Cluster Analysis Identifies Distinct Patterns of T-Cell and Humoral Immune Responses Evolution Following a Third Dose of SARS-CoV-2 Vaccine in People Living with HIV.

peer reviewed(1) Background: Many vaccines require higher, additional doses or adjuvants to provide adequate protection for people living with HIV (PLWH). Despite their potential risk of severe coronavirus disease 2019, immunological data remain sparse, and a clear consensus for the best booster strategy is lacking. (2) Methods: Using the data obtained from our previous study assessing prospective T-cell and humoral immune responses before and after administration of a third dose of SARS-CoV-2 vaccine, we assessed the correlations between immune parameters reflecting humoral and cellular immune responses. We further aimed at identifying distinct clusters of patients with similar patterns of immune response evolution to determine how these relate to demographic and clinical factors. (3) Results: Among 80 PLWH and 51 healthcare workers (HCWs) enrolled in the study, cluster analysis identified four distinct patterns of evolution characterised by specific immune patterns and clinical factors. We observed that immune responses appeared to be less robust in cluster A, whose individuals were mostly PLWH who had never been infected with SARS-CoV-2. Cluster C, whose individuals showed a particularly drastic increase in markers of humoral immune response following the third dose of vaccine, was mainly composed of female participants who experienced SARS-CoV-2. Regarding the correlation study, although we observed a strong positive correlation between markers mirroring humoral immune response, markers of T-cell response following vaccination correlated only in a lesser extent with markers of humoral immunity. This suggests that neutralising antibody titers alone are not always a reliable reflection of the magnitude of the whole immune response. (4) Conclusions: Our findings show heterogeneity in immune responses among SARS-CoV-2 vaccinated PLWH. Specific subgroups could therefore benefit from distinct immunization strategies. Prior or breakthrough natural infection enhances the activity of vaccines and must be taken into account for informing global vaccine strategies among PLWH, even those with a viro-immunologically controlled infection

Kinetics and persistence of the cellular and humoral immune responses to BNT162b2 mRNA vaccine in SARS-CoV-2-naive and -experienced subjects

Background: Understanding and measuring the individual level of immune protection and its persistence at both humoral and cellular levels after SARS-CoV-2 vaccination is mandatory for the management of the vaccination booster campaign. Our prospective study was designed to assess the immunogenicity of the BNT162b2 mRNA vaccine in triggering the humoral and the cellular immune response in healthcare workers up to 6 months after two doses vaccination. Methods: This prospective study enrolled 208 healthcare workers from the Liège University Hospital (CHU) of Liège in Belgium. All participants received two doses of BioNTech/Pfizer COVID-19 vaccine (BNT162b2). Fifty participants were SARS-CoV-2 experienced (self-reported SARS-CoV-2 infection) and 158 were naïve (no reported SARS-CoV-2 infection) before the vaccination. Blood sampling was performed at the day of the first (T0) and second (T1) vaccine doses administration, then at 2 weeks (T2), 4 weeks (T3) and 6 months (T4) after the 1st vaccine dose administration. A total of 1024 blood samples were collected. All samples were tested for the presence of anti-Spike antibodies using DiaSorin LIAISON SARS-CoV-2 TrimericS IgG assay. Neutralizing antibodies against the SARS-CoV-2 Wuhan-like variant strain were quantified in all samples using a Vero E6 cell-based neutralization-based assay. Cell-mediated immune response was evaluated at T4 on 80 participants by measuring the secretion of IFN- on peripheral blood lymphocytes using the QuantiFERON Human IFN- SARS-CoV-2, Qiagen. All participants were monitored on weekly-basis for the novo SARS-COV-2 infection for 4 weeks after the 1st vaccine dose administration. We analyzed separately the naïve and experienced participants. Findings: We found that anti-spike antibodies and neutralization capacity levels were significantly higher in SARS-CoV-2 experienced healthcare workers (HCWs) compared to naïve HCWs at all time points analyzed. Cellular immune response was similar in the two groups six months following 2nd dose of the vaccine. Reassuringly, most participants had a detectable cellular immune response to SARS-CoV-2 six months after vaccination. Besides the impact of SARS-CoV-2 infection history on immune response to BNT162b2 mRNA vaccine, we observed a significant negative correlation between age and persistence of humoral response. Cellular immune response was, however, not significantly correlated to age, although a trend towards a negative impact of age was observed. Conclusions: Our data strengthen previous findings demonstrating that immunization through vaccination combined with natural infection is better than 2 vaccine doses immunization or natural infection alone. It may have implications for personalizing mRNA vaccination regimens used to prevent severe COVID-19 and reduce the impact of the pandemic on the healthcare system. More specifically, it may help prioritizing vaccination, including for the deployment of booster doses

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Mitochondrial physiology

As the knowledge base and importance of mitochondrial physiology to evolution, health and disease expands, the necessity for harmonizing the terminology concerning mitochondrial respiratory states and rates has become increasingly apparent. The chemiosmotic theory establishes the mechanism of energy transformation and coupling in oxidative phosphorylation. The unifying concept of the protonmotive force provides the framework for developing a consistent theoretical foundation of mitochondrial physiology and bioenergetics. We follow the latest SI guidelines and those of the International Union of Pure and Applied Chemistry (IUPAC) on terminology in physical chemistry, extended by considerations of open systems and thermodynamics of irreversible processes. The concept-driven constructive terminology incorporates the meaning of each quantity and aligns concepts and symbols with the nomenclature of classical bioenergetics. We endeavour to provide a balanced view of mitochondrial respiratory control and a critical discussion on reporting data of mitochondrial respiration in terms of metabolic flows and fluxes. Uniform standards for evaluation of respiratory states and rates will ultimately contribute to reproducibility between laboratories and thus support the development of data repositories of mitochondrial respiratory function in species, tissues, and cells. Clarity of concept and consistency of nomenclature facilitate effective transdisciplinary communication, education, and ultimately further discovery

Variation in general supportive and preventive intensive care management of traumatic brain injury: a survey in 66 neurotrauma centers participating in the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study

Abstract Background General supportive and preventive measures in the intensive care management of traumatic brain injury (TBI) aim to prevent or limit secondary brain injury and optimize recovery. The aim of this survey was to assess and quantify variation in perceptions on intensive care unit (ICU) management of patients with TBI in European neurotrauma centers. Methods We performed a survey as part of the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. We analyzed 23 questions focused on: 1) circulatory and respiratory management; 2) fever control; 3) use of corticosteroids; 4) nutrition and glucose management; and 5) seizure prophylaxis and treatment. Results The survey was completed predominantly by intensivists (n = 33, 50%) and neurosurgeons (n = 23, 35%) from 66 centers (97% response rate). The most common cerebral perfusion pressure (CPP) target was > 60 mmHg (n = 39, 60%) and/or an individualized target (n = 25, 38%). To support CPP, crystalloid fluid loading (n = 60, 91%) was generally preferred over albumin (n = 15, 23%), and vasopressors (n = 63, 96%) over inotropes (n = 29, 44%). The most commonly reported target of partial pressure of carbon dioxide in arterial blood (PaCO2) was 36–40 mmHg (4.8–5.3 kPa) in case of controlled intracranial pressure (ICP) < 20 mmHg (n = 45, 69%) and PaCO2 target of 30–35 mmHg (4–4.7 kPa) in case of raised ICP (n = 40, 62%). Almost all respondents indicated to generally treat fever (n = 65, 98%) with paracetamol (n = 61, 92%) and/or external cooling (n = 49, 74%). Conventional glucose management (n = 43, 66%) was preferred over tight glycemic control (n = 18, 28%). More than half of the respondents indicated to aim for full caloric replacement within 7 days (n = 43, 66%) using enteral nutrition (n = 60, 92%). Indications for and duration of seizure prophylaxis varied, and levetiracetam was mostly reported as the agent of choice for both seizure prophylaxis (n = 32, 49%) and treatment (n = 40, 61%). Conclusions Practice preferences vary substantially regarding general supportive and preventive measures in TBI patients at ICUs of European neurotrauma centers. These results provide an opportunity for future comparative effectiveness research, since a more evidence-based uniformity in good practices in general ICU management could have a major impact on TBI outcome

Methodology for the integration of low temperature district network in urban area

The energy services delivered to urban areas in Switzerland make up more than 45% of the national energy consumption. Thus, in the framework of the Tetraener European project, a methodology has been developed to design low temperature thermal networks based on process integration techniques and GIS (geographical information system) database. Water is the renewable energy vector which brings the resource from a lake or river to the end-users. Connecting buildings to the network reduces the external energetic dependency of a given urban area as well as it contributes to reduce the CO2 and other pollutant emissions in a densely populated place. Heat pumps located in the buildings ensure the heat transfer from the district network to the domestic loops. The grid use is versatile since it can either act as a heat source or sink depending on the need (heating/cooling). This work aims for an optimal integration of heating/cooling using pinch analysis for the design and/or retrofit of the network and building temperature control strategy. The combined use of process integration techniques and GIS energy platform is illustrated with the GLN (Geneva Lake Nation) case study. This network located down-town Geneva uses water from the nearby Lake Geneva as an energy source for the surrounding buildings to take advantage of this local resource. Connected buildings to benefit from this sustainable system include those from international organizations. The latter clients have important needs especially in terms of cooling for their large-size conference rooms. The GLN network also acts as a source of non-drinkable water for fountains and irrigation purpose in the surrounding parks

Att utvecklas som ledare : En kvalitativ studie om möjligheterna till ledarskapsutveckling genom medarbetarsamtal

Ledarskapsutveckling anses av många företag vara ett verktyg för att öka en organisations konkurrenskraft; denna utveckling sker vanligen genom kurser och utbildningar. Ett stående problem som har uppdagats gällande dessa kurser och utbildningar rör sammanhanget som de genomförs i. Ofta genomförs kurserna utanför den verklighet som ledarna normalt arbetar i; exempelvis anordnas utbildningar på annan ort. Denna problematik leder till att resurserna som investeras i ledarskapsutveckling inte resulterar i effektiva resultat, varkenför ledarna eller företagen.Ett verktyg som företag ofta använder för utveckling av sin personal i allmänhet är medarbetarsamtal. Dessa samtal är regelbundna och sker i samma kontext som personalen vanligen arbetar i. Ledarskapsutveckling och den svenska varianten medarbetarsamtal är två områden som oss veterligen inte har sammankopplats i tidigare forskning. Vårt syfte i denna uppsats är att skapa förståelse gällande vilka möjligheter som finns för ledarskapsutveckling genom medarbetarsamtal. Vidare har vi även sökt förståelse för huruvida individuella skillnader, såsom synen på sitt eget ledarskap samt ledares benägenheten till självutveckling, potentiellt påverkar utvecklingen som sker genom medarbetarsamtal. För att skapa förståelse kring dessa områden behandlar vi i denna uppsats tidigare forskning gällande ledarskapsutveckling, medarbetarsamtal, transaktionellt-transformerande ledarskap samt självutveckling för ledare. Utifrån denna teoretiska förståelse har vi använt oss av en kvalitativ metod och semistrukturerade intervjuer för att besvara vår frågeställning och uppfylla vårt syfte.I uppsatsen har vi valt att avgränsa oss till tjänstesektorn och efter intervjuer med sju respondenter, som alla är ledare, har vi använt oss av en tematisk analys därvikopplar deras svar till befintlig teori och även söker att uppfylla uppsatsens syfte. Utifrån vår analys har vi kunnat konstatera att det finns möjligheter för ledarskapsutveckling genom medarbetarsamtal. Vi menar att dessa möjligheter främst gäller inommänsklig utveckling, snarare än mellanmänsklig, samt att åtminstone två faktorer påverkar potentialen av denna utveckling. Den överordnade ledaren i samtalen har en stor betydelse för möjligheterna till ledarskapsutveckling genom dessa samtal. Den andra påverkande faktorn är huruvida medarbetarsamtalen har formella inslag av ledarskap eller ej. Vi har inte kunnat se att synen ledarna har på sitt eget ledarskap eller att benägenheten till självutveckling påverkar vad ledarna har lärt sig om ledarskap av medarbetarsamtalen

Differential Frankia protein patterns induced by phenolic extracts from Myricaceae seeds

Two-dimensional gel electrophoresis was used to identify differentially displayed proteins expressed during the early symbiotic interactions between the bacterium Frankia and actinorhizal plants. Myricaceae, the most primitive actinorhizal family, was used as an experimental model to study specificity mechanisms because it includes species with either narrowor large specificity. Seed phenolic extracts from two Myricaceae species, Myrica gale, a narrow specificity host and Morella cerifera considered as a promiscuous host, were used to induce three Frankia strains ACN14a, M16467 and Ea112. The global protein pattern was altered by exposure to the plant extracts. The addition of 30 mg l21 of seed phenolic extracts provoked the inhibition of many protein biosynthesis whereas 1 and 10 mg l21 induced a global reprogramming of Frankia protein pattern. Changes in intensity of 115 spots in response to seed extracts were detected and analyzed by matrix-assisted laser desorption/ ionization time of flight mass spectrometry. Fifty proteins were efficiently identified with Frankia protein data banks deduced from the sequences of Frankia strains ACN14a and EaN1pec genomes. Differential proteins were involved in different metabolism pathways such as glycolysis and gluconeogenesis, transcription, fatty acids, carbohydrates, coenzymes and purines metabolisms. Chaperones biosynthesis and iron transport regulation, essential for nitrogen fixation, seem to be strain dependant. Several proteins possibly involved in the regulation of nodulation were also differentially expressed. The most obvious response was the upregulation of oxidative stress proteins such as FeSOD and Tellurium resistance proteins, suggesting a reorganization of Frankia metabolism to protect against host plant defense

Frankia alni proteome under nitrogen-fixing and nitrogen-replete conditions

Frankia alni induces root nodules on Alnus, in which the bacterium differentiates into nitrogen (N)-fixing cells called vesicles. In culture, F. alni also undergoes major morphological changes as it alternates between N-replete and N-fixing conditions. Lack of biologically available N induces the synthesis of vesicles in which nitrogenase is protected from molecular oxygen by a thick lipid hopanoid envelope. Very little is known about the molecular basis of Frankia–host interaction as well as Frankia cell differentiation. The recent determination of the complete genome sequence of F. alni strain ACN14a has permitted us to characterize its proteome, particularly in the extracellular compartment, which could be involved in Frankia–host interaction, and in the switch from N-replete to N-fixing conditions. To that end, 126 bacterial proteins were analyzed by two-dimensional protein gel electrophoresis and identified by matrix-assisted laser desorption/ionization time of flight fingerprinting using a F. alni proteome database. Interestingly, the extracellular fraction contains some glycolytic enzymes lacking secretion signals, already reported to be extracellularly localized in some streptococci, as well as some abundant stress-resistance proteins. As expected, several proteins involved in N assimilation and oxidative defense system were upregulated in F. alni grown under N-fixing vs N-replete conditions. Furthermore, two Raf kinase inhibitor protein homologs that could play a role in cellular signaling, and a hemoglobin-like protein HbN that could be involved in detoxification of nitric oxide were also upregulated. More surprising, a succinate dehydrogenase was strongly downregulated, which could be linked to the need of pyruvate for the biosynthesis of hopanoids or to reduced oxygen diffusion in vesicles

Solid-phase extraction as sample preparation of water samples for cell-based and other in vitro bioassays

In vitro bioassays are increasingly used for water quality monitoring. Surface water samples often need to be enriched to observe an effect and solid-phase extraction (SPE) is commonly applied for this purpose. The applied methods are typically optimised for the recovery of target chemicals and not for effect recovery for bioassays. A review of the few studies that have evaluated SPE recovery for bioassays showed a lack of experimentally determined recoveries. Therefore, we systematically measured effect recovery of a mixture of 579 organic chemicals covering a wide range of physicochemical properties that were spiked into a pristine water sample and extracted using large volume solid-phase extraction (LVSPE). Assays indicative of activation of xenobiotic metabolism, hormone receptor-mediated effects and adaptive stress responses were applied, with non-specific effects determined through cytotoxicity measurements. Overall, effect recovery was found to be similar to chemical recovery for the majority of bioassays and LVSPE blanks had no effect. Multi-layer SPE exhibited greater recovery of spiked chemicals compared to LVSPE, but the blanks triggered cytotoxicity at high enrichment. Chemical recovery data together with single chemical effect data were used to retrospectively estimate with reverse recovery modelling that there was typically less than 30% effect loss expected due to reduced SPE recovery in published surface water monitoring studies. The combination of targeted experiments and mixture modelling clearly shows the utility of SPE as a sample preparation method for surface water samples, but also emphasizes the need for adequate controls when extraction methods are adapted from chemical analysis workflows