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Preventive and modeling approaches to address the COVID-19 pandemic have been primarily based on the age or occupation, and often disregard the importance of heterogeneity in population contact structure and individual connectivity. To address this gap, we developed models based on Erdős-Rényi and a power law degree distribution that first incorporate the role of heterogeneity and connectivity and then can be expanded to make assumptions about demographic characteristics. Results demonstrate that variations in the number of connections of individuals within a population modify the impact of public health interventions such as lockdown or vaccination approaches. We conclude that the most effective strategy will vary depending on the underlying contact structure of individuals within a population and on timing of the interventions., Competing Interests: The authors have declared that no competing interests exist.

Nutrition in pregnancy and early childhood affects later blood pressure and precursors of atherosclerosis, but its influence on arterial stiffness is unexplored. This study determines whether exposure to improved nutrition during early life influences Augmentation index (AI) and pulse wave velocity (PWV) in mid-adulthood. We included 1221 adults (37-54y) who participated in a cluster-randomized nutritional supplementation trial of a protein-energy beverage (Atole), conducted between 1969-1977 in Guatemala. The comparison group received Fresco, a low-calorie protein-free beverage. In 2015-17, we measured anthropometry (weight, height, and waist-to-height ratio); AI and PWV (using carotid-femoral tonometry); blood pressure; fasting plasma glucose and serum lipids; and sociodemographic characteristics. Based on patterns of exposure, we characterized participants as fully, partially or unexposed to the intervention from conception to their second birthday (the 'first 1000 days'). We fit pooled and sex-specific models using intention-to-treat, difference-in-difference regression analysis to test whether exposure to the supplement in the first 1000 days was associated with AI and PWV in adulthood adjusting for basal and current sociodemographic variables and current life-style and cardio-metabolic risk factors. Prevalence of obesity in men and women was 39.6% and 19.6%, and prevalence of hypertension was 44.0% and 36.0%, respectively. Women had higher AI (34.4±9.6%) compared to men (23.0± 9.8%), but had similar PWV (7.60±1.13 m/s and 7.60±1.31, respectively). AI did not differ significantly across intervention groups. PWV was lower in individuals with full exposure to the supplement during the first 1000 days (-0.39m/s, 95% CI -0.87, 0.09; p = 0.1) compared to unexposed individuals. This difference was similar after adjusting for cardio-metabolic risk factors (-0.45m/s; 95%C-0.93, 0.01; p = 0.06). Exposure to improved nutrition during the first 1000 days was marginally associated with lower PWV, but not with AI., Competing Interests: The authors have declared that no competing interests exist.

Growing evidence supports the role of preconception maternal nutritional status (PMNS) on birth outcomes; however, evidence of relationships with child growth are limited. We examined associations between PMNS (height, weight and body mass index- BMI) and offspring growth during the first 1000 days. We used prospective cohort data from a randomized-controlled trial of preconception micronutrient supplementation in Vietnam, PRECONCEPT (n = 1409). Poisson regression models were used to examine associations between PMNS and risk of offspring stunting (<-2 HAZ) at 2 years. We used path analytic models to examine associations with PMNS on fetal growth (ultrasound measurements) and offspring HAZ at birth and 2 years. All models were adjusted for child age, sex, gestational weight gain, education, socioeconomic status and treatment group. A third of women had a preconception height < 150cm or weight < 43 kg. Women with preconception height < 150 cm or a weight < 43 kg were at increased risk of having a stunted child at 2 years (incident risk ratio IRR: 1.85, 95% CI 1.51-2.28; IRR 1.35, 95% CI 1.10-1.65, respectively). While the traditional low BMI cut-off (< 18.5 kg/m2) was not significant, lower BMI cut-offs (< 17.5 kg/m2 or < 18.0 kg/m2) were significantly associated with 1.3 times increased risk of child stunting. In path models, PMNS were positively associated with fetal growth (ultrasound measurements) and offspring HAZ at birth and 2 years. For each 1 standard deviation (SD) increase in maternal height and weight, offspring HAZ at 2 years increased by 0.30 SD and 0.23 SD, respectively. In conclusion, PMNS influences both offspring linear growth and risk of stunting across the first 1000 days. These findings underscore the importance of expanding the scope of current policies and strategies to include the preconception period in order to reduce child stunting., Competing Interests: The authors have declared that no competing interests exist.

The CXCR4/CXCL12 axis has been extensively associated with different types of cancer correlating with higher aggressiveness and metastasis. In diffuse large B-cell lymphoma (DLBCL), the expression of the chemokine receptor CXCR4 is involved in the dissemination of malignant B cells and is a marker of poor prognosis. CXCR7 is a chemokine receptor that binds to the same ligand as CXCR4 and regulates de CXCR4-CXCL12 axis. These findings together with the report of CXCR7 prognostic value in several tumor types, led us to evaluate the expression of CXCR7 in diffuse large B-cell lymphoma biopsies. Here, we describe that CXCR7 receptor is an independent prognostic factor that associates with good clinical outcome. Moreover, the expression of CXCR7 associates with increased survival in CXCR4+ but not in CXCR4- DLBCL patients. Thus, the combined immunohistochemical evaluation of both CXCR7 and CXCR4 expression in DLBCL biopsies may improve their prognostic value as single markers. Finally, we show that CXCR7 overexpression in vitro is able to diminish DLBCL cell survival and increase their sensitivity to antitumor drugs. Hence, further studies on the CXCR7 receptor may establish its role in DLBCL and the molecular mechanisms that modulate CXCR4 activity., Competing Interests: The authors have declared that no competing interests exist.

Objective: Preconception micronutrient interventions may be a promising approach to reduce anemia and iron deficiency during pregnancy, but currently we have limited data to inform policies. We evaluated whether providing additional pre-pregnancy weekly iron-folic acid (IFA) or multiple micronutrient (MM) supplements compared to only folic acid (FA) improves iron status and anemia during pregnancy and early postpartum., Methods: We conducted a double blind randomized controlled trial in which 5011 Vietnamese women were provided with weekly supplements containing either only 2800 μg FA (control group), IFA (60 mg Fe and 2800 μg FA) or MM (15 micronutrients with similar amounts of IFA). All women who became pregnant (n = 1813) in each of the 3 groups received daily IFA (60 mg Fe and 400 μg FA) through delivery. Hematological indicators were assessed at baseline (pre-pregnancy), during pregnancy, 3 months post-partum, and in cord blood. Adjusted generalized linear models were applied to examine the impact of preconception supplementation on anemia and iron stores, using both intention to treat and per protocol analyses (women consumed supplements ≥ 26 weeks before conception)., Results: At baseline, 20% of women were anemic, but only 14% had low iron stores (ferritin <30 μg/L) and 3% had iron deficiency (ferritin <12 μg/L). The groups were balanced for baseline characteristics. Anemia prevalence increased during pregnancy and post-partum but was similar among intervention groups. In intention to treat analyses, prenatal ferritin was significantly higher among women receiving MM (geometric mean (μg/L) [95% CI]: 93.6 [89.3-98.2]) and IFA (91.9 [87.6-96.3]) compared to control (85.3 [81.5-89.2]). In per protocol analyses, women receiving MM or IFA had higher ferritin 3 months postpartum (MM 118.2 [109.3-127.8]), IFA 117.8 [108.7-127.7] vs control 101.5 [94.0-109.7]) and gave birth to infants with greater iron stores (MM 184.3 [176.1-192.9]), IFA 189.9 [181.6-198.3] vs control 175.1 [167.9-182.6])., Conclusion: Preconception supplementation with MM or IFA resulted in modest increases in maternal and infant iron stores but did not impact anemia. Further research is needed to characterize the etiology of anemia in this population and identify effective interventions for reducing prenatal anemia., Trial Registration: ClinicalTrials.Gov NCT01665378., Competing Interests: PHN, MY, IGC, HP, HN, TVT, SN, RM and UR have no conflicts of interest. KBH and GAR are employed by the institutions that funded the research. They participated in study design, but were not directly involved in the implementation of the study both during data collection and analysis. Their contributions to this manuscript include interpretation of findings and review of the final manuscripts.

Objective: To analyze the titers of the IgG and IgM antibodies against human herpesvirus 6A/B (HHV-6A/B) in multiple sclerosis (MS) patients treated with different disease modified therapies (DMTs) along two-years of follow-up., Methods: We collected 2163 serum samples from 596 MS; for 301 MS patients a 2-years follow-up was performed. Serum samples of 337 healthy controls were also analyzed. Anti-HHV-6A/B IgG and IgM were analyzed by ELISA (Panbio)., Results: We found that 129/187 (69.0%) MS patients with a decrease of the anti-HHV-6A/B IgG titers after 2-years with DMTs were free of relapses and progression vs. 46/113 (40.7%) of MS patients with an increase of the anti-HHV-6A/B IgG titers (p = 0.0000015); the higher significance was found for natalizumab. Furthermore, we found that anti-HHV-6A/B IgG titers reached their highest value two weeks before the relapse (p = 0.0142), while the anti-HHV-6A/B IgM titers reached their highest value one month before the relapse (p = 0.0344)., Conclusion: The measurement of the anti-HHV-6A/B IgG titers could be a good biomarker of clinical response to the different DMTs. The increase of the anti-HHV-6A/B IgG and IgM titers predicts the upcoming clinical relapses. However, further longitudinal studies are needed to validate these results.

Background: Micronutrient deficiencies are a public health concern worldwide negatively affecting maternal and child health outcomes. The primary underlying causes of micronutrient deficiencies are insufficient intake and poor bioavailability of micronutrients. However, reliable data on micronutrient intakes are sparse. The objectives of this study were to identify the key local food sources providing the majority of micronutrients and assess the adequacy and determinants of micronutrient intakes., Methods: The study used data from a survey of 4,983 rural women of reproductive age (WRA) participating in a preconception micronutrient supplementation trial in Vietnam. Micronutrient intakes were assessed using a validated 107-item semi-quantitative food-frequency questionnaire. Multivariate linear and logistic regression analyses were used to examine the association between socioeconomic status and micronutrient intakes., Results: Starchy staples were the main source of iron and zinc (37% and 54%, respectively) with only a small proportion from meat (10% and 18%, respectively). The primary source of folate and vitamin A were vegetables; vitamin B12 came from meat and eggs. The proportion of the population with intakes below the estimated average requirement was 25% for iron, 16% for zinc, 54% for folate, 64% for vitamin B12 and 27% for vitamin A. Socioeconomic status was the main determinant of micronutrient intakes. WRA in the highest quintile consumed 26% more iron, 19% more zinc, 36% more folate, 82% more vitamin B12 and 47% more vitamin A compared to those in the lowest quintile. Women in the upper quintiles of SES were more likely to obtain nutrients from more nutritious and higher bioavailable foods than those in the lowest quintile., Conclusions: Underprivileged women were at increased risk for insufficient micronutrient intakes due to poor diet quality. Targeted efforts to promote the consumption of local nutrient rich foods along with educational programs and social development are needed.

Background: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV) is a member of type-W endogenous retrovirus family (HERV-W), known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls., Results: 178 MS patients (62.9% women) and 124 controls (56.5% women) were included. MSRV env load (copies/pg of DNA) was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs). MSRV load was more elevated in MS patients than in controls (p = 4.15e-7). MS women presented higher MSRV load than control women (p = 0.009) and MS men also had higher load than control men (p = 2.77e-6). Besides, women had higher levels than men, both among patients (p = 0.007) and controls (p = 1.24e-6). Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively)., Conclusions: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

African horse sickness (AHS) is a lethal viral disease of equids, which is transmitted by Culicoides midges that become infected after biting a viraemic host. The use of live attenuated vaccines has been vital for the control of this disease in endemic regions. However, there are safety concerns over their use in non-endemic countries. Research efforts over the last two decades have therefore focused on developing alternative vaccines based on recombinant baculovirus or live viral vectors expressing structural components of the AHS virion. However, ethical and financial considerations, relating to the use of infected horses in high biosecurity installations, have made progress very slow. We have therefore assessed the potential of an experimental mouse-model for AHSV infection for vaccine and immunology research. We initially characterised AHSV infection in this model, then tested the protective efficacy of a recombinant vaccine based on modified vaccinia Ankara expressing AHS-4 VP2 (MVA-VP2).