RESUMO
Phosphatidyl inositol (4,5)-bisphosphate (PI(4,5)P2) plays several key roles in human biology and the lipid kinase that produces PI(4,5)P2, PIP5K, has been hypothesized to provide a potential therapeutic target of interest in the treatment of cancers. To better understand and explore the role of PIP5K in human cancers there remains an urgent need for potent and specific PIP5K inhibitor molecules. Following a high throughput screen of the AstraZeneca collection, a novel, moderately potent and selective inhibitor of PIP5K, 1, was discovered. Detailed exploration of the SAR for this novel scaffold resulted in the considerable optimization of both potency for PIP5K, and selectivity over the closely related kinase PI3Kα, as well as identifying several opportunities for the continued optimization of drug-like properties. As a result, several high quality in vitro tool compounds were identified (8, 20 and 25) that demonstrate the desired biochemical and cellular profiles required to aid better understanding of this complex area of biology.
Assuntos
Amidas/farmacologia , Inibidores Enzimáticos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Amidas/química , Amidas/metabolismo , Animais , Células CACO-2 , Relação Dose-Resposta a Droga , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Microssomos Hepáticos/química , Microssomos Hepáticos/metabolismo , Estrutura Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Ratos , Relação Estrutura-AtividadeRESUMO
BACKGROUND: Most ergonomics studies on office workstations evaluate the effects of an intervention only by subjective measures such as musculoskeletal pain and discomfort. Limited evidence has been provided regarding risk factor reduction in office environments through standardized methods assessments. The Rapid Office Strain Assessment (ROSA) tool can provide an estimation of risk factor exposure for office workers as a means by which the outcome of interventions can be quantified. PURPOSE: The aim of the study was to evaluate if ROSA scores reflect changes in risk factors after an ergonomics intervention among office workers. METHODS: Office workers (n = 60) were divided into two groups. The experimental group received a workstation intervention and the control group received no intervention. Changes in ROSA scores were compared before and after the intervention in both groups. RESULTS: Statistically significant reductions in the ROSA final and section scores occurred after the intervention in the experimental group with (mean reduction of 2.9, 0.8 and 1.6 points for sections A, B and C, respectively). In contrast, no differences were detected in the control group (mean increase of 0.1 point for sections A and C and mean reduction of 0.1 point for Section B). CONCLUSIONS: These findings show that ROSA scores reflect changes in risk factors after an ergonomics intervention in an office environment. Consequently, this tool can be used for identifying and controlling risk factors among computer workers, before and after interventions.
Assuntos
Dor Musculoesquelética , Doenças Profissionais , Rosa , Computadores , Ergonomia/métodos , Humanos , Dor Musculoesquelética/diagnóstico , Dor Musculoesquelética/etiologia , Dor Musculoesquelética/prevenção & controle , Doenças Profissionais/diagnóstico , Doenças Profissionais/etiologia , Doenças Profissionais/prevenção & controleRESUMO
We describe the assembly and annotation of a chemogenomic set of protein kinase inhibitors as an open science resource for studying kinase biology. The set only includes inhibitors that show potent kinase inhibition and a narrow spectrum of activity when screened across a large panel of kinase biochemical assays. Currently, the set contains 187 inhibitors that cover 215 human kinases. The kinase chemogenomic set (KCGS), current Version 1.0, is the most highly annotated set of selective kinase inhibitors available to researchers for use in cell-based screens.
Assuntos
Descoberta de Drogas , Inibidores de Proteínas Quinases/química , Proteínas Serina-Treonina Quinases/química , Bibliotecas de Moléculas Pequenas/química , Humanos , Inibidores de Proteínas Quinases/uso terapêutico , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Bibliotecas de Moléculas Pequenas/uso terapêutico , Relação Estrutura-AtividadeRESUMO
Soft and rigid tissue mass prediction equations have been previously developed and validated for the segments of the upper and lower extremities in living humans using simple anthropometric measurements. The reliability of these measurements has been found to be good to excellent for all measurement types (segment lengths, circumferences, breadths, skinfolds). However, the reliability of the measurements needed to develop corresponding equations for the head, neck, and trunk has yet to be determined. The purpose of this study was to quantify the inter- and intrameasurer reliability of 34 surface anthropometric measurements of the head, neck, and trunk segments. Measurements (11 lengths, 7 circumferences, 11 breadths, 5 skinfolds) were taken twice separately on 50 healthy, university-age individuals using standard anthropometric tools. The mean inter- and intrameasurer measurement differences were fairly small overall, with 64.7% and 67.6% of the relative differences less than 5%, respectively. All measurements, except for the right lateral trunk, had intraclass correlation coefficients (ICCs) greater than 0.75, and coefficients of variation (CVs) less than 10%, indicating good reliability overall. These results are consistent with previous work for the extremities and provide support for the use of the defined surface measurements for future tissue mass prediction equation development.
Assuntos
Antropometria/métodos , Composição Corporal , Cabeça/anatomia & histologia , Pescoço/anatomia & histologia , Tronco/anatomia & histologia , Adolescente , Adulto , Fenômenos Biomecânicos , Feminino , Cabeça/fisiologia , Humanos , Masculino , Pescoço/fisiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Tronco/fisiologiaRESUMO
Accurate prediction of wobbling mass (WM), fat mass (FM), lean mass (LM), and bone mineral content (BMC) of living people using regression equations developed from anthropometric measures (lengths, circumferences, breadths, skinfolds) has previously been reported, but only for the extremities. Multiple linear stepwise regression was used to generate comparable equations for the head, neck, trunk, and pelvis of young adults (38 males, 38 females). Equations were validated using actual tissue masses from an independent sample of 13 males and 13 females by manually segmenting full-body dual-energy x-ray absorptiometry scans. Prediction equations exhibited adjusted R2 values ranging from .249 to .940, with more explained variance for LM and WM than BMC and FM, especially for the head and neck. Mean relative errors between predicted and actual tissue masses ranged from -11.07% (trunk FM) to 7.61% (neck FM). Actual and predicted tissue masses from all equations were significantly correlated (R2 = .329 to .937), except head BMC (R2 = .046). These results show promise for obtaining in-vivo head, neck, trunk, and pelvis tissue mass estimates in young adults. Further research is needed to improve head and neck FM and BMC predictions and develop tissue mass prediction equations for older populations.
Assuntos
Absorciometria de Fóton , Antropometria/métodos , Composição Corporal , Feminino , Cabeça/anatomia & histologia , Humanos , Masculino , Pescoço/anatomia & histologia , Pelve/anatomia & histologia , Valor Preditivo dos Testes , Tronco/anatomia & histologia , Adulto JovemRESUMO
The discovery and optimisation of novel, potent and selective small molecule inhibitors of the α-isoform of type III phosphatidylinositol-4-kinase (PI4Kα) are described. Lead compounds show cellular activity consistent with their PI4Kα potency inhibiting the accumulation of IP1 after PDGF stimulation and reducing cellular PIP, PIP2 and PIP3 levels. Hence, these compounds are useful in vitro tools to delineate the complex biological pathways involved in signalling through PI4Kα.
Assuntos
Inibidores Enzimáticos/síntese química , Inibidores Enzimáticos/farmacologia , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Desenho de Fármacos , Ensaios de Triagem em Larga Escala , Humanos , Fosfatos de Inositol/metabolismo , Antígenos de Histocompatibilidade Menor , Modelos Moleculares , Fator de Crescimento Derivado de Plaquetas/farmacologia , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas , Relação Estrutura-AtividadeRESUMO
Anti-glomerular basement membrane (GBM) disease is a severe inflammatory renal disorder due to pathogenic autoantibodies directed mainly against the α3 chain of type IV collagen. In ~1/4 of patients with anti-GBM disease, antineutrophil cytoplasmic antibodies (ANCA) predominantly with myeloperoxidase (MPO) specificity can be detected. Although the inciting stimuli leading to the development of an immune response against the type IV collagen and neutrophils are unknown, evidence indicates that both genetic and environmental factors play a role. Of note, molecular mimicry between self-antigens and nonself-antigens such as antigenic determinants of microorganisms has been implicated in the pathogenesis of anti-GBM disease and ANCA-associated vasculitis. A mosquito-borne viral illness highly prevalent in the tropics and subtropics, dengue can be complicated by acute renal failure, proteinuria, hematuria and glomerulonephritis. We present a 66-year-old woman who was diagnosed with dengue infection and rapidly progressive glomerulonephritis during an outbreak of dengue in Honduras in the summer of 2013. Renal biopsy revealed severe crescentic glomerulonephritis. Immunofluorescence examination demonstrated strong linear IgG deposition along glomerular capillary walls. Serologic tests demonstrated antibodies against GBM, MPO and platelet glycoproteins. The patient was diagnosed with anti-GBM disease associated with p-ANCA with MPO specificity. Despite heavy immunosuppression and plasmapheresis, IgG titers against dengue virus continued to rise confirming the diagnosis of acute dengue infection. We present the first reported case of anti-GBM disease associated with p-ANCA with MPO specificity during dengue infection. This report calls for a heightened awareness of autoimmunity leading to crescentic glomerulonephritis in patients with dengue infection.
Assuntos
Doença Antimembrana Basal Glomerular/virologia , Anticorpos Anticitoplasma de Neutrófilos/imunologia , Dengue/imunologia , Dengue/patologia , Idoso , Doença Antimembrana Basal Glomerular/imunologia , Anticorpos Anticitoplasma de Neutrófilos/sangue , Feminino , HumanosRESUMO
Quantifying soft tissue motion following impact is important in human motion analysis as soft tissues attenuate potentially injurious forces resulting from activities such as running and jumping. This study determined the reliability of leg soft tissue position and velocity following heel impacts. A grid of black dots was applied to the skin of the right leg and foot (n = 20). Dots were automatically detected (ProAnalyst(®)) from high-speed records of pendulum and drop impacts. Three trained measurers selected columns of dots on each participant for analysis; one measurer 6 months later. Between- and within-measurer differences in kinematic variables were all relatively small (<0.8 cm for position; <3.7 cm/s for velocity) between-measurers and (<0.5 cm for position; <2.6 cm/s for velocity) within-measurer. Good (coefficients of variation (CV) ≤ 10%) to acceptable (CV > 10% and ≤20%) reliability was shown for 95% of the position measures, with mean CVs of 10% and 11% within-measurers and between-measures, respectively. Velocity measures were less reliable; 40% of the measures showed good to marginal (CV > 20% and ≤30%) reliability. This study established that leg soft tissue position data from skin markers could be obtained with good to acceptable reliability following heel impacts. Velocity data were less reliable but still acceptable in many cases.
Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Extremidade Inferior/fisiologia , Movimento/fisiologia , Fenômenos Fisiológicos da Pele , Acelerometria , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Gravação em Vídeo , Adulto JovemRESUMO
This study aimed to examine the effects of sex and sport on the tissue composition of the distal lower extremity of varsity athletes, in sports that involve repetitive-impact loading patterns. Fat mass, lean mass, bone mineral content and wobbling mass were predicted for the leg and leg + foot segments of varsity basketball, cross-country, soccer and volleyball athletes. The absolute masses were normalised to body mass, and also expressed relative to each other as ratios. Females and males differed on most normalised tissue masses and ratios by 11-101%. Characteristic differences were found in the normalised tissue masses across sports, with the lowest and highest values displayed by cross-country and volleyball (female)/basketball (male) athletes, respectively. Conversely, cross-country athletes had the highest wobbling mass:bone mineral content and lean mass:bone mineral content ratios for females by 10% and 16%, respectively. The differences between sports may be explained in part by different impact loading patterns characteristic of each sport. Tissue mass ratio differences between sports may suggest that the ratios of soft to rigid tissues are optimised by the body in response to typical loading patterns, and may therefore be useful in investigations of distal lower extremity injury mechanisms in athletes.
Assuntos
Basquetebol/fisiologia , Composição Corporal/fisiologia , Extremidade Inferior/fisiologia , Futebol/fisiologia , Estresse Mecânico , Voleibol/fisiologia , Tecido Adiposo , Adolescente , Adulto , Atletas , Compartimentos de Líquidos Corporais , Densidade Óssea , Osso e Ossos , Feminino , Pé , Humanos , Perna (Membro) , Masculino , Fenômenos Fisiológicos Musculoesqueléticos , Corrida , Fatores Sexuais , Adulto JovemRESUMO
BACKGROUND: Pickleball has grown tremendously in recent years, yet little evidence exists regarding pickleball-related injuries. This scoping review extends current work on pickleball participation by identifying positive and negative health effects associated with the sport. We summarize how pickleball impacts the health and well-being of adult participants. METHODS: Searches were conducted on MEDLINE, CINAHL, ProQuest Nursing, ERIC, SPORTDiscus, PsycINFO, Scopus, CBCA Complete, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and ProQuest Dissertations and Theses. Selected studies considered aspects of health and/or well-being of adult pickleball participants. Using the population/concept/context framework, participants were healthy, able-bodied adults 18 years of age or over, who had played pickleball at least once. The positive and negative outcomes of pickleball on participants' health and well-being (concept) within the context of pickleball participation were examined. Full-text articles written in English since 2013 were included. Extracted data were tabulated, and a descriptive summary with thematic analysis was completed. RESULTS: This scoping review comprised 27 articles that met the inclusion criteria. Pickleball is promising as an exercise intervention for all adults, and there is evidence of positive social and psychological effects, and health and fitness benefits to participating in pickleball by older adults. CONCLUSIONS: Although we are still in the early stages of studying pickleball, there have been some documented health benefits of using the sport as a physical exercise intervention for adults. More research is needed on the types, prevalence, and severity of pickleball injuries and the sport's impact on younger players.
Assuntos
Esportes , Humanos , Adulto , Esportes/psicologia , Traumatismos em Atletas/psicologia , Nível de SaúdeRESUMO
INTRODUCTION: Heparin-induced thrombocytopenia (HIT) results from antibodies to PF4/heparin complexes and clinical diagnosis is difficult. We evaluated the particle immunofiltration anti-platelet factor 4 (PIFA) rapid assay, in conjunction with a clinical risk score, in the diagnosis of HIT. METHODS: We performed a prospective observational study in all patients admitted to the medical intensive care unit (MICU) in a large academic medical center. Patients were screened daily for thrombocytopenia defined as either a platelet count that decreased by at least 33% or an absolute platelet count less than 150,000/µL. Patients with suspected HIT underwent PIFA and ELISA testing for anti-PF4/heparin antibodies. Available residual frozen sera were sent to a reference laboratory for serotonin release assay (SRA) testing. RESULTS: During the study period, 340 patients were admitted to the MICU, of which 143 patients met criteria for thrombocytopenia. Forty-three patients had no evidence of recent heparin exposure. PIFA and ELISA testing were performed on 100 patients, of which 92 had samples available for SRA analysis. PIFA results were negative in 62, positive in 28 and inconclusive in 2 patients. The 4Ts score showed low to intermediate risk in 57 of the PIFA negative patients. The ELISA results were negative in 86 and positive in 6 patients. SRA testing identified 3 patients with a positive SRA test and 89 patients with a negative result. All patients with a negative PIFA result also had a negative SRA result. In the one patient deemed to have clinical HIT, the pretest probability was high (4Ts score of 6) and the anti-PF4/heparin antibody testing revealed a positive SRA, inconclusive PIFA and a negative ELISA result. CONCLUSIONS: While thrombocytopenia in our population is common, the prevalence of HIT is low. The combination of a low to intermediate pretest probability with a negative PIFA test can rapidly exclude the presence of platelet activating anti-PF4/heparin antibodies and, therefore, HIT as the cause of the thrombocytopenia. Since a positive PIFA result has a low positive predictive value, a positive PIFA is not diagnostic of HIT and additional evaluation is warranted.
Assuntos
Filtração/métodos , Unidades de Terapia Intensiva , Fator Plaquetário 4/sangue , Trombocitopenia/sangue , Trombocitopenia/diagnóstico , Adulto , Idoso , Ensaio de Imunoadsorção Enzimática/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Fator Plaquetário 4/imunologia , Estudos Prospectivos , Trombocitopenia/imunologiaRESUMO
The purpose of this preliminary investigation was to determine the relative role of the distal lower extremity tissue masses of varsity athletes in predicting distal lower extremity injury sustained during a competitive season. One hundred male and female varsity athletes (basketball, volleyball, soccer, cross country) completed a questionnaire on general health, physiological, and psychosocial variables, during each sport's respective training camp. A series of anthropometric measurements were used as inputs to distal lower extremity tissue mass prediction equations to calculate lean mass, fat mass, bone mineral content and wobbling mass (lean mass + fat mass) and tissue mass ratios. Athletes were monitored throughout their respective seasons and were instructed to report any distal lower extremity injuries to a certified athletic therapist who was responsible for assessing and confirming the reports. Logistic regression analyses were performed to determine which variables significantly predicted distal lower extremity injury. Mean leg fat mass:bone mass (OR = 1.6, CI = 1.0 - 2.5), and competition surface (rubber OR = 8.5, CI = 1.5 - 47.7; artificial turf OR = 4.0, CI = 0.77 - 22.9) were identified as significant predictors of injury. Overall, tibia bone injuries were significantly associated with the ratio of fat mass:bone mineral content and the surface on which the athletes compete.
Assuntos
Tecido Adiposo , Traumatismos em Atletas/etiologia , Composição Corporal/fisiologia , Densidade Óssea , Perna (Membro)/fisiologia , Esportes/fisiologia , Tíbia/lesões , Adolescente , Adulto , Basquetebol/lesões , Basquetebol/fisiologia , Canadá , Intervalos de Confiança , Feminino , Humanos , Modelos Logísticos , Masculino , Razão de Chances , Futebol/lesões , Futebol/fisiologia , Inquéritos e Questionários , Universidades , Voleibol/lesões , Voleibol/fisiologia , Adulto JovemRESUMO
Soft tissues overlying the hip play a critical role in protecting against fractures during fall-related hip impacts. Consequently, the development of an efficient and cost-effective method for estimating hip soft tissue thicknesses in living people may prove to be valuable for assessing an individual's injury risk and need to adopt preventative measures. The present study used multiple linear stepwise regression to generate prediction equations from participant characteristics (i.e., height, sex) and anthropometric measurements of the pelvis, trunk, and thigh to estimate soft tissue thickness at the iliac crests (IC) and greater trochanters (GT) in younger (16-35 years of age: 37 males, 37 females) and older (36-65 years of age: 38 males, 38 females) adults. Equations were validated against soft tissue thicknesses measured from full body Dual-energy X-ray Absorptiometry scans of independent samples (younger: 13 males, 13 females; older: 13 males, 12 females). Younger adult prediction equations exhibited adjusted R2 values ranging from 0.704 to 0.791, with more explained variance for soft tissue thicknesses at the GT than the IC; corresponding values for the older adult equations were higher overall and ranged from 0.819 to 0.852. Predicted and actual soft tissue thicknesses were significantly correlated for both the younger (R2 = 0.466 to 0.738) and older (R2 = 0.842 to 0.848) adults, averaging ≤ 0.75cm of error. This research demonstrates that soft tissue thicknesses overlying the GT and IC can be accurately predicted from equations using anthropometric measurements. These equations can be used by clinicians to identify individuals at higher risk of hip fractures who may benefit from the use of preventative measures.
Assuntos
Fêmur , Ílio , Masculino , Feminino , Humanos , Idoso , Adulto , Antropometria/métodos , Absorciometria de Fóton/métodos , Coxa da Perna , Composição CorporalRESUMO
Synthetic biology applications would benefit from protein modules of reduced complexity that function orthogonally to cellular components. As many subcellular processes depend on peptide-protein or protein-protein interactions, de novo designed polypeptides that can bring together other proteins controllably are particularly useful. Thanks to established sequence-to-structure relationships, helical bundles provide good starting points for such designs. Typically, however, such designs are tested in vitro and function in cells is not guaranteed. Here, we describe the design, characterization, and application of de novo helical hairpins that heterodimerize to form 4-helix bundles in cells. Starting from a rationally designed homodimer, we construct a library of helical hairpins and identify complementary pairs using bimolecular fluorescence complementation in E. coli. We characterize some of the pairs using biophysics and X-ray crystallography to confirm heterodimeric 4-helix bundles. Finally, we demonstrate the function of an exemplar pair in regulating transcription in both E. coli and mammalian cells.
Assuntos
Escherichia coli , Biologia Sintética , Animais , Escherichia coli/genética , Peptídeos/química , Proteínas/química , MamíferosRESUMO
Over the course of the COVID-19 pandemic, SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and immune escape capabilities, such as Delta and Omicron, have triggered waves of new COVID-19 infections worldwide, and Omicron subvariants continue to represent a global health concern. Tracking the prevalence and dynamics of VOCs has clinical and epidemiological significance and is essential for modeling the progression and evolution of the COVID-19 pandemic. Next generation sequencing (NGS) is recognized as the gold standard for genomic characterization of SARS-CoV-2 variants, but it is labor and cost intensive and not amenable to rapid lineage identification. Here we describe a two-pronged approach for rapid, cost-effective surveillance of SARS-CoV-2 VOCs by combining reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) and periodic NGS with the ARTIC sequencing method. Variant surveillance by RT-qPCR included the commercially available TaqPath COVID-19 Combo Kit to track S-gene target failure (SGTF) associated with the spike protein deletion H69-V70, as well as two internally designed and validated RT-qPCR assays targeting two N-terminal-domain (NTD) spike gene deletions, NTD156-7 and NTD25-7. The NTD156-7 RT-qPCR assay facilitated tracking of the Delta variant, while the NTD25-7 RT-qPCR assay was used for tracking Omicron variants, including the BA.2, BA.4, and BA.5 lineages. In silico validation of the NTD156-7 and NTD25-7 primers and probes compared with publicly available SARS-CoV-2 genome databases showed low variability in regions corresponding to oligonucleotide binding sites. Similarly, in vitro validation with NGS-confirmed samples showed excellent correlation. RT-qPCR assays allow for near-real-time monitoring of circulating and emerging variants allowing for ongoing surveillance of variant dynamics in a local population. By performing periodic sequencing of variant surveillance by RT-qPCR methods, we were able to provide ongoing validation of the results obtained by RT-qPCR screening. Rapid SARS-CoV-2 variant identification and surveillance by this combined approach served to inform clinical decisions in a timely manner and permitted better utilization of sequencing resources.
Assuntos
COVID-19 , Laboratórios Clínicos , Humanos , SARS-CoV-2/genética , Florida , Pandemias , COVID-19/diagnóstico , COVID-19/epidemiologia , Sequenciamento de Nucleotídeos em Larga EscalaRESUMO
Measuring a bone's response to impact has traditionally been done using strain gauges that are attached directly to the bone. Accelerometers have also been used for this purpose because they are reusable, inexpensive and can be attached easily. However, little data are available relating measured accelerations to bone injury, or to judge if accelerometers are reasonable surrogates for strain gauges in terms of their capacity to predict bone injuries. Impacts were applied with a custom designed pneumatic impact system to eight fresh-frozen human cadaveric radius specimens. Impacts were repeatedly applied with increasing energy until ultimate failure occurred. Three multiaxial strain gauge rosettes were glued to the bone (two distally and one proximally). Two multiaxial accelerometers were attached to the distal dorsal and proximal volar aspects of the radius. Overall, peak minimum and maximum principal strains were calculated from the strain-time curves from each gauge. Peak accelerations and acceleration rates were measured parallel (axial) and perpendicular (off-axis) to the long axis of the radius. Logistic generalized estimating equations were used to create strain and acceleration-based injury prediction models. To develop strain prediction models based on the acceleration variables, Linear generalized estimating equations were employed. The logistic models were assessed according to the quasi-likelihood under independence model criterion (QIC), while the linear models were assessed by the QIC and the marginal R(2). Peak axial and off-axis accelerations increased significantly (with increasing impact energy) across all impact trials. The best injury prediction model (QIC = 9.42) included distal resultant acceleration (p < 0.001) and donor body mass index (BMI) (p < 0.001). Compressive and tensile strains were best predicted by separate uni-variate models, including peak distal axial acceleration (R(2 )= 0.79) and peak off-axis acceleration (R(2 )= 0.79), respectively. Accelerometers appear to be a valid surrogate to strain gauges for measuring the general response of the bone to impact and predicting the probability of bone injury.
Assuntos
Acelerometria/métodos , Teste de Materiais/métodos , Rádio (Anatomia)/lesões , Estresse Mecânico , Humanos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Fraturas do RádioRESUMO
Previous forward fall simulation methods have provided good kinematic and kinetic data, but are limited in that they have started the falls from a stationary position and have primarily simulated uni-directional motion. Therefore, a novel Propelled Upper Limb fall ARest Impact System (PULARIS) was designed to address these issues during assessments of a variety of fall scenarios. The purpose of this study was to present PULARIS and evaluate its ability to impact the upper extremities of participants with repeatable velocities, hand forces and hip angles in postures and with vertical and horizontal motion consistent with forward fall arrest. PULARIS consists of four steel tubing crossbars in a scissor-like arrangement that ride on metal trolleys within c-channel tracks in the ceiling. Participants are suspended beneath PULARIS by the legs and torso in a prone position and propelled horizontally via a motor and chain drive until they are quick released, and then impact floor-mounted force platforms with both hands. PULARIS velocity, hip angles and velocities and impact hand forces of ten participants (five male, five female) were collected during three fall types (straight-arm, self-selected and bent-arm) and two fall heights (0.05 m and 0.10 m) to assess the reliability of the impact conditions provided by the system. PULARIS and participant hip velocities were found to be quite repeatable (mean ICC = 0.81) with small between trial errors (mean = 0.03 m/s). The ratio of horizontal to vertical hip velocity components (~0.75) agreed well with previously reported data (0.70-0.80). Peak vertical hand impact forces were also found to be relatively consistent between trials with a mean ICC of 0.73 and mean between trial error of 13.4 N. Up to 83% of the horizontal hand impact forces displayed good to excellent reliability (ICC > 0.6) with small between trial differences. Finally, the ICCs for between trial hip angles were all classified as good to excellent. Overall, PULARIS is a reliable method and is appropriate for studying the response of the distal upper extremity to impact loading during non-stationary, multi-directional movements indicative of a forward fall. This system performed well at different fall heights, and allows for a variety of upper and lower extremity, and hip postures to be tested successfully in different landing scenarios consistent with elderly and sport-related falls.
Assuntos
Acidentes por Quedas , Biomimética/instrumentação , Quadril , Fenômenos Mecânicos , Extremidade Superior , Fenômenos Biomecânicos , Feminino , Humanos , Laboratórios , Masculino , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Observation-based posture assessment methods (e.g. RULA, 3DMatch) require classification of body postures into categories. This study investigated the effect of improving posture category salience (adding borders, shading and colour to the posture categories) on posture selection error rates and decision times of novice analysts. Ninety university students with normal or corrected normal visual acuity and who were not colourblind, were instructed to select posture categories as quickly and accurately as possible, in five salience conditions (Plain (no border, no shading, no colour); Grey Border; Red Border; Grey Shading (GS) and Red Shading (RS)) for images presented in randomised blocks (240 classifications made by each participant) on a computer interface. Participants responded quickest in the Border conditions, classifying postures about 5% faster than in the Plain condition. Coloured diagrams significantly reduced posture classification errors by approximately 1.5%. Overall, the best performance, based on both error rate and decision time combined, resulted from incorporating a Grey Border to the posture category diagrams; a simple enhancement that could be made to most current observation-based posture assessment tools. PRACTITIONER SUMMARY: The salience of posture diagrams used in observation-based posture assessment tools was evaluated with respect to analyst error rates and decision times. The best performance resulted from incorporating a grey border to the posture diagrams; a simple enhancement that can be made to most current observation-based posture assessment tools.
Assuntos
Tomada de Decisões , Postura , Percepção Visual , Adolescente , Adulto , Feminino , Humanos , Masculino , Tempo de Reação , Adulto JovemRESUMO
To date, there has not been a direct examination of the effect that tissue composition (lean mass/muscle, fat mass, bone mineral content) differences between males and females has on how the tibia responds to impacts similar to those seen during running. To evaluate this, controlled heel impacts were imparted to 36 participants (6 M and 6 F in each of low, medium and high percent body fat [BF] groups) using a human pendulum. A skin-mounted accelerometer medial to the tibial tuberosity was used to determine the tibial response parameters (peak acceleration, acceleration slope and time to peak acceleration). There were no consistent effects of BF or specific tissue masses on the un-normalized tibial response parameters. However, females experienced 25% greater peak acceleration than males. When normalized to lean mass, wobbling mass, and bone mineral content, females experienced 50%, 62% and 70% greater peak acceleration, respectively, per gram of tissue than males. Higher magnitudes of lean mass and bone mass significantly contributed to decreased acceleration responses in general.
Assuntos
Aceleração , Tecido Adiposo/fisiologia , Perna (Membro)/fisiologia , Tíbia/fisiologia , Actigrafia , Análise de Variância , Composição Corporal/fisiologia , Feminino , Humanos , Masculino , Músculo Esquelético/fisiologia , Fatores Sexuais , Estatística como Assunto , Adulto JovemRESUMO
The design of completely synthetic proteins from first principles-de novo protein design-is challenging. This is because, despite recent advances in computational protein-structure prediction and design, we do not understand fully the sequence-to-structure relationships for protein folding, assembly, and stabilization. Antiparallel 4-helix bundles are amongst the most studied scaffolds for de novo protein design. We set out to re-examine this target, and to determine clear sequence-to-structure relationships, or design rules, for the structure. Our aim was to determine a common and robust sequence background for designing multiple de novo 4-helix bundles. In turn, this could be used in chemical and synthetic biology to direct protein-protein interactions and as scaffolds for functional protein design. Our approach starts by analyzing known antiparallel 4-helix coiled-coil structures to deduce design rules. In terms of the heptad repeat, abcdefg -i.e., the sequence signature of many helical bundles-the key features that we identify are: a = Leu, d = Ile, e = Ala, g = Gln, and the use of complementary charged residues at b and c. Next, we implement these rules in the rational design of synthetic peptides to form antiparallel homo- and heterotetramers. Finally, we use the sequence of the homotetramer to derive in one step a single-chain 4-helix-bundle protein for recombinant production in E. coli. All of the assembled designs are confirmed in aqueous solution using biophysical methods, and ultimately by determining high-resolution X-ray crystal structures. Our route from peptides to proteins provides an understanding of the role of each residue in each design.