Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids

The aim of the study was to assess the total energy expenditure (TEE), resting energy expenditure (REE) and physical activity level (PAL) in home-living cachectic patients with advanced pancreatic cancer. The influence of an energy and protein dense oral supplement either enriched with or without the n-3 fatty acid eicosapentaenoic acid (EPA) and administered over an 8-week period was also determined. In total, 24 patients were studied at baseline. The total energy expenditure was measured using doubly labelled water and REE determined by indirect calorimetry. Patients were studied at baseline and then randomised to either oral nutritional supplement. Measurements were repeated at 8 weeks. At baseline, REE was increased compared with predicted values for healthy individuals (1387(42) vs 1268(32) kcal day-1, P=0.001), but TEE (1732(82) vs 1903(48) kcal day-1, P=0.023) and PAL (1.24(0.04) vs 1.50) were reduced. After 8 weeks, the REE, TEE and PAL of patients who received the control supplement did not change significantly. In contrast, although REE did not change, TEE and PAL increased significantly in those who received the n-3 (EPA) enriched supplement. In summary, patients with advanced pancreatic cancer were hypermetabolic. However, TEE was reduced and this was secondary to a reduction in physical activity. The control energy and protein dense oral supplement did not influence the physical activity component of TEE. In contrast, administration of the supplement enriched with EPA was associated with an increase in physical activity, which may reflect improved quality of life

Ad26 vector-based COVID-19 vaccine encoding a prefusion-stabilized SARS-CoV-2 Spike immunogen induces potent humoral and cellular immune responses

Development of effective preventative interventions against SARS-CoV-2, the etiologic agent of COVID-19 is urgently needed. The viral surface spike (S) protein of SARS-CoV-2 is a key target for prophylactic measures as it is critical for the viral replication cycle and the primary target of neutralizing antibodies. We evaluated design elements previously shown for other coronavirus S protein-based vaccines to be successful, e.g., prefusion-stabilizing substitutions and heterologous signal peptides, for selection of a S-based SARS-CoV-2 vaccine candidate. In vitro characterization demonstrated that the introduction of stabilizing substitutions (i.e., furin cleavage site mutations and two consecutive prolines in the hinge region of S2) increased the ratio of neutralizing versus non-neutralizing antibody binding, suggestive for a prefusion conformation of the S protein. Furthermore, the wild-type signal peptide was best suited for the correct cleavage needed for a natively folded protein. These observations translated into superior immunogenicity in mice where the Ad26 vector encoding for a membrane-bound stabilized S protein with a wild-type signal peptide elicited potent neutralizing humoral immunity and cellular immunity that was polarized towards Th1 IFN-gamma. This optimized Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in a phase I clinical trial (ClinicalTrials.gov Identifier: NCT04436276).Molecular basis of virus replication, viral pathogenesis and antiviral strategie

Single-shot Ad26 vaccine protects against SARS-CoV-2 in rhesus macaques

A safe and effective vaccine for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may be required to end the coronavirus disease 2019 (COVID-19) pandemic1–8. For global deployment and pandemic control, a vaccine that requires only a single immunization would be optimal. Here we show the immunogenicity and protective efficacy of a single dose of adenovirus serotype 26 (Ad26) vector-based vaccines expressing the SARS-CoV-2 spike (S) protein in non-human primates. Fifty-two rhesus macaques (Macaca mulatta) were immunized with Ad26 vectors that encoded S variants or sham control, and then challenged with SARS-CoV-2 by the intranasal and intratracheal routes9,10. The optimal Ad26 vaccine induced robust neutralizing antibody responses and provided complete or near-complete protection in bronchoalveolar lavage and nasal swabs after SARS-CoV-2 challenge. Titres of vaccine-elicited neutralizing antibodies correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate robust single-shot vaccine protection against SARS-CoV-2 in non-human primates. The optimal Ad26 vector-based vaccine for SARS-CoV-2, termed Ad26.COV2.S, is currently being evaluated in clinical trials

Effect of the dietary fat quality on insulin sensitivity.

Recent evidence shows that specific fatty acids affect cell metabolism, modifying the balance between fatty acid oxidation and lipogenesis. These effects may have important implications in addressing the present epidemic of nutrition-related chronic disease. Intake of dietary saturated and n-6 PUFA have increased while n-3 fatty acid intake has decreased. Obesity, type 2 diabetes and insulin resistance are highly prevalent, and both are strongly related to disorders of lipid metabolism characterized by an increased plasma and intracellular fatty acid availability. Thus, it has been hypothesized that change in the quality of dietary fat supply is able to modify the degree of insulin sensitivity. Animal studies provide support for this notion. However, there is limited human data either from normal or diabetic subjects. This review aims to analyse human studies that address this question. To this purpose, the experimental design, dietary compliance, insulin-sensitivity method used and confounding variables are discussed in order to identify the role of dietary fat quality as a risk factor for insulin resistance. Most studies (twelve of fifteen) found no effect relating to fat quality on insulin sensitivity. However, multiple study design flaws limit the validity of this conclusion. In contrast, one of the better designed studies found that consumption of a high-saturated-fat diet decreased insulin sensitivity in comparison to a high-monounsaturated-fat diet. We conclude that the role of dietary fat quality on insulin sensitivity in human subjects should be further studied, using experimental designs that address the limitations of existing data sets

Seasonal dynamics of carbon and nutrients from two contrasting tropical floodplain systems in the Zambezi River basin

Floodplains are important biogeochemical reactors during fluvial transport of carbon and nutrient species towards the oceans. In the tropics and subtropics, pronounced rainfall seasonality results in highly dynamic floodplain biogeochemistry. The massive construction of dams, however, has significantly altered the hydrography and chemical characteristics of many (sub)tropical rivers. In this study, we compare organic-matter and nutrient biogeochemistry of two large, contrasting floodplains in the Zambezi River basin in southern Africa: the Barotse Plains and the Kafue Flats. Both systems are of comparable size but differ in anthropogenic influence: while the Barotse Plains are still in large parts pristine, the Kafue Flats are bordered by two hydropower dams. The two systems exhibit different flooding dynamics, with a larger contribution of floodplain-derived water in the Kafue Flats and a stronger peak flow in the Barotse Plains. Distinct seasonal differences have been observed in carbon and nutrient concentrations, loads, and export and retention behavior in both systems. The simultaneous retention of particulate carbon and nitrogen and the net export of dissolved organic and inorganic carbon and nitrogen suggested that degradation of particulate organic matter was the dominant process influencing the river biogeochemistry during the wet season in the Barotse Plains and during the dry season in the Kafue Flats. Reverse trends during the dry season indicated that primary production was important in the Barotse Plains, whereas the Kafue Flats seemed to have both primary production and respiration occurring during the wet season, potentially occurring spatially separated in the main channel and on the floodplain. Carbon-to-nitrogen ratios of particulate organic matter showed that soil-derived material was dominant year-round in the Barotse Plains, whereas the Kafue Flats transported particulate organic matter that had been produced in the upstream reservoir during the wet season. Stable carbon isotopes suggested that inputs from the inundated floodplain to the particulate organic-matter pool were important during the wet season, whereas permanent vegetation contributed to the material transported during the dry season. This study revealed effects of dam construction on organic-matter and nutrient dynamics on the downstream floodplain that only become visible after longer periods, and it highlights how floodplains act as large biogeochemical reactors that can behave distinctly differently from the entire catchment

Suitability of PER.C6 (R) cells to generate epidemic and pandemic influenza vaccine strains by reverse genetics

Reverse genetics, the generation of influenza viruses from cDNA. presents a rapid method for creating vaccine strains. The technique necessitates the use of cultured cells. Due to technical and regulatory requirements, the choice of cell lines for production of human influenza vaccines is limited. PER.C6 (R) cells, among the most extensively characterized and documented cells, support growth of all influenza Viruses tested to date, and can be grown to high densities in large bioreactors in the absence of serum or micro carriers. Here, the suitability of these cells for the generation of influenza Viruses by reverse genetics was investigated. A range of viruses reflective of vaccine strains was rescued exclusively using PER.C6 cells by Various transfection methods, including an animal component-free procedure. Furthermore, a whole inactivated vaccine carrying the HA and NA segments of A/HK/156/97 (H5N1) that was both rescued from and propagated oil PER.C6 cells, conferred protection in a mouse model. Thus PER.C6 cells provide an attractive platform for generation of influenza vaccine strains via reverse genetics

Highly conserved protective epitopes on influenza B viruses

Identification of broadly neutralizing antibodies against influenza A viruses has raised hopes for the development of monoclonal antibody-based immunotherapy and "universal" vaccines for influenza. However, a substantial part of the annual flu burden is caused by two cocirculating, antigenically distinct lineages of influenza B viruses. Here, we report human monoclonal antibodies, CR8033, CR8071, and CR9114, that protect mice against lethal challenge from both lineages. Antibodies CR8033 and CR8071 recognize distinct conserved epitopes in the head region of the influenza B hemagglutinin (HA), whereas CR9114 binds a conserved epitope in the HA stem and protects against lethal challenge with influenza A and B viruses. These antibodies may inform on development of monoclonal antibody-based treatments and a universal flu vaccine for all influenza A and B viruses.link_to_subscribed_fulltex