Low intensity vibration mitigates tumor progression and protects bone quantity and quality in a murine model of myeloma

Myeloma facilitates destruction of bone and marrow. Since physical activity encourages musculoskeletal preservation we evaluated whether low-intensity vibrations (LIV), a component of mechanical signaling, could protect bone and marrow during myeloma progression. Immunocompromised-mice (n=25) were injected with human-myeloma cells, while 8 (AC) were saline-injected. Myeloma-injected mice (LIV; n=13) were subjected to daily-mechanical loading (15min/d; 0.3g @ 90Hz) while 12 (MM) were sham-handled. At 8w, femurs had 85% less trabecular bone volume (BV) fraction in MM versus AC, yet only a 21% decrease in LIV as compared to as compared to AC, reflecting a 76% increase versus MM. Cortical BV was 21% and 15% lower in MM and LIV, respectively, than AC; LIV showing 30% improvement over MM. Similar outcomes were observed in the axial skeleton, showing a 35% loss in MM with a 27% improved retention of bone in L5 of LIV-treated mice as compared to MM. Transcortical-perforations in the femur from myeloma-induced osteolysis were 9× higher in MM versus AC, reduced by 57% in LIV. Serum-TRACP5b, 61% greater in MM versus AC, rose by 33% in LIV compared to AC, a 45% reduction in activity when compared to MM. Histomorphometric analyses of trabecular bone demonstrated a 70% elevation in eroded surfaces of MM versus AC, while measures in LIV were 58% below those in MM. 72% of marrow in the femur of MM mice contained tumor, contrasted by a 31% lower burden in LIV. MM mice (42%) presented advanced-stage necrosis of marrow in the tibia while present in just 8% of LIV. Myeloma infiltration inversely correlated to measures of bone quality, while LIV slowed systemic myeloma-associated decline in bone quality and inhibited tumor progression through the hindlimbs

Measurement of the W-boson mass in pp collisions at s√=7TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370=80370±7 (stat.)±11(exp. syst.)±14 (mod. syst.) MeV±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W− bosons yields mW+−mW−=−29±28 MeV

Measurement of the W-boson mass in pp collisions at s√=7TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8×106 candidates in the W→μν channel and 5.9×106 candidates in the W→eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW=80370=80370±7 (stat.)±11(exp. syst.)±14 (mod. syst.) MeV±19MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W− bosons yields mW+−mW−=−29±28 MeV

Measurement of the W-boson mass in pp collisions at root s=7 TeV with the ATLAS detector

A measurement of the mass of the W boson is presented based on proton–proton collision data recorded in 2011 at a centre-of-mass energy of 7 TeV with the ATLAS detector at the LHC, and corresponding to 4.6 fb−1 of integrated luminosity. The selected data sample consists of 7.8 × 106 candidates in the W → μν channel and 5.9 × 106 candidates in the W → eν channel. The W-boson mass is obtained from template fits to the reconstructed distributions of the charged lepton transverse momentum and of the W boson transverse mass in the electron and muon decay channels, yielding mW = 80370 ± 7 (stat.) ± 11(exp. syst.) ± 14 (mod. syst.) MeV = 80370 ± 19 MeV, where the first uncertainty is statistical, the second corresponds to the experimental systematic uncertainty, and the third to the physics-modelling systematic uncertainty. A measurement of the mass difference between the W+ and W− bosons yields mW+ − mW− = − 29 ± 28 MeV

Rising rural body-mass index is the main driver of the global obesity epidemic in adults

Body-mass index (BMI) has increased steadily in most countries in parallel with a rise in the proportion of the population who live in cities 1,2 . This has led to a widely reported view that urbanization is one of the most important drivers of the global rise in obesity 3�6 . Here we use 2,009 population-based studies, with measurements of height and weight in more than 112 million adults, to report national, regional and global trends in mean BMI segregated by place of residence (a rural or urban area) from 1985 to 2017. We show that, contrary to the dominant paradigm, more than 55 of the global rise in mean BMI from 1985 to 2017�and more than 80 in some low- and middle-income regions�was due to increases in BMI in rural areas. This large contribution stems from the fact that, with the exception of women in sub-Saharan Africa, BMI is increasing at the same rate or faster in rural areas than in cities in low- and middle-income regions. These trends have in turn resulted in a closing�and in some countries reversal�of the gap in BMI between urban and rural areas in low- and middle-income countries, especially for women. In high-income and industrialized countries, we noted a persistently higher rural BMI, especially for women. There is an urgent need for an integrated approach to rural nutrition that enhances financial and physical access to healthy foods, to avoid replacing the rural undernutrition disadvantage in poor countries with a more general malnutrition disadvantage that entails excessive consumption of low-quality calories. © 2019, The Author(s)

High fat diet rapidly suppresses B lymphopoiesis by disrupting the supportive capacity of the bone marrow niche.

The bone marrow (BM) niche is the primary site of hematopoiesis, and cues from this microenvironment are critical to maintain hematopoiesis. Obesity increases lifetime susceptibility to a host of chronic diseases, and has been linked to defective leukogenesis. The pressures obesity exerts on hematopoietic tissues led us to study the effects of a high fat diet (HFD: 60% Kcal from fat) on B cell development in BM. Seven week old male C57Bl/6J mice were fed either a high fat (HFD) or regular chow (RD) diet for periods of 2 days, 1 week and 6 weeks. B-cell populations (B220+) were not altered after 2 d of HFD, within 1 w B-cell proportions were reduced by -10%, and by 6 w by -25% as compared to RD (p<0.05). BM RNA was extracted to track the expression of B-cell development markers Il-7, Ebf-1 and Pax-5. At 2 d, the expression of Il-7 and Ebf-1 were reduced by -20% (p = 0.08) and -11% (p = 0.06) whereas Pax-5 was not significantly impacted. At one week, however, the expressions of Il-7, Ebf-1, and Pax-5 in HFD mice fell by -19%, -20% and -16%, and by six weeks were further reduced to -23%, -29% and -34% as compared to RD (p<0.05 for all), a suppression paralleled by a +363% increase in adipose encroachment within the marrow space (p<0.01). Il-7 is a critical factor in the early B-cell lineage which is secreted by supportive cells in the BM niche, and is necessary for B-cell commitment. These data indicate that BM Il-7 expression, and by extension B-cell differentiation, are rapidly impaired by HFD. The trend towards suppressed expression of Il-7 following only 2 d of HFD demonstrates how susceptible the BM niche, and the cells which rely on it, are to diet, which ultimately could contribute to disease susceptibility in metabolic disorders such as obesity

High Fat Diet Induces an Obese Phenotype.

<p>(a,b) At 6 weeks HF animals have expanded total abdominal adiposity with a prominent shift in the location of this adiposity from primarily subcutaneous to the visceral compartment. (c) The expansion and relocation of adiposity is illustrated in 3D reconstructions of abdominal μCT images which have been thresholded for adiposity (n = 9). In these images gray represents subcutaneous fat and pink represents visceral fat. *<i>P</i><0.05 vs. RD.</p

High Fat Diet Alters the Total Population Sizes of BM Leukocytes.

<p>(a) Total BM cells harvested for flow cytometry were not different between HF and RD animals at any time point, but a trend of increase was observed at 6W. (b) The total number of B-cells was not changed at 2D or 1W contrary to a decline in the phenotypic population at 1W. However, B-cells were reduced at 6W, despite a slight increase in total cellularity, demonstrating the degree of population reduction. (c,d) Total population sizes of both T-cells and Myeloid lineages tracked well with the phenotypic population proportions. *<i>P</i><0.05 vs. RD.</p

Hematopoietic Progenitors Rapidly Respond to High Fat Diet Mediated Damage.

<p>(a) A representative gating scheme to isolate KLS and SP-KLS cells is shown. HSCs (SP-KLS) were assessed to determine the hematopoietic response to obesity driven leukocyte mis-allocation but no differences were found at any time point studied. (b) Hematopoietic progenitors rapidly respond to obesity mediated damage displaying an early response to HFD with HF animals having elevated KLS populations at 1 week. By 6 weeks this response was no longer evident in HF animals. *<i>P</i><0.05 vs. RD.</p

Six Weeks of HFD Rapidly Remodels the Bone Marrow Towards Adiposity.

<p>(a,b,d) The percentage of BM space taken up by adipose tissue, as assessed by histology, increased by almost 4 fold in HFD animals compared to control, an increase at least partially due to increasing adipocyte size (n = 6). (c) This leads to an increase in BM triglyceride storage (n = 10). The inclusion of adipocytes in the BM is significant because of the deleterious paracrine and inflammatory consequences adipocytes are thought to present to hematopoiesis. Additionally, BM adiposity in general represents a decline in BM quality and health, as is demonstrated by increased BM adiposity in osteoporosis and anorexia nervosa. *<i>P</i><0.05 vs. RD.</p