142 research outputs found
Novel approaches to the diagnosis of Sarcopenia
No full textSarcopenia is common in older people and is associated with disability, reduced mobility, hospitalization, and various comorbidities. Although it has been recognized for over a quarter of a century, we do not currently have a universally adopted definition. This limits our ability to compare results from different studies and impedes the development of novel therapies. Although sarcopenia was initially defined purely based on low muscle mass, the importance of measures of muscle function has been realized and these have been included in recent operational definitions. These continue to evolve with some including an assessment of adiposity and others adding further components of musculoskeletal health in a score-based approach. This review describes the importance of reaching a widely accepted method to define sarcopenia in both research and clinical practice. It details the ways in which the definition has changed since its initial inception and explores how it may continue to evolve in the future. The different methods by which components of sarcopenia can be measured are described, and the various advantages and disadvantages of these techniques are evaluated. Clearly, there are several other similar syndromes in older people, such as frailty and cachexia; their relationships and overlap with sarcopenia are also explored
Definitions of Sarcopenia: associations with previous falls and fracture in a population sample
No full textSarcopenia is common in later life and may be associated with adverse health outcomes such as disability, falls and fracture. There is no consensus definition for its diagnosis although diagnostic algorithms have been proposed by the European Working Group for Sarcopenia in Older People (EWGSOP), the International Working Group on Sarcopenia (IWGS) and the Foundation for the National Institutes of Health Sarcopenia Project (FNIH). More recently, Binkley and colleagues devised a score-based system for the diagnosis of “dysmobility syndrome” in an attempt to combine adverse musculoskeletal phenotypes, including sarcopenia and osteoporosis, in order to identify older individuals at particular risk. We applied these criteria to participants from the Hertfordshire Cohort Study to define their prevalence in an unselected cohort of UK community-dwelling older adults and assess their relationships with previous falls and fracture. Body composition and areal bone mineral density were measured using dual-energy X-ray absorptiometry, gait speed was determined by a 3-m walk test and grip strength was assessed with a Jamar hand-held dynamometer. Researcher-administered questionnaires were completed detailing falls and fracture history. The prevalence of sarcopenia in this cohort was 3.3, 8.3 and 2.0 % using the EWGSOP, IWGS and related definition of FNIH, respectively; 24.8 % of individuals had dysmobility syndrome. Individuals with dysmobility reported significantly higher number of falls (last year and since the age of 45 years) (p < 0.01) than those without it, but no increased fracture rate was observed in this group (p = 0.96). Those with sarcopenia as defined by the IWGS reported significantly higher falls in the last year and prevalent fractures (falls in the last year: OR 2.51; CI 1.09–5.81; p = 0.03; fractures OR 2.50; CI 1.05–5.92; p = 0.04) but these significant associations were not seen when the EWGSOP definition was applied. The IWGS definition of sarcopenia appears to be an effective means of identifying individuals at risk of prevalent adverse musculoskeletal events
Cinnamyl-3,4-Dihydroxy-{alpha}-Cyanocinnamate Is a Potent Inhibitor of 5-Lipoxygenase.
No full textLipoxygenases (LOs) are iron-containing enzymes that catalyze the conversion of arachidonic acid into hydroperoxyeicosatetraenoic acids (HPETEs) and other bioactive lipid mediators. In mammals, 5-LO, 15-LO, and 12-LO enzymes seem to have distinct roles in pathophysiological contexts, which have emphasized the need for selective inhibitors. Cinnamyl-3,4-dihydroxy-α-cyanocinnamate (CDC) has been proposed as potent and selective inhibitor of platelet-type 12-LO (p12-LO). Here, we re-evaluated the selectivity profile of CDC on LOs, and we show that CDC is a potent and direct inhibitor of 5-LO. CDC reduced 5-LO activity in cell-free assays (purified human recombinant enzyme or leukocyte homogenates), with IC(50) values in the low nanomolar range (9-25 nM) and a selectivity index of approximately 35 and 15 over p12-LO and 15-LO1, respectively. Likewise, CDC inhibited 5-LO product formation in intact human polymorphonuclear leukocytes and monocytes (IC(50) = 0.45-0.8 μM). A lower potency was observed for 15-LO1, whereas p12-LO activity in platelets was hardly affected. In human whole blood, CDC efficiently reduced the formation of 5-LO products, and similar effects were observed for 12(S)-H(P)ETE and 15(S)-H(P)ETE. Finally, CDC (3.5 and 7 mg/kg i.p.) was effective in vivo in the platelet-activating factor-induced shock in mice and reduced formation of the 5-LO product leukotriene B(4) in the rat carrageenan-induced pleurisy after a single oral dose of 10 mg/kg. Together, our data demonstrate that CDC is a potent inhibitor of 5-LO with efficacy in vivo and encourage further development of CDC as the lead compound
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Development of an Enzyme-Linked Immunosorbent Assay to Determine the Seroprevalence of Bovine Leukemia Virus Antibodies in Humans
No full textBreast cancer is a leading cause of morbidity and mortality worldwide. About 5-10% of breast cancer cases are associated with hereditary factors (such as mutations of the BRCA-1 or BRCA-2 gene), but the exact causes for most breast cancers are unknown. The remaining 90% of breast cancer cases may potentially be caused by external initiators such as radiation, chemical carcinogens, or infectious agents. Infectious agents cause about 23% of all malignancies in developing countries, and approximately 8% of malignancies in developed countries. Currently, six viruses are causally associated with human cancers: Epstein-Barr virus (EBV), human T-lymphotropic virus type 1 (HTLV-1), hepatitis B virus (HBV), hepatitis C virus (HCV), human papilloma virus (HPV), and human herpes virus 8 (HHV-8). No infectious agent has yet been causally associated with human breast cancer. One candidate virus is bovine leukemia virus (BLV), a retrovirus closely related to HTLV and the causative agent of enzootic bovine lymphosarcoma. In cattle, BLV is transmitted by transfer of infected lymphocytes via blood or milk. Humans are potentially exposed to BLV by consumption of cow's milk and meat.One part of the process of proving that an infectious agent causes a particular disease is proving that the organism infects humans. Production of immunoglobulins specific to the organism is often evidence of infection. Utilizing an immunoblot assay with a chemiluminescent endpoint, Buehring et al. demonstrated the presence of anti-BLVp24gag IgG, IgM, and IgA in human sera. Competition studies with pre-immune and immune goat sera further verified the human anti-BLV specificity. Since immunoblotting is a labor-intensive and inefficient method compared to ELISA, an ELISA assay was developed in this study to detect anti-BLVp24gag IgG and IgM in human serum and plasma samples. Receiver operator curve analysis was used to compare the ELISA to the immunoblot. The ELISA method developed here has poor ability (IgG AUC=0.51, IgM AUC= 0.56) to discriminate between people with and without antibodies to BLV p24gag, compared to immunoblot. ROC analysis is concordant with the unimodal IgG and IgM frequency distributions. The cut-off value derived from ROC analysis for IgG is 77800 RLUs, which gives a sensitivity of 76.47% and a specificity of 26.1%. The cut-off value for IgM is 26244 RLUs, giving a sensitivity of 80.9% and a specificity of 28.05%. Initial competition studies with a monoclonal anti-human secondary antibody indicates that the Assay may show specificity for the BLV p24 protein. However, an appropriate antigen control was not available to rule out non-specific reactions with the antigen matrix. Therefore, this ELISA needs further development to assure specificity of the assay for the recombinant BLV p2gag protein before solid conclusions can be made regarding the seroprevalence of BLV antibodies in humans.However, this developmental stage ELISA was used to estimate the frequency of anti-BLVp24gag IgG and IgM in our study population, using the ROC derived cut-off points. In the 0-3 month age category, the frequency of IgG is 14.2%, declining to 0% by the age of 6 months. The frequency of IgM in the 0-3 month age group is 23.9%, increasing to 70% by 6 months of age. The presence of IgG in the 0-3 month age group is most likely maternal IgG that wanes by age 6 months, while IgM is indicative of the child's own immune response to a new antigen. The level of IgG peaks at 30-39 years of age, plateaus, and then begins to decrease at 60 years of age. IgM peaks in adolescence and then begins a slow decline after 30 years of age, but never falls below 60% prevalence. Continuing high IgM titers may be indicative of constant reexposure to BLV via dairy and meat consumption, or to episodes of viral reactivation. The relatively high overall percentage of IgM seropositivity (73.3%) compared to IgG seropositivity (49.3%) may be due to the low median age of the study population. Using the preliminary ELISA method being developed here, this study may indicate that both vertical and sexual transmission of BLV potentially occur. However, presence of antibodies to the BLV p24gag protein do not necessarily indicate infection, but may result from exposure to the antigen from consumption of dairy products. In addition, confirmation of the specificity of this ELISA is necessary to make firm conclusions. Further prospective studies are warranted in order to determine precisely at what point(s) in the perinatal period vertical transmission could occur, and to elucidate whether sexual transmission is truly occurring. Prospective studies may also permit a study sample more representative of the target population to be developed. In conclusion, widespread consumption of BLV-contaminated dairy and beef may potentially be responsible for a significant proportion of breast cancer cases worldwide. If the pathogenicity of BLV for humans is established, the implications are far-reaching and may indicate the need for primary preventative measures to avert continuing infection of humans
Changes in lower extremity muscle function after 56 days of bed rest
No full textPreservation of muscle function, known to decline in microgravity and simulation (bed rest), is important for successful spaceflight missions. Hence, there is great interest in developing interventions to prevent musclefunction
loss. In this study, 20 males underwent 56 days of bed rest.
Ten volunteers were randomized to do resistive vibration exercise (RVE). The other 10 served as controls. RVE consisted of muscle contractions against resistance and concurrent whole-body vibration.
Main outcome parameters were maximal isometric plantar-flexion force (IPFF), electromyography (EMG)/force ratio, as well as jumping power and height. Measurements were obtained before and after bed rest, including a morning and evening assessment on the first day of recovery from bed rest. IPFF (-17.1%), jumping peak power (-24.1%), and height (-28.5%) declined (P < 0.05) in the control
group. There was a trend to EMG/force ratio decrease (-20%; P < 0.051). RVE preserved IPFF and mitigated the decline of countermovement jump performance (peak power -12.2%; height -14.2%). In both groups, IPFF was reduced between the two measurements of the first day of reambulation. This study indicates that bed rest and countermeasure exercises differentially affect the various functions of skeletal muscle. Moreover, the time course during recovery needs to
be considered more thoroughly in future studies, as IPFF declined not only with bed rest but also within the first day of reambulation. RVE was effective in maintaining IPFF but only mitigated the decline in jumping performance. More research is needed to develop countermeasures that maintain muscle strength as well as other muscle functions including power
Designing memorable guest experiences : development of constructs and value generating factors in luxury hotels
No full text202203 bcwhAccepted ManuscriptSelf-fundedPublishedGreen (AAM
Texas Teacher Experiences in Mexico-United States Border Classrooms: a Phenomenological Qualitative Study
No full textThe purpose of this phenomenological qualitative design study was to describe the lived experiences of 10 Texas teachers who teach along the Mexico-United States international border, because although there was much research regarding education in Mexico-United States border towns, there was not much regarding how teachers perceive their lived experience in these schools. The target population of teachers taught in Texas public schools operating along the United States border with Mexico. The researcher used an interview guide during 10 virtual face to face interviews with the participants using a web conferencing platform. The phenomenological qualitative research design allowed for developing a deeper understanding of the experiences of this teacher population serving the Mexico-United States border students in Texas public schools. All 10 teachers infused two important actualities into their responses to the interview questions that included the following (a) they taught at a school near the Mexico-United States border, (b) the need to speak and write the English language in the schools affected students, (c) their school was affected by the culture of the students living on the Mexico- United States border, and (d) they needed to have connections and relationships with the students. These overarching actualities influenced how the themes developed and appeared within the themes that answered the research questions. The information gained by this study has allowed demonstrated unique experiences of the Mexico-United States border teacher and provided the teachers’ perspectives of the border student experience. The findings led to implications for districtwide cultural awareness training as well as teacher support initiatives during which teachers can share effective strategies regarding how to best serve the border student. Several recommendations for future study are also made in Chapter 5
Bovine leukemia virus linked to breast cancer in Australian women and identified before breast cancer development.
No full textBovine leukemia virus (BLV), a common virus of cattle globally, was believed for decades not to infect humans. More recent techniques (in situ PCR and DNA sequencing) enabled detection of BLV in human breast tissue, and determination of its significant association with breast cancer in a US population. Using similar techniques to study 96 Australian women, we report here detection of retrotranscribed BLV DNA in breast tissue of 40/50(80%) of women with breast cancer versus 19/46(41%) of women with no history of breast cancer, indicating an age-adjusted odds ratio and confidence interval of 4.72(1.71-13.05). These results corroborate the findings of the previous study of US women with an even higher odds ratio for the Australian population. For 48 of the subjects, paired breast tissue samples, removed 3-10 years apart in two unrelated procedures, were available. For 23/31 (74%) of these, in which the first specimen was diagnosed as nonmalignant (benign or premalignant) and the second as malignant, BLV was already present in benign breast tissue years 3-10 years before the malignancy was diagnosed. This is consistent with the supposition of a causative temporal relationship between BLV infection and subsequent development of cancer
The receptor tyrosine kinase p185HER2 is expressed on a subset of B-lymphoid blasts from patients with acute lymphoblastic leukemia and chronic myelogenous leukemia
No full textThe class I receptor tyrosine kinase (RTK) HER2 is an oncoprotein that is frequently involved in the pathogenesis of tumors of epithelial origin. Here we report mRNA expression in peripheral blood and bone marrow cells from healthy donors in hematopoietic cell lines and leukemic blasts from patients with acute lymphoblastic leukemia (ALL), acute myeloblastic leukemia (AML), chronic lymphoblastic leukemia (CLL), and chronic myeloid leukemia (CML). However, cell surface expression of HER2 protein (p185HER2) was found exclusively on a subset of leukemic cells of the B-lymphoblastic lineage. p185HER2 expression was found on blasts in 2 of 15 samples from infants, 9 of 19 samples from adult patients with C-ALL (CD19+CD10+), and 1 of 2 samples from patients with pro-B ALL (CD19+CD10-), whereas none of the leukemic cells from patients with AML (0/30), T-ALL (0/7), CLL (0/5) (CD19+CD5+), or CML in chronic and accelerated phase (0/5) or in blast crisis with myeloid differentiation (0/14) were positive for p185HER2. However, cells from 3 of 4 patients with CML in B-lymphoid blast crisis (CD19+CD10+) expressed high levels of p185HER2, which was also found on the surface of the CML-derived B-cell lines BV-173 and Nalm-1. Our study shows p185HER2 expression on malignant cells of hematopoietic origin for the first time. Aberrant expression of this oncogenic receptor tyrosine kinase in hematopoietic cell types may be an oncogenic event contributing to the development of a subset of B-lymphoblastic leukemias
Emerg Infect Dis
No full textBovine leukemia virus (BLV), a deltaretrovirus, causes B-cell leukemia/lymphoma in cattle and is prevalent in herds globally. A previous finding of antibodies against BLV in humans led us to examine the possibility of human infection with BLV. We focused on breast tissue because, in cattle, BLV DNA and protein have been found to be more abundant in mammary epithelium than in lymphocytes. In human breast tissue specimens, we identified BLV DNA by using nested liquid-phase PCR and DNA sequencing. Variations from the bovine reference sequence were infrequent and limited to base substitutions. In situ PCR and immunohistochemical testing localized BLV to the secretory epithelium of the breast. Our finding of BLV in human tissues indicates a risk for the acquisition and proliferation of this virus in humans. Further research is needed to determine whether BLV may play a direct role in human disease
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