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1.
Clin Radiol ; 75(9): 705-708, 2020 09.
Article in English | MEDLINE | ID: mdl-32600651

ABSTRACT

AIM: To report on a snap audit of all departments in the UK as to the value of preoperative thoracic imaging, preferably computed tomography (CT), of patients undergoing any surgery to assess for changes consistent with COVID-19 preoperatively. MATERIALS AND METHODS: All Imaging departments in the UK were contacted and asked to record the number of preoperative CT examinations performed in patients being considered for both emergency and elective surgical intervention over a 5-day period in May 2020. RESULTS: Forty-seven percent of departments replied with data provided on >820 patients. Nineteen percent of additional preoperative CT was in patients undergoing elective intervention and 81% in patients presenting with surgical abdominal pain. There was a high rate of false positives in patients who tested negative for COVID-19, producing a sensitivity for thoracic CT of 68.4%. CONCLUSION: This UK-wide audit demonstrates that a large number of additional thoracic imaging examinations over a 5-day period were performed with a low sensitivity for the identification of COVID-19 in this preoperative group of patients. Given these findings, it is difficult to justify this additional examination in this group of patients.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnostic imaging , Medical Audit/methods , Pneumonia, Viral/diagnostic imaging , Preoperative Care/methods , Surgical Procedures, Operative , Tomography, X-Ray Computed/methods , COVID-19 , Humans , Lung/diagnostic imaging , Medical Audit/statistics & numerical data , Pandemics , Prospective Studies , Radiography, Thoracic , Reproducibility of Results , SARS-CoV-2 , Sensitivity and Specificity , United Kingdom
2.
BMC Genomics ; 19(1): 687, 2018 Sep 19.
Article in English | MEDLINE | ID: mdl-30231878

ABSTRACT

BACKGROUND: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs. RESULTS: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds. CONCLUSION: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.


Subject(s)
Body Size , Chromosomes , Polymorphism, Single Nucleotide , Selection, Genetic , Sequence Analysis, DNA/veterinary , Whole Genome Sequencing/methods , Animals , Female , Haplotypes , Male , Molecular Sequence Annotation , Phenotype , Phylogeny , Quantitative Trait Loci , Swine , Swine, Miniature
4.
Anim Genet ; 49(1): 90-93, 2018 Feb.
Article in English | MEDLINE | ID: mdl-29333704

ABSTRACT

Humans have shaped the population history of the horse ever since domestication about 5500 years ago. Comparative analyses of the Y chromosome can illuminate the paternal origin of modern horse breeds. This may also reveal different breeding strategies that led to the formation of extant breeds. Recently, a horse Y-chromosomal phylogeny of modern horses based on 1.46 Mb of the male-specific Y (MSY) was generated. We extended this dataset with 52 samples from five European, two American and seven Asian breeds. As in the previous study, almost all modern European horses fall into a crown group, connected via a few autochthonous Northern European lineages to the outgroup, the Przewalski's Horse. In total, we now distinguish 42 MSY haplotypes determined by 158 variants within domestic horses. Asian horses show much higher diversity than previously found in European breeds. The Asian breeds also introduce a deep split to the phylogeny, preliminarily dated to 5527 ± 872 years. We conclude that the deep splitting Asian Y haplotypes are remnants of a far more diverse ancient horse population, whose haplotypes were lost in other lineages.


Subject(s)
Horses/genetics , Animals , Domestication , Horses/classification , Male , Phylogeny , Y Chromosome
5.
Osteoporos Int ; 28(4): 1255-1263, 2017 04.
Article in English | MEDLINE | ID: mdl-27909781

ABSTRACT

We sought to determine whether low-magnitude mechanical stimulation (LMMS) normalizes bone turnover among adolescents hospitalized for anorexia nervosa (AN). Brief, daily LMMS prevents the decline in bone turnover typically seen during bed rest in AN. LMMS may have application for patients with AN in the inpatient setting to protect bone health. INTRODUCTION: Malnourished adolescents with AN requiring medical hospitalization are at high risk for rapid reduction in skeletal quality. Even short-term bed rest can suppress normal patterns of bone turnover. We sought to determine whether LMMS normalizes bone turnover among adolescents hospitalized for complications of AN. METHODS: In this randomized, double-blind trial, we prospectively enrolled adolescent females (n = 41) with AN, age 16.3 ± 1.9 years (mean ± SD) and BMI 15.6 ± 1.7 kg/m2. Participants were randomized to stand on a platform delivering LMMS (0.3 g at 32-37 Hz) or placebo platform for 10 min/day for 5 days. Serum markers of bone formation [bone-specific alkaline phosphatase (BSAP)], turnover [osteocalcin (OC)], and bone resorption [serum C-telopeptides (CTx)] were measured. From a random coefficients model, we constructed estimates and confidence intervals for all outcomes. RESULTS: BSAP decreased by 2.8% per day in the placebo arm (p = 0.03) but remained stable in the LMMS group (p = 0.51, pdiff = 0.04). CTx did not change with placebo (p = 0.56) but increased in the LMMS arm (+6.2% per day, p = 0.04; pdiff = 0.01). Serum OC did not change in either group (p > 0.70). CONCLUSIONS: Bed rest during hospitalization for patients with AN is associated with a suppression of bone turnover, which may contribute to diminished bone quality. Brief, daily LMMS prevents a decline in bone turnover during bed rest in AN. Protocols prescribing strict bed rest may not be appropriate for protecting bone health for these patients. LMMS may have application for these patients in the inpatient setting.


Subject(s)
Anorexia Nervosa/complications , Bone Remodeling/physiology , Osteoporosis/etiology , Osteoporosis/prevention & control , Vibration/therapeutic use , Adolescent , Anorexia Nervosa/physiopathology , Bed Rest/adverse effects , Biomarkers/blood , Double-Blind Method , Female , Hospitalization , Humans , Osteoporosis/physiopathology , Physical Stimulation/methods , Young Adult
6.
Ann Hematol ; 96(6): 919-927, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28062906

ABSTRACT

Myeloproliferative neoplasms (MPNs) are clonal hematopoietic diseases that belong to the spectrum of myeloid malignancies (MyMs), which also include myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelogenous leukemia (CML). While hematopoietic stem cell transplantation (HSCT) is a potentially curative therapeutic approach to many MyMs, the associated morbidity and mortality have necessitated the development of non-HSCT therapeutics for symptom management and disease course modification. Immune checkpoint inhibition, in particular along the programmed cell death protein 1 (PD-1)/B7-H1 (PD-L1) axis, is an established strategy in solid tumors with potential as an adjunctive therapy in hematologic malignancies. Seminal studies suggest that the pro-inflammatory microenvironment of MyMs can suppress T lymphocyte-mediated immunity via PD-1 signaling and that response to mainstay epigenetic therapies for MyMs may be governed by PD-1 gene regulation. Although the role of PD-1 signaling in MPN pathogenesis and progression is as yet unclear, research in MPN patients has revealed expansion of myeloid-derived suppressor cells (MDSCs), which may effect host immune tolerance of tumor via temporally and spatially specific activation of PD-1/PD-L1 signaling. The current understanding of immune dysfunction in MPNs and analogous MyMs offers a compelling rationale to study PD-1/PD-L1 inhibition in patients as a novel treatment option.


Subject(s)
B7-H1 Antigen/metabolism , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/metabolism , Leukemia, Myeloid/metabolism , Myelodysplastic Syndromes/metabolism , Programmed Cell Death 1 Receptor/metabolism , Acute Disease , Antibodies, Monoclonal/therapeutic use , Humans , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/drug therapy , Leukemia, Myelogenous, Chronic, BCR-ABL Positive/pathology , Leukemia, Myeloid/drug therapy , Leukemia, Myeloid/pathology , Molecular Targeted Therapy/methods , Molecular Targeted Therapy/trends , Myelodysplastic Syndromes/drug therapy , Myelodysplastic Syndromes/pathology , Signal Transduction/drug effects
7.
Anim Genet ; 48(5): 551-559, 2017 Oct.
Article in English | MEDLINE | ID: mdl-28741731

ABSTRACT

A previous study revealed a strong association between the DMRT3:Ser301STOP mutation in horses and alternate gaits as well as performance in harness racing. Several follow-up studies have confirmed a high frequency of the mutation in gaited horse breeds and an effect on gait quality. The aim of this study was to determine when and where the mutation arose, to identify additional potential causal mutations and to determine the coalescence time for contemporary haplotypes carrying the stop mutation. We utilized sequences from 89 horses representing 26 breeds to identify 102 SNPs encompassing the DMRT3 gene that are in strong linkage disequilibrium with the stop mutation. These 102 SNPs were genotyped in an additional 382 horses representing 72 breeds, and we identified 14 unique haplotypes. The results provided conclusive evidence that DMRT3:Ser301STOP is causal, as no other sequence polymorphisms showed an equally strong association to locomotion traits. The low sequence diversity among mutant chromosomes demonstrated that they must have diverged from a common ancestral sequence within the last 10 000 years. Thus, the mutation occurred either just before domestication or more likely some time after domestication and then spread across the world as a result of selection on locomotion traits.


Subject(s)
Evolution, Molecular , Gait/genetics , Haplotypes , Horses/genetics , Transcription Factors/genetics , Animals , Breeding , Codon, Terminator/genetics , DNA Mutational Analysis , Linkage Disequilibrium , Mutation , Phenotype , Polymorphism, Single Nucleotide
8.
Osteoporos Int ; 27(2): 747-56, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26323329

ABSTRACT

UNLABELLED: Ovariectomized mice were used to assess the ability of low-intensity vibrations to protect bone microarchitecture and marrow composition. Results indicate that low-intensity vibrations (LIV), introduced 2 weeks postsurgery, slows marrow adipogenesis in OVX mice but does not restore the bone within the period studied. However, immediate application of LIV partially protects quality. INTRODUCTION: The aim of this study was to evaluate consequences of estrogen depletion on bone marrow (BM) phenotype and bone microarchitecture, and effects of mechanical signals delivered as LIV on modulating these changes. METHODS: LIV (0.3 g, 90 Hz) was applied to C57BL/6 mice immediately following ovariectomy or 2 weeks postestrogen withdrawal for 2 (ST-LIV) or 6 weeks (LT-LIV), respectively. Sham-operated age-matched controls (ST-AC, LT-AC) and ovariectomized controls (ST-OVX, LT-OVX) received sham LIV treatment. Bone microstructure was evaluated through µCT and BM adipogenesis through histomorphometry, serum markers, and genes expression analysis. RESULTS: LT-OVX increased BM adipogenesis relative to LT-AC (+136 %, p ≤ 0.05), while LT-LIV introduced for 6w suppressed this adipose encroachment (-55 %, p ≤ 0.05). In parallel with the fatty marrow, LT-OVX showed a marked loss of trabecular bone, -40 % (p ≤ 0.05) in the first 2 weeks following ovariectomy compared to LT-AC. Application of LT-LIV for 6w following this initial 2w bone loss failed to restore the lost trabeculae but did initiate an anabolic response as indicated by increased serum alkaline phosphatase (+26 %, p ≤ 0.05). In contrast, application of LIV immediately following ovariectomy was more efficacious in the protection of trabecular bone, with a +29 % (p > 0.05) greater BV/TV compared to ST-OVX at the 2w time period. CONCLUSIONS: LIV can mitigate adipocyte accumulation in OVX marrow and protect it by favoring osteoblastogenesis over adipogenesis. These data also emphasize the rapidity of bone loss with OVX and provide perspective in the timing of treatments for postmenopausal osteoporosis where sooner is better than later.


Subject(s)
Adipogenesis/physiology , Bone Marrow/pathology , Osteoporosis, Postmenopausal/prevention & control , Vibration/therapeutic use , Adipocytes/pathology , Animals , Estrogens/deficiency , Female , Humans , Mice, Inbred C57BL , Osteoblasts/physiology , Ovariectomy , Time Factors , Weight Gain/physiology , X-Ray Microtomography/methods
9.
Eur J Clin Microbiol Infect Dis ; 34(8): 1603-13, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25972251

ABSTRACT

Data on community-associated (CA) methicillin-resistant Staphylococcus aureus (MRSA) in Israel are scarce. The objective of this study was to characterize the major CA-MRSA clones in Israel. All clinical MRSA isolates detected in the community during a period of 2.5 years (2011-2013) from individuals insured by a major health maintenance organization in Israel were collected, with additional data from medical records. Antibiotic susceptibility patterns and staphylococcal chromosomal cassette mec (SCCmec) typing were determined. SCCmec IV and V isolates were further typed by pulsed-field gel electrophoresis (PFGE), spa typing, and detection of a panel of toxin genes. MRSA were detected in 280 patients, mostly from skin infections. Patients with SCCmec IV (n = 120, 43 %) were younger (p < 0.0001) and reported less contact with healthcare facilities. Almost all isolates were trimethoprim-sulfamethoxazole susceptible (98 %). spa-CC032, a typical nosocomial MRSA clone, accounted for 28 % of SCCmec IV. The two major CA-MRSA clones were t008 USA300 (13 %) and t991 (10 %); t991 was isolated mainly from children (75 %), was Panton-Valentine leukocidin (PVL) negative but eta-positive, and was typically susceptible to most antibiotic groups. PVL-positive strains (n = 31) included mainly USA300 (52 %) and t019 (13 %). While multiple genetic lineages were evident among community-onset MRSA in Israel, approximately 20 % are typical CA-MRSA clones, mainly USA300 and a local clone, t991.


Subject(s)
Community-Acquired Infections/epidemiology , Genotype , Methicillin-Resistant Staphylococcus aureus/classification , Methicillin-Resistant Staphylococcus aureus/isolation & purification , Molecular Typing , Staphylococcal Infections/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Community-Acquired Infections/microbiology , Drug Resistance, Bacterial , Female , Genetic Variation , Humans , Infant , Israel/epidemiology , Male , Methicillin-Resistant Staphylococcus aureus/genetics , Microbial Sensitivity Tests , Middle Aged , Molecular Epidemiology , Prospective Studies , Staphylococcal Infections/microbiology , Young Adult
10.
Mol Ecol ; 23(9): 2275-86, 2014 May.
Article in English | MEDLINE | ID: mdl-24655072

ABSTRACT

Sexual selection and the ornaments that inform such choices have been extensively studied, particularly from a phenotypic perspective. Although more is being revealed about the genetic architecture of sexual ornaments, much still remains to be discovered. The comb of the chicken is one of the most widely recognized sexual ornaments, which has been shown to be correlated with both fecundity and bone allocation. In this study, we use a combination of multiple intercrosses between White Leghorn populations and wild-derived Red Junglefowl to, first, map quantitative trait loci (QTL) for bone allocation and, second, to identify expression QTL that correlate and colocalize with comb mass. These candidate quantitative genes were then assessed for potential pleiotropic effects on bone tissue and fecundity traits. We identify genes that correlate with both relative comb mass and bone traits suggesting a combination of both pleiotropy and linkage mediates gene regulatory variation in these traits.


Subject(s)
Bone and Bones/anatomy & histology , Chickens/anatomy & histology , Chickens/genetics , Comb and Wattles/anatomy & histology , Genetic Linkage , Genetic Pleiotropy , Quantitative Trait Loci , Animals , Chromosome Mapping , Crosses, Genetic , Female , Fertility/genetics , Male , Phenotype
11.
Disabil Rehabil ; 45(6): 1063-1078, 2023 03.
Article in English | MEDLINE | ID: mdl-35352609

ABSTRACT

PURPOSE: Primary progressive aphasia (PPA) is a language-led dementia associated with Alzheimer's pathology and fronto-temporal lobar degeneration. Multiple tailored speech and language interventions have been developed for people with PPA. Speech and language therapists/speech-language pathologists (SLT/Ps) report lacking confidence in identifying the most pertinent interventions options relevant to their clients living with PPA during their illness trajectory. MATERIALS AND METHODS: The aim of this study was to establish a consensus amongst 15 clinical-academic SLT/Ps on best practice in selection and delivery of speech and language therapy interventions for people with PPA. An online nominal group technique (NGT) and consequent focus group session were held. NGT rankings were aggregated and focus groups video recorded, transcribed, and reflexive thematic analysis undertaken. RESULTS: The results of the NGT identified 17 items. Two main themes and seven further subthemes were identified in the focus groups. The main themes comprised (1) philosophy of person-centredness and (2) complexity. The seven subthemes were knowing people deeply, preventing disasters, practical issues, professional development, connectedness, barriers and limitations, and peer support and mentoring towards a shared understanding. CONCLUSIONS: This study describes the philosophy of expert practice and outlines a set of best practice principles when working with people with PPA.Implications for rehabilitationPrimary progressive aphasia (PPA) describes a group of language led dementias which deteriorate inexorably over time.Providing speech and language therapy for people with PPA is complex and must be person centred and bespoke.This study describes the philosophy of expert practice and outlines a set of best practice principles for speech and language therapists/pathologists working with people with people with PPA.


Subject(s)
Aphasia, Primary Progressive , Language Therapy , Humans , Language Therapy/methods , Speech , Consensus , Aphasia, Primary Progressive/therapy , Philosophy
12.
Psychol Med ; 42(12): 2579-89, 2012 Dec.
Article in English | MEDLINE | ID: mdl-22717026

ABSTRACT

BACKGROUND: It is unclear whether pubertal status or timing of puberty explains the increase in depressive symptoms in girls during adolescence. METHOD: This is a longitudinal study based on 2506 girls from the Avon Longitudinal Study of Parents and Children (ALSPAC). Self-reported depressive symptoms at 10.5, 13 and 14 years were assessed using the Short Mood and Feelings Questionnaire (SMFQ). Pubertal status (Tanner breast and pubic hair stage) and timing of menarche were derived from questionnaires administered from age 8 to 14 years. We used multivariable regression models to examine the relative contributions of pubertal status and timing in accounting for increases in level of depressive symptoms at 14 years. RESULTS: With increasing age, the association between breast development and depressive symptoms strengthened. Pubertal status (breast stage), rather than timing of menarche, was independently associated with depressive symptoms at 14 years. There was strong evidence for a linear relationship between breast stage and depressive symptoms at 14 years [increase in 0.17 S.D. (range 0.10-0.24) of depressive symptoms for advancement of each breast stage]. CONCLUSIONS: Depressive symptoms in mid-adolescence were more strongly influenced by breast stage than timing of menarche. This could imply that the female rise in depression during adolescence is due to increasing estrogen levels, and might explain why the gender difference in rates of depression emerges at this stage. Future research should be aimed at identifying the mechanism of action of pubertal change, including direct effects of pubertal hormones and indirect effects mediated by psychosocial factors.


Subject(s)
Depressive Disorder/epidemiology , Depressive Disorder/psychology , Puberty/psychology , Adolescent , Case-Control Studies , Child , Cohort Studies , Depressive Disorder/diagnosis , Female , Humans , Longitudinal Studies , Menarche/psychology , Risk Factors , Social Environment , Statistics as Topic , Surveys and Questionnaires , United Kingdom
13.
Reprod Domest Anim ; 47 Suppl 1: 31-6, 2012 Jan.
Article in English | MEDLINE | ID: mdl-22212210

ABSTRACT

Onset of sexual maturation is a trait of extreme importance both evolutionarily and economically. Unsurprisingly therefore, domestication has acted to reduce the time to sexual maturation in a variety of animals, including the chicken. In comparison with wild progenitor chickens [the Red Junglefowl (RJF)], domestic layer hens attain maturity approximately 20% earlier. In addition, domestic layers also possess larger combs (a sexual ornament), produce more eggs and have denser bones. A large quantitative trait loci (QTL) analysis (n=377) was performed using an F(2) intercross between a White Leghorn layer breed and a RJF population, with onset of sexual maturity measured and mapped to three separate loci. This cross has already been analysed for comb mass, egg production and bone allocation. Onset of sexual maturity significantly correlated with comb mass, whilst the genetic architecture for sexual maturity and comb mass overlapped at all three loci. For two of these loci, the QTL for sexual maturity and comb mass were statistically indistinguishable from pleiotropy, suggesting that the alleles that increase comb mass also decrease onset of sexual maturity.


Subject(s)
Chickens/genetics , Chickens/physiology , Comb and Wattles , Fertility/genetics , Sexual Maturation/genetics , Sexual Maturation/physiology , Animals , Female , Genotype , Male , Quantitative Trait Loci
14.
Methods ; 50(1): 14-9, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19523519

ABSTRACT

Non-invasive three-dimensional imaging of live rodents is a powerful research tool that has become critical for advances in many biomedical fields. For investigations into adipose development, obesity, or diabetes, accurate and precise techniques that quantify adiposity in vivo are critical. Because total body fat mass does not accurately predict health risks associated with the metabolic syndrome, imaging modalities should be able to stratify total adiposity into subcutaneous and visceral adiposity. Micro-computed tomography (micro-CT) acquires high-resolution images based on the physical density of the material and can readily discriminate between subcutaneous and visceral fat. Here, a micro-CT based method to image the adiposity of live rodents is described. An automated and validated algorithm to quantify the volume of discrete fat deposits from the computed tomography is available. Data indicate that scanning the abdomen provides sufficient information to estimate total body fat. Very high correlations between micro-CT determined adipose volumes and the weight of explanted fat pads demonstrate that micro-CT can accurately monitor site-specific changes in adiposity. Taken together, in vivo micro-CT is a non-invasive, highly quantitative imaging modality with greater resolution and selectivity, but potentially lower throughput, than many other methods to precisely determine total and regional adipose volumes and fat infiltration in live rodents.


Subject(s)
Adipose Tissue/diagnostic imaging , Intra-Abdominal Fat/diagnostic imaging , X-Ray Microtomography/instrumentation , X-Ray Microtomography/methods , Animals , Disease Models, Animal , Electronic Data Processing , Equipment Design , Image Processing, Computer-Assisted/methods , Imaging, Three-Dimensional/methods , Mice , Normal Distribution , Obesity/diagnostic imaging , Rats , Time Factors
15.
Bone ; 150: 115998, 2021 09.
Article in English | MEDLINE | ID: mdl-33971314

ABSTRACT

Patients afflicted with or being treated for cancer constitute a distinct and alarming subpopulation who exhibit elevated fracture risk and heightened susceptibility to developing secondary osteoporosis. Cancer cells uncouple the regulatory processes central for the adequate regulation of musculoskeletal tissue. Systemically taxing treatments to target tumors or disrupt the molecular elements driving tumor growth place considerable strain on recovery efforts. Skeletal tissue is inherently sensitive to mechanical forces, therefore attention to exercise and mechanical loading as non-pharmacological means to preserve bone during treatment and in post-treatment rehabilitative efforts have been topics of recent focus. This review discusses the dysregulation that cancers and the ensuing metabolic dysfunction that confer adverse effects on musculoskeletal tissues. Additionally, we describe foundational mechanotransduction pathways and the mechanisms by which they influence both musculoskeletal and cancerous cells. Functional and biological implications of mechanical loading at the tissue and cellular levels will be discussed, highlighting the current understanding in the field. Herein, in vitro, translational, and clinical data are summarized to consider the positive impact of exercise and low magnitude mechanical loading on tumor-bearing skeletal tissue.


Subject(s)
Bone Diseases, Metabolic , Neoplasms , Osteoporosis , Bone and Bones , Humans , Mechanotransduction, Cellular , Stress, Mechanical
16.
Int J Obes (Lond) ; 34(2): 401-5, 2010 Feb.
Article in English | MEDLINE | ID: mdl-19935747

ABSTRACT

The age-induced decline in the body's ability to fight disease is exacerbated by obesity and metabolic disease. Using a mouse model of diet-induced obesity, the combined challenge of a high-fat diet and age on liver morphology and biochemistry was characterized, while evaluating the potential of 15 min per day of high frequency (90 Hz), extremely low-magnitude (0.2 G) mechanical signals (LMMS) to suppress lipid accumulation in the liver. Following a 36-week protocol (animals 43 weeks of age), suppression of hepatomegaly and steatosis was reflected by a 29% lower liver mass in LMMS animals as compared with controls. Average triglyceride content was 101.7+/-19.4 microg mg(-1) tissue in the livers of high-fat diet control (HFD) animals, whereas HFD+LMMS animals realized a 27% reduction to 73.8+/-22.8 microg mg(-1) tissue. In HFD+LMMS animals, liver free fatty acids were also reduced to 0.026+/-0.009 microEq mg(-1) tissue from 0.035+/-0.005 microEq mg(-1) tissue in HFD. Moderate to severe micro- and macrovesicular steatosis in HFD was contrasted to a 49% reduction in area covered by the vacuoles of at least 15 microm(2) in size in HFD+LMMS animals. These data provide preliminary evidence of the ability of LMMS to attenuate the progression of fatty liver disease, most likely achieved indirectly by suppressing adipogenesis and thus the total adipose burden through life, thereby reducing a downstream challenge to liver morphology and function.


Subject(s)
Dietary Fats/administration & dosage , Fatty Liver/prevention & control , Obesity/etiology , Animals , Fatty Liver/etiology , Lipid Metabolism , Liver/metabolism , Male , Mice , Triglycerides/metabolism
17.
Mol Ecol ; 19(23): 5140-56, 2010 Dec.
Article in English | MEDLINE | ID: mdl-21040053

ABSTRACT

The extent of pleiotropy and epistasis in quantitative traits remains equivocal. In the case of pleiotropy, multiple quantitative trait loci are often taken to be pleiotropic if their confidence intervals overlap, without formal statistical tests being used to ascertain if these overlapping loci are statistically significantly pleiotropic. Additionally, the degree to which the genetic correlations between phenotypic traits are reflected in these pleiotropic quantitative trait loci is often variable, especially in the case of antagonistic pleiotropy. Similarly, the extent of epistasis in various morphological, behavioural and life-history traits is also debated, with a general problem being the sample sizes required to detect such effects. Domestication involves a large number of trade-offs, which are reflected in numerous behavioural, morphological and life-history traits which have evolved as a consequence of adaptation to selective pressures exerted by humans and captivity. The comparison between wild and domestic animals allows the genetic analysis of the traits that differ between these population types, as well as being a general model of evolution. Using a large F(2) intercross between wild and domesticated chickens, in combination with a dense SNP and microsatellite marker map, both pleiotropy and epistasis were analysed. The majority of traits were found to segregate in 11 tight 'blocks' and reflected the trade-offs associated with domestication. These blocks were shown to have a pleiotropic 'core' surrounded by more loosely linked loci. In contrast, epistatic interactions were almost entirely absent, with only six pairs identified over all traits analysed. These results give insights both into the extent of such blocks in evolution and the development of domestication itself.


Subject(s)
Chickens/genetics , Genetic Linkage , Genetic Pleiotropy , Quantitative Trait Loci , Animals , Crosses, Genetic , Epistasis, Genetic , Evolution, Molecular , Genotype , Microsatellite Repeats , Polymorphism, Single Nucleotide , Sequence Analysis, DNA
18.
J Musculoskelet Neuronal Interact ; 10(1): 3-11, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20190375

ABSTRACT

Bone formation and resorption are sensitive to both external loads arising from gravitational loading as well to internal loads generated by muscular activity. The question as to which of the two sources provides the dominant stimulus for bone homeostasis and new bone accretion is arguably tied to the specific type of activity and anatomical site but it is often assumed that, because of their purportedly greater magnitude, muscle loads modulate changes in bone morphology. High-frequency mechanical signals may provide benefits at low- (<1g) and high- (>1g) acceleration magnitudes. While the mechanisms by which cells perceive high-frequency signals are largely unknown, higher magnitude vibrations can cause large muscle loads and may therefore be sensed by pathways similar to those associated with exercise. Here, we review experimental data to examine whether vibrations applied at very low magnitudes may be sensed directly by transmittance of the signal through the skeleton or whether muscle activity modulates, and perhaps amplifies, the externally applied mechanical stimulus. Current data indicate that the anabolic and anti-catabolic effects of whole body vibrations on the skeleton are unlikely to require muscular activity to become effective. Even high-frequency signals that induce bone matrix deformations of far less than five microstrain can promote bone formation in the absence of muscular activity. This independence of cells on large strains suggests that mechanical interventions can be designed that are both safe and effective.


Subject(s)
Bone Development/physiology , Muscle Contraction/physiology , Muscle, Skeletal/physiology , Musculoskeletal Development/physiology , Osteogenesis/physiology , Vibration/therapeutic use , Animals , Humans , Physical Stimulation , Signal Transduction/physiology , Stress, Mechanical , Weight-Bearing/physiology
19.
J Musculoskelet Neuronal Interact ; 10(1): 12-24, 2010 Mar.
Article in English | MEDLINE | ID: mdl-20190376

ABSTRACT

To identify mechanotransductive signals for combating musculoskeletal deterioration, it is essential to determine the components and mechanisms critical to the anabolic processes of musculoskeletal tissues. It is hypothesized that the interaction between bone and muscle may depend on fluid exchange in these tissues by mechanical loading. It has been shown that intramedullary pressure (ImP) and low-level bone strain induced by muscle stimulation (MS) has the potential to mitigate bone loss induced by disuse osteopenia. Optimized MS signals, i.e., low-intensity and high frequency, may be critical in maintaining bone mass and mitigating muscle atrophy. The objectives for this review are to discuss the potential for MS to induce ImP and strains on bone, to regulate bone adaptation, and to identify optimized stimulation frequency in the loading regimen. The potential for MS to regulate blood and fluid flow will also be discussed. The results suggest that oscillatory MS regulates fluid dynamics with minimal mechanical strain in bone. The response was shown to be dependent on loading frequency, serving as a critical mediator in mitigating bone loss. A specific regimen of dynamic MS may be optimized in vivo to attenuate disuse osteopenia and serve as a biomechanical intervention in the clinical setting.


Subject(s)
Bone Development/physiology , Bone Diseases, Metabolic/therapy , Muscular Disorders, Atrophic/therapy , Musculoskeletal Development/physiology , Osteogenesis/physiology , Adaptation, Physiological/physiology , Animals , Bone Diseases, Metabolic/physiopathology , Electric Stimulation Therapy/methods , Humans , Mechanotransduction, Cellular/physiology , Muscle Contraction/physiology , Muscular Disorders, Atrophic/physiopathology , Muscular Disorders, Atrophic/prevention & control , Rats , Stress, Mechanical
20.
Clin Microbiol Infect ; 26(8): 1052-1057, 2020 Aug.
Article in English | MEDLINE | ID: mdl-31904567

ABSTRACT

OBJECTIVES: The aim was to compare the burden of environmental shedding of toxigenic Clostridioides difficile among asymptomatic carriers, C. difficile-infected (CDI) patients and non-carriers in an inpatient non-epidemic setting. METHODS: C. difficile carriage was determined by positive toxin-B PCR from rectal swabs of asymptomatic patients. Active CDI was defined as a positive two-step enzyme immunoassay/polymerase chain reaction (EIA/PCR) test in patients with more than three unformed stools/24 hr. C. difficile environmental contamination was assessed by obtaining specimens from ten sites in the patients' rooms. Toxigenic strains were identified by PCR. We created a contamination scale to define the overall level of room contamination that ranged from clean to heavy contamination. RESULTS: One hundred and seventeen rooms were screened: 70 rooms inhabited by C. difficile carriers, 30 rooms by active CDI patients and 17 rooms by non C. difficile -carriers (control). In the carrier rooms 29 (41%) had more than residual contamination, from which 17 (24%) were heavily contaminated. In the CDI rooms 12 (40%) had more than residual contamination from which three (10%) were heavily contaminated, while in the control rooms, one room (6%) had more than residual contamination and none were heavily contaminated. In a multivariate analysis, the contamination score of rooms inhabited by carriers did not differ from rooms of CDI patients, yet both were significantly more contaminated than those of non-carriers odd ratio 12.23 and 11.16 (95% confidence interval 1.5-99.96 p 0.0195, and 1.19-104.49 p 0.035), respectively. DISCUSSION: Here we show that the rooms of C. difficile carriers are as contaminated as those of patients with active CDI and significantly more than those of non-carriers.


Subject(s)
Bacterial Proteins/genetics , Bacterial Toxins/genetics , Carrier State/diagnosis , Clostridioides difficile/physiology , Clostridium Infections/diagnosis , Aged , Aged, 80 and over , Bacterial Shedding , Carrier State/microbiology , Clostridioides difficile/genetics , Clostridioides difficile/isolation & purification , Clostridium Infections/microbiology , Environmental Microbiology , Feces/microbiology , Female , Humans , Inpatients , Male , Middle Aged , Prospective Studies
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