Oral vaccination with heat inactivated Mycobacterium bovis activates the complement system to protect against tuberculosis

Tuberculosis (TB) remains a pandemic affecting billions of people worldwide, thus stressing the need for new vaccines. Defining the correlates of vaccine protection is essential to achieve this goal. In this study, we used the wild boar model for mycobacterial infection and TB to characterize the protective mechanisms elicited by a new heat inactivated Mycobacterium bovis vaccine (IV). Oral vaccination with the IV resulted in significantly lower culture and lesion scores, particularly in the thorax, suggesting that the IV might provide a novel vaccine for TB control with special impact on the prevention of pulmonary disease, which is one of the limitations of current vaccines. Oral vaccination with the IV induced an adaptive antibody response and activation of the innate immune response including the complement component C3 and inflammasome. Mycobacterial DNA/RNA was not involved in inflammasome activation but increased C3 production by a still unknown mechanism. The results also suggested a protective mechanism mediated by the activation of IFN-γ producing CD8+ T cells by MHC I antigen presenting dendritic cells (DCs) in response to vaccination with the IV, without a clear role for Th1 CD4+ T cells. These results support a role for DCs in triggering the immune response to the IV through a mechanism similar to the phagocyte response to PAMPs with a central role for C3 in protection against mycobacterial infection. Higher C3 levels may allow increased opsonophagocytosis and effective bacterial clearance, while interfering with CR3-mediated opsonic and nonopsonic phagocytosis of mycobacteria, a process that could be enhanced by specific antibodies against mycobacterial proteins induced by vaccination with the IV. These results suggest that the IV acts through novel mechanisms to protect against TB in wild boar

Implementation and evaluation of a multi-level mental health promotion intervention for the workplace (MENTUPP): study protocol for a cluster randomised controlled trial

Background Well-organised and managed workplaces can be a source of wellbeing. The construction, healthcare and information and communication technology sectors are characterised by work-related stressors (e.g. high workloads, tight deadlines) which are associated with poorer mental health and wellbeing. The MENTUPP intervention is a flexibly delivered, multi-level approach to supporting small- and medium-sized enterprises (SMEs) in creating mentally healthy workplaces. The online intervention is tailored to each sector and designed to support employees and leaders dealing with mental health difficulties (e.g. stress), clinical level anxiety and depression, and combatting mental health-related stigma. This paper presents the protocol for the cluster randomised controlled trial (cRCT) of the MENTUPP intervention in eight European countries and Australia. Methods Each intervention country will aim to recruit at least two SMEs in each of the three sectors. The design of the cRCT is based on the experiences of a pilot study and guided by a Theory of Change process that describes how the intervention is assumed to work. SMEs will be randomly assigned to the intervention or control conditions. The aim of the cRCT is to assess whether the MENTUPP intervention is effective in improving mental health and wellbeing (primary outcome) and reducing stigma, depression and suicidal behaviour (secondary outcome) in employees. The study will also involve a process and economic evaluation. Conclusions At present, there is no known multi-level, tailored, flexible and accessible workplace-based intervention for the prevention of non-clinical and clinical symptoms of depression, anxiety and burnout, and the promotion of mental wellbeing. The results of this study will provide a comprehensive overview of the implementation and effectiveness of such an intervention in a variety of contexts, languages and cultures leading to the overall goal of delivering an evidence-based intervention for mental health in the workplace

Genomic assessment of quarantine measures to prevent SARS-CoV-2 importation and transmission

Mitigation of SARS-CoV-2 transmission from international travel is a priority. We evaluated the effectiveness of travellers being required to quarantine for 14-days on return to England in Summer 2020. We identified 4,207 travel-related SARS-CoV-2 cases and their contacts, and identified 827 associated SARS-CoV-2 genomes. Overall, quarantine was associated with a lower rate of contacts, and the impact of quarantine was greatest in the 16–20 age-group. 186 SARS-CoV-2 genomes were sufficiently unique to identify travel-related clusters. Fewer genomically-linked cases were observed for index cases who returned from countries with quarantine requirement compared to countries with no quarantine requirement. This difference was explained by fewer importation events per identified genome for these cases, as opposed to fewer onward contacts per case. Overall, our study demonstrates that a 14-day quarantine period reduces, but does not completely eliminate, the onward transmission of imported cases, mainly by dissuading travel to countries with a quarantine requirement

Changes in symptomatology, reinfection, and transmissibility associated with the SARS-CoV-2 variant B.1.1.7: an ecological study

Background The SARS-CoV-2 variant B.1.1.7 was first identified in December, 2020, in England. We aimed to investigate whether increases in the proportion of infections with this variant are associated with differences in symptoms or disease course, reinfection rates, or transmissibility. Methods We did an ecological study to examine the association between the regional proportion of infections with the SARS-CoV-2 B.1.1.7 variant and reported symptoms, disease course, rates of reinfection, and transmissibility. Data on types and duration of symptoms were obtained from longitudinal reports from users of the COVID Symptom Study app who reported a positive test for COVID-19 between Sept 28 and Dec 27, 2020 (during which the prevalence of B.1.1.7 increased most notably in parts of the UK). From this dataset, we also estimated the frequency of possible reinfection, defined as the presence of two reported positive tests separated by more than 90 days with a period of reporting no symptoms for more than 7 days before the second positive test. The proportion of SARS-CoV-2 infections with the B.1.1.7 variant across the UK was estimated with use of genomic data from the COVID-19 Genomics UK Consortium and data from Public Health England on spike-gene target failure (a non-specific indicator of the B.1.1.7 variant) in community cases in England. We used linear regression to examine the association between reported symptoms and proportion of B.1.1.7. We assessed the Spearman correlation between the proportion of B.1.1.7 cases and number of reinfections over time, and between the number of positive tests and reinfections. We estimated incidence for B.1.1.7 and previous variants, and compared the effective reproduction number, Rt, for the two incidence estimates. Findings From Sept 28 to Dec 27, 2020, positive COVID-19 tests were reported by 36 920 COVID Symptom Study app users whose region was known and who reported as healthy on app sign-up. We found no changes in reported symptoms or disease duration associated with B.1.1.7. For the same period, possible reinfections were identified in 249 (0·7% [95% CI 0·6–0·8]) of 36 509 app users who reported a positive swab test before Oct 1, 2020, but there was no evidence that the frequency of reinfections was higher for the B.1.1.7 variant than for pre-existing variants. Reinfection occurrences were more positively correlated with the overall regional rise in cases (Spearman correlation 0·56–0·69 for South East, London, and East of England) than with the regional increase in the proportion of infections with the B.1.1.7 variant (Spearman correlation 0·38–0·56 in the same regions), suggesting B.1.1.7 does not substantially alter the risk of reinfection. We found a multiplicative increase in the Rt of B.1.1.7 by a factor of 1·35 (95% CI 1·02–1·69) relative to pre-existing variants. However, Rt fell below 1 during regional and national lockdowns, even in regions with high proportions of infections with the B.1.1.7 variant. Interpretation The lack of change in symptoms identified in this study indicates that existing testing and surveillance infrastructure do not need to change specifically for the B.1.1.7 variant. In addition, given that there was no apparent increase in the reinfection rate, vaccines are likely to remain effective against the B.1.1.7 variant. Funding Zoe Global, Department of Health (UK), Wellcome Trust, Engineering and Physical Sciences Research Council (UK), National Institute for Health Research (UK), Medical Research Council (UK), Alzheimer's Society

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

Hospital admission and emergency care attendance risk for SARS-CoV-2 delta (B.1.617.2) compared with alpha (B.1.1.7) variants of concern: a cohort study

Background: The SARS-CoV-2 delta (B.1.617.2) variant was first detected in England in March, 2021. It has since rapidly become the predominant lineage, owing to high transmissibility. It is suspected that the delta variant is associated with more severe disease than the previously dominant alpha (B.1.1.7) variant. We aimed to characterise the severity of the delta variant compared with the alpha variant by determining the relative risk of hospital attendance outcomes. Methods: This cohort study was done among all patients with COVID-19 in England between March 29 and May 23, 2021, who were identified as being infected with either the alpha or delta SARS-CoV-2 variant through whole-genome sequencing. Individual-level data on these patients were linked to routine health-care datasets on vaccination, emergency care attendance, hospital admission, and mortality (data from Public Health England's Second Generation Surveillance System and COVID-19-associated deaths dataset; the National Immunisation Management System; and NHS Digital Secondary Uses Services and Emergency Care Data Set). The risk for hospital admission and emergency care attendance were compared between patients with sequencing-confirmed delta and alpha variants for the whole cohort and by vaccination status subgroups. Stratified Cox regression was used to adjust for age, sex, ethnicity, deprivation, recent international travel, area of residence, calendar week, and vaccination status. Findings: Individual-level data on 43 338 COVID-19-positive patients (8682 with the delta variant, 34 656 with the alpha variant; median age 31 years [IQR 17–43]) were included in our analysis. 196 (2·3%) patients with the delta variant versus 764 (2·2%) patients with the alpha variant were admitted to hospital within 14 days after the specimen was taken (adjusted hazard ratio [HR] 2·26 [95% CI 1·32–3·89]). 498 (5·7%) patients with the delta variant versus 1448 (4·2%) patients with the alpha variant were admitted to hospital or attended emergency care within 14 days (adjusted HR 1·45 [1·08–1·95]). Most patients were unvaccinated (32 078 [74·0%] across both groups). The HRs for vaccinated patients with the delta variant versus the alpha variant (adjusted HR for hospital admission 1·94 [95% CI 0·47–8·05] and for hospital admission or emergency care attendance 1·58 [0·69–3·61]) were similar to the HRs for unvaccinated patients (2·32 [1·29–4·16] and 1·43 [1·04–1·97]; p=0·82 for both) but the precision for the vaccinated subgroup was low. Interpretation: This large national study found a higher hospital admission or emergency care attendance risk for patients with COVID-19 infected with the delta variant compared with the alpha variant. Results suggest that outbreaks of the delta variant in unvaccinated populations might lead to a greater burden on health-care services than the alpha variant. Funding: Medical Research Council; UK Research and Innovation; Department of Health and Social Care; and National Institute for Health Research

Green Nanocomposites Based on Thermoplastic Starch: A Review

The development of bio-based materials has been a consequence of the environmental awareness generated over time. The versatility of native starch is a promising starting point for manufacturing environmentally friendly materials. This work aims to compile information on the advancements in research on thermoplastic starch (TPS) nanocomposites after the addition of mainly these four nanofillers: natural montmorillonite (MMT), organically modified montmorillonite (O-MMT), cellulose nanocrystals (CNC), and cellulose nanofibers (CNF). The analyzed properties of nanocomposites were mechanical, barrier, optical, and degradability. The most important results were that as the nanofiller increases, the TPS modulus and strength increase; however, the elongation decreases. Furthermore, the barrier properties indicate that that the incorporation of nanofillers confers superior hydrophobicity. However, the optical properties (transparency and luminosity) are mostly reduced, and the color variation is more evident with the addition of these fillers. The biodegradability rate increases with these nanocompounds, as demonstrated by the study of the method of burial in the soil. The results of this compilation show that the compatibility, proper dispersion, and distribution of nanofiller through the TPS matrix are critical factors in overcoming the limitations of starch when extending the applications of these biomaterials. TPS nanocomposites are materials with great potential for improvement. Exploring new sources of starch and natural nano-reinforcement could lead to a genuinely eco-friendly material that can replace traditional polymers in applications such as packaging

Competition between supernucleation and plasticization in the crystallization and rheological behavior of PCL/CNT-based nanocomposites and nanohybrids

16 pags., 14 figs., 4 tabs.PCL was blended with pristine multiwalled carbon nanotubes (MWCNT) and with a nanohybrid obtained from the same MWCNT but grafted with low molecular weight PCL, employing concentrations of 0.25 to 5 wt % of MWCNT and MWCNT-g-PCL. Excellent CNT dispersion was found in all samples leading to supernucleation of both nanofiller types. Nanohybrids with 1 wt % or less MWCNTs crystallize faster than nanocomposites (due to supernucleation), while the trend eventually reverses at higher nanotubes content (because of plasticization). Rheological results show that yield-like behavior develops in both nanocomposites, even for the minimum content of carbon nanotubes. In addition, the MWCNT-g-PCL family, when compared with the neat polymer, exhibits lower values of viscosity and modulus in oscillatory shear, and higher compliance in creep. These rheological differences are discussed in terms of the plasticization effect caused by the existence of low molecular weight free and grafted PCL chains in the nanohybrids. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2017, 55, 1310–1325.The authors acknowledge funding support from: the Spanish Ministerio de Economıa y Competitividad (MINECO) for the Project: MAT2012-36341-FEDER, Decanato de Investigación y Desarrollo Universidad Simón Bolívar DID G02. The POLYMAT/ UPV/EHU team acknowledges funding from the following projects: “UPV/EHU Infrastructure: INF 14/38”; “Mineco/ FEDER: SINF 130I001726XV1/Ref.: UNPV13–4E10–1726,” and “MinecoMAT2014–53437-C2-P.” R. A. Pérez-Camargo gratefully acknowledges the award of a PhD fellowship by POLYMAT Basque Center for Macromolecular Design and EngineeringPeer Reviewe