ABSTRACT
Social distancing, during previous epidemics, has been shown to lead to poor mental health outcomes and reduced physical activity. The purpose of the present study was to examine the relationships between self-reported psychological state and physical activity behaviors of individuals under social distancing policies during the COVID-19 pandemic. 199 individuals (29.85 ± 10.22 yrs) in the United States who had been in social distancing for 2-4 weeks participated in this study. Participants answered a questionnaire regarding feelings of loneliness, depression, anxiety, mood state, and physical activity. 66.8% of participants had depressive symptoms and 72.8% had symptoms of anxiety. Loneliness was correlated with depression (r = 0.66), trait anxiety (r = 0.36), fatigue (r = 0.38), confusion (r = 0.39), and total mood disturbance (TMD;r = 0.62). Participation in total physical activity was negatively associated with depressive symptoms (r =-0.16) and TMD (r =-0.16). State anxiety was positively associated with participation in total physical activity (r = 0.22). In addition, a binomial logistic regression was performed to predict participation in sufficient physical activity. The model explained 45% of the variance in physical activity participation and correctly categorized 77% of cases. Individuals with higher vigor scores had an increased likelihood of participating in sufficient physical activity. Loneliness was associated with negative psychological mood state. Individuals with higher feelings of loneliness, depressive symptoms, trait anxiety, and negative mood state were observed to spend less time engaged in physical activity. Higher state anxiety was positively associated with engagement in physical activity. © 2022, Western Kentucky University. All rights reserved.
ABSTRACT
Background. Lymphovascular invasion (LVI) and breast tumor emboli within dermal and breast lymphatic vessels are prognostic for metastatic spread and poor outcomes, and are abundant in Inflammatory breast cancer (IBC). IBC is an aggressive breast cancer that presents suddenly with breast swelling and redness due to tumor emboli in lymphatics. Lack of breast-feeding and obesity are IBC risk factors. We sought to demonstrate the combinatorial effects of a high-fat diet and nursing on lymphatic function and compare these to IBC tumor induced changes in lymphatic function. We hypothesize that risk factors for aggressive breast cancer may alter lymphatic function in the normal gland prior to tumor initiation. Methods. Following two rounds of pregnancy in 20 multiparous SCID Beige immunocompromised mice, half of the mice were force weaned while half nursed pups. Prior to forced weaning, half of each of these groups were fed a high fat diet (HFD: 60 Kcal %, N = 10) while the other half received a low-fat diet (LFD: 10 Kcal %, N = 10). Consecutive dynamic near-infrared fluorescence (NIRF) lymphatic imaging was performed at 6-7 months (covid interruption) and 14 months after initiating the diet by injecting a near-IR fluorophore into the mammary fatpad and recording lymphatic pulsing over 8 minutes using V++. Matlab and ImageJ were used to quantify pulsing rates on the ventral lymphatics in each animal. Fatpads were Ssubsequently inoculated with SUM149 IBC cells and imaging was repeated 16 months post diet initiation. Lymphatic imaging over time by HFD vs LFD was further studied in nulliparous animals. Tissues were collected for further analyses. ResultsData analysis prior to tumor injection, demonstrated lymphatic pulsing (pulses/4 minutes) increased over time in HFD force weaned (HFFW) and HFD nursing (HFN) animals only (65.5 vs 72.6, P=0.059;60.1 vs 76.6, P=0.0099, respectively). Comparing HFFW and HFN to matched LFD groups (LFFW and LFN), at 14 weeks HFD was associated with increased pumping after forced weaning (62.3 vs. 72.6, P=0.074), and nursing (62.5 vs 76.6, P=0.0023). There was an increase in pulsing after tumor initiation (16 months after initiation of diet) in all groups (80.1, 84.1, 83.2, 82.4, P > 0.05 all comparisons to initial timepoint). In a separate experiment examining HFD (N=5) vs LFD (N=5) in nulliparous mice, lymphatic contractile activity increased in all animals over. time, average ventral lymphatic contractile frequency for LFD and HFD at week 8, 11 and 14 weeks after diet initiation were 5, 8.64, 15.9 pumps/4 mins vs 11.8, 18.5, 28.2 pumps/4 mins, (P = 0.01, 0.05, and 0.0005 respectively). ConclusionsHFD increased lymphatic pulsing rate over time to a significantly greater extent than LFD continuing over 14 months independent of reproductive and nursing status. Tumor initiation prompted further increased pulsing rates beyond that observed after HFD across all groups. The magnitude of the effect of HFD on lymphatic pulsing approached the rate after tumor initiation, while reproductive variables did not impact lymphatic pulsing. Further studies are warranted to demonstrate the relationship if any between lymphatic pumping pre-initiation and LVI after tumor initiation and examine the role of intervention on reducing LVI.
ABSTRACT
The efficacy of COVID-19 vaccines in cancer populations remain unknown. Myeloproliferative neoplasms (MPNs), including chronic myeloid leukemia (CML), essential thrombocythemia (ET), polycythemia vera (PV), and myelofibrosis (MF) remain a vulnerable patient population and are immunocompromised due to impaired innate and adaptive immunity, heightened inflammation, and effects of ongoing treatment. We evaluate antibody and T-cell responses in MPN patients following completion of the BNT162b2 (Pfizer/BioNTech) and mRNA-1273 (Moderna) COVID-19 vaccine series. Patients with a known diagnosis of MPN presenting at Massachusetts General Hospital and eligible for COVID-19 vaccination were recruited. All participants gave informed consent and the study protocol was approved by the Institutional Review Board. 33 MPN patients were enrolled and 23 patients completed vaccination. Baseline and post-vaccination peripheral blood samples were collected and peripheral blood mononuclear cells (PBMCs) isolated. 26 vaccinated participants with no history of malignancy were included as healthy controls (PMID 33972942). Baseline characteristics are tabled below. Qualitative ELISA for human IgG/A/M against SARS-CoV-2 spike protein using donor serum was performed per manufacturer instructions. Seroconversion occurred in 22/23 (96%) of MPN patients and 25/26 (96%) of healthy controls (Figure). To measure SARS-CoV-2 T-cell immunity, an IFNγ ELISpot assay previously developed in convalescent and vaccinated healthy individuals was used. Freshly isolated PBMCs from patients were stimulated with commercially available overlapping 15mer peptide pools spanning the SARS-CoV-2 spike and nucleocapsid proteins. Given its size, the spike protein was split into two pools (Spike A or B). IFNγ-producing T-cells were quantified by counting the median spot forming units (SFU) per 2.5x10 5 PBMCs from duplicate wells. A positive threshold was defined as >6 SFUs per 2.5x105 PBMCs to either Spike A or B after subtraction of background, based on prior receiver operator curve (ROC) analysis of ELISpot responses (sensitivity 90% specificity 92%). Post-vaccination ELISpot responses occurred in 21/23 (91%) of MPN patients and 26/26 (100%) of healthy controls (p=0.99) (Figure). The median SFU to total spike protein (Spike A+B) increased after vaccination in both MPN patients (0 to 38, p=0.02) and healthy controls (6 to 134, p=0.002). MPN patients had significantly lower median SFU's on post-vaccination ELISpot compared to healthy controls (38 vs 134, p=0.044), although this was not significant after adjusting for age in multivariable logistic regression. MF patients had the lowest seroconversion and ELISpot response rates, and lowest median post-vaccination SFUs, although this was not significant. There were no other differences in post-vaccination SFUs with regards to gender, vaccine type, number of days postvaccine, treatment, and absolute lymphocyte count. Whole-blood assay based on the in vitro diagnostic QuantiFERON TB Gold Plus assay was also used to assess T-cell response. Heparinized whole blood from donors was stimulated with S1 and S2 subdomains for the SARS-CoV-2 spike protein, with measurement of IFNγ released into plasma with the QuantiFERON ELISA. IFNγ release of >0.3 IU/mL was considered a positive threshold, based on prior ROC analysis (sensitivity and specificity 100%). MPN patients had significantly lower IFNγ response rates compared to healthy controls (57% versus 100%, p=0.003) (Figure). Our findings demonstrate robust antibody and T-cell responses to BNT162b2 and mRNA-1273 vaccination in MPN patients, with >90% serologic and ELISpot responder rates. We detected subtle differences in T-cell responses in MPN patients compared to healthy controls. MPN patients had lower median post-vaccination ELISpot SFUs and lower rates of T-cell responses on IFNγ-whole blood assay compared to healthy controls. As the whole blood assay uses whole protein antigen rather than peptide pools, differences from ELISpot testing may reflect deficiencies in antigen pr cessing and presentation. It is unclear whether these subtle differences translate into less clinical protection from COVID-19, or to what extent our results are confounded by the older age of MPN patients. Further evaluation of B and T-cell responses to COVID-19 vaccination in a larger sample size of MPN patients is warranted.
ABSTRACT
This paper discusses the water law and the response to COVID-19 of the Navajo Nation. The aims of water law can be divided into three agendas. The Blue Agenda focuses on equitable and sustainable water access. The Green Agenda focuses on the protection of water quality. The Red Agenda focuses on public health and the control of disease transmission associated with water. The outbreak of COVID-19 in the Navajo Nation provides a case study for examining how the Red Agenda could be better integrated with the Blue and Green Agendas in water policy.