Menthol Cigarette Smoking and Obesity in Young Adult Daily Smokers in Hawaii

This study investigates 1) the relationship between menthol cigarette smoking and obesity and 2) the association of body mass index with the nicotine metabolite ratio among menthol and non-menthol daily smokers aged 18–35 (n = 175). A brief survey on smoking and measures of height and weight, carbon monoxide, and saliva samples were collected from participants from May to December 2013 in Honolulu, Hawaii. Multiple regression was used to estimate differences in body mass index among menthol and non-menthol smokers and the association of menthol smoking with obesity. We calculated the log of the nicotine metabolite ratio to examine differences in the nicotine metabolite ratio among normal, overweight, and obese smokers. Sixty-eight percent of smokers used menthol cigarettes. Results showed that 62% of normal, 54% of overweight, and 91% of obese smokers used menthol cigarettes (p = .000). The mean body mass index was significantly higher among menthol compared with non-menthol smokers (29.4 versus 24.5, p = .000). After controlling for gender, marital status, educational attainment, employment status, and race/ethnicity, menthol smokers were more than 3 times as likely as non-menthol smokers to be obese (p = .04). The nicotine metabolite ratio was significantly lower for overweight menthol smokers compared with non-menthol smokers (.16 versus .26, p = .02) in the unadjusted model, but was not significant after adjusting for the covariates. Consistent with prior studies, our data show that menthol smokers are more likely to be obese compared with non-menthol smokers. Future studies are needed to determine how flavored tobacco products influence obesity among smokers

TWEAK and Fn14 expression in the pathogenesis of joint inflammation and bone erosion in rheumatoid arthritis

Extent: 10p.INTRODUCTION: TNF-like weak inducer of apoptosis (TWEAK) has been proposed as a mediator of inflammation and bone erosion in rheumatoid arthritis (RA). This study aimed to investigate TWEAK and TWEAK receptor (Fn14) expression in synovial tissue from patients with active and inactive rheumatoid arthritis (RA), osteoarthritis (OA) and normal controls and assess soluble (s)TWEAK levels in the synovial fluids from patients with active RA and OA. Effects of sTWEAK on osteoclasts and osteoblasts were investigated in vitro. METHODS: TWEAK and Fn14 expression were detected in synovial tissues by immunohistochemistry (IHC). Selected tissues were dual labelled with antibodies specific for TWEAK and lineage-selective cell surface markers CD68, Tryptase G, CD22 and CD38. TWEAK mRNA expression was examined in human peripheral blood mononuclear cells (PBMC) sorted on the basis of their expression of CD22. sTWEAK was detected in synovial fluid from OA and RA patients by ELISA. The effect of sTWEAK on PBMC and RAW 264.7 osteoclastogenesis was examined. The effect of sTWEAK on cell surface receptor activator of NF Kappa B Ligand (RANKL) expression by human osteoblasts was determined by flow cytometry. RESULTS: TWEAK and Fn14 expression were significantly higher in synovial tissue from all patient groups compared to the synovial tissue from control subjects (P < 0.05). TWEAK was significantly higher in active compared with inactive RA tissues (P < 0.05). TWEAK expression co-localised with a subset of CD38+ plasma cells and with CD22+ B-lymphocytes in RA tissues. Abundant TWEAK mRNA expression was detected in normal human CD22+ B cells. Higher levels of sTWEAK were observed in synovial fluids isolated from active RA compared with OA patients. sTWEAK did not stimulate osteoclast formation directly from PBMC, however, sTWEAK induced the surface expression of RANKL by human immature, STRO-1+ osteoblasts. CONCLUSIONS: The expression of TWEAK by CD22+ B cells and CD38+ plasma cells in RA synovium represents a novel potential pathogenic pathway. High levels of sTWEAK in active RA synovial fluid and of TWEAK and Fn14 in active RA tissue, together with the effect of TWEAK to induce osteoblastic RANKL expression, is consistent with TWEAK/Fn14 signalling being important in the pathogenesis of inflammation and bone erosion in RA.Anak A. S. S. K. Dharmapatni, Malcolm D. Smith, Tania N. Crotti, Christopher A. Holding, Cristina Vincent, Helen M. Weedon, Andrew C. W. Zannettino, Timothy S. Zheng, David M. Findlay, Gerald J. Atkins and David R. Hayne

Evaluating the Cellular Targets of Anti-4-1BB Agonist Antibody during Immunotherapy of a Pre-Established Tumor in Mice

Manipulation of the immune system represents a promising avenue for cancer therapy. Rational advances in immunotherapy of cancer will require an understanding of the precise correlates of protection. Agonistic antibodies against the tumor necrosis factor receptor family member 4-1BB are emerging as a promising tool in cancer therapy, with evidence that these antibodies expand both T cells as well as innate immune cells. Depletion studies have suggested that several cell types can play a role in these immunotherapeutic regimens, but do not reveal which cells must directly receive the 4-1BB signals for effective therapy.We show that re-activated memory T cells are superior to resting memory T cells in control of an 8-day pre-established E.G7 tumor in mice. We find that ex vivo activation of the memory T cells allows the activated effectors to continue to divide and enter the tumor, regardless of antigen-specificity; however, only antigen-specific reactivated memory T cells show any efficacy in tumor control. When agonistic anti-4-1BB antibody is combined with this optimized adoptive T cell therapy, 80% of mice survive and are fully protected from tumor rechallenge. Using 4-1BB-deficient mice and mixed bone marrow chimeras, we find that it is sufficient to have 4-1BB only on the endogenous host alphabeta T cells or only on the transferred T cells for the effects of anti-4-1BB to be realized. Conversely, although multiple immune cell types express 4-1BB and both T cells and APC expand during anti-4-1BB therapy, 4-1BB on cells other than alphabeta T cells is neither necessary nor sufficient for the effect of anti-4-1BB in this adoptive immunotherapy model.This study establishes alphabeta T cells rather than innate immune cells as the critical target in anti-4-1BB therapy of a pre-established tumor. The study also demonstrates that ex vivo activation of memory T cells prior to infusion allows antigen-specific tumor control without the need for reactivation of the memory T cells in the tumor

Effects of Mountain Pine Beetle on Fuels and Expected Fire Behavior in Lodgepole Pine Forests, Colorado, USA

In Colorado and southern Wyoming, mountain pine beetle (MPB) has affected over 1.6 million ha of predominantly lodgepole pine forests, raising concerns about effects of MPB-caused mortality on subsequent wildfire risk and behavior. Using empirical data we modeled potential fire behavior across a gradient of wind speeds and moisture scenarios in Green stands compared three stages since MPB attack (Red [1–3 yrs], Grey [4–10 yrs], and Old-MPB [∼30 yrs]). MPB killed 50% of the trees and 70% of the basal area in Red and Grey stages. Across moisture scenarios, canopy fuel moisture was one-third lower in Red and Grey stages compared to the Green stage, making active crown fire possible at lower wind speeds and less extreme moisture conditions. More-open canopies and high loads of large surface fuels due to treefall in Grey and Old-MPB stages significantly increased surface fireline intensities, facilitating active crown fire at lower wind speeds (>30–55 km/hr) across all moisture scenarios. Not accounting for low foliar moistures in Red and Grey stages, and large surface fuels in Grey and Old-MPB stages, underestimates the occurrence of active crown fire. Under extreme burning conditions, minimum wind speeds for active crown fire were 25–35 km/hr lower for Red, Grey and Old-MPB stands compared to Green. However, if transition to crown fire occurs (outside the stand, or within the stand via ladder fuels or wind gusts >65 km/hr), active crown fire would be sustained at similar wind speeds, suggesting observed fire behavior may not be qualitatively different among MPB stages under extreme burning conditions. Overall, the risk (probability) of active crown fire appears elevated in MPB-affected stands, but the predominant fire hazard (crown fire) is similar across MPB stages and is characteristic of lodgepole pine forests where extremely dry, gusty weather conditions are key factors in determining fire behavior

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Predictors of physical activity in colorectal cancer survivors after participation in a telephone-delivered multiple health behavior change intervention

Purpose: Physical activity improves the health outcomes of colorectal cancer (CRC) survivors, yet few are exercising at levels known to yield health benefits. Baseline demographic, clinical, behavioral, and psychosocial predictors of physical activity at 12 months were investigated in CRC survivors. Methods: Participants were CRC survivors (n = 410) who completed a 12-month multiple health behavior change intervention trial (CanChange). The outcome variable was 12 month sufficient physical activity (≥150 min of moderate–vigorous physical activity/week). Baseline predictors included demographics and clinical variables, health behaviors, and psychosocial variables. Results: Multivariate linear regression revealed that baseline sufficient physical activity (p < 0.001), unemployment (p = 0.004), private health insurance (p = 0.040), higher cancer-specific quality of life (p = 0.031) and higher post-traumatic growth (p = 0.008) were independent predictors of sufficient physical activity at 12 months. The model explained 28.6 % of the variance. Conclusions: Assessment of demographics, health behaviors, and psychosocial functioning following a diagnosis of CRC may help to develop effective physical activity programs

Improving Soil Resource Uptake by Plants Through Capitalizing on Synergies Between Root Architecture and Anatomy and Root-Associated Microorganisms

Root architectural and anatomical phenotypes are highly diverse. Specific root phenotypes can be associated with better plant growth under low nutrient and water availability. Therefore, root ideotypes have been proposed as breeding targets for more stress-resilient and resource-efficient crops. For example, root phenotypes that correspond to the Topsoil Foraging ideotype are associated with better plant growth under suboptimal phosphorus availability, and root phenotypes that correspond to the Steep, Cheap and Deep ideotype are linked to better performance under suboptimal availability of nitrogen and water. We propose that natural variation in root phenotypes translates into a diversity of different niches for microbial associations in the rhizosphere, rhizoplane and root cortex, and that microbial traits could have synergistic effects with the beneficial effect of specific root phenotypes. Oxygen and water content, carbon rhizodeposition, nutrient availability, and root surface area are all factors that are modified by root anatomy and architecture and determine the structure and function of the associated microbial communities. Recent research results indicate that root characteristics that may modify microbial communities associated with maize include aerenchyma, rooting angle, root hairs, and lateral root branching density. Therefore, the selection of root phenotypes linked to better plant growth under specific edaphic conditions should be accompanied by investigating and selecting microbial partners better adapted to each set of conditions created by the corresponding root phenotype. Microbial traits such as nitrogen transformation, phosphorus solubilization, and water retention could have synergistic effects when correctly matched with promising plant root ideotypes for improved nutrient and water capture. We propose that elucidation of the interactive effects of root phenotypes and microbial functions on plant nutrient and water uptake offers new opportunities to increase crop yields and agroecosystem sustainability.ISSN:1664-462