Additional Protection Research Articles

Protecting Japanese giant salamanders (Andrias japonicus) in the Nawa River Basin, Japan: policy recommendations addressing water pollution and waterway disruption

The Japanese giant salamander, Andrias japonicus, is an iconic but declining species of aquatic amphibian. A population within the Nawa River Basin of Tottori Prefecture persists but faces two significant threats. The first major threat is waterway obstructions, in the form of dams, weirs, and concrete embankments, which severely fragment and degrade the habitat. The second is water pollution, primarily caused by runoff from animal farms. Both threats to A. japonicus can be mitigated with proper actions. We provide science-based recommendations, advocating for the modification of dams and weirs by implementing ladderways to restore habitat connectivity and the provisioning of adequate breeding habitat in the form of artificial nest boxes. We also recommend the implementation of regular water quality monitoring and the enforcement of regulations regarding allowed runoff from animal farms. The Nawa River Basin could also be designated as an official sanctuary area for the Japanese Giant Salamander, lending additional formal protection and providing ecotourism opportunities for economically declining rural areas. Though the threats to A. japonicus are serious, the implementation of these mitigation measures and continual monitoring can allow this remarkable species to thrive.

Occlusal considerations in maintaining health of implants and their restorations

Dental implants are a regular feature in daily clinical practice and there is a need to undertake routine assessment and maintenance of implants and their restorations on par with that provided for natural teeth. Occlusal checks form an important part of the maintenance regime for preserving the integrity of implants, their restorations, and health of the peri-implant tissues. Implant restorations are subjected to the full characteristics and magnitude of occlusal forces, including those associated with parafunction. Compared with the periodontal ligament around teeth, the biophysical response to occlusal forces of osseointegration is different through the more rigid link of implant to bone and reduced proprioception. Risks attributable to occlusal forces primarily affect implant restorations and they are elevated in the presence of bruxism. The occlusal guidelines recommended by the literature are aimed at reducing these risks and regular assessment and maintenance of the occlusion is essential. A four-step sequence is presented to ensure that the annual occlusal checks include the patient's input and evaluation of restoration integrity, occlusal scheme, additional protection, and spatial changes.

MOBILE ADDITIONAL ARMOR PROTECTION FOR A TRUCK

BACKGROUND: The use of armored vehicles allows, under the threat of constant enemy influence, to protect special vehicles and special equipment from the effects of light and heavy small arms, landmines, hand grenade launchers during marches or special operations. However, at present, the issue of protecting freight transport used for transporting personnel, mortar crews, materiel, etc. is quite acute. The goal of the work is to develop a mobile set of additional armor protection for the body of a truck in order to reduce the likelihood of injury to personnel during their transportation by firearms, cumulative ammunition, fragments of artillery ammunition, as well as military equipment during its transportation. Materials and methods. Determination of parameters for the duration of the penetration process and subsequent behavior of armor protection, obtaining accurate data on the resistance and effectiveness of additional armor, analysis of the stress-strain state was performed in the Ansys program. Data were obtained on the penetration process, transition energy and subsequent behavior of armor protection, which will be used to improve armored structures and structures, as well as to improve the safety of equipment in real combat conditions. Results. The article discusses the problem of armor protection of vehicles. Examples are given of the use of additional armor protection for weapons, military and special equipment, in particular in the context of a special military operation. The study presents a mobile set of additional armor protection for the body of a truck, designed to protect personnel from injury from firearms and fragments from exploding ammunition when transported on trucks. Armor protection is made in the form of hinged armor plates, anti-cumulative grilles, secured on the outside with fastening elements. Installed on the outside of the body, armor screens act as barriers, which significantly increases the protective properties when fired from firearms. The article simulates the proposed protection set and analyzes the stress-strain state. Conclusion. Based on the calculations, the values of the maximum speeds and flight range of the bullet were determined for the strength of the additional set of armor protection.

Using preoperative planning software to assess the effect of head length on prosthetic range of motion in a high-risk population: a three-dimensional modeling study.

Concurrent use of minus heads with tapered stems in total hip arthroplasty (THA) decreases the prosthetic range of motion (pROM). Three-dimensional preoperative templating can simulate the location of the impingement by taking the hip through a virtual pROM. This enables surgeons to simulate how modifying the type of implant, orientation, and position influences impingement. We hypothesized that CT-based modeling would result in a decrease in the pROM, thereby increasing the risk of impingement when minus heads are used. Forty-three patients who underwent robotic-assisted primary THAs were included. Prosthetic head diameter (32/36-mm) and head length (minus/zero/plus) were the predictors. Maximum external rotation at full hip extension and internal rotation at 90° and 100° of flexion prior to prosthetic impingement were the outcome variables. A CT-based preoperative planning software was used for pROM estimation and impingement detection. Significant decreases in pROM were found for both head diameters as the head length decreased and was more pronounced in external rotation during full hip extension (changes of 2.8-3.4° for the 32-mm head and 1.6-2.8° for the 36-mm head (p = 0.00011)). The magnitude of loss in pROM when using a minus head was larger than the gain provided by a plus head in tapered stems (p < 0.0001). Head length affects the offset and pROM. When the use of minus heads or smaller heads is indicated, 3D preoperative templating for assessing postoperative pROM and impingement provides surgeons with options to consider alternate surgical plans offering additional assurance and protection from dislocation.

Initial Despair and Current Hope of Identifying a Clinically Useful Treatment of Myocardial Reperfusion Injury: Insights Derived from Studies of Platelet P2Y12 Antagonists and Interference with Inflammation and NLRP3 Assembly

Myocardial necrosis following the successful reperfusion of a coronary artery occluded by thrombus in a patient presenting with ST-elevation myocardial infarction (STEMI) continues to be a serious problem, despite the multiple attempts to attenuate the necrosis with agents that have shown promise in pre-clinical investigations. Possible reasons include confounding clinical risk factors, the delayed application of protective agents, poorly designed pre-clinical investigations, the possible effects of routinely administered agents that might unknowingly already have protected the myocardium or that might have blocked protection, and the biological differences of the myocardium in humans and experimental animals. A better understanding of the pathobiology of myocardial infarction is needed to stem this reperfusion injury. P2Y12 receptor antagonists minimize platelet aggregation and are currently part of the standard treatment to prevent thrombus formation and propagation in STEMI protocols. Serendipitously, these P2Y12 antagonists also dramatically attenuate reperfusion injury in experimental animals and are presumed to provide a similar protection in STEMI patients. However, additional protective agents are needed to further diminish reperfusion injury. It is possible to achieve additive protection if the added intervention protects by a mechanism different from that of P2Y12 antagonists. Inflammation is now recognized to be a critical factor in the complex intracellular response to ischemia and reperfusion that leads to tissue necrosis. Interference with cardiomyocyte inflammasome assembly and activation has shown great promise in attenuating reperfusion injury in pre-clinical animal models. And the blockade of the executioner protease caspase-1, indeed, supplements the protection already seen after the administration of P2Y12 antagonists. Importantly, protective interventions must be applied in the first minutes of reperfusion, if protection is to be achieved. The promise of such a combination of protective strategies provides hope that the successful attenuation of reperfusion injury is attainable.

Corrosion Behavior of Ni-Cr Alloys with Different Cr Contents in NaCl-KCl-MgCl2.

This study investigates the corrosion behavior of Ni-Cr binary alloys, including Ni-10Cr, Ni-15Cr, Ni-20Cr, Ni-25Cr, and Ni-30Cr, in a NaCl-KCl-MgCl2 molten salt mixture through gravimetric analysis. Corrosion tests were conducted at 700 °C, with the maximum immersion time reaching up to 100 h. The corrosion rate was determined by measuring the mass loss of the specimens at various time intervals. Verifying corrosion rates by combining mass loss results with the determination of element dissolution in molten salts using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Detailed examinations of the corrosion products and morphology were conducted using X-ray diffraction (XRD) and scanning electron microscopy (SEM). Micro-area elemental analysis on the corroded surfaces was performed using an energy dispersive spectrometer (EDS), and the elemental distribution across the corrosion cross-sections was mapped. The results indicate that alloys with lower Cr content exhibit superior corrosion resistance in the NaCl-KCl-MgCl2 molten salt under an argon atmosphere compared to those with higher Cr content; no corrosion products were retained on the surfaces of the lower Cr alloys (Ni-10Cr, Ni-15Cr). For the higher Cr alloys (Ni-20Cr, Ni-25Cr, Ni-30Cr), after 20 h of corrosion, a protective layer was observed in certain areas. The formation of a stable Cr2O3 layer in the initial stages of corrosion for high-Cr content alloys, which reacts with MgO in the molten salt to form a stable MgCr2O4 spinel structure, provides additional protection for the alloys. However, over time, even under argon protection, the MgCr2O4 protective layer gradually degrades due to chloride ion infiltration and chemical reactions at high temperatures. Further analysis revealed that chloride ions play a pivotal role in the corrosion process, not only facilitating the destruction of the Cr2O3 layer on the alloy surfaces but also possibly accelerating the corrosion of the metallic matrix through electrochemical reactions. In conclusion, the corrosion behavior of Ni-Cr alloys in the NaCl-KCl-MgCl2 molten salt environment is influenced by a combination of factors, including Cr content, chloride ion activity, and the formation and degradation of protective layers. This study not only provides new insights into the corrosion resistance of Ni-Cr alloys in high-temperature molten salt environments but also offers significant theoretical support for the design and optimization of corrosion-resistant alloy materials.

Combination of ADAM17 knockdown with eplerenone is more effective than single therapy in ameliorating diabetic cardiomyopathy.

The renin-angiotensin-aldosterone system (RAAS) members, especially Ang II and aldosterone, play key roles in the pathogenesis of diabetic cardiomyopathy (DCM). Angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers combined with aldosterone receptor antagonists (mineralocorticoid receptor antagonists) have substantially improved clinical outcomes in patients with DCM. However, the use of the combination has been limited due to its high risk of inducing hyperkalemia. Type 1 diabetes was induced in 8-week-old male C57BL/6J mice by intraperitoneal injection of streptozotocin at a dose of 55mg/kg for 5 consecutive days. Adeno-associated virus 9-mediated short-hairpin RNA (shRNA) was used to knock down the expression of ADAM17 in mice hearts. Eplerenone was administered via gavage at 200mg/kg daily for 4weeks. Primary cardiac fibroblasts were exposed to high glucose (HG) in vitro for 24h to examine the cardiac fibroblasts to myofibroblasts transformation (CMT). Cardiac collagen deposition and CMT increased in diabetic mice, leading to cardiac fibrosis and dysfunction. In addition, ADAM17 expression and activity increased in the hearts of diabetic mice. ADAM17 inhibition and eplerenone treatment both improved diabetes-induced cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction, ADAM17 deficiency combined with eplerenone further reduced the effects of cardiac fibrosis, cardiac hypertrophy and cardiac dysfunction compared with single therapy in vivo. High-glucose stimulation promotes CMT in vitro and leads to increased ADAM17 expression and activity. ADAM17 knockdown and eplerenone pretreatment can reduce the CMT of fibroblasts that is induced by high glucose levels by inhibiting TGFβ1/Smad3 activation; the combination of the two can further reduce CMT compared with single therapy in vitro. Our findings indicated that ADAM17 knockout could improve diabetes-induced cardiac dysfunction and remodeling through the inhibition of RAAS overactivation when combined with eplerenone treatment, which reduced TGF-β1/Smad3 pathway activation-mediated CMT. The combined intervention of ADAM17 deficiency and eplerenone therapy provided additional cardiac protection compared with a single therapy alone without disturbing potassium level. Therefore, the combination of ADAM17 inhibition and eplerenone is a potential therapeutic strategy for human DCM.

Architectural and Urban Changes in a Residential Environment—Implications for Design Science

Current spatial changes involving broad urban landscapes affect people’s perceptions of their surroundings, sense of place, and attachment to a place, constituting a disruption to these. As a result, on a social scale, they translate into people’s well-being. The following study of the impact of large-scale architectural and urban developments on the place of residence is based on the assumption that physical space determines the quality of life in the living place and the changes in the process condition residents to adapt to their new surroundings—based on the three pillars of place, people, and process (3Ps). The article consists of two parts. The first is theoretical, which conceptualises spatial change based on the theory of human dependence on place. The second part–an empirical study—discusses the transformation of the post-industrial area of Bicocca (Milan), which, 40 years after the intervention, has led to conclusions and recommendations for urban planning. The results demonstrate the different sensitivities of the urban areas to the process of functional–spatial change, the essence of the accessibility of public space, public facilities, and transport infrastructure. The planning process can positively influence social adaptation to spatial change mitigation. Residential areas may be subject to additional protection procedures. The study is relevant to a sustainable planning process in the inevitable transformation of urban areas. The interdisciplinary nature of the issue prompts the integration of research findings and knowledge transfer in the socio-technological subsystem (STS).

Connexin 43 modulates reverse electron transfer in cardiac mitochondria from inducible knock-out Cx43Cre-ER(T)/fl mice by altering the coenzyme Q pool.

Succinate accumulates during myocardial ischemia and is rapidly oxidized during reperfusion, leading to reactive oxygen species (ROS) production through reverse electron transfer (RET) from mitochondrial complex II to complex I, and favoring cell death. Given that connexin 43 (Cx43) modulates mitochondrial ROS production, we investigated whether Cx43 influences RET using inducible knock-out Cx43Cre-ER(T)/fl mice. Oxygen consumption, ROS production, membrane potential and coenzyme Q (CoQ) pool were analyzed in subsarcolemmal (SSM, expressing Cx43) and interfibrillar (IFM) cardiac mitochondria isolated from wild-type Cx43fl/fl mice and Cx43Cre-ER(T)/fl knock-out animals treated with 4-hydroxytamoxifen (4OHT). In addition, infarct size was assessed in isolated hearts from these animals submitted to ischemia-reperfusion (IR), and treated or not with malonate, a complex II inhibitor attenuating RET. Succinate-dependent ROS production and RET were significantly lower in SSM, but not IFM, from Cx43-deficient animals. Mitochondrial membrane potential, a RET driver, was similar between groups, whereas CoQ pool (2.165±0.338 vs. 4.18±0.55 nmol/mg protein, p<0.05) and its reduction state were significantly lower in Cx43-deficient animals. Isolated hearts from Cx43Cre-ER(T)/fl mice treated with 4OHT had a smaller infarct size after IR compared to Cx43fl/fl, despite similar concentration of succinate at the end of ischemia, and no additional protection by malonate. Cx43 deficiency attenuates ROS production by RET in SSM, but not IFM, and was associated with a decrease in CoQ levels and a change in its redox state. These results may partially explain the reduced infarct size observed in these animals and their lack of protection by malonate.

Machine perfusion in liver transplantation: recent advances and coming challenges.

Machine perfusion has been adopted into clinical practice in Europe since the mid-2010s and, more recently, in the United States (US) following approval of normothermic machine perfusion (NMP). We aim to review recent advances, provide discussion of potential future directions, and summarize challenges currently facing the field. Both NMP and hypothermic-oxygenated perfusion (HOPE) improve overall outcomes after liver transplantation versus traditional static cold storage (SCS) and offer improved logistical flexibility. HOPE offers additional protection to the biliary system stemming from its' protection of mitochondria and lessening of ischemia-reperfusion injury. Normothermic regional perfusion (NRP) is touted to offer similar protective effects on the biliary system, though this has not been studied prospectively.The most critical question remaining is the optimal use cases for each of the three techniques (NMP, HOPE, and NRP), particularly as HOPE and NRP become more available in the US. There are additional questions regarding the most effective criteria for viability assessment and the true economic impact of these techniques. Finally, with each technique purported to allow well tolerated use of riskier grafts, there is an urgent need to define terminology for graft risk, as baseline population differences make comparison of current data challenging. Machine perfusion is now widely available in all western countries and has become an essential tool in liver transplantation. Identification of the ideal technique for each graft, optimization of viability assessment, cost-effectiveness analyses, and proper definition of graft risk are the next steps to maximizing the utility of these powerful tools.

Inferior long-term Results of a Prospective Randomized Controlled Trial initially demonstrating enhanced Sensory Nerve Recovery using a Chitosan Nerve Tube.

Traumatic peripheral nerve injuries can result in significant functional impairments and long-term sequelae. This study evaluated the long-term outcomes of a chitosan tube implantation protecting the epineural coaptation after peripheral nerve injuries using two different tube versions (V 1.0 and V 2.0 with different wall thickness and resorption characteristics) compared to a control group. The study focused on pain levels, sensory function, and overall functional outcomes. Patients who received tube implantation around direct coaptation sites of digital nerves were prospectively randomized and compared to control patients without additional tube protection. Pain levels, sensory function, grip force, and functional scores were assessed at different time points, ranging from three months to five years after the procedure. Furthermore, biodegradation of the tubes was measured via high-resolution MR-neurography (MRN) and categorized. Long-term evaluation revealed that patients with V 1.0 had higher pain levels compared to the control group after five years. They also reported more symptoms of numbness and hypersensitivity. V 2.0 patients exhibited higher pain levels at three months, which did not persist at six months. However, they showed compromised sensory function, with higher values of two-point discrimination compared to V 1.0 and the control group. No differences were found in grip force or functional scores between the groups. MRI displayed remnants of implants even in long-term follow-up. The findings suggest potential limitations due to pain increase and impaired sensory function associated with tube implantation in the long term. However, in the short term, the material seemed to have a protective effect (as published previously). The resorption process was not completed at the end of the observation period of five years. This might explain the prolonged scarring and inferior long-term results. Future research should focus on improving tube materials and design to minimize adverse effects and enhance functional outcomes in patients with peripheral nerve injuries.

Laser-induced graphene formation on different wood species: Dependence of electronic performance on intrinsic features of certain types of wood

Conductive, 3D, porous graphene can be produced with a CO2 laser from a large variety of materials, including wood, at room temperature, and under inert atmosphere or after treatment for fire protection. Here, we investigated the suitability for direct conversion of 46 typical European and Asian woods into laser-induced graphene (LIG), without pre-treatment. The LIG was characterized by resistance measurements to determine if a conductive layer had formed, and via Raman spectroscopy. Here, we show, for the first time, that it is possible to produce LIG on certain woods under atmospheric conditions without additional fire protection treatment. We determined that the ability to produce LIG on untreated, natural wood under ambient atmosphere is favoured overall by a high density and a diffuse-porous xylem structure, as well as a high soluble lignin content. Some of these characteristics are similar to those required for high yields in char production. Problematic for the production of LIG-based electronics is the presence of pronounced growth rings, or other geometric wood features, with density variations, which can be reduced using specific cuts with minimized growth rings and absence of rays. This is the first time that untreated wood has been directly converted into LIG using a conventional CO2 laser and ambient atmosphere. Our results represent a further step towards the development of a new generation of sustainable electronics relying on natural materials.

Formal Analysis and Detection for ROS2 Communication Security Vulnerability

Robotic systems have been widely used in various industries, so the security of communication between robots and their components has become an issue that needs to be focused on. As a framework for developing robotic systems, the security of ROS2 (Robot Operating System 2) can directly affect the security of the upper-level robotic systems. Therefore, it is a worthwhile research topic to detect and analyze the security of ROS2. In this study, we adopted a formal approach to analyze the security of the communication mechanism of ROS2. First, we used a state transition system to model the potential vulnerabilities of ROS2 based on the ROS2 communication mechanism and the basic process of penetration testing. Secondly, we introduced a CIA model based on the established vulnerability model and used linear temporal logic to define its security properties. Then, we designed and implemented a vulnerability detection tool for ROS2 applications based on the vulnerability model and security properties. Finally, we experimentally tested some ROS2-based applications, and the results show that ROS2 has vulnerabilities without additional protection safeguards.

Video-tracked Anopheles arabiensis entry and exit behaviour at washed and damaged pyrethroid-treated bednets.

Insecticide-treated nets (ITNs) are the most effective method for malaria prevention in Africa. Using near-infrared video tracking in a laboratory environment, we recorded and assessed bednet entry and exit by a northern Tanzanian population of Anopheles arabiensis at a human-occupied untreated net and a PermaNet® 2.0 ITN. Both had 12 holes, each 10 cm in diameter, punctured at specific locations, and the ITN was washed 20 times to further simulate the wear and tear of ageing. Washing reduced the insecticide content of ITNs by 61%, which then showed similar rates to the untreated nets for net entry (39% entered untreated net and 41% entered ITN; p = 0.84) and exit (37% and 43%, respectively; p = 0.67). Regardless of treatment, approximately 40% of mosquitoes entered nets within 20 s of first appearing in the field of view and reached the volunteer's skin within 5 s of entering the net. Mortality rates post-exposure were significantly higher (p = 0.048) at ITNs (26.6%; 95% CI 13.4%-39.7%) than at untreated controls (6.4%; 95% CI 1.8%-14.6%). The washed and aged ITN provided little additional personal protection for the sleeper over an untreated net. Simple adjustments to materials and design that could extend the effective lifespan of ITNs are discussed.

Correlates of protection against symptomatic SARS-CoV-2 in vaccinated children

The paucity of information on longevity of vaccine-induced immune responses and uncertainty of the correlates of protection hinder the development of evidence-based COVID-19 vaccination policies for new birth cohorts. Here, to address these knowledge gaps, we conducted a cohort study of healthy 5–12-year-olds vaccinated with BNT162b2. We serially measured binding and neutralizing antibody titers (nAbs), spike-specific memory B cell (MBC) and spike-reactive T cell responses over 1 year. We found that children mounted antibody, MBC and T cell responses after two doses of BNT162b2, with higher antibody and T cell responses than adults 6 months after vaccination. A booster (third) dose only improved antibody titers without impacting MBC and T cell responses. Among children with hybrid immunity, nAbs and T cell responses were highest in those infected after two vaccine doses. Binding IgG titers, MBC and T cell responses were predictive, with T cells being the most important predictor of protection against symptomatic infection before hybrid immunity; nAbs only correlated with protection after hybrid immunity. The stable MBC and T cell responses over time suggest sustained protection against symptomatic SARS-CoV-2 infection, even when nAbs wane. Booster vaccinations do not confer additional immunological protection to healthy children.

Adding ultrasound to treat-to-target shows no benefit in achieving clinical remission nor in slowing radiographic progression in rheumatoid arthritis: results from a multicenter prospective cohort.

To assess whether using ultrasound (US) in addition to clinical information versus only clinical information in a treat-to-target (T2T) strategy leads to more clinical remission and to less radiographic progression in RA. Patients with RA from the 2-year prospective BIODAM cohort were included. Clinical and US data (US7-score) were collected every 3months and hands and feet radiographs every 6months. At each visit, it was decided whether patients were treated according to the clinical definition of T2T with DAS44 remission as benchmark (T2T-DAS44). T2T-DAS44 was correctly applied if: (i) DAS44 remission had been achieved or (ii) if not, treatment was intensified. A T2T strategy also considering US data (T2T-DAS44-US) was correctly applied if: (i) both DAS44 and US remission (synovitis-score < 2, Doppler-score = 0) were present; or (ii) if not, treatment was intensified. The effect of T2T-DAS44-US on attaining clinical remission and on change in Sharp-van der Heijde score compared to T2T-DAS44 was analysed. A total of 1016 visits of 128 patients were included. T2T-DAS44 was correctly followed in 24% of visits and T2T-DAS44-US in 41%. DAS44 < 1.6 was achieved in 39% of visits. Compared to T2T-DAS44, using the T2T-DAS44-US strategy resulted in a 41% lower likelihood of DAS44 remission [OR (95% CI): 0.59 (0.40;0.87)] and had no effect on radiographic progression [β(95% CI): 0.11 (- 0.16;0.39)] assessed at various intervals up to 12months later. Our results do not suggest a benefit of using the US7-score in addition to clinical information as a T2T benchmark compared to clinical information alone. Key Points • Ultrasound has a valuable role in diagnostic evaluation of rheumatoid arthritis, but it is unclear whether adding ultrasound to the clinical assessment in a treat-to-target (T2T) strategy leads to more patients achieving remission and reduction in radiographic progression. • Our data from a real-world study demonstrated that adding information from ultrasound to the clinical assessment in a T2T strategy led to a lower rather than a higher likelihood of obtaining clinical remission as compared to using only clinical assessment. • Our data demonstrated that adding ultrasound data to a T2T strategy based only on clinical assessment did not offer additional protection against radiographic progression in patients with RA. • Adding US to a T2T strategy based on clinical assessment led to far more treatment intensifications (with consequences for costs and exposure to adverse events) without yielding a meaningful clinical benefit.

Relative effectiveness of a heterologous booster dose with adenovirus type 5 vectored COVID-19 vaccine versus three doses of inactivated COVID-19 vaccine in adults during a nationwide outbreak of omicron predominance, in China: a retrospective, individually matched cohort-control study

ABSTRACT Effectiveness of heterologous booster regimes with ad5 vectored COVID-19 vaccine in a large, diverse population during the national-scale outbreak of SARS-CoV-2 omicron predominance in China has not been reported, yet. We conducted a large-scale cohort-control study in six provinces in China, and did a retrospective survey on the COVID-19 attack risk during this outbreak. Participant aged ≥18 years in five previous trials who were primed with 1 to 3 doses of ICV received heterologous booster with either intramuscular or orally inhaled ad5 vectored COVID-19 vaccine were included in the heterologous-trial cohort. We performed propensity score-matching at a ratio of 1:4 to match participants in the heterologous-trial cohort individually with the community individuals who received three-dose of ICV as a control (ICV-community cohort). From February 4 to April 10, 2023, 41504 (74.5%) of 55710 individuals completed the survey. The median time since the most recent vaccination to the onset of the symptoms of COVID-19 was 303.0 days (IQR 293.0-322.0). The attack rate of COVID-19 in the heterologous-trial cohort was 55.8%, while that in the ICV-community cohort was 64.6%, resulting in a relative effectiveness of 13.7% (95% CI 11.9 to 15.3). In addition, a higher relative effectiveness against COVID-19 associated outpatient visits, and admission to hospital was demonstrated, which was 25.1% (95% CI 18.9 to 30.9), and 48.9% (95% CI 27.0 to 64.2), respectively. The heterologous booster with ad5 vectored COVID-19 vaccine still offered some additional protection in preventing COVID-19 breakthrough infection versus homologous three-dose regimen with ICV, 10 months after vaccination.

Method of hyaluronidase immobilization to produce an oral dosage form

Hyaluronidase is an enzyme that helps maintain an optimal balance of hyaluronic acid in connective tissue and ensures full tissue regeneration. Currently, hyaluronidase drugs are used in various fields of medicine. Meanwhile, there are no oral preparations based on hyaluronidase on the pharmaceutical market due to its low bioavailability in this method of administration. One of the options to increase enzyme bioavailability is electron-beam pegylation, which involves obtaining drugs with a modified pharmacokinetic profile in the direction of increasing enteral bioavailability, as well as having additional protection from the action of proteolytic enzymes. Aim of the study was using the electron beam pegylation method to obtain a laboratory batch of a preparation based on highly purified hyaluronidase, which can be further used in the development of an oral drug product. Material and methods. Hyaluronidase, which was isolated from bovine testicular hyaluronidase and polyethylene glycols of different molecular weight, was used in the experimental study. Experiments were carried out using a pulsed linear accelerator ILU-10 for enzyme electron beam immobilization on a water-soluble polymer matrix of polyethylene glycol molecules. The formation of hyaluronidase and polyethylene glycols conjugates was confirmed by exclusion chromatography. Results. As a result of accelerated electron irradiation of hyaluronidase and polyethylene glycol of molecular mass 1500 Da conjugates of enzyme and polymer matrix were formed. After electron-beam pegylation, the specific activity of the enzyme was retained. Conclusions. A laboratory batch of prototype pharmaceutical substance based on immobilised hyaluronidase on polyethylene glycol was obtained.

A Chronic Aquatic Hazard Assessment for the Perfume Raw Material Octahydro-tetramethyl-naphthalenyl-ethanone.

Octahydro-tetramethyl-naphthalenyl-ethanone (OTNE) is a high-production volume fragrance material used in various down-the-drain consumer products. To assess aquatic risk, the Research Institute for Fragrance Materials (RIFM) uses a tiered data-driven framework to determine a risk characterization ratio, where the ratio of the predicted-environmental concentration to the predicted-no-effect concentration (PNEC) of <1 indicates an acceptable level of risk. Owing to its high production volume and the conservative nature of the RIFM framework, RIFM identified the need to utilize a species sensitivity distribution (SSD) approach to reduce the PNEC uncertainty for OTNE. Adding to the existing Daphnia magna, Danio rerio, and Desmodesmus subspicatus chronic studies, eight new chronic toxicity studies were conducted on the following species: Navicula pelliculosa, Chironomus riparius, Lemna gibba, Ceriodaphnia dubia, Hyalella azteca, Pimephales promelas, Anabaena flos-aquae, and Daphnia pulex. All toxicity data were summarized as chronic 10% effect concentration estimates using the most sensitive biological response. Daphnia magna was the most sensitive (0.032 mg/L), and D. subspicatus was the least sensitive (>2.6 mg/L, the OTNE solubility limit). The 5th percentile hazardous concentration (HC5) derived from the cumulative probability distribution of the chronic toxicity values for the 11 species was determined to be 0.0498 mg/L (95% confidence interval 0.0097-0.1159 mg/L). A series of "leave-one-out" and "add-one-in" simulations indicated the SSD was stable and robust. Add-one-in simulations determined that the probability of finding a species sensitive enough to lower the HC5 two- or threefold was 1/504 and 1/15,300, respectively. Given the high statistical confidence in this robust SSD, an additional application factor protection is likely not necessary. Nevertheless, to further ensure the protection of the environment, an application factor of 2 to the HC5, resulting in a PNEC of 0.0249 mg/L, is recommended. When combined with environmental exposure information, the overall hazard assessment is suitable for a probabilistic environmental risk assessment. Environ Toxicol Chem 2024;43:1378-1389. © 2024 SETAC.

Codification of European Private International Law!

Codification of European Private International Law!