Non-thermal plasma (NTP) treatment of Trigonella foenum-graecum L. seeds stimulates the sprout growth and the production of nutraceutical compounds.

The possibility to stimulate the production of some nutraceutical properties of fenugreek (Trigonella foenum-graecum L.) sprouts by non-thermal plasma (NTP) processing of the seeds in different conditions was studied. The non-thermal plasma used in this work was a surface dielectric barrier discharge. Two types of processing were performed: direct NTP treatment and NTP with a cover treatment, to simulate the processing of packaged seeds. For all treatments, the effect of pre-soaking of the seeds was studied as well. The analyses of the seeds after processing indicated an increase of the hydrophilicity of their surface for NTP direct treatment as resulted from the water contact angle measurements, which could be due to the strong etching evidenced by scanning electron microscopy imaging. A significant (p < 0.05) increase of the seedling growth, by up to 50%, was found especially for the pre-soaked seeds. These results were correlated with the increase of chlorophyll pigments concentrations, with higher concentrations in the case of NTP direct treatment than for the NTP with cover treatments. Direct NTP treatment for 30 s of dry seeds led to the highest increase of the flavonoid concentration of about three times compared to that obtained for untreated seeds. For the polyphenols and antioxidant activity, NTP with cover treatments proved to be better, with a significant increase, especially for 90 s treatment of the pre-soaked seeds. All the results indicate the possibility of tuning the nutraceutical properties of fenugreek sprouts by NTP treatment.

Understanding clinical outcomes and factors influencing mortality in intensive care unit patients with COVID-19-associated candidemia.

BACKGROUND: During the COVID pandemic, research has shown an increase in candidemia cases following severe COVID infection and the identification of risk factors associated with candidemia. However, there is a lack of studies that specifically explore clinical outcomes and mortality rates related to candidemia after COVID infection. OBJECTIVES: The aim of this international study was to evaluate the clinical outcomes and identify factors influencing mortality in patients who developed candidemia during their COVID infection. PATIENTS/METHODS: This study included adult patients (18 years of age or older) admitted to the intensive care unit (ICU) and diagnosed with COVID-associated candidemia (CAC). The research was conducted through ID-IRI network and in collaboration with 34 medical centres across 18 countries retrospectively, spanning from the beginning of the COVID pandemic until December 2021. RESULTS: A total of 293 patients diagnosed with CAC were included. The median age of the patients was 67, and 63% of them were male. The most common Candida species detected was C. albicans. The crude 30-day mortality rate was recorded at 62.4%. The logistic regression analysis identified several factors significantly impacting mortality, including age (odds ratio [OR] 1.04, 95% confidence interval [CI] 1.02-1.07, p < .0005), SOFA score (OR 1.307, 95% CI 1.17-1.45, p < .0005), invasive mechanical ventilation (OR 7.95, 95% CI 1.44-43.83, p < .017) and duration of mechanical ventilation (OR 0.98, 95% CI 0.96-0.99, p < .020). CONCLUSIONS: By recognising these prognostic factors, medical professionals can customise their treatment approaches to offer more targeted care, leading to improved patient outcomes and higher survival rates for individuals with COVID-associated candidemia.

How to Personalize General Anesthesia-A Prospective Theoretical Approach to Conformational Changes of Halogenated Anesthetics in Fire Smoke Poisoning.

Smoke intoxication is a central event in mass burn incidents, and toxic smoke acts at different levels of the body, blocking breathing and oxygenation. The majority of these patients require early induction of anesthesia to preserve vital functions. We studied the influence of hemoglobin (HMG) and myoglobin (MGB) blockade by hydrochloric acid (HCl) in an interaction model with gaseous anesthetics using molecular docking techniques. In the next part of the study, molecular dynamics (MD) simulations were performed on the top-scoring ligand-receptor complexes to investigate the stability of the ligand-receptor complexes and the interactions between ligands and receptors in more detail. Through docking analysis, we observed that hemoglobin creates more stable complexes with anesthetic gases than myoglobin. Intoxication with gaseous hydrochloric acid produces conformational and binding energy changes of anesthetic gases to the substrate (both the pathway and the binding site), the most significant being recorded in the case of desflurane and sevoflurane, while for halothane and isoflurane, they remain unchanged. According to our theoretical model, the selection of anesthetic agents for patients affected by fire smoke containing hydrochloric acid is critical to ensure optimal anesthetic effects. In this regard, our model suggests that halothane and isoflurane are the most suitable choices for predicting the anesthetic effects in such patients when compared to sevoflurane and desflurane.

Surgical Endoscopic Treatment of Odontogenic Sinusitis.

Introduction: Odontogenic sinusitis is a frequent disease of the maxillary sinus, resulting from a dental inflammatory condition or a foreign body migrated in the sinus cavity. We performed a clinical retrospective study aimed to review the two surgical endoscopic approaches for odontogenic maxillary sinusitis middle and inferior meatotomy, in terms of realistic indications, efficacy, outcomes, and possible complications. Materials and Methods: In our study, we included a number of 400 patients with odontogenic maxillary sinusitis divided into two groups, treated in our hospital over five years, from January 2019 to December 2023. The patients included in this research were over 18 years old, diagnosed with odontogenic maxillary sinusitis, and underwent either middle meatal antrostomy or inferior meatotomy. Results: We examined the medical records of 400 patients. The vast majority of patients had a history of dental interventions, and the most affected tooth was the first maxillary molar. The symptoms at admission were typical for sinusitis: nasal obstruction, anterior or posterior rhinorrhea, hyposmia to anosmia, cacosmia, and pain or facial pressure. 80% of the patients in the study underwent middle meatal antrostomy, while 20% underwent inferior meatotomy. There were no significant differences between these two approaches in terms of efficacy, complication rates, recovery, or relapses. The complications that occurred after the surgical treatment were minor and with a very low frequency. The most reported were middle meatus synechiae and the persistence of the meatotomy ostium, with mucus recirculation (in patients with inferior meatotomy). Conclusions: Endoscopic surgical treatment of odontogenic maxillary sinusitis can be done as middle or inferior meatotomy, each having specific indications. The maxillary antrostomy is preferred in the majority of cases, as it is a procedure in which the natural ostium of the maxillary sinus is enlarged, thereby maintaining the natural drainage pathway of the sinus. However, the inferior meatotomy is preferred in the case of foreign bodies or maxillary sinus retention cysts localized at the level of the sinus floor or in the alveolar or lateral recesses, or as part of a combined approach (inferior and middle meatotomy), when the ablation of a "fungus ball" is required.

Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19.

BACKGROUND: Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19. METHODS: Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed. RESULTS: No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28. CONCLUSION: In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema. GOV IDENTIFIER: NCT04409509. Date of registration: 28 May, 2020.

Diagnosis of Liver Fibrosis Using Artificial Intelligence: A Systematic Review.

Background and Objectives: The development of liver fibrosis as a consequence of continuous inflammation represents a turning point in the evolution of chronic liver diseases. The recent developments of artificial intelligence (AI) applications show a high potential for improving the accuracy of diagnosis, involving large sets of clinical data. For this reason, the aim of this systematic review is to provide a comprehensive overview of current AI applications and analyze the accuracy of these systems to perform an automated diagnosis of liver fibrosis. Materials and Methods: We searched PubMed, Cochrane Library, EMBASE, and WILEY databases using predefined keywords. Articles were screened for relevant publications about AI applications capable of diagnosing liver fibrosis. Exclusion criteria were animal studies, case reports, abstracts, letters to the editor, conference presentations, pediatric studies, studies written in languages other than English, and editorials. Results: Our search identified a total of 24 articles analyzing the automated imagistic diagnosis of liver fibrosis, out of which six studies analyze liver ultrasound images, seven studies analyze computer tomography images, five studies analyze magnetic resonance images, and six studies analyze liver biopsies. The studies included in our systematic review showed that AI-assisted non-invasive techniques performed as accurately as human experts in detecting and staging liver fibrosis. Nevertheless, the findings of these studies need to be confirmed through clinical trials to be implemented into clinical practice. Conclusions: The current systematic review provides a comprehensive analysis of the performance of AI systems in diagnosing liver fibrosis. Automatic diagnosis, staging, and risk stratification for liver fibrosis is currently possible considering the accuracy of the AI systems, which can overcome the limitations of non-invasive diagnosis methods.

Multifaceted Role of Matrix Metalloproteinases in Neurodegenerative Diseases: Pathophysiological and Therapeutic Perspectives.

Neurodegeneration is the pathological condition, in which the nervous system or neuron loses its structure, function, or both, leading to progressive degeneration or the death of neurons, and well-defined associations of tissue system, resulting in clinical manifestations. Neuroinflammation has been shown to precede neurodegeneration in several neurodegenerative diseases (NDs). No drug is yet known to delay or treat neurodegeneration. Although the etiology and potential causes of NDs remain widely indefinable, matrix metalloproteinases (MMPs) evidently have a crucial role in the progression of NDs. MMPs, a protein family of zinc (Zn2+)-containing endopeptidases, are pivotal agents that are involved in various biological and pathological processes in the central nervous system (CNS). The current review delineates the several emerging evidence demonstrating the effects of MMPs in the progression of NDs, wherein they regulate several processes, such as (neuro)inflammation, microglial activation, amyloid peptide degradation, blood brain barrier (BBB) disruption, dopaminergic apoptosis, and α-synuclein modulation, leading to neurotoxicity and neuron death. Published papers to date were searched via PubMed, MEDLINE, etc., while using selective keywords highlighted in our manuscript. We also aim to shed a light on pathophysiological effect of MMPs in the CNS and focus our attention on its detrimental and beneficial effects in NDs, with a special focus on Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), Alzheimer's disease (AD), multiple sclerosis (MS), and Huntington's disease (HD), and discussed various therapeutic strategies targeting MMPs, which could serve as potential modulators in NDs. Over time, several agents have been developed in order to overcome challenges and open up the possibilities for making selective modulators of MMPs to decipher the multifaceted functions of MMPs in NDs. There is still a greater need to explore them in clinics.

Current Trends in Neurodegeneration: Cross Talks between Oxidative Stress, Cell Death, and Inflammation.

The human body is highly complex and comprises a variety of living cells and extracellular material, which forms tissues, organs, and organ systems. Human cells tend to turn over readily to maintain homeostasis in tissues. However, postmitotic nerve cells exceptionally have an ability to regenerate and be sustained for the entire life of an individual, to safeguard the physiological functioning of the central nervous system. For efficient functioning of the CNS, neuronal death is essential, but extreme loss of neurons diminishes the functioning of the nervous system and leads to the onset of neurodegenerative diseases. Neurodegenerative diseases range from acute to chronic severe life-altering conditions like Parkinson's disease and Alzheimer's disease. Millions of individuals worldwide are suffering from neurodegenerative disorders with little or negligible treatment available, thereby leading to a decline in their quality of life. Neuropathological studies have identified a series of factors that explain the etiology of neuronal degradation and its progression in neurodegenerative disease. The onset of neurological diseases depends on a combination of factors that causes a disruption of neurons, such as environmental, biological, physiological, and genetic factors. The current review highlights some of the major pathological factors responsible for neuronal degradation, such as oxidative stress, cell death, and neuroinflammation. All these factors have been described in detail to enhance the understanding of their mechanisms and target them for disease management.

Elucidating the Multi-Targeted Role of Nutraceuticals: A Complementary Therapy to Starve Neurodegenerative Diseases.

The mechanisms underlying multifactorial diseases are always complex and challenging. Neurodegenerative disorders (NDs) are common around the globe, posing a critical healthcare issue and financial burden to the country. However, integrative evidence implies some common shared mechanisms and pathways in NDs, which include mitochondrial dysfunction, neuroinflammation, oxidative stress, intracellular calcium overload, protein aggregates, oxidative stress (OS), and neuronal destruction in specific regions of the brain, owing to multifaceted pathologies. The co-existence of these multiple pathways often limits the advantages of available therapies. The nutraceutical-based approach has opened the doors to target these common multifaceted pathways in a slow and more physiological manner to starve the NDs. Peer-reviewed articles were searched via MEDLINE and PubMed published to date for in-depth research and database collection. Considered to be complementary therapy with current clinical management and common drug therapy, the intake of nutraceuticals is considered safe to target multiple mechanisms of action in NDs. The current review summarizes the popular nutraceuticals showing different effects (anti-inflammatory, antioxidant, neuro-protectant, mitochondrial homeostasis, neurogenesis promotion, and autophagy regulation) on vital molecular mechanisms involved in NDs, which can be considered as complementary therapy to first-line treatment. Moreover, owing to its natural source, lower toxicity, therapeutic interventions, biocompatibility, potential nutritional effects, and presence of various anti-oxidative and neuroprotective constituents, the nutraceuticals serve as an attractive option to tackle NDs.

Chemo-Preventive Action of Resveratrol: Suppression of p53-A Molecular Targeting Approach.

Extensive experimental, clinical, and epidemiological evidence has explained and proven that products of natural origin are significantly important in preventing and/or ameliorating various disorders, including different types of cancer that researchers are extremely focused on. Among these studies on natural active substances, one can distinguish the emphasis on resveratrol and its properties, especially the potential anticancer role. Resveratrol is a natural product proven for its therapeutic activity, with remarkable anti-inflammatory properties. Various other benefits/actions have also been reported, such as cardioprotective, anti-ageing, antioxidant, etc. and its rapid digestion/absorption as well. This review aims to collect and present the latest published studies on resveratrol and its impact on cancer prevention, molecular signals (especially p53 protein participation), and its therapeutic prospects. The most recent information regarding the healing action of resveratrol is presented and concentrated to create an updated database focused on this topic presented above.

Sintered and 3D-Printed Bulks of MgB2-Based Materials with Antimicrobial Properties.

Pristine high-density bulk disks of MgB2 with added hexagonal BN (10 wt.%) were prepared using spark plasma sintering. The BN-added samples are machinable by chipping them into desired geometries. Complex shapes of different sizes can also be obtained by the 3D printing of polylactic acid filaments embedded with MgB2 powder particles (10 wt.%). Our present work aims to assess antimicrobial activity quantified as viable cells (CFU/mL) vs. time of sintered and 3D-printed materials. In vitro antimicrobial tests were performed against the bacterial strains Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus ATCC 25923, Enterococcus faecium DSM 13590, and Enterococcus faecalis ATCC 29212; and the yeast strain Candida parapsilosis ATCC 22019. The antimicrobial effects were found to depend on the tested samples and microbes, with E. faecium being the most resistant and E. coli the most susceptible.

Antimicrobial Activity of MgB2 Powders Produced via Reactive Liquid Infiltration Method.

We report for the first time on the antimicrobial activity of MgB2 powders produced via the Reactive Liquid Infiltration (RLI) process. Samples with MgB2 wt.% ranging from 2% to 99% were obtained and characterized, observing different levels of grain aggregation and of impurity phases. Their antimicrobial activity was tested against Staphylococcus aureus ATCC BAA 1026, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, and Candida albicans ATCC 10231. A general correlation is observed between the antibacterial activity and the MgB2 wt.%, but the sample microstructure also appears to be very important. RLI-MgB2 powders show better performances compared to commercial powders against microbial strains in the planktonic form, and their activity against biofilms is also very similar.

The Lipid Paradox as a Metabolic Checkpoint and Its Therapeutic Significance in Ameliorating the Associated Cardiovascular Risks in Rheumatoid Arthritis Patients.

While the most common manifestations associated with rheumatoid arthritis (RA) are synovial damage and inflammation, the systemic effects of this autoimmune disorder are life-threatening, and are prevalent in 0.5-1% of the population, mainly associated with cardiovascular disorders (CVDs). Such effects have been instigated by an altered lipid profile in RA patients, which has been reported to correlate with CV risks. Altered lipid paradox is related to inflammatory burden in RA patients. The review highlights general lipid pathways (exogenous and endogenous), along with the changes in different forms of lipids and lipoproteins in RA conditions, which further contribute to elevated risks of CVDs like ischemic heart disease, atherosclerosis, myocardial infarction etc. The authors provide a deep insight on altered levels of low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and triglycerides (TGs) in RA patients and their consequence on the cardiovascular health of the patient. This is followed by a detailed description of the impact of anti-rheumatoid therapy on the lipid profile in RA patients, comprising DMARDs, corticosteroids, anti-TNF agents, anti-IL-6 agents, JAK inhibitors and statins. Furthermore, this review elaborates on the prospects to be considered to optimize future investigation on management of RA and treatment therapies targeting altered lipid paradigms in patients.

Promising Roles of Alternative Medicine and Plant-Based Nanotechnology as Remedies for Urinary Tract Infections.

Urinary tract infections (UTIs) are considered to be the most common infections worldwide, having an incidence rate of 40-60% in women. Moreover, the prevalence of this disorder in adult women is 30 times more than in men. UTIs are usually found in many hospitals and clinical practice; as disorders, they are complicated and uncomplicated; in uncomplicated cases, there is no structural or functional abnormality in the urogenital tract. However, obstruction, retention of urine flow and use of catheters increase the complexity. There are several bacteria (e.g., E. coli, Klebsiella pneumoniae, Proteus vulgaris, etc.) successfully residing in the tract. The diagnosis must not only be accurate but rapid, so early detection is an important step in the control of UTIs caused by uropathogens. The treatment of UTIs includes appropriate antimicrobial therapy to control the infection and kill the causal microbes inside the body. A long-time usage of antibiotics has resulted in multidrug resistance causing an impediment in treatment. Thus, alternative, combinatorial medication approaches have given some hope. Available treatments considered Homeopathic, Ayurvedic, Unani, and other herbal-based drugs. There are new upcoming roles of nanoparticles in combating UTIs which needs further validation. The role of medicinal plant-based nanotechnology approaches has shown promising results. Therefore, there must be active research in phyto-based therapies of UTIs, such as Ayurvedic Biology.

Impact of General Anesthesia Guided by State Entropy (SE) and Response Entropy (RE) on Perioperative Stability in Elective Laparoscopic Cholecystectomy Patients-A Prospective Observational Randomized Monocentric Study.

Laparoscopic cholecystectomy is one of the most frequently performed interventions in general surgery departments. Some of the most important aims in achieving perioperative stability in these patients is diminishing the impact of general anesthesia on the hemodynamic stability and the optimization of anesthetic drug doses based on the individual clinical profile of each patient. The objective of this study is the evaluation of the impact, as monitored through entropy (both state entropy (SE) and response entropy (RE)), that the depth of anesthesia has on the hemodynamic stability, as well as the doses of volatile anesthetic. A prospective, observational, randomized, and monocentric study was carried out between January and December 2019 in the Clinic of Anesthesia and Intensive Care of the "Pius Brînzeu" Emergency County Hospital in Timișoara, Romania. The patients included in the study were divided in two study groups: patients in Group A (target group) received multimodal monitoring, which included monitoring of standard parameters and of entropy (SE and RE); while the patients in Group B (control group) only received standard monitoring. The anesthetic dose in group A was optimized to achieve a target entropy of 40-60. A total of 68 patients met the inclusion criteria and were allocated to one of the two study groups: group A (N = 43) or group B (N = 25). There were no statistically significant differences identified between the two groups for both demographical and clinical characteristics (p > 0.05). Statistically significant differences were identified for the number of hypotensive episodes (p = 0.011, 95% CI: [0.1851, 0.7042]) and for the number of episodes of bradycardia (p < 0.0001, 95% CI: [0.3296, 0.7923]). Moreover, there was a significant difference in the Sevoflurane consumption between the two study groups (p = 0.0498, 95% CI: [-0.3942, 0.9047]). The implementation of the multimodal monitoring protocol, including the standard parameters and the measurement of entropy for determining the depth of anesthesia (SE and RE) led to a considerable improvement in perioperative hemodynamic stability. Furthermore, optimizing the doses of anesthetic drugs based on the individual clinical profile of each patient led to a considerable decrease in drug consumption, as well as to a lower incidence of hemodynamic side-effects.

Burns in the Emergency Department: A One-Year Single Center Analysis on 355 Cases.

Background: Burns are common reasons for emergency department presentations. While extensive or special burns require treatment in a specialized center, the majority are amenable to ambulatory treatment or hospitalization in a surgical ward. Romania has a national data collecting mechanism regarding all hospitalized patients, but there are no available statistics concerning non-hospitalized burn cases. This study aims to explore the amplitude of burn trauma by analyzing data from an Emergency Department at a major Romanian regional trauma center. Methods: This is a retrospective single-center 1-year study of all burn-related emergency department presentations at the trauma referral center for Romania's North-East region, in 2015. Included in the study were all cases of burns, indiscriminate of their etiology. Results: A total of 355 burn cases were analyzed. The average monthly number of cases was 29.58, with a maximum of 54 and a minimum of 18. There were 206 males and 149 females and 57.7% urban residents. Only 134 cases have been hospitalized during this period. Conclusions: Almost two-thirds of cases have not been hospitalized, thus missing from national statistics. Precise epidemiological data is paramount for a successful national burn management strategy. Creation of a national burn registry is suggested.

Emergency Surgery and Oncologic Resection for Complicated Colon Cancer: What Can We Expect? A Medium Volume Experience in Romania.

Introduction: Complicated colon cancer most frequently presents as obstruction and needs emergency surgery. Most of these patients receive their diagnosis when presenting for complicated disease and by that time the disease is usually advanced. While concerned first with the survival of the patient, the curative intent of the resection following the principles of oncologic resection may come in second place. Materials and methods: We retrospectively analyzed 68 consecutive patients with complicated colon cancer that suffered emergency surgery between January 2017 and September 2018. The principles of oncologic resection were analyzed in terms of resection margins and retrieved lymph nodes and/or multivisceral resections in order to achieve clear margins. Intestinal obstruction was observed in 58 patients (85.3%), perforation was found in 8 patients (11.8%) while lower gastrointestinal bleeding complicated 2 cases (2.9%). Twenty-two patients had distant metastases at presentation, and overall 29 patients (42,6%) had stage IV disease. Clear circumferential margins were achieved in 55 cases while longitudinal margins were found to be invaded in 2 cases and the mean number of retrieved lymph nodes was greater than 13.7. The mean hospital stay was 13.9 days and the observed in hospital mortality was 19.1%. Results: The outcomes of surgery for complicated colon cancer in our department fall within the reported literature results. Conclusion: The principles of oncologic resection in terms of surgical margins and retrieved lymph nodescan be respected during emergency surgery and offer the intent of cure for these patients with advanced disease.

Safety and immunogenicity of a mRNA rabies vaccine in healthy adults: an open-label, non-randomised, prospective, first-in-human phase 1 clinical trial.

BACKGROUND: Vaccines based on mRNA coding for antigens have been shown to be safe and immunogenic in preclinical models. We aimed to report results of the first-in-human proof-of-concept clinical trial in healthy adults of a prophylactic mRNA-based vaccine encoding rabies virus glycoprotein (CV7201). METHODS: We did an open-label, uncontrolled, prospective, phase 1 clinical trial at one centre in Munich, Germany. Healthy male and female volunteers (aged 18-40 years) with no history of rabies vaccination were sequentially enrolled. They received three doses of CV7201 intradermally or intramuscularly by needle-syringe or one of three needle-free devices. Escalating doses were given to subsequent cohorts, and one cohort received a booster dose after 1 year. The primary endpoint was safety and tolerability. The secondary endpoint was to determine the lowest dose of CV7201 to elicit rabies virus neutralising titres equal to or greater than the WHO-specified protective antibody titre of 0·5 IU/mL. The study is continuing for long-term safety and immunogenicity follow-up. This trial is registered with ClinicalTrials.gov, number NCT02241135. FINDINGS: Between Oct 21, 2013, and Jan 11, 2016, we enrolled and vaccinated 101 participants with 306 doses of mRNA (80-640 µg) by needle-syringe (18 intradermally and 24 intramuscularly) or needle-free devices (46 intradermally and 13 intramuscularly). In the 7 days post vaccination, 60 (94%) of 64 intradermally vaccinated participants and 36 (97%) of 37 intramuscularly vaccinated participants reported solicited injection site reactions, and 50 (78%) of 64 intradermally vaccinated participants and 29 (78%) of 37 intramuscularly vaccinated participants reported solicited systemic adverse events, including ten grade 3 events. One unexpected, possibly related, serious adverse reaction that occurred 7 days after a 640 µg intramuscular dose resolved without sequelae. mRNA vaccination by needle-free intradermal or intramuscular device injection induced virus neutralising antibody titres of 0·5 IU/mL or more across dose levels and schedules in 32 (71%) of 45 participants given 80 µg or 160 µg CV7201 doses intradermally and six (46%) of 13 participants given 200 µg or 400 µg CV7201 doses intramuscularly. 1 year later, eight (57%) of 14 participants boosted with an 80 µg needle-free intradermal dose of CV7201 achieved titres of 0·5 IU/mL or more. Conversely, intradermal or intramuscular needle-syringe injection was ineffective, with only one participant (who received 320 µg intradermally) showing a detectable immune response. INTERPRETATION: This first-ever demonstration in human beings shows that a prophylactic mRNA-based candidate vaccine can induce boostable functional antibodies against a viral antigen when administered with a needle-free device, although not when injected by a needle-syringe. The vaccine was generally safe with a reasonable tolerability profile. FUNDING: CureVac AG.

Tailoring the Surface Functionalities of Radio Frequency Magnetron-Sputtered ZnO Thin Films by Ar/NH3 Gas Mixture Surface-Wave Plasmas.

The surface functionalization of radio frequency magnetron-sputtered zinc oxide (ZnO) thin films tailored by low-pressure Ar/NH3 mixture surface-wave plasmas (SWPs) is discussed based on the results of photoluminescence (PL), X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), and spectrophotometric measurements. At an Ar/NH3 gas mixture ratio of 70%/30%, both the PL intensity of the near-band-edge emission and the XRD intensity of the ZnO(002) reflection peak were enhanced by about 5.5 and 8 times, respectively, compared to the values for the as-grown sample. Furthermore, the XPS and spectrophotometric analyses using the fluorescent dye showed that the amine group functionalization over the surface of the ZnO films reached their maximum values at the same gas ratio. From the results of optical emission spectroscopic and ion mass spectrometric measurements in the Ar/NH3 mixture SWPs, it is inferred that the nitrogen-containing reactive species, such as NH x+ ( x = 1-4) ions and NH y ( y = 1, 2) molecules in addition to H radicals might crucially interact with the defective ZnO surface lattices to repair the ZnO thin films from compressive to strain-free crystallized structures, enhance the PL intensity, and produce the amine group surface functionalization.

Copper induced hollow carbon nanospheres by arc discharge method: controlled synthesis and formation mechanism.

Hollow carbon nanospheres with controlled morphologies were synthesized via the copper-carbon direct current arc discharge method by alternating the concentrations of methane in the reactant gas mixture. A self-healing process to keep the structural integrity of encapsulated graphitic shells was evolved gradually by adding methane gas from 0% to 20%. The outer part of the coated layers expanded and hollow nanospheres grew to be large fluffy ones with high methane concentrations from 30% to 50%. A self-repairing function by the reattachment of broken graphitic layers initiated from near-electrode space to distance was also distinctly exhibited. By comparing several comparable metals (e.g. copper, silver, gold, zinc, iron and nickel)-carbon arc discharge products, a catalytic carbon-encapsulation mechanism combined with a core-escaping process has been proposed. Specifically, on the basis of the experimental results, copper could be applied as a unique model for both the catalysis of graphitic encapsulation and as an adequate template for the formation of hollow nanostructures.