Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation.

OBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. DESIGN: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study. SETTING: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation. PATIENTS OR SUBJECTS: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia. INTERVENTIONS: During our comparison, we did not perform any intervention. MEASUREMENTS AND MAIN RESULTS: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites. CONCLUSIONS: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.

Modulation of Metabolomic Profile in Sepsis According to the State of Immune Activation.

OBJECTIVE: To investigate the metabolomic profiles associated with different immune activation states in sepsis patients. DESIGN: Subgroup analysis of the PROVIDE (a Personalized Randomized trial of Validation and restoration of Immune Dysfunction in severe infections and Sepsis) prospective clinical study. SETTING: Results of the PROVIDE study showed that patients with sepsis may be classified into three states of immune activation: 1) macrophage-activation-like syndrome (MALS) characterized by hyperinflammation, sepsis-induced immunoparalysis, and 3) unclassified or intermediate patients without severe immune dysregulation. PATIENTS OR SUBJECTS: Two hundred ten patients from 14 clinical sites in Greece meeting the Sepsis-3 definitions with lung infection, acute cholangitis, or primary bacteremia. INTERVENTIONS: During our comparison, we did not perform any intervention. MEASUREMENTS AND MAIN RESULTS: Untargeted metabolomics analysis was performed on plasma samples from 210 patients (a total of 1394 products). Differential abundance analysis identified 221 significantly different metabolites across the immune states. Metabolites were enriched in pathways related to ubiquinone biosynthesis, tyrosine metabolism, and tryptophan metabolism when comparing MALS to immunoparalysis and unclassified patients. When comparing MALS to unclassified, 312 significantly different metabolites were found, and pathway analysis indicated enrichment in multiple pathways. Comparing immunoparalysis to unclassified patients revealed only two differentially regulated metabolites. CONCLUSIONS: Findings suggest distinct metabolic dysregulation patterns associated with different immune dysfunctions in sepsis: the strongest metabolic dysregulation is associated with MALS.

Noncovalent Functionalization of Graphene Nanoplatelets and Their Applications in Supercapacitors.

We demonstrate a simple noncovalent functionalization technique, which involves graphite exfoliation and subsequent coating of the resulting graphene nanoplatelets (GNPs) with trimellitic anhydride (TMA), using a thermomechanical exfoliation process. TMA adsorbs on the surface of the GNPs, resulting in a reduction of the specific surface area to 312 ± 9 m2/g compared to 410 ± 12 m2/g for the unmodified GNPs. Detailed imaging, thermogravimetric, and X-ray diffraction analysis showed that the modified GNPs (TMA-GNPs) maintain similar structure to the unmodified GNPs. The presence of functional groups, confirmed by X-ray photoelectron spectroscopy analysis, caused an increase in the surface energy from 45.6 mJ/m2 for the GNPs to 57.9 mJ/m2 for TMA-GNPs. The resulting coated TMA-GNPs form stable dispersions in water while maintaining their inherent conductive properties, thus enabling applications, such as the manufacture of conductive films and supercapacitors. As a proof-of-concept, electrodes for supercapacitors are prepared from concentrated aqueous dispersions of the functionalized GNPs. Electrochemical characterization of the supercapacitors using electrochemical impedance spectroscopy, cyclic voltammetry and galvanostatic charge/discharge tests showed a specific capacitance of 22.2 F/cm3 at a scan rate of 1 mV/s from cyclic voltammetry and 17.3 F/cm3 at a current density of 1 A/g from galvanostatic charge/discharge tests, with a 90% capacitance retention after 10,000 cycles.

Clarithromycin for early anti-inflammatory responses in community-acquired pneumonia in Greece (ACCESS): a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Addition of macrolide antibiotics to ß-lactam antibiotics for the treatment of patients in hospital with community-acquired pneumonia is based on results from observational studies and meta-analyses rather than randomised clinical trials. We investigated if addition of the macrolide clarithromycin to treatment with a ß-lactam antibiotic in this population could improve early clinical response-the new regulatory endpoint for community-acquired pneumonia-and explored the possible contribution of modulation of the inflammatory host response to that outcome. METHODS: The ACCESS trial was a phase 3 prospective, double-blind, randomised controlled trial, in which adults in hospital with community-acquired pneumonia who had systemic inflammatory response syndrome, Sequential Organ Failure Assessment (SOFA) score of 2 or more, and procalcitonin 0·25 ng/mL or more were enrolled in 18 internal medicine departments of public Greek hospitals. Patients were randomly assigned (1:1) by computer-generated block randomisation to standard of care medication (including intravenous administration of a third-generation cephalosporin or intravenous administration of ß-lactam plus ß-lactamase inhibitor combination) plus either oral placebo or oral clarithromycin 500 mg twice daily for 7 days. Investigators, staff, and patients were masked to group allocation. The primary composite endpoint required that patients fulfilled both of the following conditions after 72 hours (ie, day 4 of treatment): (1) decrease in respiratory symptom severity score of 50% or more as an indicator of early clinical response and (2) decrease in SOFA score of at least 30% or favourable procalcitonin kinetics (defined as ≥80% decrease from baseline or procalcitonin <0·25 ng/mL), or both, as an indicator of early inflammatory response. Participants who were randomly assigned and received allocated treatment were included in the primary analysis population. This trial is complete and is registered with the EU Clinical Trials Register (2020-004452-15) and ClinicalTrials.gov (NCT04724044). FINDINGS: Patients were enrolled between Jan 25, 2021, and April 11, 2023, and 278 individuals were randomly allocated to receive standard of care in combination with either clarithromycin (n=139) or placebo (n=139). 134 patients in the clarithromycin group (five withdrew consent) and 133 patients in the placebo group (six withdrew consent) were included in the analysis of the primary endpoint. The primary endpoint was met in 91 (68%) patients in the clarithromycin group and 51 (38%) patients in the placebo group (difference 29·6% [95% CI 17·7-40·3]; odds ratio [OR] 3·40 [95% CI 2·06-5·63]; p<0·0001). Serious treatment-emergent adverse events (TEAEs) occurred in 58 (43%) patients in the clarithromycin group and 70 (53%) patients in the placebo group (difference 9·4% [95% CI -2·6 to 20·9]; OR 0·67 [95% CI 0·42 to 1·11]; p=0·14). None of the serious TEAEs was judged to be related to treatment assignment. INTERPRETATION: Addition of clarithromycin to standard of care enhances early clinical response and attenuates the inflammatory burden of community-acquired pneumonia. The mechanism of benefit is associated with changes in the immune response. These findings suggest the importance of adding clarithromycin to ß-lactams for treatment of patients in hospital with community-acquired pneumonia to achieve early clinical response and early decrease of the inflammatory burden. FUNDING: Hellenic Institute for the Study of Sepsis and Abbott Products Operations.

Developing a Tool for Differentiation Between Bacterial and Viral Respiratory Infections Using Myxovirus Resistance Protein A and C-Reactive Protein.

INTRODUCTION: The aim was to assess the performance of a blood assay combining measurements of MxA (myxovirus resistance protein A) and CRP (C-reactive protein) to differentiate viral from bacterial respiratory infections. METHODS: In a prospective study, MxA and CRP were measured in the blood by the AFIAS panel in adults admitted with respiratory infection. Patients were split into discovery and validation cohorts. Final diagnosis was adjudicated by a panel of experts. Microbiology-confirmed cases comprised the discovery cohort, and infections adjudicated as highly probable viral or bacterial comprised the validation cohort. RESULTS: A total of 537 patients were analyzed: 136 patients were adjudicated with definitive viral infections and 131 patients with definitive bacterial infections. Using logistic regression analysis, an equation was developed to calculate the probability for bacterial infection using the absolute value of MxA and CRP. Calculated probability ≥ 0.5 and/or MxA to CRP ratio less than 2 applied as the diagnostic rule for bacterial infections. This rule provided 91.6% sensitivity and 90.4% negative predictive value for the diagnosis of bacterial infections. This diagnostic sensitivity was confirmed in the validation cohort. A MxA/CRP ratio less than 0.15 was associated with unfavorable outcome. CONCLUSION: The calculation of the probability for bacterial infection using MxA and CRP may efficiently discriminate between viral and bacterial respiratory infections.

Pertinence of Salt-Related Knowledge and Reported Behaviour on Salt Intake in Adults: A Cross-Sectional Study.

The association between salt-related knowledge, attitude, behaviour (KAB) and actual salt consumption in Greek adults is uncertain. This study investigates the correlation between salt intake, gauged by 24-h urinary sodium excretion, with salt-related KAB. It further explores how socio-demographic factors influence these behaviors. Salt consumption was evaluated using a 24-h urinary sodium test, and compared to self-reported KAB data. Knowledge and behavior scores related to salt were computed. An overall cohort-adjusted model examined the relationship between daily salt consumption, knowledge and behavior scores, and certain covariates. Through the stratification by the cohort random effect, two models were established (Cohort I Adults; Cohort II Students) examining the same relationships of the overall cohort model. 463 Greek adults participated. The average salt intake was 9.54 g/day, nearly double the WHO recommendation. Significant differences in knowledge scores were noted based on sex, age, education, and BMI. A trend suggesting lower discretionary salt use with increased salt intake was observed (p = 0.06). However, comprehensive analysis revealed no direct correlation between salt intake and either knowledge (p = 0.562) or behavior scores (p = 0.210). The results emphasize the need for food product reforms by industry stakeholders and accelerated efforts towards reducing salt intake.

Physical Health-Related Quality of Life in Relation to Mediterranean Diet Adherence in a Sample of Greek Asthma Patients: A Pilot Study.

The role of nutrition in the management of asthma in obese patients is of increasing interest due to their limited response to inhaled corticosteroids. Some studies note that through diet and lifestyle, there can be an improvement in asthma control. The aim of the present study was to investigate the adherence to the Mediterranean Diet and its association with asthma severity and quality of life in patients with bronchial asthma. This is a cross-sectional study of 85 patients (70.6% female), with a mean age of 57 years, from the General University Hospital of Larissa and, more specifically, patients of the outpatient asthma clinic. Data were collected with the use of specific questionnaires. In relation to BMI, 12.9% of participants were of a normal weight, 45.9% were overweight, 25.9% were obese level I, 5.9% were obese level II, and 9.4% were in the morbidly obese range. Based on the Med Diet Score (ranging from 21 to 35), most participants (85.9%) reported moderate adherence to the Mediterranean Diet. Further analysis examined the correlations of the PCS-12 score with the frequency of consumption of each of the 11 food categories, as well as all demographic and health behavior variables. The ranked correlations indicated a significant relationship between PCS-12 score and Med Diet adherence and the consumption of alcoholic beverages (r = 0.437, p < 0.05), in accordance with the Mediterranean Diet suggestions, as well as a negative relationship with BMI score (r = -0.454, p < 0.010). Moreover, significant correlations were also present between the physical quality of life and AQLQ score and work type, as well as gender, age, and marital status. The results of our study showed a high rate of obesity in patients with asthma at the General University Hospital of Larissa and moderate adherence to the Mediterranean Diet. Increased BMI and alcoholic beverage consumption in asthma patients were significant predictors of lower physical health-related quality of life. In conclusion, personal and society-level interventions are required to effectively address obesity and poor diet in patients with asthma.

Dietary Supplementation Practices Among Undergraduate Students in Greece During the COVID-19 Pandemic and Their Association with COVID-19-related Anxiety.

Background: Despite the lack of evidence-based guidance on supplement use for the prevention and treatment of COVID-19, consumption of dietary supplements has been shown to increase in many countries. Objective: This study aimed to explore the use of dietary supplements among undergraduate students. Methods: An online cross-sectional survey was conducted between May and June 2021, involving a total of 536 participants (57.8% female) aged between 18-30 years in two university towns in central and northern Greece. Two validated questionnaires were used regarding dietary supplements and stress during COVID-19. Results: The prevalence of dietary supplement use was 67.5%. The three most popular supplements consumed were vitamin C (65.2%), followed by vitamin D (58.3%), and multivitamin and mineral supplements (56.9%). The use of CAS-5 indicated that 13.1% of students were classified as having dysfunctional anxiety due to COVID-19 (CAS-5 score ≥5). Logistic regression analysis showed that those who exhibited CAS-5 ≥5 were over two times more likely to consume supplements compared to no-stress participants (OR 2.29, 95%CI: 1.09-4.82). Particularly vitamin D use was associated with CAS score ≥5 (OR 2.18, 95%CI 1.22-3.89) a finding that was not observed with other types of dietary supplements. Conclusion: Women, passive smokers, and those who believe that DS are necessary during the COVID-19 pandemic were also more likely to consume dietary supplements. The use of dietary supplements is widespread among Greek students. Future studies should be conducted to monitor whether these increases in DS use are maintained.

D-ROMs and PAT Tests Reveal a High Level of Oxidative Stress in Patients with Severe Well-Controlled Asthma, and D-ROMs Are Positively Correlated with R20 Values That Indicate Approximate Central Airway Resistance.

BACKGROUND: The derivatives-reactive oxygen metabolites (d-ROMs) and plasma antioxidant capacity (PAT) tests are oxidative indexes. Severe asthma has been related to oxidative stress. We aimed to investigate d-ROMs and PAT values in severely controlled asthmatics and the correlation of these values with lung function. METHODS: Blood samples were collected from severely controlled asthmatics and centrifuged at 3000 rpm for 10 min. The supernatant was collected. The assays were performed within three hours of collection. The fraction of exhaled nitric oxide (FeNO), impulse oscillometry (IOS), and spirometry were determined. Symptom control was recorded using the asthma control test (ACT). RESULTS: Approximately 40 patients with severe controlled asthma (75%: women), mean age of 62 ± 12 years, were recruited. Approximately 5% had obstructive spirometry. The IOS revealed airway abnormalities even though the spirometric results were within the normal range, with it being more sensitive than spirometry. The D-ROMs and PAT test values were higher than normal, indicating oxidative stress in severe asthmatics with controlled asthma. D-ROMs were positively correlated with R20 values, indicating central airway resistance. CONCLUSIONS: The IOS technique revealed an otherwise hidden airway obstruction with spirometry. The D-ROMs and PAT tests revealed a high level of oxidative stress in severe controlled asthmatics. D-ROMs correlate with R20, indicating central airway resistance.

In vitro activities of omadacycline, eravacycline, cefiderocol, apramycin, and comparator antibiotics against Acinetobacter baumannii causing bloodstream infections in Greece, 2020-2021: a multicenter study.

Resistance of Acinetobacter baumannii to multiple clinically important antimicrobials has increased to very high rates in Greece, rendering most of them obsolete. The aim of this study was to determine the molecular epidemiology and susceptibilities of A. baumannii isolates collected from different hospitals across Greece. Single-patient A. baumannii strains isolated from blood cultures (n = 271), from 19 hospitals, in a 6-month period (November 2020-April 2021) were subjected to minimum inhibitory concentration determination and molecular testing for carbapenemase, 16S rRNA methyltransferase and mcr gene detection and epidemiological evaluation. 98.9% of all isolates produced carbapenemase OXA-23. The vast majority (91.8%) of OXA-23 producers harbored the armA and were assigned mainly (94.3%) to sequence group G1, corresponding to IC II. Apramycin (EBL-1003) was the most active agent inhibiting 100% of the isolates at ≤16 mg/L, followed by cefiderocol which was active against at least 86% of them. Minocycline, colistin and ampicillin-sulbactam exhibited only sparse activity (S <19%), while eravacycline was 8- and 2-fold more active than minocycline and tigecycline respectively, by comparison of their MIC50/90 values. OXA-23-ArmA producing A. baumannii of international clone II appears to be the prevailing epidemiological type of this organism in Greece. Cefiderocol could provide a useful alternative for difficult to treat Gram-negative infections, while apramycin (EBL-1003), the structurally unique aminoglycoside currently in clinical development, may represent a highly promising agent against multi-drug resistant A. baumanni infections, due to its high susceptibility rates and low toxicity.

Adhesive Wearable Sensors for Electroencephalography from Hairy Scalp.

Electroencephalography has garnered interest for applications in mobile healthcare, human-machine interfaces, and Internet of Things. Conventional electroencephalography relies on wet and dry electrodes. Despite favorable interface impedance of wet electrodes and skin, the application of a large amount of gel at their interface with skin limits the electroencephalography spatial resolution, increases the risk of shorting between electrodes, and makes them unsuited for long-term mobile recording. In contrast, dry electrodes are better suited for long-term recordings but susceptible to motion artifacts. In addition, both wet and dry electrodes are non-adhesive to the hairy scalp and mechanical support, or chemical adhesives are used to hold them in place. Herein, a conical microstructure array (CMSA) based sensor made of carbon nanotube-polydimethylsiloxane composite is reported. The CMSA sensor is fabricated using the innovative, cost-effective, and scalable method of viscosity-controlled dip-pull process. The sensor adheres to the hairy scalp by generating negative pressure in its conical microstructures when it is pressed against scalp. Aided by the application of a trace amount of gel, CMSA sensor establishes good electrical contact with the skin, enabling its applications in mobile electroencephalography over extended periods. Notably, the signal quality of CMSA sensors is comparable to that of medical-grade wet gel electrodes.

Oral minocycline plus rifampicin versus oral linezolid for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: The AIDA open label, randomized, controlled Phase 4 trial.

Background: The need for oral, cost-effective treatment for complicated skin and skin structure infections (cSSSIs) due to methicillin-resistant Staphylococcus aureus (MRSA) was addressed by the non-inferiority comparisons of oral minocycline plus rifampicin with linezolid. Methods: In the AIDA multicenter, open label, randomized, controlled clinical trial, hospitalized adults with cSSSI and documented MRSA were randomly assigned at a 2:1 ratio to either oral 600 mg rifampicin qd plus 100 mg minocycline bid or oral 600 mg linezolid bid for 10 days. The primary endpoint was the clinical cure rate in the clinically evaluable (CE) population at the test-of-cure visit (14 days). Non-inferiority was confirmed if the lower confidence limit (CI) did not fall below the accepted error margin of 15%. The study is registered with EudraCT number 2014-001276-56. Findings: 123 patients recruited between November 2014 and January 2017 were randomly assigned to treatment (81 patients to minocycline plus rifampicin and 42 patients to linezolid). Cure rates were 78.% (46/59, 90% CI 67.3-86.5) and 68.6% (24/35, 90% CI 53.4-81.3), respectively (P = 0.337). The percent difference in cure rates was 9.4% (90% CI -7.2 to 26.8%). Minocycline plus rifampicin combination was deemed non-inferior to linezolid as the lower CI was -7.2% i.e. smaller than the accepted error margin of -15%. Although statistically not significant, the overall rate of adverse events was higher in the linezolid group (47.6%, 20/42 versus 38.3%, 31/81). Interpretation: Oral minocycline plus rifampicin was non-inferior to oral linezolid treatment providing alternative oral treatment for cSSSI. Funding: The EU Seventh Research Framework Programme.

The Use of Dietary Supplements and Their Association with COVID-19-Related Anxiety among Non-Institutionalized Elderly in Northern Greece.

The elderly constitute a vulnerable group for increased anxiety and poor diet during the COVID-19 pandemic. There is limited research on the levels of COVID-19-related anxiety and dietary habits including dietary supplementation practices among the elderly and very elderly in Greece. A cross-sectional survey was conducted in 364 non-institutionalized elderly (65-74 y) and very elderly (≥75 y) living in northern Greece, with the aim to investigate the use of dietary supplements and their association with other factors, particularly the COVID-19-related anxiety. Levels of anxiety were assessed with the use of the Coronavirus Anxiety Scale (CAS-5). The percentage of dietary supplement users was 62.6%. The most popular dietary supplements used were vitamin D followed by vitamin C and multivitamin and mineral supplements. Multivariate analysis showed that the very elderly and overweight individuals were less likely to consume vitamin D supplements. Approximately a third of the participants (33.8%) exhibited signs of COVID-19-related anxiety but only 8% showed dysfunctional levels of anxiety. Regression analysis indicated that women, former smokers, and people exhibiting any sign of COVID-19 anxiety were approximately two times more likely to consume dietary supplements of any kind (Gender: OR 2.34, 95% CI 1.30-4.19; Smoking: OR 2.15, 95% CI: 1.08-4.26; COVID-19 anxiety: OR 2.16, 95 % CI: 1.20-3.91). Our results provide useful insights into the current practices of dietary supplement use in this population group and could be used by dietetic and medical associations as well as public authorities in the formulation of targeted, safe, and effective interventions for the protection of public health.

On the Current Care Situation and Treatment of Ocular Mucous Membrane Pemphigoid in Germany. / Zur Versorgungssituation und konservativen Therapie des okulären vernarbenden Schleimhautpemphigoids in Deutschland.

BACKGROUND: Ocular involvement in mucous membrane pemphigoid (MMP) is relatively rare, with a prevalence of 25 cases per million population, equating to approx. 2,100 patients throughout Germany. Diagnosis can be difficult - especially in cases of isolated ocular involvement - and treatment can be complex and lengthy. Immunosuppressants or immunomodulatory drugs are often used. Due to the complexity of diagnosis and treatment, MMP patients are usually referred to specialized centers. The aim of this project was to evaluate the current care situation of patients with ocular MMP in Germany. METHODS: A paper-based survey was designed and sent to all university eye clinics and other specialized centers in Germany in April 2020. The survey asked about the existence of a specialized outpatient service, the total annual number of patients with MMP, the annual number of newly diagnosed patients, any interdisciplinary collaboration for diagnostic or therapeutic purposes, as well as the local and systemic therapy used. RESULTS: Of a total of 44 clinics, 28 (64%) responded, reporting a total average of 27 ± 42 (0 - 200) patients and 3.6 ± 2.2 (0 - 10) new cases per year. This corresponds to a total of 741 patients. Only nine (32%) of the responding clinics offer specialized MMP clinics. 93% of the centers collaborate with the local dermatology department. 79% perform serological and histological diagnostics in-house. About half of the centers (n = 16) apply a standardized treatment regime. Systemic glucocorticoids (66.7%) are most commonly used, followed by mycophenolate mofetil and dapsone (57.1%), rituximab (33.3%), azathioprine and cyclophosphamide (28.6%), as well as methotrexate (19.0%). The least frequently used treatment is intravenous immunoglobulin (14.3%). CONCLUSION: This survey of German ophthalmology departments obtained data from about one third of the estimated total cohort of all patients with MMP in Germany. These are presumed to be exclusively patients with at least one ocular involvement. The complex care of these patients is usually provided in collaboration with a dermatologist and with the use of systemic anti-inflammatory medication. Currently, an ophthalmological MMP register is being established to better record the epidemiology and care situation of this rare disease in Germany and to improve it in the long term.

Poly(vinyl alcohol) Molecular Bottlebrushes Nucleate Ice.

Ice binding proteins (IBP) have evolved to limit the growth of ice but also to promote ice formation by ice-nucleating proteins (INPs). IBPs, which modulate these seemingly distinct processes, often have high sequence similarities, and molecular size/assembly is hypothesized to be a crucial determinant. There are only a few synthetic materials that reproduce INP function, and rational design of ice nucleators has not been achieved due to outstanding questions about the mechanisms of ice binding. Poly(vinyl alcohol) (PVA) is a water-soluble synthetic polymer well known to effectively block ice recrystallization, by binding to ice. Here, we report the synthesis of a polymeric ice nucleator, which mimics the dense assembly of IBPs, using confined ice-binding polymers in a high-molar-mass molecular bottlebrush. Poly(vinyl alcohol)-based molecular bottlebrushes with different side-chain densities were synthesized via a combination of ring-opening metathesis polymerization (ROMP) and reversible addition-fragmentation chain-transfer (RAFT) polymerization, using "grafting-to" and "grafting-through" approaches. The facile preparation of the PVA bottlebrushes was performed via selective hydrolysis of the acetate of the poly(vinyl acetate) (PVAc) side chains of the PVAc bottlebrush precursors. Ice-binding polymer side-chain density was shown to be crucial for nucleation activity, with less dense brushes resulting in colder nucleation than denser brushes. This bio-inspired approach provides a synthetic framework for probing heterogeneous ice nucleation and a route toward defined synthetic nucleators for biotechnological applications.

Toward personalized immunotherapy in sepsis: The PROVIDE randomized clinical trial.

The state of immune activation may guide targeted immunotherapy in sepsis. In a double-blind, double-dummy randomized clinical study, 240 patients with sepsis due to lung infection, bacteremia, or acute cholangitis were subjected to measurements of serum ferritin and HLA-DR/CD14. Patients with macrophage activation-like syndrome (MALS) or immunoparalysis were randomized to treatment with anakinra or recombinant interferon-gamma or placebo. Twenty-eight-day mortality was the primary endpoint; sepsis immune classification was the secondary endpoint. Using ferritin >4,420 ng/mL and <5,000 HLA-DR receptors/monocytes as biomarkers, patients were classified into MALS (20.0%), immunoparalysis (42.9%), and intermediate (37.1%). Mortality was 79.1%, 66.9%, and 41.6%, respectively. Survival after 7 days with SOFA score decrease was achieved in 42.9% of patients of the immunotherapy arm and 10.0% of the placebo arm (p = 0.042). Three independent immune classification strata are recognized in sepsis. MALS and immunoparalysis are proposed as stratification for personalized adjuvant immunotherapy. Clinicaltrials.gov registration NCT03332225.

Knowledge and awareness about and use of iodised salt among students in Germany and Greece.

BACKGROUND: Iodine is an essential trace element, which is important for human metabolism, growth and mental development. Iodine deficiency may still occur in Europe and the use of iodised salt is an effective measure to enhance iodine intake. Knowledge and awareness about the importance of iodine in nutrition and health can have a positive impact on the use of iodised salt. Therefore, the aim of this study was to assess the knowledge about and use of iodised salt among university students in two European countries. METHOD: Data from two countries (Germany and Greece) were extracted from a multi-centre cross-sectional survey, conducted among non-nutrition science/non-medical students from October 2018 to April 2019. RESULTS: Among the 359 participants in Germany (35% females, median age: 22 years) and the 403 participants in Greece (51% females, median age: 21 years), 41% and 37%, respectively, reported use of iodised salt at home. Users and non-users did not differ by age, gender and Body Mass Index or general interest in nutrition in both cohorts. However, those who had a better knowledge about iodine and (iodised) salt or had previously attended nutrition classes were more likely to report iodised salt usage. CONCLUSION: The results suggest that strengthening the imparting of nutritional information and additional education of young adults are needed and may improve knowledge about and usage of iodised salt.

Synthesis of poly(vinyl alcohol) by blue light bismuth oxide photocatalysed RAFT. Evaluation of the impact of freeze/thaw cycling on ice recrystallisation inhibition.

Poly(vinyl alcohol), PVA, is the most potent polymeric ice recrystallisation inhibitor (IRI), mimicking a complex function of ice binding proteins. The IRI activity of PVA scales with its molecular weight and hence broad molecular weight distributions in free radical-derived PVAs lead to activity measurements dominated by small amounts of heavier fractions. Well-defined PVA can be prepared by thermally initiated RAFT/MADIX polymerization using xanthates by the polymerization of the less activated monomer vinyl acetate. The low conversions and molecular weights obtained during this approach, often requires feeding of additional initiator and bulk polymerization. Here we employ bismuth oxide photo-RAFT in solution, using blue light (450 nm), rather than previously reported white light, to obtain a library of PVA's. The use of blue light enabled quantitative conversion and acceptable dispersities. Purple light (380 nm) was also used, but asymmetric molecular weight distributions were obtained in some cases. High concentrations of high molecular weight PVA is known to form cryogels during freeze/thaw which has led to speculation this might limit the use of PVA in environments where the temperature cycles e.g. the construction industry. After 4 freeze/thaw cycles there was only small changes in observable IRI for all synthesised PVAs and two commercial standards. In an extended test, activity was retained after 100 freeze/thaw cycles, mitigating concerns that PVA could not be used in situations where freeze/thaw cycles occur. This work presents a convenient method to obtain well-defined PVAs for cryoscience studies compared to conventional thermal-RAFT and indicates that cryogelation concerns may not prevent their use.