 2/química , Sítios de Ligação , Humanos , Modelos Moleculares , Simulação de Acoplamento Molecular , Nisina/química , Ligação Proteica , Domínios Proteicos , Receptores Virais/química , Alinhamento de Sequência , Glicoproteína da Espícula de Coronavírus/química
16.
Sci Rep ; 10(1): 14208, 2020 08 26.
Artigo em Inglês | MEDLINE | ID: mdl-32848149

RESUMO

Nanoscale mineralized collagen fibrils may be important determinants of whole-bone mechanical properties and contribute to the risk of age-related fractures. In a cross-sectional study nano- and tissue-level mechanics were compared across trabecular sections from the proximal femora of three groups (n = 10 each): ageing non-fractured donors (Controls); untreated fracture patients (Fx-Untreated); bisphosphonate-treated fracture patients (Fx-BisTreated). Collagen fibril, mineral and tissue mechanics were measured using synchrotron X-Ray diffraction of bone sections under load. Mechanical data were compared across groups, and tissue-level data were regressed against nano. Compared to controls fracture patients exhibited significantly lower critical tissue strain, max strain and normalized strength, with lower peak fibril and mineral strain. Bisphosphonate-treated exhibited the lowest properties. In all three groups, peak mineral strain coincided with maximum tissue strength (i.e. ultimate stress), whilst peak fibril strain occurred afterwards (i.e. higher tissue strain). Tissue strain and strength were positively and strongly correlated with peak fibril and mineral strains. Age-related fractures were associated with lower peak fibril and mineral strain irrespective of treatment. Indicating earlier mineral disengagement and the subsequent onset of fibril sliding is one of the key mechanisms leading to fracture. Treatments for fragility should target collagen-mineral interactions to restore nano-scale strain to that of healthy bone.


Assuntos
Envelhecimento/fisiologia , Osso e Ossos/fisiologia , Colágenos Fibrilares/fisiologia , Fraturas do Quadril/etiologia , Osteoporose/complicações , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Masculino , Nanoestruturas , Osteoporose/fisiopatologia
17.
Eur J Orthop Surg Traumatol ; 30(6): 951-954, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32591913
18.
Acta Orthop ; 91(5): 556-561, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32573331

RESUMO

Background and purpose - The COVID-19 pandemic has been recognized as an unprecedented global health crisis. This is the first observational study to evaluate its impact on the orthopedic workload in a London level 1 trauma center (i.e., a major trauma center [MTC]) before (2019) and during (2020) the "golden month" post-COVID-19 lockdown.Patients and methods - We performed a longitudinal observational prevalence study of both acute orthopedic trauma referrals, operative and anesthetic casemix for the first "golden" month from March 17, 2020. We compared the data with the same period in 2019. Statistical analyses included median (median absolute deviation), risk and odds ratios, as well as Fisher's exact test to calculate the statistical significance, set at p ≤ 0.05.Results - Acute trauma referrals in the post-COVID period were almost halved compared with 2019, with similar distribution between pediatric and adult patients, requiring a significant 19% more admissions (RR 1.3, OR 2.6, p = 0.003). Hip fractures and polytrauma cases accounted for an additional 11% of the modal number of injuries in 2020, but with 19% reduction in isolated limb injuries that were modal in 2019. Total operative cases fell by a third during the COVID-19 outbreak. There was a decrease of 14% (RR 0.85, OR 0.20, p = 0.006) in aerosol-generating anesthetic techniques used.Interpretation - The impact of the COVID-19 pandemic has led to a decline in the number of acute trauma referrals, admissions (but increased risk and odds ratio), operations, and aerosolizing anesthetic procedures since implementing social distancing and lockdown measures during the "golden month."


Assuntos
COVID-19 , Sistema Musculoesquelético/lesões , Carga de Trabalho/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Londres , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Encaminhamento e Consulta/estatística & dados numéricos , Centros de Traumatologia/estatística & dados numéricos , Ferimentos e Lesões/epidemiologia , Ferimentos e Lesões/cirurgia , Adulto Jovem
19.
Injury ; 51(7): 1642-1646, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32434715

RESUMO

Aims The aim of this study was to assess functional outcome, at medium-term follow up, in patients undergoing intra-medullary nailing of tibial shaft fractures, using the supra-patellar approach. Materials and methods The study included patients with intra-medullary nailing, for diaphysial tibia fractures, between March 2013 to August 2015. An initial audit compared short-term functional outcomes at 15 months, between the supra and infra-patellar approaches, using a cohort of 20 patients (10 in each group). Subsequently, a larger cohort of 22 patients with supra-patellar nailing, were reviewed for medium term assessment of their functional outcomes at average 60 months (50 - 78 months) and the results between all 3 groups were compared. All patients were assessed using the Kujala and Oxford Knee Scores. Results The mean age of the cohorts was 38 years (18-87years). The mean follow-up was 15 months for the initial audit and 60 months for the medium-term results. The initial audit showed that the supra-patellar group had statistically significantly better Oxford and Kujala scores when compared to infra-patellar group (p < 0.05). At 5 years following supra-patellar nailing, the medium-term cohort showed improved outcome scores compared to the infra-patellar group at 1 year (p < 0.01) but showed no difference with the supra-patellar group at 1 year (p value >0.1). Conclusion Our study suggests that patients undergoing supra-patellar tibial nailing have better outcomes at 15 months compared to traditional infra-patellar nailing and more importantly, they continue to do well even at 5 years, despite perceived risks associated with this technique.


Assuntos
Pinos Ortopédicos , Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Fraturas da Tíbia/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Articulação do Joelho/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Dor Pós-Operatória/etiologia , Dor Pós-Operatória/fisiopatologia , Radiografia , Amplitude de Movimento Articular , Recuperação de Função Fisiológica , Fraturas da Tíbia/fisiopatologia , Centros de Traumatologia , Adulto Jovem
20.
Bone Joint Res ; 9(3): 108-119, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32435463

RESUMO

AIMS: Metabolic profiling is a top-down method of analysis looking at metabolites, which are the intermediate or end products of various cellular pathways. Our primary objective was to perform a systematic review of the published literature to identify metabolites in human synovial fluid (HSF), which have been categorized by metabolic profiling techniques. A secondary objective was to identify any metabolites that may represent potential biomarkers of orthopaedic disease processes. METHODS: A systematic review was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines using the MEDLINE, Embase, PubMed, and Cochrane databases. Studies included were case series, case control series, and cohort studies looking specifically at HSF. RESULTS: The primary analysis, which pooled the results from 17 published studies and four meeting abstracts, identified over 200 metabolites. Seven of these studies (six published studies, one meeting abstract) had asymptomatic control groups and collectively suggested 26 putative biomarkers in osteoarthritis, inflammatory arthropathies, and trauma. These can broadly be categorized into amino acids plus related metabolites, fatty acids, ketones, and sugars. CONCLUSION: The role of metabolic profiling in orthopaedics is fast evolving with many metabolites already identified in a variety of pathologies. However, these results need to be interpreted with caution due to the presence of multiple confounding factors in many of the studies. Future research should include largescale epidemiological metabolic profiling studies incorporating various confounding factors with appropriate statistical analysis to account for multiple testing of the data.Cite this article: Bone Joint Res. 2020;9(3):108-119.

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