Home enteral nutrition (HEN) is recommended for patients with nutritional requirements who can stay in the familiar environment. HEN guidelines recommend assessing health-related quality of life (HRQoL) to evaluate the effect of the treatment. NutriQoL® is a specific questionnaire developed to assess HRQoL in patients receiving HEN and validated in Spanish population. An observational, descriptive, and prospective study was carried out in two Spanish hospitals to describe the evolution of HRQoL, nutritional and health status in patients receiving HEN in routine clinical practice. Fifty-seven patients participated in the study, of whom 36 were followed-up after their inclusion. Most of them were at risk or moderate malnutrition (61.1%) or showed severe malnutrition (27.8%) at baseline. Patients with HEN showed an overall good HRQoL with a mean basal NutriQoL® score of 69.4, which increased to 74.3 after 12 months of follow-up; fifteen patients showed a clinically significant difference (≥4 points) after three months. The proportion of at-risk or severely malnourished patients decreased at the end of the follow-up period and, according to the physicians, their health status improved. Additionally, physicians considered useful the HRQoL evaluation in clinical practice. In conclusion, HRQoL is probably related to nutritional status improvement and, thus, should be considered for nutritional evaluation in clinical practice.

Inappropriate expression of histone deacetylase (HDAC6) and deregulation of the phosphatidylinositol 3-kinase (PI3K) signaling pathway are common aberrations observed in cancers. LASSBio-2208, was previously described as a dual inhibitor in the nanomolar range of HDAC6 and PI3Kα, being three times more potent in inhibiting HDAC-6. In this paper we described the cytotoxic and antiproliferative potency of LASSBio-2208 on different tumour cell lines, its possible synergism effect in association with PI3K and HDAC-6 inhibitors, and its DMPK in vitro profile. Our studies have demonstrated that LASSBio-2208 has moderate cytotoxic potency on MCF-7 (IC50 = 23 µM), CCRF-CEM (IC50 = 8.54 µM) and MOLT-4 (IC50 = 7.15 µM), with no cytotoxic effect on hPBMC. In addition, it has a good antiproliferative effect on MCF-7 cells (IC50 = 5.44 µM), low absorption by PAMPA-GIT and low permeation through the blood-brain barrier by PAMPA-BBB, exhibiting high metabolic stability in rat plasma. Moreover, LASSBio-2208 exhibited synergism when combined with getadolisib and tubastatin A, using the concentration corresponding to their CC50 values on MOLT-4 and CCRF-CEM cells.

To advance probiotic research, a comprehensive understanding of bacterial interactions with human physiology at the molecular and cellular levels is fundamental. Lacticaseibacillus rhamnosus LGG® is a bacterial strain that has long been recognized for its beneficial effects on human health. Probiotic effector molecules derived from LGG®, including secreted proteins, surface-anchored proteins, polysaccharides, and lipoteichoic acids, that interact with host physiological processes have been identified. In vitro and animal studies have revealed that specific LGG® effector molecules stimulate epithelial cell survival, preserve intestinal barrier integrity, reduce oxidative stress, mitigate excessive mucosal inflammation, enhance IgA secretion, and provide long-term protection through epigenetic imprinting. Pili on the cell surface of LGG® promote adhesion to the intestinal mucosa and ensure close contact to host cells. Extracellular vesicles produced by LGG® recapitulate many of these effects through their cargo of effector molecules. Collectively, the effector molecules of LGG® exert a significant influence on both the gut mucosa and immune system, that promotes intestinal homeostasis and immune tolerance.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

Diarrhoea is a serious cause of mortality worldwide that can lead to dehydration, gut barrier function impairment, nutrient malabsorption, and alterations of the gut microbiota (dysbiosis). Current solutions for its management, such as oral rehydration salts (ORS), inhibitors of the gut motility, antibiotics, and living probiotics only partially counteract the mechanisms of the disease and do not provide a full coverage of the problem. Potential risks of the use of living probiotic strains, particularly in immunocompromised patients, can be eliminated with the use of tyndallized (heat-killed) postbiotic bacteria and yeast. ABB C22® is a postbiotic combination of three tyndallized yeasts, namely Saccharomyces boulardii, Saccharomyces cerevisiae, and Kluyveromyces marxianus. To assess the action of the postbiotic combination on diarrhoea, immune and gut epithelial cell signaling assays, gut barrier formation assay and rotavirus gene expression assay were performed. ABB C22® showed a strong anti-inflammatory effect, an induction of the build-up of the gut epithelium, and a degree of protection against rotavirus infection. These experimental studies support the use of the postbiotic ABB C22® as a solution for the management of diarrhoea and gastrointestinal conditions, alone or in combination with existing but incomplete treatments.

The current research investigated the environmental risk of the polycyclic musk compounds, Galaxolide® (HHCB) and Tonalide® (AHTN), in the marine environments. These substances are lipophilic, bioaccumulated and potentially biomagnified in aquatic organisms. To understand the toxicity of HHCB and AHTN, we performed acute toxicity tests by exposing marine microalgae (Phaeodactylum tricornutum, Tretraselmis chuii and Isochrysis galbana), crustaceans (Artemia franciscana), echinoderms (Paracentrotus lividus), bivalves (Mytilus galloprovincialis), fish (Sparus aurata) and a candidate freshwater microalga (Raphidocelis subcapitata) to environmentally relevant concentrations (0.005 - 5 µg/L) following standardized protocols. The effects of both substances on microalgae growth were incipient and only I. galbana was sensitive to HHCB and AHTN, with IC10 values of 5.22 µg/L and 0.328 µg/L, respectively. Significant (p < 0.01) concentration dependent responses were measured in P. lividus and M. galloprovincialis larvae developments as well as S. aurata mortality tested with HHCB. The effect of HHCB on P. lividus larvae development was the most sensitive endpoint recorded, producing an EC50 value of 4.07 µg/L. Our results show that HHCB represents a high risk to P. lividus larvae development for early life stages in marine environments.

(1) Background: SARS-CoV-2 infection is mostly accompanied by mild COVID-19 symptoms in children. However, the multisystem inflammatory syndrome (MIS-C) and long-term sequelae are often severe complications. Therefore, the protection of the pediatric population against SARS-CoV-2 with effective vaccines is particularly important. Here we compare the humoral and cellular immune responses elicited in children (n=15) aged 5-11 years vaccinated with RBD-based vaccines combined in a heterologous scheme of SOBERANA® 02 and SOBERANA® Plus with those from children (n=10) aged 4-11 years who recovered from mild symptomatic COVID-19. (2) Methods: Blood samples were taken 14 days after last dose for vaccinated and 45-60 days after the infection diagnosis for COVID-19 recovered children. Anti-RBD IgG and ACE2-RBD inhibition were assessed by ELISA; IgA, cytokine and cytotoxic related proteins profile were determined by multiplex assays. Total B and T cell subpopulations and IFN-γ release were measured by multiparametric flow cytometry using a large panel of antibodies after in vitro stimulation with S1 peptides. (3) Results: Significant higher levels of specific anti-RBD IgG and IgA and ACE2-RBD inhibition capacity were found in vaccinated children in comparison to COVID-19 recovered children. Th1-like and Th2-like CD4+ T cells were also significantly higher in vaccinated subjects. IFN-γ secretion were higher in central memory CD4+ T cells of COVID-19 recovered children, but no differences between both groups were found in CD4+ and CD8+ T cells effector, terminal and naïve T cell subpopulations. High levels of IL-2, IL-6, IFN-γ and IL-10 in contrast to low levels of IL-4 suggesting a predominant Th1 cell polarization. Cytotoxic-related proteins granzyme A and B, perforin and granulin were also found in the supernatant after S1 stimulation in both vaccinated and recovered children. (4) Conclusions: Vaccination with the heterologous scheme of SOBERANA® 02/ SOBERANA® Plus induces strong antibody and cellular immune response compared to natural infections of young children.

Skin ageing is a progressive but modifiable, multi-factorial disorder that involves all skin tissues. Pertaining to its wide range of physiological and psychosocial complications, skin ageing requires rigorous clinical attention. Topical retinoids and per-oral proteoglycans are promising, non-invasive, therapeutic modalities. To overcome the low bioavailability of conventional free retinoids, Nourella® cream with Retilex-A® (Pharma Medico, Aarhus, Denmark) was developed using a proprietary nano-encapsulation technology. The nano-encapsulation is a sophisticated ‘permeation/penetration enhancer’ that optimises topical drug delivery by increasing surface availability and net absorption ratio. Treatment adherence is also improved by minimising skin irritation. Interventional evidence supports the higher efficacy of Retilex-A® in improving skin thickness and elasticity compared with conventional free forms. It is also reported that the rejuvenating efficacy of Retilex-A® and tretinoin are comparable. Another skin anti-ageing approach is proteoglycan replacement therapy (PRT) with Vercilex®. Vercilex® in Nourella® tablet has the potential to ameliorate proteoglycan dysmetabolism in the aged skin by activating skin cells and improving collagen/elastin turnover. Replicated clinical trials evidenced that PRT can significantly enhance the density, elasticity and thickness of both intrinsically aged and photoaged skin. Evidently, Vercilex® and Retilex-A® share a range of bioactivities, which underlies their synergistic activity observed in a clinical trial. Dual therapy with Nourella® tablets and cream produced higher effect sizes on skin characteristics than monotherapy with each of the two treatments. In conclusion, Nourella® cream and tablets are safe and effective treatments for skin ageing; however, combining the two in a ‘dual skin rejuvenation system’ significantly improves treatment outcomes.

The Xpert® Xpress SARS-CoV-2 and Xpert® Xpress SARS-CoV-2/Flu/RSV tests were rapidly developed and widely used during the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. In response to emerging genetic variability, a new SARS-CoV-2 target (RNA-dependent RNA-polymerase) has been added to both tests: Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus test. A rapid evaluation of both tests was performed in South Africa, using residual respiratory specimens. Residual respiratory specimens (n=125) were used to evaluate the Xpert® Xpress CoV-2 plus test and included 50 genotyped specimens. The Xpert® Xpress CoV-2/Flu/RSV plus test was assessed using 45 genotyped SARS-CoV-2 specimens, ten influenza A, ten Influenza B and twenty respiratory syncytial virus specimens. Results were com-pared to in-country standard of care tests. Genotyped specimens tested the performance of the test under pressure from circulating SARS-CoV-2 variants of concern. Reference material was included to assess the test limits and linearity. The Xpert® Xpress CoV-2 plus test performance compared to reference results across residual respiratory specimens was good (positive per-centage agreement (PPA)=95.2%, negative percentage agreement (NPA)=95.0%) The Xpert® Xpress CoV-2/Flu/RSV plus test showed good performance across all residual respiratory specimens (PPA=100%, NPA=98.3%). All genotyped variants of concern were detected by both tests. The Xpert® Xpress CoV-2 plus and Xpert® Xpress CoV-2/Flu/RSV plus tests can be used to diagnose SARS-CoV-2, and to diagnose and differentiate SARS-CoV-2, influenza A, influenza B and respiratory syncytial virus respectively. The NPA was lower than the recommended 99%, but was influenced by the low number of negative specimens tested. The variants of concern assessed did not affect test performance. It is recommended that sites perform their own assessments compared to in-country standard of care tests.

The XEN® gel stent reduces intraocular pressure (IOP) in glaucoma. XEN®-45 is widely used while the newer XEN®-63 has a larger lumen that may lower IOP more. We retrospectively compared the first 15 XEN®-63 cases to 15 matched XEN®-45 controls. With a preoperative IOP of 18.1 ± 3.9 mmHg (mean ± SD) and a final IOP of 9.2 ± 4.2 mmHg, XEN®-63 implantation resulted in an IOP reduction of 48.0 ± 23.3%. Similarly, with a preoperative IOP of 18.3 ± 4.5 mmHg and a final IOP of 10.5 ± 2.3 mmHg, XEN®-45 implantation resulted in an IOP reduction of 39.5 ± 17.81%. The median follow-up period was 57 days for the XEN®-63 group and 183 days for the XEN®-45 group. 5/15 eyes of each group underwent open conjunctival bleb revision within the period of observation. Two eyes of the XEN®-63 group also had secondary glaucoma surgery. In both groups only one eye required restart of antiglaucomatous medication. XEN®-63 and XEN®-45 effectively lower IOP and medication. XEN-63 achieved lower IOP over a short follow-up. Com-plication and revision rates were similar.

The aim of this study is to solve the problems of complicated pretreatment and high analytical cost in the detection technology of trace drug toxicants in municipal wastewater. A high-performance magnetic sorbent was synthesized for enrichment of trace drug substances in wastewater to develop magnetic solid-phase extraction pretreatment combined with the acoustic ejection mass spectrometry (AEMS) analytical methods for the molecules in wastewater drug toxicants. The magnetic nanospheres was successfully prepared by magnetic nanoparticles modified with divinylbenzene and vinyl pyrrolidone.The results showed that the linear dynamic range of 17 drugs was 1-500 ng/L, the recovery was 43%-105%, the matrix effect was more than 67%, the limit of quantitative detection was 1-2 ng/L, and the detection time of each sample was 2.98s. It can be seen that the developed magnetic solid-phase extraction (MSPE) method is a good solution to the problem of complicated pre-treatment and analytical cost in the detection of drugs in wastewater. The developed magnetic material and acoustic excitation coupled mass spectrometry analysis method can realize the low-cost, efficient enrichment and fast analysis of different kinds of drug molecules in urban sewage.

Addressing non-unions involves stabilizing the affected area through osteosynthesis and improving bone biology using bone grafts. However, there is no consensus on the optimal treatment method. This study aims to compare outcomes of non-union revision using conventional treatment methods (metal hardware ± graft) versus osteosynthesis with the human, allogeneic cortical bone screw (Shark Screw®). Thirty-four patients underwent conventional treatment, while 28 cases received Shark Screws®. Patient demographics, bone healing, time to bone healing, and complications were assessed. Results revealed a healing rate of 96.4% for the Shark Screw® group, compared to 82.3% for the conventionally treated group. The Shark Screw® group exhibited a tendency for faster bone healing (9.4±3.2 vs. 12.9±8.5 weeks, p=0.05061). Hardware irritations led to six metal removals in the conventional group versus two in the Shark Screw® group. The Shark Screw® emerges as a promising option for personalized non-union treatment in the foot, ankle, and select lower leg cases, facilitating effective osteosynthesis and grafting within a single construct, promoting high union rates, low complications, and a rapid healing process.

Interpolyelectrolyte complexes Eudragit® EPO/L100 received in different pH were characterized by different degree of swelling in mimicking fasted stomach medium (0.1 M HCl) and saved their shape during 6 hours of the experiment. The microenvironmental changes in IPECs structure during swelling testing were inves-tigated using FT-IR spectroscopy, thermal and elemental analysis. Both samples of IPECs during swelling were transformed to a similar structure with approximately the same composition. IPEC samples showed bioadhesive properties that was not significantly different from the positive control (Carbopol) in the test with the mucin compacts. The release rate of metronidazole (class I BCS) from IPEC matrices increased with the increasing degree of swelling. IPEC 1 provided 49.62 ± 6.20% and IPEC 2 – 87.69 ± 5.15 % of metronidazole release after 6 hours in mimicking fasted stomach medium (0.1 M HCl). Total amount of released acyclovir (class III BCS) from IPEC 1 was 25.76 ± 5.67 % and from IPEC 2 was 21.48 ± 5.00 %. Release of both drugs was controlled by relaxation of polymeric chains in matrices according to the Peppas-Sahlin model. According to the received results, investigated interpolymer complexes are perspective for further evalua-tion as carriers for gastroretentive bioadhesive systems.

Chronic gastroduodenal symptoms are prevalent worldwide, and there is a need for new diagnostic and treatment approaches. Several overlapping processes may contribute to these symptoms, including gastric dysmotility, hypersensitivity, gut-brain axis disorders, gastric outflow resistance, and duodenal inflammation. Gastric Alimetry® (Alimetry, New Zealand) is a non-invasive test for evaluating gastric function that combines body surface gastric mapping (high-resolution electrophysiology) with validated symptom profiling. Together, these complementary data streams enable important new clinical insights into gastric disorders and their symptom correlations, with emerging therapeutic implications. A comprehensive database has been established, currently comprising >2,000 Gastric Alimetry tests, including both controls and patients with various gastroduodenal disorders. From studies employing this database, this pa-per presents a systematic methodology for Gastric Alimetry test interpretation, together with an extensive supporting literature review. Reporting is grouped into four sections: Test Quality, Spectral Analysis, Symptoms, and Conclusions. This review compiles, assesses, and evaluates each of these aspects of test assessment, with discussion of relevant evidence, example cases, limitations, and areas for future work. The resultant interpretation methodology is recommended for use in clinical practice and research to assist clinicians in their use of Gastric Alimetry as a diagnostic aid, and is expected to continue to evolve with further development.

DNA damage response (DDR) pathways in keto-enol genotoxicity have not been characterized, and few studies have reported genotoxic effects in non-target organisms. The present study shows that concentrations of 11.2, 22.4, 37.3 mg/L of Movento® 240SC and 12.3, 24.6, 41.1 mg/L of Envidor® 240SC for 72 h oral exposure induced DSBs by significantly increasing the percentage of γH2AV expression in regions 2b and 3 from the germarium of wildtype females of Drosophila melanogaster Oregon R, compared to the control group (0.0 mg/L of insecticides), by confocal immunofluorescence microscopy. The comparison between both insecticides’ revels that only the Envidor® 240SC induces concentration-dependent DNA damage, as well as structural changes in the germarium. We determined that the DDR induced by Movento® 240SC depends on the activation of the ATMtefu, Chk1grp and Chk2lok kinases by significantly increasing the percentage of expression of γH2AX in regions 2b and 3 of the germarium, and that ATRmei-29D and p53dp53 kinases only respond at the highest concentration of 37.3 mg/L of Movento® 240SC. With the Envidor® 240SC insecticide, we determined that the DDR depends on the activation of the ATRmei-29D/Chk1grp and ATMtefu/Chk2lok kinases, and p53dp53 by significantly increasing the percentage of expression of γH2AX in the germarium.

Teledermatology, the dermatological consultation and diagnosis via digital communication technologies, has become increasingly important in modern healthcare. The integration of teledermatology into clinical practice has gained significant interest, especially during the COVID-19 pandemic. Numerous studies have shown the effectiveness and reliability of teledermatology, with high levels of patient satisfaction and diagnostic accuracy. Pathpoint® eDerma is a cloud-based dermatology platform that aims to streamline the documentation and management of dermatological conditions. It offers several clinical benefits, including faster diagnosis, reduced unnecessary procedures, improved access to care, and cost savings. The platform follows a comprehensive risk management plan and complies with safety regulations. It undergoes regular recertification and reviews to ensure its safety and effectiveness. The clinical evaluation of eDerma confirms its ability to deliver significant clinical benefits while effectively mitigating risks. The benefit-risk ratio of eDerma is highly acceptable, supporting its use in clinical settings to enhance dermatological care.

Polymer-based composites are widely used in the automotive, security, aeronautical and space industries, to mention a few. This is because of their good mechanical properties, which are similar to those of metals but with the attraction of being lightweight. Kevlar® as a reinforcement is extensively used in the security industry owing to its good ballistic properties. This investigation presents the mechanical characterization based on in-plane quasi-static tensile testing of Kevlar® composite using a universal testing system. The methodology developed for the preparation of coupons is based on pressure, temperature and time. As a result of this work, elastic moduli (EL and ET), Poisson’s ratio (νLT), shear modulus (GLT) and strengths (XT, YT, S) were obtained. It is worth mentioning that there is scarce or no characterization of this material in the literature, and those studies that do characterize it do not present the coupon thermoforming conditions or the reasons of the specimen dimensions (width, length and thickness).

Alzheimer's disease (AD) is a complex disease involving multiple factors such as amyloid plaque formation, mitochondrial dysfunction, telomere length, and oxidative stress. As the disease began 20 years before the onset of clinical symptoms, treatment of AD after its onset is likely to be too late to have a significant effect. Therefore, prevention from an early stage is important. Twendee X®︎ (TwX, Oxicut®︎) is an antioxidant supplement consisting of eight ingredients. TwX has been proven to prevent dementia in patients with mild cognitive impairment (MCI) in a multicenter, randomized, double-blind, placebo-controlled, prospective intervention trial. To elucidate the mechanisms of TwX on brain and cellular function, TwX was administered in in vitro experiments and in a C57BL/6 old wild-type, and spontaneous hyperglycemia model with accelerated cognitive decline, and its effects on diabetes, brain autophagy, neurogenesis, and telomere length were evaluated in comparison with those of the non-treated groups. TwX protected mitochondria from oxidative stress with higher antioxidant capacity than a single antioxidant. TwX not only lowered blood glucose levels, but also suppressed reduction of brain neurogenesis and loss of autophagy. Telomeres in aged mice were significantly longer than those in non-TwX-treated mice. Development of dementia is based on many factors of brain function. TwX was suggested to prevent dementia not only by its antioxidant effects, but also by its effects on diabetes, brain neurogenesis, telomere deficiency, and energy production.

Exposure to sun radiation leads to higher risk of sunburn, pigmentation, immunosuppression, photoaging and skin cancer. In addition to ultraviolet radiation (UVR), recent research indicates that infrared radiation (IR) and visible light (VIS) can play an important role in the pathogenesis of some of these processes. Detrimental effects associated to sun exposure are well known, but new studies have shown that DNA damage continues to occur long after exposure to solar radiation has ended. Regarding photoprotection strategies, natural substances are emerging for topical and oral photoprotection. In this sense, Fernblock®, a standardized aqueous extract of the fern Polypodium Leucotomos (PLE), has been widely administered both topically and orally with a strong safety profile. Thus, this extract has been used extensively in clinical practice, including as a complement to photodynamic therapy (PDT) for treating actinic keratoses (AKs) and field cancerization. It has also been used to treat skin diseases such as photodermatoses, photoaggravated inflammatory conditions and pigmentary disorders. This review examines the most recent developments in the clinical application of Fernblock® and assesses how newly investigated action mechanisms may influence its clinical use.

To create normative scores for all CrossFit® Open (CFO) workouts and compare male and female performances, official scores were collected from the official competition leaderboard for all competitors of the 2011-2022 CFO competitions. Percentiles were calculated in athletes (18 – 54 years) who completed all workouts within a single year ‘as prescribed’ and met minimum scoring thresholds. Independent t-tests revealed significant (p &lt; 0.05) sex differences for 56 of 60 workouts. In workouts scored by repetitions completed, men completed more repetitions in 18 workouts by small-to-large differences (d = 0.22-0.81), whereas women completed more repetitions in 6 workouts by small-to-medium differences (d = 0.36-0.77). When workouts were scored by time-to-completion, men were faster in 10 workouts by small-to-large differences (d = 0.23-1.12), while women were faster in three workouts by small differences (d = 0.46). In three workouts scored by load lifted, men lifted more weight by large differences (d = 2.00-2.98). All other differences were either trivial or not significant. Despite adjusted programming for men and women, the persistence of performances differences across all CFO workouts suggest resultant challenges are not the same. These normative values may be useful to training and research in male and female CrossFit® athletes.

Affinity chromatography on procainamide-Sepharose has been an important step in the purification of butyrylcholinesterase (BChE) and acetylcholinesterase (AChE) since its introduction in 1978. The procainamide affinity gel has limitations. In the present report a new affinity gel called Hupresin^® was evaluated for its ability to purify truncated, partly-deglycosylated human butyrylcholinesterase (rHuBChE) expressed in a stably transfected CHO cell line. We present a detailed example of the purification of rHuBChE secreted into 3940 mL of serum-free culture medium. The starting material contained 13,163 units of BChE activity (20.9 mg). rHuBChE was purified to homogeneity in a single step by passage over 82 mL of Hupresin^® and elution with 0.1 M tetramethylammonium bromide in 20 mM TrisCl pH 7.5. The fraction with the highest specific activity of 630 units/mg contained 11 mg of BChE. Hupresin^® is superior to procainamide-Sepharose for purification of BChE, but is not suitable for purifying native AChE because Hupresin^® binds AChE so tightly that AChE is desorbed with denaturing solvents such as 50% acetonitrile or 1% trifluoroacetic acid. Procainamide-Sepharose will continue to be useful for purification of AChE.

In the production of green parts from powder, there is unavoidable slight deviation in the die filling, even when high-quality powders are used. The quantity of powder in the die varies and thus affects the weight of the compact. This filling variation results in variation of the pressing force, and thus influences the part geometry. The development of the DORST Netshape® System was conceived as an autonomous manufacturing system in order to compensate for these effects. Based on the Dorst Industry 4.0 innovations for part weight measuring immediately after pressing in combination with a laser dimension measuring system, this technology package attempts to reach enhanced precision and consistency in production. The paper presents results from various trials that show the capability of this new system, designed to improve the quality of pressed parts.

This work investigates the influence of strain rate on the stress/strain behaviour of Scalmalloy. This material is an aluminium-scandium-magnesium alloy, specifically developed for additive manufacturing. The bulk yield stress of the material processed by Selective Laser Melting is approximately 340 MPa which can be increased by heat-treating to approximately 530 MPa. These numbers, combined with the low mass density of 2.7 g/cm3, make Scalmalloy an interesting candidate for lightweight crash-absorbing structures. As this application is inherently dynamic, it is of interest to study the loading rate sensitivity, which is difficult to predict: Al-Sc alloys exhibit classic strain rate sensitivity with an increased yield stress at elevated strain rates. However, Al-Mg alloys are known to show the contrary effect, they exhibit less strength as strain rate is increased. To answer the question how these effects combine, we study the dynamic behaviour at four different strain rates ranging from 10−3 /s to 1000 /s using servo-hydraulic and Split-Hopkinson testing methods. The resulting data is analysed in terms of strain rate sensitivity of tensile strength and failure strain. A constitutive model based on a simplified Johnson-Cook approach is employed to simulate the tensile tests and provides good agreement with the experimental observations.

Surface treatment of implants facilitates osseointegration, with nanostructured surfaces exhibiting accelerated peri-implant bone regeneration. This study compared bone-to-implant contact (BIC) in implants with hydroxyapatite (HA), sand-blasted and acid-etched (SLA), and SLA with calcium (Ca)-coated (XPEED®) surfaces. Seventy-five disk-shaped grade 4 Ti specimens divided into three groups were prepared, with 16 implants per group tested in New Zealand white rabbits. Surface characterization was performed using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), digital microscopy, and a contact angle analyzer. Cell viability, proliferation, and adhesion were assessed using MC3T3-E1 cells. Apatite formation was evaluated using modified simulated body fluid (m-SBF) incubation. After 4 weeks of healing, the outcomes reviewed were BIC, bone area (BA), removal torque tests, and histomorphometric evaluation. Microstructure analysis revealed irregular pores across all groups, with the XPEED group exhibiting a nanostructured Ca-coated surface. Surface characterization showed a crystalline CaTiO3 layer on XPEED surfaces, with evenly distributed Ca penetrating the implants. All surfaces provided excellent environments for cell growth. The XPEED and SLA groups showed significantly higher cell density and viability with superior osseointegration than HA (p &lt; 0.05); XPEED exhibited the highest absorbance values. Thus, XPEED surface treatment improved implant performance, biocompatibility, stability, and osseointegration.

The temporary immersion system bioreactor named GreenTray®[2], [3]presents advantages over the existing ones. Firstly, there is no need to use forceps to move the shoots or plantlets in or out of the recipient, neither the use of scalpel to divide them. Secondly, the basis of the shoot can remain in the GreenTray® and can sprout again in several cycles of growth. These two characteristics reduce the costs in the process of micropropagation. Besides, shoots or plantlets development is enhanced by the aeration of the recipient, thus enriching with CO2 the recipient atmosphere. The chapter describes and provides images and values of interest in (1) the micropropagation process of some commercial Prunus or Pyrus rootstocks; (2) the plantlet growth under autotrophic conditions; and (2) the inoculation of plants with pathogens that reproduce in vitro the symptoms observed in vivo, using the GreenTray® bioreactor.

This paper shows a method for pipeline leak detection using a transient-based method with MATLAB® functions. The simulation of a pipeline systems in the time domain are very complex. In the case of the dissipative model, transfer functions are hyperbolic Bessel functions. Simulating a pipeline system in the frequency domain using a dissipative model we could find an approximate transfer function with equal frequency domain response to in order get the pipeline system's time domain response. The method described in this paper can be used to detect, by comparison, to detect a leak in a pipeline system model.

Dyslipidemia presents high levels of serum cholesterol, being characterized as a risk factor for cardiovascular diseases, especially for the development of atherosclerosis. E. oleracea (OFEO), A. esculentus (OFAE), B. orellana (OFBO) and granulated (CHR) oils are rich in bioactive compounds with potential to treat changes in lipid metabolism. This study investigated the effects of treatments with oils from A. esculentus, E. oleracea, B. orellana and granules (Chronic SM®) on saturated fat-induced dyslipidemia Cocos nucifera L. The chromatographic profile showed the majority of unsaturated fatty acids in the tested oils. The quantification of tocotrienols and geranylgeraniol was obtained in OFBO and CHR. Treatments with OFEO, OFAE, OFBO and CHR were able to significantly reduce glycemia with p&gt;0.001, as well as hypertriglyceridemia, total cholesterol and LDL-cholesterol, in addition to increasing HDL-cholesterol. The treatments inhibited the formation of atheromatous plaques in the vascular endothelium of the treated rats. The obtained results suggest that the OFEO, OFAE, OFBO and CHR groups have antidyslipidemic effects and antiatherogenic activity.

Background: Gait analysis systems offer invaluable insights for rehabilitation, yet their expense limits clinician access. We developed GAITWell®, a low-cost modular system for capturing spatiotemporal gait variables, and evaluated its measurement properties. Methods: The GAITWell® uses discreet binary sensors on interconnected boards to collect gait data, which is then analyzed using the DBSCAN algorithm on the Cartesian points from sensor outputs. Reliability was assessed using ICC2,1, standard error of the mean (SEM) and Bland-Altman plots. Validity was determined by comparing GAITWell® with the Qualisys Pro-Reflex system. Results: Participated 38 healthy adults, with an average age of 33.2 years (SD 13.0). Correlations between GAITWell® and the Qualisys system ranged from moderate to very high for most gait variables, with the exception of stride length, which demonstrated a low but significant correlation (r = .360, p &lt; .05). The ICC2,1 indicated moderate to good agreement for most gait variables. Stance and double support times, cadence, and base of support exhibited poor reliability, characterized by larger SEM and limits of agreement. Conclusions: Our findings indicate that the GAITWell® system is a promising tool for gait analysis. Future research will enhance sensor accuracy and refine algorithms to improve reliability.

Paper-based analytical devices have been substantially developed in recent decades. Many fabrication techniques for paper-based analytical devices have been demonstrated and reported. Herein we report a relatively rapid, simple, and inexpensive method for fabricating paper-based analytical devices using parafilm hot pressing. We studied and optimized the effect of the key fabrication parameters, namely pressure, temperature, and pressing time. We discerned the optimal conditions, including pressure of 3.8 MPa (3 tons), temperature of 80oC, and 3 minutes of pressing time, with the smallest hydrophobic barrier size (821 µm) being governed by laminate mask and parafilm dispersal from pressure and heat. Physical and biochemical properties were evaluated to substantiate the paper functionality for analytical devices. Wicking speed in the fabricated paper strips was slightly slower than that of non-processed paper, resulting from reducing paper pore size. A colorimetric immunological assay was performed to demonstrate the protein binding capacity of the paper-based device after exposure to pressure and heat from the fabrication. Moreover, mixing in two-dimensional paper-based device and flowing in a three-dimensional counterpart were thoroughly investigated, demonstrating that the paper device from this fabrication process is potentially applicable as analytical devices for biomolecule detection. Fast, easy, and inexpensive parafilm hot press fabrication presents an opportunity for researchers to develop paper-based analytical devices in resource-limited environments.

Hydrothermal /super critical processes are important process to synthesize materials which are otherwise difficult to form under normal conditions. A mathematical model is developed using standard transport equations to calculate the time for heating of hydrothermal reactor and computer simulation of the model was carried out in SOLIDWORKS® to validate it. The materials used to form reactor vessel were stainless steel (outer body) and TEFLON (PFA) (inner vessel). It was shown that composite wall, its geometry, construction & properties greatly affect the time and pattern of heat transfer. The time calculated and pattern generated were found to be in good agreement with experimental values.

The West-African variety of Sorghum bicolor leaf sheath (SBLS) Jobelyn® is a natural remedy, which has gained international recognition for its anti-anemic effect and energy boosting qualities in debilitating diseases. The widespread use of traditional medicine in the region usually confirms its safety, but not its efficacy or deep assessment of their pharmacological properties. The other major issue for herbal-based treatments is the lack of definite and complete information about the composition of the extracts. Despite limitations, efforts have been made in isolation and characterisation of active compounds in this specie of sorghum showing various subclasses of flavonoids including apigeninidin, a stable 3-deoxyanthocyanidin and potential fungal growth inhibitor, which accounts for 84% of the total extract. Non-clinical in vitro and in vivo studies support previous indications that this variety of Sorghum bicolor possesses several biologically active compounds with potent antioxidant, anti-inflammatory, anti-aging and neuro-protective properties. Clinical studies show that SBLS has the ability to boost hemoglobin concentrations in anemic conditions and most remarkably to increase CD4 count in HIV-positive patients. The multiple effects and high safety profiles of this extract may encourage its development as a therapeutic agent for the treatment of anemia, chronic inflammatory conditions or in the symptomatic management of HIV infections. This review describes the potential therapeutic aspects of SBLS extract and its potential benefits.

The human gut microbiota (GM) is a complex and dynamic ecosystem that hosts trillions of commensal and potentially pathogenic microorganisms. It is crucial in protecting humans from pathogens and in maintaining immune and metabolic homeostasis. Numerous studies have demonstrated that GM has a significant impact on health and disease, including Alzheimer’s disease (AD). AD is a progressive neurodegenerative disorder characterized by impaired short-term memory and cognitive deficits. Patients with AD have been reported to exhibit abnormalities in GM density and species composition. Oxidative stress (OS) has been implicated in the onset and progression of AD, however, the relationship between OS and gut microbiota in AD onset and progression is not clear. Twendee X®︎ (TwX), an oral supplement consisting of 8 active ingredients, has been shown to prevent dementia in mild cognitive impairment (MCI) in humans and substantially improve cognitive impairment in mouse models of AD. This positive effect is achieved through the potency of the combined antioxidants that regulate OS and therefore similar results cannot be achieved by a single antioxidant ingredient. To examine the impact of long-term OS elevation as seen in AD on the body and GM, we examined GM alterations during the initial OS elevation using a rat 2-week OS loading model, and examined the effects of TwX on OS and GM. Furthermore, using a questionnaire survey and fecal samples, we analyzed the impact of TwX on healthy individuals' gut bacteria and the associated effect on their quality of life (QOL). TwX was found to increase the number of bacteria species and their diversity in GM, as well as butyrate-producing bacteria, which tend to be reduced in AD patients. Additionally, TwX improved defecation condition and QOL. The gut bacteria function as part of the homeostatic function during OS elevation, and prophylactic administration of TwX strengthened this function. The results suggests that the preventative effect of TwX on dementia may involve the GM in addition to the other effects previously demonstrated.

Insufficient physical activity (PA) is associated with low cardiorespiratory fitness, which favors cardiovascular and other non-communicable diseases. Besides, it evidentially affects mental health. Considering the WHO PA guidelines, CrossFit® represents a versatile exercise program, combining aerobic and resistance training with mobility and could help lowering disease incidences among sedentary people. Yet, long-term CrossFit research is sparse. We conducted a nine-months intervention (≥ 2 CrossFit workouts/week) in sixteen beginners (14 males, 35  6.8 years, 180  8.6 cm, 85. 5  19.1 kg). As primary endpoint, VO2max was assessed at baseline, after four, and nine months. A repeated-measures ANOVA and pearson correlation were conducted. Well-being was investigated by WHO-5-index pre- and post-intervention. For exploratory purpose, body composition was tracked. Main outcome was an 11.5 % VO2max improvement with large effect (p < .01, η_p^2 = .27). Strong negative correlations between baseline VO2max and its progression after nine months (p = .006, r = -.654) were found. Well-being increased by 8.7 % (p = .024, d = .51). Body composition improved without statistical significance. Resting metabolic rate increased by 2.2 % (p = .042). This study reveals the potential of CrossFit to enhance physiological and psychological health in beginners. For more robust results, bigger sample sizes with higher proportion of women are needed.

VarroMed® is a soft acaricide registered for honey bees on the European Union market since 2017 for Varroa control. Researchers involved were partners of different countries of the Varroa control task force of COLOSS Association. Our goal was to evaluate performances (acaricide efficacy and toxic effects on honey bees) of VarroMed® in different climatic conditions. Our results in the tested apiaries showed an efficacy ranging from 71.2 to 89.3 % in summer/autumn, and from 71.8 % to 95.6 % in winter. No toxic effects on bees were observed, except in one apiary, where severe cold climatic conditions played a crucial role. The treatment could be efficiently applied in brood right as well as in broodless colonies. Integrated pest management (IPM) recommendations for bee-keepers are provided in order to apply the best Varroa control protocol.

During the casting in a warmer tropical temperature, a setting time delay is required to maintain the workability of the concrete, commonly achieved by the addition of admixtures i.e. silica fume (SF), fly ash (FA), and Plastrocrete®. However, high sugar content Coca-Cola in niche conditions is proposed as an ingredient for delaying concrete setting time in combination with conventional admixtures. This research aims to compare the setting time of admixtures from Coca-Cola and Plastocrete® RT6 plus in concrete mixing with control data of concrete mixed with SF or FA. The second aim is to measure the compression strengths between combinations of Coca-Cola and Plastocrete® RT6 plus. Concretes were produced with admixtures of SF, FA, Plastocrete® RT6plus, or Coca-Cola. The concrete used to control was f'c20 and f'c 25, while other concrete mixes were produced with the addition of Coca-Cola at 0.15% from the weight of cement at variation of moisture treatments. The first method to produce concrete (f'c20+Plas0.23%+Cola0.15% and f'c25+Plas0.23%+Cola0.15%) did not employ water reduction. The second concrete productions (f'c25+Plas0.46%+Cola0.15% and f'c25+Plas0.46%+Cola0.15%) reduced the addition of water at 8.8% (v/w). The first concrete production method had a setting time 44% longer than control. The reduced water concrete in the second productions had a setting time 34% longer than control. Meanwhile, the Plastocrete® RT6 Plus admixture with the reduced water delayed the concrete setting time by 26% longer than control. The delayed setting time of Plastocrete® RT6 Plus admixture with reduction of water was shorter than in the treatment with Coca-Cola. The combination of the addition of Coca-Cola with Plastocrete® RT6 plus by reducing the amount of adding Coca-Cola to 0.10% with Plastocrete® RT6 plus can delay concrete setting time by 51% longer than normal concrete and increase concrete compressive strength by 13% higher than normal concrete. Mixing Coca-Cola with Plastocrete® RT6 plus not only provided an optimal delay effect on setting time but also significantly increase the compressive strength that was desired during the casting in warm tropical weather applied in building construction of Mulawarman University, Samarinda, Indonesia.

Advanced oxidation processes, including photocatalysis, have been proven effective at organic dye degradation. Tailored porous materials with regulated pore size, shape and morphology offer a sustainable solution to the water pollution problem, by acting as support materials to grafted photocatalytic nanoparticles (NPs). This research investigates the influence of pore and particle sizes of photocatalytic MICROSCAFS®, on the degradation of methyl orange (MO) in aqueous solution (10 mg/L). Photocatalytic MICROSCAFS® are made of binder-less supported P25 TiO2 NPs within MICROSCAFS®, which are silica-titania microspheres with controlled size and intercon-nected macroporosity, synthesized by an adapted sol-gel method that involves a polymeriza-tion-induced phase separation process. Photocatalytic experiments were done both in batch and flow reactors, these latter ones targeting real-life conditions. Photocatalytic degradation of 87% in 2 hours (batch) and 29% in 5 hours (flow), was achieved, using a calibrated solar light simulator (1 sun) and a photocatalyst/pollutant mass ratio of 23. This study introduces a novel flow kinetic model which provides the modeling and simulation of the photocatalytic MICROSCAFS® per-formance. A scavenger study was performed enabling in-depth mechanistic understanding. Fi-nally, the transformation products resulting from the MO photocatalytic degradation were elu-cidated by high-resolution mass spectrometry experiments and subjected to in-silico toxicity as-sessment.

The study describes the acute and delayed time course of recovery following the CrossFit® Benchmark Workout Karen. Eight trained men (28.4±6.4 years; 1RM back squat 139.1±26.0 kg) undertook the Karen protocol. The protocol consists of 150 Wall Balls, aiming to hit a target 3 meters high. Countermovement jump height (CMJ), creatine kinase (CK), and perceived recovery status scale (PRS) (general, lower and upper limbs) were assessed pre, post-0h, 24h, 48h and 72h after the session. The CK concentration 24h after was higher than pre-exercise (338.4 U/L vs. 143.3 U/L; effect size: 0.74; p≤0.05). At 48h and 72h following exercise, CK concentration had returned to baseline levels. The PRS general and of the lower limbs were lower in the 24-hours post-exercise compared to pre-exercise (PRS general: 4.7 ±1.5 and 7.9 ±1.7 mmol/L; and PRS of the lower limbs: 4.0 ±2.5 and 7.9 ±0.8, respectively). The PRS general, lower, and upper limbs were reduced at 48-post exercise compared to 72-hours post-exercise scores. Our findings provide insights into the fatigue profile and recovery in acute CrossFit® and can be useful to coaches effectively design the daily session.

Background: In the 2022 National Youth Tobacco Survey disposable e-cigarette devices are shown to be the most widely used e-cigarette devices amongst U.S. youth. In this paper we report the results of research designed to estimate the prevalence of use of BIDI® Stick branded e-cigarettes amongst youth (aged 13 to 17), and under-age young adults (aged 18 to 20) in the U.S. Methods: Cross sectional online survey of a nationally representative sample of 1,215 youth (13 17 years) recruited via the IPSOS probability-based KnowledgePanel and 3,370 young adults aged 18 to 24 - amongst whom 1,125 were aged 18 to 20. Results: Amongst youth aged 13 to 17, 0.91% [95% CI: 0.44-1.68] or 190,000 [95% CI: 90,000-350,000] youth reported having ever used a BIDI® Stick branded product and 0.04% [95% CI: 0.00-0.38] or less than 10,000 youth reported currently using a BIDI® Stick branded product. Amongst those young adults aged 18 to 20, 3.90% [95% CI: 2.49-5.81] or 470,000 [95%CI: 300,000-700,000] reported having ever used a BIDI® Stick product whilst 0.60% [95% CI: 0.17-1.55] or 70,000 [95% CI: 20,000-180,000] reported they now use a BIDI® Stick product “every day” or “some days”. Conclusions: The low prevalence of youth and underage adult current use of the BIDI® Stick e cigarette suggests that this product is not responsible for the recent growth in the use of disposable e-cigarettes by youth within the U.S. as demonstrated by the 2022 National Youth Tobacco Survey.

In the present study Aprepitant (APT) ternary solid dispersions (SDs) were developed and evaluated for the first time. Specifically, ternary SDs of APT with Poloxamer 188 and Soluplus^® (SOL) were prepared via melt mixing and compared to binary APT/Poloxamer 188 and APT/SOL SDs. Initially, combined thermo-gravimetric and hot-stage polarized light microscopy studies indicated that all tested compounds were thermally stable up to 280 °C, while Poloxamer 188 acted as a plasticizer to SOL by significantly reducing the temperature required to fully solubilize the API during SD preparation. Differential scanning calorimetry combined with wide angle X-ray diffraction studies showed that crystalline API was dispersed in both binary and ternary SDs, while Fourier transformation-infrared spectroscopy studies revealed no molecular interactions among the components. Scanning electron microscopy combined with EDAX element analysis showed that the API was dispersed in nano-scale within the polymer matrices, while increasing APT content led to increasing API nano-crystals within the SDs. Finally, dissolution studies showed that the prepared formulations enhanced dissolution of Aprepitant and its mechanism analysis was further studied. A mathematical model was also investigated to evaluate the drug release mechanism

The effect of sonication on the molecular characteristics of poliacrylic acid (Carbopol® Ultrez 10) and its rheological behavior in aqueous dispersions and microgels containing 0.25 wt. % of the polymer was analyzed in this work by rheometry, weight-average molecular weight (Mw) measurements via static light scattering (SLS), Fourier transform infrared (FTIR) spectroscopy and confocal microscopy. For this, the precursor dispersion and the microgels were sonicated in a commercial ultrasound bath at constant power and different times. We observed a softening of the microgel microstructure consisting of a systematic decrease in its shear modulus, yield stress and viscosity with increasing sonication time, while their overall Herschel-Bulkley (H-B) behavior was preserved. SLS measurements evidenced a reduction of Mw of polyacrylic acid with sonication time. Separately, FTIR measurements indicate that sonication produces scission in the C-C links of the Carbopol® backbone, which results in chains with the same chemistry but lower molecular weight. Finally, confocal microscopy measurements revealed a concomitant diminution of the size of the microsponge domains with sonication time, which is reflected in a softer microstructure resulting from reduction of the molecular weight of polyacrylic acid. The present results indicate that both the microstructure and the rheological behavior of Carbopol® microgels, in particular, and complex fluids in general, may be manipulated or tailored by high-power ultrasonication.

The purpose of the present study was to compare heart rate (HR), blood lactate and training load between different CrossFit® workouts, with equalized total volume in men and women. The study included 23 individuals (13 men and 10 women) experienced in CrossFit® training, who performed two workouts with different training types (as many reps as possible - AMRAP and for time) but equalized volume. Measurements of lactate, HR and rating of perceived exertion (RPE) were performed. The results showed that there was no HR interaction between workout time and sex (p = 0.822; η2 = 0.006] and between workout type and sex (p = 0.064, η2 = 0.803). HR significantly differed during each workout type (p <0.001, η2 = 0.621), but not between the two workout types (p = 0.552, η2 = 0.017). Lactate showed no difference between the workout types (p = 0.474, η2 = 0.768), although the training load was higher (p = 0.033, η2 = 0.199) in women when they performed AMRAP. Altogether, HR was not significantly different between training types or sex, while RPE, lactate and training load showed small differences depending on the group (women or men) or workout type (AMRAP or 'for time').

Objectives We tested the hypothesis that poor adherence is associated with a greater risk of alcohol-caused mortality and morbidities within the first year of discontinuing this medication. Materials and Methods Retrospective cohort study of 3319 individuals who received Acamprosate® in the East of Scotland in a 10-year period using a health informatics approach with record linkage of dispensing data, hospital utilization (SMR) and General Register Office of Scotland (GROS) data. Primary outcome was adherence between one to six months of initiating Acamprosate® medication. Secondary outcome was all cause morbidities and mortality. Results Of the total 3319 individuals identified, good adherence index of >80% was found in 59% of those prescribed Acamprosate® after three months and 6% after six months. There were significant linear trends of poorer adherence with increased risk of alcohol-caused mortality (HR1.2), medical morbidities especially neoplasm (HR 4.1|) and poisoning (HR 1.4) and psychiatric morbidities especially stress (HR 35.1), psychotic (HR 5.6) and neurotic disorders and directly alcohol induced conditions (7.4 HR) after adjustment for other factors within a one-year period of initiation of Acamprosate® treatment. Discussion and Conclusions Further exploratory studies using this digitalized approach should be encouraged in order to capture role of compliance to Acamprosate® and other types of medication that are known to reduce relapse into alcohol dependence and its direct relationship to mortality and morbidities in this population.

Systemic sclerosis (SSc) is an autoimmune connective tissue disease characterized by debilitating symptoms including skin and visceral fibrosis, systemic skin hardening, Raynaud's phenomenon and other vascular dysfunctions, and immune abnormalities. The disease poses a significant medical challenge with no cure currently available. As such, SSc is designated as an intractable disease in Japan, with patients receiving government subsidies for medical expenses. Oxidative stress (OS) is implicated in the pathogenesis of SSc and the antioxidant combination Tweendee X®︎ (TwX) has shown promising results in mitigating OS-related conditions. HOCl-induced SSc-mice are known to exhibit similar skin and visceral fibrosis, vascular disorders, and autoimmunity observed in human. In a study done using these mice, Twx demonstrated a significant reduction in lung and skin fibrosis compared to untreated HOCl-induced SSc mice. TwX also significantly reduced advanced oxidized protein products (AOPP) in serum, Col-1 gene expression and the activation of B cells involved in autoimmunity. SSc is a disease state in which autoimmune abnormalities, fibrosis, and vascular disorders are intertwined, and therefore for a treatment to be effective it needs to address multiple issues. Thus the efficacy of TwX may stem from its strong antioxidant capacity to regulate OS, which cannot be achieved by a single antioxidant on its own. In other studies, targeting other OS-related conditions, TwX was safe and proved to be effective at prevent dementia in humans with mild cognitive impairment and to significantly improve cognitive impairment in Alzheimer's (AD) mouse models. TwX may offer a new approach to antioxidant treatment for SSc, to address multiple abnormalities that are characteristic of the disease.

Chronic fatigue syndrome (CFS) is a disease in which fatigue that interferes with daily life persists for six months or longer. The number of patients with CFS is increasing, as CFS-like symptoms have been reported to occur in the sequelae of both COVID-19 infection and the SARS-CoV-2 vaccine, both of which have become significant issues in recent years. While the pathogenesis mechanism is not yet fully understood, research suggests that oxidative stress (OS) may play a role in the development of CFS. In this paper, we discuss the antioxidant potential of the antioxidant formulation Twendee M® (TwM) and the results of a questionnaire that monitored changes in symptoms before and after TwM in a total of 23 men and women diagnosed with CFS. TwM is a supplement containing 15 different ingredients, and has a strong antioxidant capacity that cannot be achieved with a single antioxidant ingredient. The results of the questionnaire showed that TwM significantly improved all of the major symptoms of CFS, including fatigue, muscle pain, joint pain, sleep disturbance, decreased memory and concentration, and headache. TwM was shown to alleviate various symptoms of CFS and improve quality of life.

Background: Fermented milks are a source of bioactive peptides with different potential benefits on human health (mainly antioxidant and antihypertensive effects) and may be considered as functional foods. Furthermore, those made with sheep milk have higher nutritional value and higher concentrations of proteins, fats, minerals, and vitamins, if compared to milk of other species. Objectives: Aim of this study was to perform a biochemical characterization and a comparison between sheep fermented milk (SFM) made with commercial starter cultures and sheep milk YoAlp®, a fermented milk obtained using local strains of lactic acid bacteria (LABs) (Streptococcus thermophilus and Lactobacillus delbrueckii) which have been isolated during years in Aosta Valley mountain dairy cattle farm. Methods: Sheep milk and fermented milk (Sarda and Lacaune breeds) have been collected and immediately analyzed. Biochemical characterization, by a proteomic approach, GC/MS and microtiter plate assay methods, have been conducted to evaluate their peptide, fatty acid and aromatic profile, and to assess potential health promoting effects. Results: The comparison between SFM and YoAlp® peptide profile shows a higher number of peptides using autochthonous starter cultures (52) than commercial starter cultures (35). Among these peptides 20,78% and 29,87%, respectively, are supposed to be potentially bioactive (DPP - dipeptidyl peptidase-IV - inhibitor, ACE - angiotensin converting enzyme – inhibitor and antioxidant). In both products, the fatty acids profile was similar to that of origin sheep milk; concerning aromatic profile, YoAlp® shows yogurt typical aromatic assets, similar to the commercial one. As far as bioactivity is concerned, ACE inhibitor activity is high for both samples. Similar values, as expected by peptide profile analysis, have been obtained using commercial and autochthonous starters. Even in the case of antioxidant capacity, peptide profile bioactivity prediction has been confirmed by the assay showing a DPPH inhibition higher for SFM than for YoAlp®, but this difference is not statistically significative. Conclusions: Local strains of lactic acid bacteria from Aosta Valley seems to work as well as the commercial, preserving biodiversity and typicality. However, further analyses are needed to identify peptides generated by autochthonous LABs in order to understand microbial proteolytic activities and to investigate gastric digestion resistance of bioactive peptides which can have positive effects on human health.

The phytonutraceutical Ormona® is a product composed of: purified oil of Bixa orellana Linné; dry extract of Myrciaria dubia McVaugh; dry extract of Trifolium pratense L. and dry extract of Euterpe oleracea Mart. obtained using Evolve® technology. This study evaluated the effects of Ormona® on Wistar rats affected by ovariectomy-induced osteoporosis. Pre-treatment was conducted for 15 days before surgery and continued for a further 45 days after the surgical procedure. The experimental design consisted of 5 groups (n=5): OVW: treated with distilled water (1 mL/ kg, p.o); ADS: alendronate sodium (4 mg/ kg p.o); EST: conjugated estrogen (2 ug/ kg, p.o); ORM: Ormona® (20 mg/kg, p.o); ORM + EST: Ormona® (20 mg/kg + conjugated estrogen 2 ug/ kg, p.o. Biochemical and hormonal parameters, along with bone histopathology and trabecular and femoral diaphysis size, were evaluated through Scanning Electron Microscopy (SEM) and bone calcium quantification by atomic absorption spectrophotometry. The results show that ovariectomy caused bone alterations such as loss of femoral microarchitecture, decreased bone homeostasis parameters, and changes in the lipid profile. Estrogen supplementation reduced parameters such as cholesterol, LDL, and Ca2+ concentration. However, Ormona® showed higher serum estradiol levels (p&lt; 0.01), effects on the lipid profile, including parameters that estrogen replacement and alendronate sodium did not affect, with an increase in HDL, and positive modulation of bone metabolism, increasing osteocytes and the presence of osteoblasts. Ormona®, therefore, produced better results than the groups treated with estrogen and alendronate sodium.

Objective: The goal of the present study was to evaluate the treatment with Canephron® after the diagnosis of acute cystitis or urinary tract infection (UTI) with regards to the risk of a sporadic recurrent UTI, frequent recurrent UTIs, UTI associated sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis) compared to standard antibiotic treatment. Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 in general practitioner (GP), gynecologist, or urologist practices from which data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI associated sick leave, amount of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson Comorbidity Score (CCI). Results: 2,320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with less sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio [OR]: 0.66; 95% confidence interval [CI]: 0.58–0.72), as well as with less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49–0.88), and with minor additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86–1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16) and occurrences of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real world data show that Canephron® is an effective and safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment in particular also to strengthen antimicrobial stewardship strategies.

Denture wearers often complain about jeopardized function and reduced quality of life due to lack of prosthesis’ retention. Implant retained mandibular overdentures, on 2 non-connected implants (2IOD) are well-proven solutions to overcome these issues. We prospectively assessed 69 patients and scrutinized clinical records until at least 7 years of function. Thirty-six were retained on Locator ® Abutments (LA) and thirty-tree on Ball Abutments (BA). Both systems were compared regarding the type, amount and total cost of required maintenance. One implants was lost, yielding 98.7% survival after 7 years. In total 438 technical issues occurred: 121 (27.35%) in BA and 317 (72.4%) in LA. Out of these, 343 events (78%) were solved chairside: 191 (43.6%) were replacements of retention caps, 113 (25.8%) were minor acrylic repairs, in 26 (5.9%) pressure ulcers had to be relieved and 13 (3%) related to abutments. LA required 179 insert replacements compared to 12 in the BA group. The overall initial treatment cost was 3850 euro. The average total maintenance cost in relation to the initial cost for the LA and BA groups was 19.11% (range 0% - 82.24%) and 18.91% (range 0% - 113.26%) respectively (P=0.540). Conclusions: The 7-years maintenance costs for a 2IOD is acceptable when the patient is regularly checked and professionally maintained. Most events are easily solvable chairside, but a few patients required more expensive interventions, regardless of the type of attachment used.

This study evaluated the anti-inflammatory effects, protection of gut barrier integrity, and stimulation of phagocytosis in peripheral cells of a nutritional supplement based on a synergistic combination of yeast-based ingredients with a unique 1,3/1,6-glucan complex and a consortium of postbiotic Saccharomyces cerevisiae rich in selenium and zinc. The anti-inflammatory effect in Caco-2 cells in the presence and absence of a pro-inflammatory challenge (tumour necrosis factor alpha [TNF-α]/interferon gamma [IFN-ɣ]) showed statistically significant reductions of IFN-ɣ induced protein-10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) levels vs. controls (p &lt; 0.001). Disruption of the gut integrity in the presence or absence of Escherichia coli (ETEC H10407) showed transepithelial electrical resistance (TEER) values higher in the ABB C1® group after 6 hours of testing. Spontaneous build-up of the gut epithelium monolayer over 22 days was also greater in the ABB C1® condition vs. a negative control. ABB C1® showed a significantly higher capacity to stimulate phagocytosis as compared with controls of algae β-1,3-glucan and yeast β-1,3/1,6 glucan (p &lt; 0.001). This study supports the mechanism of action by which ABB C1® may improve the immune response and be useful to prevent infection and allergy in clinical practice.

Mild cognitive impairment (MCI) and mild dementia are a clinically relevant health problem in the elderly and Alzheimer's disease being the most common neurodegenerative disorder. Furthermore, MCI and mild dementia are characterized by a deterioration of cognitive function and their diagnosis is mainly based on cognitive examination and, the prognosis of the disease seems to be an essential reason for the diagnosis, because there is a high risk of cognitive decline in the two syndromes. This review describes the effectiveness of Ginkgo biloba (EGb761®) leaf extract for the treatment of dementia syndrome and EGb761® combination therapy with other medications for symptomatic dementia. Tebonin® is a drug of plant origin based on the active ingredient “Ginkgo biloba”. This drug has shown encouraging results, improving cognitive function, neuropsychiatric disorders and consequent reduction of caregiver stress and maintenance of autonomy in patients with age-related cognitive decline, MCI and mild dementia. Nowadays, there is little evidence to support the efficacy of EGb761® combination therapy with anti-dementia drugs and, therefore, more evidence is needed to evaluate the role of EGb761® in mixed therapy.

Background: Newer personalized medicine including targeted therapies such as PARP inhibitors and CDK 4/6 inhibitors have shown to improve survival of breast and gynaecological cancer patients. However, efficacy outcomes may be hampered by treatment discontinuation due to targeted therapy-related adverse drug reactions or resistance. Studies suggest that add-on mistletoe (Viscum album L., VA) improves quality of life and ameliorates cytotoxic side effects of standard oncological therapy in cancer patients. The primary objective of this real-world data study was to determine the safety profile of targeted therapy in combination with add-on Helixor® VA therapy in breast and gynecological cancer patients. Methods: The present study is a real-world data study utilizing demographic and treatment data from the accredited national Network Oncology (NO) registry. The study has received ethics approval. The safety profile of targeted with or without Helixor® VA therapy as well as safety - associated variables were evaluated by univariate and adjusted multivariable regression analyses. Results: All stage breast or gynecological cancer patients (n = 242) were on average 54.5±14.2 years old. One hundred and sixty patients (66.1%) were in the control (CTRL, targeted therapy) and 82 patients (33.9%) in the combinational (COMB, targeted plus Helixor® VA therapy) group. The addition of Helixor® VA did not hamper the safety profile (χ2 = 0.107, p-value = 0.99) of targeted therapy. Furthermore, no adverse events and a trend towards an improved targeted therapy adherence were observed in the COMB group. Conclusions: The present study is the first of its kind showing the applicability of Helixor® VA in combination with targeted therapies. The results indicate that add-on Helixor® VA does not negatively alter the safety profile of targeted therapies in breast and gynaecological cancer patients.

Background DaVinci Single-Port (SP) robotic surgery offers several benefits compared to traditional multiport laparoscopic or robotic surgeries. One of the main advantages is that it allows for a minimally invasive approach, resulting in a single, smaller incision and reduced trauma to the patient’s body leading to less postoperative pain, faster recovery, and reduced risk of complications. The cosmesis of a single port with minimal visible scarring is also an attractive aspect to the patients; however, many surgeons use an additional port for energy device, stapler use, and drain insertion. Pure single port surgery with one incision is still rare. Here we share our experience of first 10 cases using SP robotic platform in colorectal surgery. Methods From May 2023 to December 2023, colorectal patients who underwent SP-robotic surgery were analyzed. Placement of the incision was umbilicus for 8 patients, and right lower quadrant for 2 patients through which ileostomy maturation was performed. Data including perioperative parameters and postoperative outcomes were analyzed with a median follow-up of 4.6months (range 0.6-7.4months). Results A total number of 10 colorectal patients underwent DaVinci Single-Port robotic colorectal surgery at our institution during this period. Demographics of the patients showed 4 males (40%) and 6 females (60%) with a median age of 63.5years (range 50-75years). Median body mass index (BMI) was 22.89kg/m2 (range 19.92-26.84kg/m2), and 9 patients were diagnosed with colorectal cancer and 1 patient was diagnosed with rectal gastrointestinal tumor. One patient underwent anterior resection and cholecystectomy simultaneously. Mean operation time was 222min (range 142-316min), and mean wound size was 3.25cm (range 2.5-4.5cm). Nine patients underwent surgery with single incision through which single port trocar was inserted, and one patient had one additional port for drain insertion. Mean hospital stay was 6 days (range 4-8 days) with 1 postoperative complication of bleeding requiring transfusion, but there was no re-admission within 30 days. Conclusion Overall, our experience with single-port robotic colorectal surgery has been promising. With only one patient with additional port for drain insertion, all nine patients underwent SP-robotic surgery with single incision for colon as well as rectal surgeries. Compared to an average postoperative length of stay of 6.5-8 days in laparoscopic colorectal surgeries reported in literature, SP-robotic surgery showed faster recovery of 6 days highlighting its benefits in patient recovery and satisfaction.

Angiogenesis is a process whereby new blood vessels are born from preexistent ones, which has a role in transporting oxygen and nutrients. On the other hand, inhibiting this process is a strategy used to treat some diseases, including cancers, diabetic retinopathy, and rheumatoid arthritis. This study investigates the effect of a new nutraceutical (Terasen®) on angiogenesis. Terasen® is made from a standardized extract of Euterpe oleraceae (Açaí), Myrciaria dubia (Camu-Camu), and purified oil of Bixa orellana (Annatto) and Astrocaryum aculeatum (Tucumã). The in vivo angiogenesis model used was the chorioallantoic membrane (CAM) from chicken embryos. The embryos were divided into seven groups: a vehicle control treated with ethanol solution (ETH), a naïve control treated only with saline solution (SOR), a positive control treated with dexamethasone (DEX), and four groups treated with Terasen® at different concentrations (0.5, 1, 2, and 3 mg/ml). The parameters assessed were the vessels’ area, length, and amount. The results show a statistically significant and concentration-dependent inhibition of angiogenesis caused by Terasen®. Our results suggest the nutraceutical has a high antiangiogenesis potential, possibly due to its bioactive compounds, including anthocyanins, quercetin, and tocotrienols.

The quality of veterinary medicinal products (VMP) is essential for efficient disease management. Therefore, VMPs that do not meet the required standards of quality can lead to increased sickness, death, and the development of antimicrobial resistance, posing a danger to both animals and humans. This study aimed to identify substandard and falsified VMPs on the Rwandan market using the Global Pharma Health Fund (GPHF)-Minilab™. VMP samples were purchased and collected in a cross-sectional study from veterinary retail pharmacies from five districts in four provinces of Rwanda, during May and June 2023. These samples were transported to the Veterinary Laboratory of the School of Animal Sciences and Veterinary Medicine, Nyagatare campus, University of Rwanda, and stored until analysis. The samples were subjected to physical and chemical analysis following the GPHF-Minilab™’s guidelines. A total of 130 samples from two categories of VMP were purchased from 10 veterinary retail pharmacies in urban and rural areas. The results of this study revealed that none of the assessed VMP samples failed physical tests (visual inspection, weight verification, and disintegration test). 10 samples (Sulfamethoxazole/Trimethoprim) out of 130 (7.7%) passed the visual inspections but later failed to comply with Thin-Layer Chromatography result specifications. This is an indication of the presence of substandard and falsified VMP circulating in Rwanda that warrants regular inspection and chemical quality control of VMPs along the supply chain.

Background: Functional beverages are ordinary foods with components or ingredients able to provide specific health effects other than purely nutritional effect. Aim: This study aims to formulate a new functional beverage obtained from the recovery of YoAlp® whey, a bovine fermented milk obtained using autochthonous starter cultures, added with Renetta Canada/Golden Delicious-Raspberry (YWL), Renetta Canada-Aronia (YWA) and Ravèntse (YWR) fruit juices to improve the functionality of the beverage. Methods: Microbiological analysis and chemical characterization, by a proteomic approach and spectrophotometric microassay, have been conducted on beverages to investigate the expected shelf-life and potential health promoting effects. Results: The microbiological assessment confirmed the safety of the beverages and the probiotic bacteria vitality over a shelf life of seven days. Biochemical analysis performed highlight the presence of different bioactive peptides (ACE inhibitory and antioxidant), and the betacasomorphin 9 (BCM-9), marker of A2 variant of β-casein typically present in Aosta Valley cattle breeds. Moreover, high amounts of total polyphenols, which concur to the antioxidant activity values observed, have been found. Furthermore, ACE inhibitory activity is well correlated to the bioactive peptides detected. Finally, a consumer test confirmed the YoAlp® whey-based beverages appreciation. Conclusions: The production of these beverages could represent a huge opportunity for Aosta Valley’s farms to increase their income and competitiveness, creating a circular economy by recovering a by-product like whey and following sustainability and healthy trends, which are driving the food sector.

In patients with presumed pancreatic ductal adenocarcinoma (PDAC), biomarkers that may open for personalised, risk-adapted treatment are lacking. The study analysed the impact of circulating tumour cells (CTCs) on the patterns of recurrence and survival in 98 patients resected for PDAC with 5-10 years of follow-up. Preoperative samples were analysed by the CellSearch® system for EpCAM+/DAPI+/CK+/CD45- CTCs. CTCs were detected in 7 of the 98 patients. CTCs predicted a significantly shorter median DFS of 3.3 vs. 9.2 months and a median CSS of 6.3 vs. 18.5 months. Relapse status was confirmed by imaging for 87 patients. Of these, 58 developed distant metastases (DM) and 29 cases isolated local recurrence (ILR) as first event. All patients with CTCs experienced DM. pN-status and histological grade &gt;2 were other independent risk factors for DM, but only CTCs predicted significantly shorter cancer-specific, disease-free and post-recurrence survival. We conclude that CTC presence in resected PDAC patients predicted early distant metastasis and impaired survival. The impact of CTCs was comparable to that of histopathological risk factors and exceeded the effect size of other preoperative parameters. Thus, preoperative CTCs alone or in combination with histopathological factors may guide initial treatment decisions in patients with resectable PDAC in the future.

The control of classical swine fever (CSF) in endemic areas has been attempted with modified live vaccines. However, in some regions, the implementation of imperfect vaccination programs has led to a reduction in the genetic diversity of the circulating strains and a change in their virulence. Porvac® subunit vaccine has been shown to provide a rapid onset of protection against the “Margarita” strain. The aim of this study was to evaluate whether the immune response induced by Porvac® is also effective against autochthonous isolates of low, medium or high virulence. All pigs vaccinated with Porvac® were protected against the disease after the challenge. PR-11/10–3 isolate caused a very mild disease in controls, whilst Holguin_2009 isolate produced mild to moderate signs of CSF and one of the pigs died. Finally, controls inoculated with PR-2016 isolate developed moderate to severe signs of CSF and two of them died. Viral replication was detected in controls, but not in pigs immunized with Porvac®. Finally, anti-Erns antibodies were induced in five out of six control pigs but in any of the vaccinated pigs. These results support the use of Porvac® for the control and elimination of CSF in Cuba and other endemic regions.

KLEPTOSE® CRYSMEB is a methylated cyclodextrin derivative displaying less methylated group substitution than randomly methylated cyclodextrin. It has demonstrated an impact on atherosclerosis and neurological diseases. linked in part to cholesterol complexation and immune response, but the impact on inflammatory cascade pathways was not clear. Thus, the impact of KLEPTOSE® CRYSMEB on various pharmacological targets was assessed using human umbilical vein endothelial cells in physiological and inflammatory conditions, followed by screening against twelve human primary cell-based systems designed to model complex human tissue and disease biology of the vasculature, skin, lung, and inflammatory tissues using the BioMAP® Diversity PLUS® Panel. Finally, the anti-inflammatory mechanism was investigated on peripheral blood mononuclear cells to evaluate anti-inflammatory or pro-resolving properties. The results showed that KLEPTOSE® CRYSMEB can modulate the immune system in vitro and potentially manage vascular issues by stimulating the expression of molecules involved in the crosstalk between immune cells and other cell types. It showed anti-inflammatory effects driven by pro-inflammatory cytokine secretion inhibition and could have different impacts on different tissue types. Moreover, this cyclodextrin showed no clear impact on pro-resolving lipid mediators. Finally, it appeared that the mechanism of action of KLEPTOSE® CRYSMEB seems to not be shared by well-known anti-inflammatory molecules.

To elucidate the cellular immune response to coronavirus disease (COVID-19) among children, we assessed cellular immunity in 8 children post-vaccination for COVID-19 and 11 children after severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, using the T-SPOT®.COVID assay for both the spike (S) and nucleocapsid (N) proteins. In the vaccinated group, the T-SPOT®.COVID assay for the S protein yielded positive results in all eight children. In contrast, in the post-infection group, the assay for the N protein was positive in 5 of 11 children, with 3 of these 5 children requiring hospital admission, including 2 who needed mechanical ventilation. Therefore, the T-SPOT®.COVID assay is valuable for assessing cellular immunity against COVID-19, and most children infected with COVID-19 may not develop such immunity unless the disease severity is significant.

Aging is a complex process associated with tissue degeneration and an increased risk of age-related diseases. This study aimed to evaluate the impact of Terasen®, a nutraceutical containing standardized extracts of Euterpe oleracea, Myrciaria dubia, and purified oil of Bixa orellana and Astrocaryum aculeatum on the lifespan of Caenorhabditis elegans, a widely used model organism for aging research. The findings demonstrated that Terasen® exhibited significant antioxidant activity and influenced the feeding behavior of C. elegans, leading to a reduced pharyngeal pumping rate and a decreased number of offspring produced by treated individuals. Notably, Terasen® also displayed a remarkable ability to extend the lifespan of C. elegans. These findings suggest that Terasen® may possess promising anti-aging effects in vivo, warranting further investigation.

Live-attenuated, oral rotavirus vaccines have significantly reduced rotavirus-associated diarrhoea morbidity and infant mortality. However, vaccine immunogenicity is diminished in low-income countries. We investigated whether maternal and infant intrinsic susceptibility to rotavirus infection via histo-blood group antigen (HBGA) profiles influenced rotavirus (ROTARIX®) vaccine-induced responses in Zambia. We studied 135 mother-infant pairs under a rotavirus vaccine clinical trial aged 6 to 12 weeks at pre-vaccination up to 12 months old. We determined maternal and infant ABO/H, Lewis, and secretor HBGA phenotypes, and infant FUT2 HBGA genotypes. Vaccine immunogenicity was measured as anti-rotavirus IgA antibody titres. Overall, 34 (31.3%) of children were seroconverted at 14 weeks, and no statistically significant difference in seroconversion was observed across the various HBGA profiles in early infant life. We also observed a statistically significant difference in rotavirus-IgA titres across infant HBGA profiles at 12 months though no statistically significant difference was observed between study arms. There was no association between maternal HBGA profiles and infant vaccine immunogenicity. Overall, infant HBGA was associated with RV-Vaccine immunogenicity at 12 months as opposed to early infant life. Further investigation into the low efficacy of ROTARIX® and appropriate intervention is key to unlocking full vaccine benefits for U5 children.

Infective endocarditis (IE) is a rare but severe disease with high mortality and healthcare burden. Cardiac surgery plays a major role in the contemporary clinical management of IE patients. During cardiac surgery, cardiopulmonary bypass significantly contributes to an increased risk for organ dysfunction and mortality by inducing an acute inflammatory response, vascular endothelial cell injury, impairment of the coagulation cascade, and ischemia‒reperfusion injury. During the past decade, the use of extracorporeal hemoadsorption therapy with the CytoSorb® hemoadsorber has been proposed as an adjuvant therapy to mediate inflammatory responses in IE patients receiving cardiac surgery with cardiopulmonary bypass. However, there is currently a lack of systemic evaluation of the effect of CytoSorb® hemoadsorption on clinical outcomes such as hemodynamics, organ dysfunction, and mortality in patients with IE. Therefore, in this review, we exclusively discuss contemporary findings concerning the rationale, clinical evidence and future perspectives for CytoSorb® hemoadsorption therapy in IE patients.

This prospective single-center study was designed to assess the clinical utility of the FilmArray® blood culture identification (BCID) panel for improving the diagnostic accuracy in neonatal sepsis. Results obtained using the FilmArray® BCID panel were correlated with results of blood culture in all consecutive neonates with suspicion of early-onset (EOS) and late-onset sepsis (LOS) attended in our service over a 2-year period. A total of 102 blood cultures from 92 neonates were included, 69 (67.5%) in cases of EOS and 33 (32.3%) in LOS. The FilmArray® BCID panel was performed in negative culture bottles at a median of 10 hours of blood culture incubation (range 7.5-20 hours), without differences by the type of sepsis. The FilmArray® BCID panel showed a 66.7% sensitivity, 100% specificity, 100% positive predictive value, and 95.7% negative predictive value. There were four false-negative cases, three of which of Streptococcus epidermidis in neonates with LOS and one case of Granulicatella adiacens in one neonate with EOS. We conclude that the use of the FilmArray® BCID panel in negative blood cultures from neonates with clinical suspicion of sepsis is useful in decision-making of starting or early withdrawal of empirical antimicrobials because of the high specificity and negative predictive values of this assay.

Modern advances in molecular medicine have led to reframing osteoarthritis as a metabolically active, inflammatory disorder with local and systemic contributing factors. According to the ‘inflammatory theory’ of osteoarthritis, immune response to an initial damage is the key trigger that leads to progressive joint destruction. Several intertwined pathways are known to induce and govern articular inflammation, cartilage matrix degradation, and subchondral bone changes. Effective treatments capable of halting or delaying the progression of osteoarthritis remain elusive. As a result, supplements such as glucosamine and chondroitin sulphate are commonly used despite the lack of scientific consensus. A novel option for adjunctive therapy of osteoarthritis is LithoLexal®, a marine-derived, mineral-rich extract, that exhibited significant efficacy in clinical trials. LithoLexal® has a lattice microstructure containing a combination of bioactive rare minerals. Mechanistic research suggests that this novel treatment possesses various potential disease-modifying properties, such as suppression of nuclear factor kappa-B, interleukin 1β, tumour necrosis factor α, and cyclooxygenase-2. Accordingly, LithoLexal® can be considered a disease-modifying adjunctive therapy (DMAT). LithoLexal® monotherapy in patients with knee osteoarthritis has significantly improved symptoms and walking ability with higher efficacy than glucosamine. Preliminary evidence also suggests that LithoLexal® may allow clinicians to reduce the dose of nonsteroidal anti-inflammatory drugs in osteoarthritic patients by up to 50%. In conclusion, the multi-mineral complex, LithoLexal®, appears to be a promising candidate for DMAT of osteoarthritis, which may narrow the existing gap in clinical practice.

Understanding platelet functionality has undergone a sea change in the last decade. No longer are platelets viewed simply as regulators of haemostasis; they are now acknowledged to be pivotal in coordinating the inflammatory and immune responses. This expanded role for platelets brings new opportunities for controlling a range of health conditions, targeting platelet activation and their interactions with other vascular cells. Antiplatelet drugs may be of wider utility than ever expected but often cause too strong a platelet suppression to be used out of clinical settings. Dietary antiplatelets represent a nutritional approach that can be efficacious while safe for general use. Here we review potential new uses for dietary antiplatelets outside the field of cardiovascular health, with specific reference to the water-soluble tomato extract Fruitflow®. Uses in different aspects of inflammation and immune function are discussed, highlighting exercise-induced inflammation, mediating the effects of air pollution, and controlling thrombotic aspects of the immune response. Potential future developments in women’s health, erectile dysfunction, and the allergic response give an indication of how wide-ranging the utility of dietary antiplatelets can possibly be.

The effective detection of viruses in aircraft wastewater is crucial to establish surveillance programs for monitoring virus spread via aircraft passengers. This study aimed to compare the performance of two virus concentration workflows, adsorption-extraction (AE) and Nanotrap® Microbiome A Particles (NMAP), in detecting the prevalence and concentrations of 15 endogenous viruses in aircraft lavatory wastewater samples. The viruses tested include two indicator viruses, four enteric viruses, and nine respiratory viruses. The results showed that cross-assembly phage (crAssphage), human polyomavirus (HPyV), rhinovirus A (RhV A), and rhinovirus B (RhV B) were detected in all wastewater samples using both workflows. However, enterovirus (EV), human norovirus (HNoV GII), human adenovirus (HAdV), bocavirus (BoV), parechovirus (PeV), epstein-barr virus (EBV), influenza A virus (IAV), and respiratory syncytial virus B (RsV B) were infrequently detected by both workflows, and hepatitis A virus (HAV), influenza B virus (IBV), and respiratory syncytial virus B (RsV A) were not detected in any samples. The NMAP workflow had greater detection rates of EV, PeV, and RsV B than the AE workflow, while the AE workflow had greater detection rates of HAdV, BoV, and EBV than the NMAP workflow. The concentration of each virus was also analyzed, and the results showed that CrAssphage had the highest mean concentration (6.76 log₁₀ GC/12.5 mL) followed by HPyV (5.46 log₁₀ GC/12.5 mL using the AE workflow, while the mean concentrations of enteric and respiratory viruses ranged from 2.48 to 3.63 log₁₀ GC/12.5 mL. Using the NMAP workflow, the mean concentration of crAssphage was 5.18 log₁₀ GC/12.5 mL and the mean concentration of HPyV was 4.20 log₁₀ GC/12.5 mL, while mean concentrations of enteric and respiratory viruses ranged from 2.55 to 3.74 log₁₀ GC/12.5 mL. The mean concentrations of CrAssphage, HPyV, RhV A, and RhV B between the two workflows were statistically significant (p < 0.05). In summary, the present study provides valuable insights into the performance of virus concentration workflows in detecting and quantifying different viruses in aircraft lavatory wastewater samples. The findings can aid in the selection of an appropriate concentration workflow for virus surveillance studies and contribute to the development of efficient and reliable virus detection methods.

The aim of this paper is to study the main areas in which Artificial Intelligence (AI) will impact the field of project management that relates to cost, risk and scheduling. The research model was based on a previous study of the ten project management knowledge areas presented in the PMI’s PMBOK 6th edition where project schedule-, cost- and risk management knowledge areas were identified as being the ones most likely to be affected by the development of AI. A group of experts that participated in the study agreed that AI will affect the project management profession in the future. Different elements of the three knowledge areas were considered to be affected more by AI than others. The schedule baseline is the element believed to be affected the most out of the project schedule management elements. For project cost management, the estimation of resource cost is believed to be affected the most. In the case of project risk management, the application of AI will have the strongest impact on the probability and impact format.

Insecticides with novel modes of action are required to complement the pyrethroids currently relied upon for controlling malaria vectors. One example of this is the neonicotinoid clothianidin, which is found in SumiShield™ 50WG used in indoor residual spraying (IRS). In a preliminary experiment, mortality in insecticide susceptible and resistant An. gambiae adults exposed to SumiShield™ 50WG-treated filter papers reached 80% by 3-days post-exposure and 100% by 6-days post-exposure. Next, cement, wood, and mud tiles were treated with SumiShield™ 50WG or K-Othrine® WG250 (deltamethrin IRS formulation) and insecticide resistant and susceptible Anopheles and Aedes were exposed to these surfaces periodically for up to 18-months. Pyrethroid resistant Cx. quinquefasciatus were also exposed at 9 months. Between exposures tiles were stored in heat and relative humidity conditions reflecting those found in the field. On these surfaces, SumiShield™ 50WG was effective at killing both susceptible and resistant An. gambiae for 18 months post-treatment, while mortality amongst the resistant strains when exposed to deltamethrin (K-Othrine® WG250) IRS was not above that of the negative control. Greater efficacy of SumiShield™ 50WG was also demonstrated against insecticide resistant strains of An. funestus compared to deltamethrin, though the potency was lower when compared with An. gambiae. In general, a higher efficacy of SumiShield™ 50WG was observed on cement and mud compared to wood. SumiShield™ 50WG demonstrated poor residual activity against Aedes aegypti and Culex quinquefasciatus. Overall, the results suggest SumiShield™ 50WG is well suited for malaria control.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) is the key regulator of low-density lipoprotein cholesterol (LDL-C) plasma levels. We previously observed that treatment of dyslipidemic subjects with nutraceutical combination containing red yeast rice (monacolin K 3.3 mg), Berberis aristata cortex extract (Berberine 531.25 mg) and Morus alba leaves extract (1-deoxynojirimycin 4 mg) (LopiGLIK®) did not alter the plasma PCSK9 levels. Thus, the aim of the present study was to investigate the effect of these three components on PCSK9 expression in HepG2 cell line in relationship to their effects on LDL-C cellular uptake. HepG2 cell line were incubated with Berberis aristata cortex extract (BCE), red yeast rice (RYR) and Morus alba leaves extract (MLE) alone or in combination for 24 h. RYR (50 µg/mL) increased PCSK9 protein expression (WB and ELISA assays), PCSK9 mRNA and its promoter activity. BCE (40 µg/mL) reduced PCSK9 expression, mRNA levels and promoter activity. MLE determined a concentration-dependent inhibition of PCSK9 at mRNA and protein levels, with a maximal reduction at 1 mg/mL; no significant changes in PCSK9 promoter activity were found. MLE also downregulates the expression of fatty acid synthase and HMG-CoA reductase mRNA levels. The combination of RYR, BCE and MLE reduced PCSK9 at mRNA, protein, and promoter activity. Finally, this combination induced the LDL receptor and LDL-C uptake by HepG2 cells. In conclusion, the positive effect of MLE on PCSK9 supports the rational of using this nutraceutical combination to control hyperlipidemic conditions.

Background and aim. The study aimed to assess the efficacy of the treatment of Kan Jang®, a fixed combination of Andrographis paniculata (Burm. F.) Wall. ex. Nees and Eleutherococcus senticosus (Rupr. & Maxim.) Maxim in patients with mild symptoms of COVID-19. Methods. One hundred forty patients received six capsules of Kan Jang® (n = 68, daily dose of andrographolides – 90 mg) or placebo (n=72) and supportive treatment (paracetamol) for 14 consecutive days in a randomized, quadruple-blinded, placebo-controlled, two-parallel-group design. The efficacy outcomes were the rate of cases turning to severe, the detection rate of SARS-CoV-2 virus over the time of treatment, the duration and the severity of symptoms (sore throat, runny nose, cough, headache, fatigue, loss of smell, taste, pain in muscles) in the acute phase of the disease. Other efficacy measures included improving cognitive and physical performance, quality of life, and the levels of inflammatory blood markers - IL-6, c-reactive protein, and D-dimer. Results. Kan Jang® significantly (p < 0.05) reduced the rate of cases turning to severe (5.36%) compared to placebo (17.86%) and decreased the detection rate of SARS-CoV-2 virus over the time of treatment. The statistical difference in the rates of patients with clinical deterioration in the Kan Jang treatment and placebo control groups was significant (p = 0.0176) both in 112 patients included per protocol (IPP) analysis and in 140 patients included per intention to treat (ITT) analysis (p = 0.0236); the absolute risk reduction of cases by Kan Jang treatment was 12.5%, and the number Needed to Treat by Kan Jang was 8. The patient's recovery time (Number of sick days at the home/clinic) was shorter in the Kan Jang group compared with the placebo group. The rate of resolution of inflammatory symptoms in the Kan Jang® group was significantly higher compared with the placebo group, and relief of the severity of cough, sore throat/pain, runny nose, and muscle soreness. Kan Jang® significantly decreased the Wisconsin Upper Respiratory Symptoms scores compared to placebo in the sample size of 140 patients. However, the relief of fatigue and headache and the decrease of IL-6 in the blood was observed only in a subset of the 86 patients infected during the second three waves of the pandemic. Kan Jang® significantly increased physical activity and workout; however, it did not affect cognitive functions (attention and memory), Quality of life Score, inflammatory markers D-dimer, and c-reactive protein compared with the placebo group. Conclusions. Overall, the results of this study suggest that Kan Jang® is effective in treating mild and moderate COVID-19 irrespective of SARS-Cov-2 variants infection.

Aim of this study was to evaluate the accuracy and usability of a novel continuous glucose moni-toring (CGM) system designed for needle-free insertion and reduced environmental impact. We assessed sensor performance of two GlucoMen® Day CGM systems worn simultaneously in eight participants with type 1 diabetes. Self-monitoring of blood glucose (SMBG) was performed reg-ularly over 14 days at home. Participants underwent two standardized 5-hour meal challenges with frequent plasma glucose (PG) measurements using a laboratory reference instrument at the research center. When comparing CGM to PG the overall mean absolute relative difference (MARD) was 9.7 [2.6-14.6]%. The overall MARD of CGM vs SMBG was 13.1 [3.5-18.6]%. In the consensus error grid (CEG) analysis, 98% of both CGM/PG and CGM/SMBG pairs were in the clinically acceptable zones A and B. The analysis confirms that GlucoMen® Day CGM meets the clinical requirements for state-of-the-art CGM. The needle-free insertion technology is well toler-ated by users and reduces medical waste compared to conventional CGM systems.

Docking the tail of lambs is a standard husbandry procedure and is achieved through several techniques including clamps, hot or cold knives and latex rings, the last of which is the most popular. All tail docking methods cause acute pain which can be reduced by application of local anesthetic, however precise anatomical injection for optimal efficacy requires considerable skill. This pen trial evaluated the ability of local anesthetic delivered with a dual function ring applicator / injector to alleviate acute tail docking pain. Thirty ewe lambs were assigned to one of three treatment groups (n = 10 per group): ring plus local anesthetic (Ring LA), ring only (Ring) and sham handled control (Sham). Lambs were videoed and behavior categorized every 5 minutes for the first hour and every 10 min for the subsequent 2 hours after treatment. There was a significant effect (p &lt; 0.001) of treatment on total active pain related behaviors in the first hour, with Ring lambs showing higher counts compared to Ring LA or Sham. Ring lambs also displayed a significantly higher count of combined abnormal postures (p &lt; 0.001) than Ring LA or Sham lambs. Delivery of 1.5ml of 2% lignocaine via the dual action device abolished abnormal behaviors and signs of pain in Ring LA lambs. However, lambs in the Ring LA group spent less time attempting to suckle compared to Ring and Sham lambs, suggesting that some residual discomfort remained.

Metallic glass matrix composites are unique new materials which have superior mechanical properties as compared to existing conventional materials. Owing to this, they are potential candidates for various future structural applications. However, they suffer from disadvantages of brittleness, poor ductility and little or no toughness and they manifest catastrophic failure on application of force. Their behavior is dubious and require extensive experimentation to draw conclusive results. In present study, which is continuation of previous study by author, an effort has been made to overcome this pitfall by simulation. A quantitative mathematical model based on KGT theory has been developed to describe nucleation and growth of crystalline phase dendrites in glassy matrix during solidification. It yields information about numerical parameters to understand the behavior of each individual element in a phase in multicomponent sluggish slurry and their effect on final microstructural evolution. Model is programmed and simulated in MATLAB®. Its validation is done by comparison with identical curves reported in literature previously for similar alloys. Results indicate that effect of incorporating all heat transfer coefficients at macroscopic level and diffusion coefficients at microscopic level play a vital role in refining the model and bringing it closer to actual experimental observations. Two types of hypoeutectic and eutectic systems namely Zr₆₅Cu₁₅Al₁₀Ni₁₀ and Zr_47.5Cu_45.5Al₅Co₂ respectively were studied. Simulation results were found to be in good agreement with prior simulated and experimental values

Objectives: Studies evaluating machine learning (ML) algorithms on cross-lingual RadLex® mappings for developing context-sensitive radiological reporting tools are lacking. Therefore, we investigated whether ML-based approaches can be utilized to assist radiologists in providing key imaging biomarkers – such as The Alberta stroke programme early CT score (APECTS). Material and Methods: A stratified random sample (age, gender, year) of CT reports (n=206) with suspected ischemic stroke was generated out of 3997 reports signed off between 2015-2019. Three independent, blinded readers assessed these reports and manually annotated clinico-radiologically relevant key features. The primary outcome was whether ASPECTS should have been provided (yes/no: 154/52). For all reports, both the findings and impressions underwent cross-lingual (German to English) RadLex®-mappings using natural language processing. Well-established ML-algorithms including classification trees, random forests, elastic net, support vector machines (SVMs) and boosted trees were evaluated in a 5 x 5-fold nested cross-validation framework. Further, a linear classifier (fastText) was directly fitted on the German reports. Ensemble learning was used to provide robust importance rankings of these ML-algorithms. Performance was evaluated using derivates of the confusion matrix and metrics of calibration including AUC, brier score and log loss as well as visually by calibration plots. Results: On this imbalanced classification task SVMs showed the highest accuracies both on human-extracted- (87%) and fully automated RadLex® features (findings: 82.5%; impressions: 85.4%). FastText without pre-trained language model showed the highest accuracy (89.3%) and AUC (92%) on the impressions. Ensemble learner revealed that boosted trees, fastText and SVMs are the most important ML-classifiers. Boosted trees fitted on the findings showed the best overall calibration curve. Conclusions: Contextual ML-based assistance suggesting ASPECTS while reporting neuroradiological emergencies is feasible, even if ML-models are restricted to be developed on limited and highly imbalanced data sets.

Background: Study to assess glucose levels of people with type 1 diabetes (T1D) overnight based on insulin type and timing. Methods: Real-world, retrospective study in T1D using multiple daily insulin injections. Contin-uous glucose monitoring and insulin injections data were collected for ten hours after dinner us-ing the Insulclock® connected cap. Meal events were identified using ROC detection methodology. The timing of rapid insulin, second injections, and the type of insulin analogs used were evaluat-ed. Results: Nocturnal profiles (n=775, 49 subjects) were analyzed. Higher glucose AUC over 180mg/dL was observed in delayed injections (number; %; mg/dL x h): -45-15min (n=136; 17.5%, 175.9 ±271.0); -15-0min (n= 231; 29.8%, 164.0 ±237.1); 0+45min (n= 408; 52.6%, 203.6 ±260.9), (p 0.049). The use of ultrarapid (FiAsp®) (URI) vs rapid insulin analogs (RI) was associated with less hypoglycemia events (7.1 vs 13.6%; p 0.005) and TBR70 (1.7 +6.9 vs 4.6 +13.9%; p 0.003). Us-ers of glargine U300 vs degludec had higher TIR (70.7 vs 58.5 %) (Adjusted R-squared: 0.22, p < 0.001). The use of a correction injection (n= 144, 18.6%) was associated with higher hypoglycemia events (18.1 vs 9.5%; p 0.003), TBR70 (5.5 +14.2 vs 3.0 +11.1%; p 0.003), glucose AUC over 180 mg/dL (226.1 +257.8 vs 178.0 +255.3 mg/dL x h; p 0.001), and lower TIR (56.0 +27.4 vs 62.7 +29.6 mg/dL x h; p 0.004). Conclusions: Dinner rapid insulin timing, insulin types and correction injections affect nocturnal glucose profile in T1D.

Verminosis causes great damage to the producer, with reduced milk production and decreased development of young animals. The use of bioproducts are an alternative to control worms. This study evaluated the effects of oral administration of one commercial formulations, based on the fungus Duddingtonia flagrans (Bioverm®) and experimental formulations D. flagrans associated with Pochonia chlamydosporia, on the control of worms in naturally infected cattle on February pasture to October 2021. Eighteen Holstein x Zebu cattle were divided into groups of six animals (group 1 Bioverm®, group 2 Association and control), separated into paddocks naturally infected with helminth larvae (L3). The parasite load was by means of fecal samples and pasture collection to determine L3 infestation. The study demonstrated low recovery of L3 in the pasture due to low rainfall during the experiment. The EPG was lower in groups 1 and 2 compared to the control in April, May and July, while in March the values were lower only in treatment 1 compared to the control. Individual or combined administration of fungal products reduced the presence of eggs and larvae in pastures at certain months of the year, indicating their effectiveness in the strategic control of gastrointestinal parasites in cattle.

The aim of this study is to evaluate the efficacy of taking a daily supplement based on active compounds (AUDISTIM® Day Night: A D/N) in alleviating tinnitus-related disability, as suggested by previous real-life studies. This double-blind randomized placebo-controlled study was conducted in adult with mild to severe tinnitus receiving a 3 month-supplementation. Tinnitus-related handicap (THI), psychological stress (MSP-9) and sleep quality (PSQI) were assessed at baseline and during intervention, perceived impression of tinnitus improvement at the end of the follow-up. The full set analysis included 114 patients (59 A D/N, 55 placebo) aged 53.8±11.4 years, 58% women, with fluctuating (45%) or permanent (55%) tinnitus from 9.3±9.4 years. A D/N supplementation led to greater changes in THI (-13.2±16.0 vs -6.2±14.4, p=0.0158, Cohen’s d=0.44) at 3 months, especially with continuous tinnitus (-15.0±16.3 vs -4.6±12.8, p=0.0065), and, to a lesser extent, at 1 month (-9.8±13.1 for A vs -4.3±12.1, p=0.0213). PSQI significantly improved over time in both groups, MSP-9 only with A D/N. In lines with previous observational studies, both clinical (THI score &gt; 7 pts) and statistical (vs. placebo) improvement, more pronounced in permanent tinnitus, demonstrate the effectiveness of the combination of active compounds and support its use in the management of mild to severe tinnitus.

Respiratory syncytial virus (RSV) is associated with adverse outcomes among immunocompromised patients. Inhaled ribavirin has been shown to improve mortality rates. The Small-Particle Aerosol Generator delivery system (SPAG-2) is the only FDA-cleared device to deliver inhaled ribavirin. However, it is difficult to set up and maintain. We developed a method for delivery of this medication using the vibrating mesh nebulizer (Aerogen®). We did not observe any adverse events with this method.

Background: This study aimed to investigate the effect of fascial manipulation (FM) of the deep cervical fascia (DCF) and sequential yoga poses (SYP) on pain and function in individuals with mechanical neck pain (MNP). Method: Following the predefined criteria, ninety-nine individuals with MNP were recruited, randomised and assigned to either the intervention group (IG) (n=51) or the control group (CG) (n=48). Individuals in the IG received FM (4 sessions in 4 weeks) along with the home-based SYP (4 weeks). The CG participants received the usual care (cervical mobilization and thoracic manipulation (4 sessions in 4 weeks) along with unsupervised therapeutic exercises (4 weeks). The participants underwent baseline and weekly follow-up measurements of pain using a numerical pain rating scale (NPRS) and elbow extension range of motion (EEROM) during upper limb neurodynamic test 1 (ULNT1). The baseline and the 4th session follow-up measurements of the Patient-specific Functional Scale (PSFS) and Fear-avoidance Behavior Questionnaire (FABQ) were also taken. Results: A repeated-measures ANOVA was performed. The mean differences between the IG and CG on NPRS 3rd and 4th sessions are -1.009 (p&lt; 0.05) and -1.701 (p&lt; 0.001), respectively; on EEROM in the 4th session is 20.120 (p&lt; 0.001); on FABQ during the follow-up is -5.036 (p&lt;0.001), showing a statistically significant difference, whereas on PSFS during follow-up is 0.263 (p=0.566), suggesting no significant differences in PSFS. Conclusion: FM and SYP can aid in reducing pain and fear avoidance behavior as well as improving the function and extensibility of the upper quarter region.

The paper focuses on the application of a multilevel, integrative and territorial approach to the protection of cultural heritage through planning instruments in Serbia. It points out the problems of the sectoral approach and discusses international recommendations that can be integrated into the planning methodology. The case study is the area of Djerdap National Park, which has an already established international and national importance. The research suggests that the cultural heritage in the area, with the exception of the Roman limes, is still recognized at the level of individual localities. The study emphasizes the importance of aligning all levels of governance to safeguard the whole spatial entity rather than focusing solely on its particular areas. The interna-tional and national importance of the planning area contributes to the strengthening of awareness of heritage and its institutional protection. However, the vitality of the area, which is key to its sustainable development, comes from the local level. Planning documents contribute to the inte-gration of local values and local communities into development programs and projects.

Glioblastoma multiforme (GBM) is the most frequent and aggressive primary brain tumor. GBM is formed by a very heterogeneous astrocyte population, neurons, neovascularization and infiltrating myeloid cells (microglia and monocyte derived macrophages). The IQGAP1 scaffold protein interacts with components of the cytoskeleton, cell adhesion molecules, and several signaling molecules to regulate cell morphology and motility, cell cycle and other cellular functions. IQGAP1 overexpression and delocalization has been observed in several tumors, suggesting a role for this protein in cell proliferation, transformation and invasion. IQGAP1 has been identified as a marker of amplifying cancer cells in GBMs. To determine the involvement of IQGAP1 in the onco-biology of GBM, we performed immunohistochemical confocal microscopic analysis of the IQGAP1 protein in human GBM tissue samples using cell type-specific markers. IQGAP1 immunostaining and subcellular localization was heterogeneous; the protein was located in the plasma membrane and, at variable levels, in nucleus and/or cytosol. Moreover, IQGAP1 positive staining was found in podosome/invadopodia-like structures. IQGAP1⁺ staining was observed in neurons (Map2⁺ cells), in cancer stem cells (CSC; nestin⁺) and in several macrophages (CD31⁺ or Iba1⁺). Our results indicate that the IQGAP1 protein is involved in normal cell physiology as well as oncologic processes.

Mucus plugging of the respiratory tract occurs in airway diseases, including asthma, chronic obstructive pulmonary disease and cystic fibrosis. It can cause blockage of airways, leading to breathlessness and lung failure. Here, we demonstrate the effect of BromAc® in dissolving mucus plugs in an novel ex-vivo ovine obstructive lung model using a ventilatory setup. Mucus simulant was filled into the trachea of freshly slaughtered ovine lungs and ventilated via an endotracheal tube (ETT) using Continuous Mandatory Ventilation. Predetermined single or repeated doses of Bromelain, Acetylcysteine (Ac), BromAc® and saline control were administered via an Aerogen® vibrating nebuliser and ventilated for 30 or 60 minutes. Ventilatory recording of resistance, compliance, tidal volume was conducted and rheology pre and post treatment were measured. A significant decline in airway resistance (p&lt;0.0001) compared to saline control was observed when treated with Bromelain, Ac and BromAc®, with the latter showing a stronger mucolytic effect than single agents. The decline in resistance was also effective in shorter timepoint (p&lt;0.05) at lower doses of the drugs. Changes in compliance, peak pressure and tidal volume was not observed post-administration of the drugs. Rheology measurements revealed that BromAc®™ significantly reduced the viscosity of the mucin at the end of 30-minute and 60-minute time points (p&lt;0.001) compared to the saline control. BromAc® showed complete dissolution of the respiratory mucus simulant and improved ventilatory airflow parameters in the ex-vivo ovine model.

Thermoregulation is important for maintaining homeostasis of our body. It can be easily broken under anesthesia. An appropriate method to measure the core body temperature is needed, especially for elderly patients because the efficiency of thermoregulation gradually decreases with age. The aim of this study was to examine the accuracy and feasibility of using of SpotOn® sensor in lower extremity orthopedic surgery in elderly patients aged over 80 years by comparing a SpotOn® sensor with two other reliable minimal-invasive methods: a tympanic membrane thermometer and a bladder thermometer. This study enrolled 45 patients aged over 80 years who were scheduled to undergo a lower extremity surgery. Body temperature was measured using a SpotOn® sensor, tympanic membrane thermometer and bladder thermometer. Agreements between the SpotOn® sensor and the other two methods were assessed using Bland and Altman plots for repeated measures adjusted for unequal numbers of measurements per patient. Compared with TempBladder, bias and limits of agreement for TempZHF were 0.07℃ ± 0.58℃. Compared with TempTympanic, bias and limits of agreement for TempZHF were -0.28℃ ± 0.61℃. 3M SpotOn® sensor using ZHF method for patients aged over 80 years undergoing lower extremity surgery shows feasible measurement value and sensitivity.

A polymer inclusion membrane (PIM) composed of 50 wt% poly(vinylidenefluoride-co-hexafluoropropylene) (PVDF-HFP) as its base polymer, 40 wt% Aliquat® 336 as its extractant and 10 wt% dibutyl phthalate (DBP) as plasticizer provided efficient extraction of vanadium(V) from its sulfate solutions adjusted to pH 2.5. It was suggested that V(V) was extracted as VO2SO4− via an anion exchange mechanism. Quantitative back-extraction was achieved in a sulfuric acid solution (6 mol L-1) containing 1 v/v% of hydrogen peroxide. It was assumed that the back-extraction process involved the oxidation of VO2+ to VO(O2)+ by hydrogen peroxide. The newly developed PIM with the optimized composition mentioned above exhibited excellent selectivity for V(V) in the presence of metallic species present in digests of spent alumina hydrodesulfurization catalysts (i.e., Al(III), Co(II), Cu(II), Fe(III), Mn(II), and Ni(II)). The co-extraction of Mo(VI) with V(V) was eliminated by its selective extraction at pH 1.1. The optimized PIM was characterized by contact angle measurements, atomic-force microscopy (AFM), energy dispersive X-ray spectroscopy (EDS), thermogravimetric analysis (TGA)/derivatives thermogravimetric analysis (DTGA), and the stress-strain measurements.

Glycosidic linkage analysis was conducted on the unfractionated polysaccharides in the alcohol-insoluble residues (AIRs) prepared from six red seaweeds (Gracilariopsis sp., Prionitis sp., Mastocarpus papillatus, Callophyllis sp., Mazzaella splendens, and Palmaria palmata) using GC-MS/FID analysis of partially methylated alditol acetates (PMAAs). The cell walls of P. palmata primarily contained mixed-linkage xylans and small amounts of sulfated galactans and cellulose. In contrast, the unfractionated polysaccharides of the other five species were rich in galactans displaying diverse 3,6-anhydro-galactose and galactose linkages with varied sulfation patterns. Different levels of cellulose were also observed. This glycosidic linkage method offers advantages for cellulose analysis over traditional monosaccharide analysis that is known for underrepresenting glucose in crystalline cellulose. Relative linkage compositions calculated from GC-MS and GC-FID measurements showed that anhydro sugar linkages generated more response in the latter detection method. This improved linkage workflow presents a useful tool for studying polysaccharide structural variations across red seaweed species. Furthermore, for the first time, relative linkage compositions from GC-MS and GC-FID measurements, along with normalized FID and total ion current (TIC) chromatograms without peak assignments, were analyzed using principal component analysis (PCA) as a proof-of-concept demonstration of the technique's potential to differentiate various red seaweed species.

Background: Educating college students about the importance of good sleep habits could lead to the adoption of healthier sleep routines, including sufficient sleep duration and sleep quality. The current pre-post study examines the impact of completing a sleep education program called “Sleep 101” on (1) sleep hygiene practices, (2) sleep quality, and (3) weekday and weekend sleep behaviors among college students. “Sleep 101” is an interactive online course developed to educate college students about the importance of sleep by addressing basic sleep physiology, the impact of sleep on mood, academic and physical performance, the interactions between sleep and various substances, and common sleep disorders. Methods: 338 college students were recruited from a midsized public university in the US and invited to participate in “Sleep 101”, of which 25 participants completed the baseline and post-intervention questionnaire. The Sleep Hygiene Index (SHI) was utilized to evaluate sleep hygiene practices, while standard questions were employed to assess weekday and weekend sleep behaviors and overall sleep quality. Results: Those who completed the study demonstrated a significant increase in weekday sleep duration and were less likely to engage in negative prior bedtime activities. In addition, 40% of those who completed baseline and post-intervention assessments noticed improvements in their sleep quality. Conclusion: These findings suggest that a brief online program is beneficial in improving sleep behaviors among college and could be a scalable approach to addressing current sleep issues and preventing future sleep problems in college students.

The profile of secondary metabolites occurring in apple cuticular layer is not only characteristic for particular apple cultivar, but also dynamically reflects various external factors in growing environment. In this study, the possibility to authenticate apple samples based on analysis of their cuticular layer extracts was investigated. Ultra-high-performance liquid chromatography coupled to high resolution tandem mass spectrometry (UHPLC-HRMS/MS) was employed for obtaining metabolomic fingerprints. In total, 274 authentic apple samples, four cultivars harvested within the seasons 2020 to 2022 in the Czech Republic and Poland were analysed. The generated complex data processed by univariate and multivariate statistical methods enabled to build classification models for discrimination of apple cultivars as well as their geographical origin. The models showed very good performance in differentiation of Czech and Polish samples for three of four cultivars: ‘Gala’, ‘Golden Delicious’ and ‘Idared’, moreover, the validity of the models was verified over harvest seasons. The diagnostic markers, besides metabolites of triterpene biosynthetic pathway, mainly represented wax esters. ‘Jonagold’, which is known to be susceptible to mutations, was the only cultivar for which the unambiguous classification of geographical origin was not possible.

Strawberry root rot caused by Neopestalotiopsis clavispora is one of the main diseases of strawberry and significantly impacts the yield and quality of strawberry fruit. There are now no effective control techniques available except for fungicide sprays, which may directly impact consumers. Biological control is becoming an alternative method for the control of plant diseases to replace or decrease the application of traditional synthetic chemical fungicides. Trichoderma is widely used as a biological agent for controlling strawberry root rot. In order to provide resources for screening the highly effective biocontrol fungus for controlling strawberry root rot caused by Neopestalotiopsis clavispora, the biocontrol mechanism,the control effects of Trichoderma asperellum CMT10 against strawberry root rot and growth-promoting effects on strawberry seedlings were investigated by plate culture, microscopy observation and root drenching methods.The results showed that CMT10 had obvious competitive, antibiotic and hyperparasitism effects on Neopestalotiopsis clavispora CMGF3. The CMT10 could quickly occupy nutritional space, and the inhibition rates of CMT10 against CMGF3 in confrontation culture on 7 d was 65.49%. The inhibition rates of volatile metabolite and fermentation metabolite produced by CMT10 against CMGF3 were 79.67% and 69.84%, respectively. The mycelium of strain CMT10 can act as hyperparasites by making contacting, winding and penetrating hyphae of CMGF3. Pot experiment showed that the biocontrol efficacy of CMT10 on strawberry root rot caused by Neopestalotiopsis clavispora was 63.00%. CMT10 had obvious promotion effect on strawberry growth, the plant height, root length, total fresh weight, root fresh weight, stem fresh weight and root dry weight, with the promotion rates were 20.09%, 22.39%, 87.11%, 101.58%, 79.82% and 72.33%, respectively. Overall, this study showed the ability of Trichoderma asperellum CMT10 to control strawberry root rot and their potential to develop as novel biocontrol agents to replace chemical fungicides for eco-friendly, sustainable agriculture.

Apis mellifera, especially weak ones, are highly vulnerable to Carpoglyphus lactis mites, which can rapidly infest and consume stored pollen, leading to weakened colonies and potentially colony collapse. This study aimed to ascertain and investigate the prevalence of this mite in honeybee colonies across 9 provinces in the Republic of Korea (ROK). A total of 615 honeybee colonies were collected, from 66 apiaries during the spring and 58 apiaries during the summer of 2023. A 1,242 bp segment of the the Cytochrome c oxidase subunit 1 (COI) gene was amplified using the polymerase chain reaction method. The detection levels of C. lactis in the honeybees were compared between winter and summer. Based on the COI sequence analysis, the nucleotide sequence similarity of C. lactis mites isolated in the ROK with those from China (NC048990.1) was found to be 99.5%, and with those from the United Kingdom (KY922482.1) was 99.3%. This study is the first report of C. lactis in Korean apiaries. The findings in this study demonstrate a significantly higher detection rate in winter, which is 4.1 times greater than that in summer (p &lt; 0.001). Furthermore, the results underscore the usefulness of molecular diagnostic techniques for detecting C. lactis mites.

COX II containing a dual core CuA active site is one of the three core subunits of mitochondrial Cco, which plays a significant role in the physiological process. In this report, the full-length cDNA of COXⅡ gene was cloned from Sitophilus zeamais, which had an ORF of 684 bp encoding 227 amino acids residues. The predicted COXⅡ protein had a molecular mass of 26.2 kDa with pI value of 6.37, and multiple sequence alignment and phylogenetic analysis indicated that Sitophilus zeamais COXⅡ had high sequence identity 78.51% with the COXⅡ of other insect species, especially similarity to sitophilus oryzae. This gene was subcloned into the prokaryotic expression vector pET-32a, and induced by IPTG in E.coli Transetta (DE3) expression system. Finally the COXⅡ with 6-His tag was purified using affinity chromatography with Ni²⁺-NTA agarose. WB showed the recombinant COXⅡ was about 44 kD, and the concentration of fusion protein was 50μg/mL. UV-spectrophotometer and infrared spectrometer analysis showed that recombinant COXⅡ could catalyze the oxidation of substrate Cytc, and influenced by AITC. It was found that AITC could form a hydrophobic region with COXⅡ protein via molecular docking, besides, a sulfur atom of AITC structure could form a length of 2.9 Å hydrogen bond with Leu-31. These results will provide valuable information for elucidating the role of COXⅡ in Sitophilus zeamais responses to AITC, meanwhile, it will helpful to carry out a point mutation in AITC binding sites for the future research.

The properties of the annual, semiannual and triennial oscillations (AO, SAO and TO) in the middle atmosphere have been investigated using the TIMED/SABER temperature data. The Lomb-Scargle and wavelet spectra were used to determine the dominant oscillations in the background temperature field. The AO is prominent at the mid-latitudes. The AO amplitudes present an asymmetry between the two Hemispheres, being larger in the mesosphere than in the stratosphere. The SAO dominates the tropical regions, with three amplitude maxima at altitudes of 45, 75, and 85 km. The SAOs in the upper mesosphere (75 km) are out of phase with those in the mesopause (85 km) in the tropical regions, which can generate an enhancement of 11 K at each equinox, contributing to the lower mesospheric inversion layer. The TO is significant in the tropical region, with amplitude being maximum at 35, 45 and 85 km. Result shows that there may be potential interaction by the TO with SAO at 85km at the equator. The relation between ENSO and TO has also been discussed. The ENSO signal may modulate the amplitude of the TO, mainly in the lower stratosphere. The real origin of the TO may lie in the wave-mean-flow interaction.

This paper is focused on typical rural settlements in the Stara Planina Mountain area in Serbia. They are distinguished by their authenticity, identity and character, and they have still not been destroyed by inappropriate development as is the case in some other mountain areas in Serbia, where the effects of urbanization, globalization and homogenization are obvious. Consequently, there is a need to prevent these effects in mountain areas where there is a threat of disbalance between development and the inherited natural and cultural values. The paper starts from several important concepts that relate contemporary approaches to cultural heritage preservation, place morphology and planning future development. The concept definitions from recent documents from related fields are used. These concepts are then applied to the area of Stara Planina Mountain and its rural settlements. The necessity for an integrative approach to planning this area with significant natural and anthropogenic potential is pointed out, including its integration into international programs of sustainable development.

The research reported on this paper was aimed at improving the overall efficiency of a PDO certified artisanal cheese production process. Being a PDO certified foodstuff by the EU, it is considered to have properties and qualities determined by the geographical environment in which is made, with its production taking place in a specific and determined geographical location, in this case the Serra da Estrela region. In that sense, the authors conducted a mapping according to a systemic perspective of the processes involved in the context of manufacturing and distribution of certified Serra da Estrela cheese. Numerous methods were used throughout the process, such as a systemic design analysis, and techniques derived from ethnographic methods, which led to the collection of data in the field and consequently provided the immersion of the researcher in genuine work situations. Critical points were identified and emphasized in the systemic map with the purpose of encouraging initiatives to address and overcome the gaps and inefficiencies detected. The systemic design analysis triggered the development of design work. Observations following an ethnographic approach identified ergonomic risks in cheese making during the process of cutting excess chips, fostering the emergence of musculoskeletal disorders at the wrist. A tool that fits best to the task at hand was developed. A prototype of the new tool enabled collecting feedback from use in the work context, in order to inform product development. The domains of agricultural production and microbiology, considering the specific microorganisms developed trough the ripening process of the cheese, turned out to be aspects of high importance for the issue under focus, contributing to a broader understanding of the ripening process and its risks, simultaneously improving the efficiency and success of cheese production. If it were not for the systemic analysis, which served as a link between the boundaries of distinct domains such as the risk of microorganism contamination, ergonomics, energy efficiency, legislation and regulation policies, transportation challenges and economic viability, approached throughout the research. Simultaneously creating bridges between them, the various problems might not have been detected in the first place, as they are usually addressed in specialized disciplines, predetermined by the restrictions of each specific area of knowledge. As a consequence of the development of this research, which was based on an analysis that sought to establish possible connections between various disciplines and tried to constantly maintain a holistic perspective, making new connections and observing the issues from a new angle, apart from the already established methodologies. All this allowed to lay out the seeds for the development of a plan to tackle the critical points identified by the systemic analysis reported in this paper.

Promoting green development has become an important way to optimize the ecological and economic structure and promote sustainable development. The Yangtze River Economic Belt is an important economic corridor in China, and it remains to be examined whether the implementation of environmental regulations has enhanced the green total factor productivity (GTFP) of cities. This paper calculates the green total factor productivity of 107 cities within the Yangtze River Economic Belt by using the super-efficient SBM model and the GML index with Chinese city panel data from 2007-2019 and measures the intensity of environmental regulations through textual analysis. The bidirectional fixed-effects model constructed in this paper suggests an inverted U-shaped relationship between environmental regulation and GTFP, which is confirmed by a series of robustness tests. Green technology innovation and advanced industrial structure play a mechanism role in this. In regions with lower levels of green technology and industrial structure, the inverted U-shaped relationship between environmental regulation and green total factor productivity is more significant. In addition, the phenomenon of GTFP rising and then falling because of environmental regulation is more obvious in cities in the middle and upper reaches of the Yangtze River and outside the urban agglomerations. Therefore, when formulating environmental regulation policies, it is necessary to balance the relationship between economic development and environmental protection and harmonize the environment and economic development of the entire Yangtze River Basin.

The wetlands in northeastern Bangladesh are home to some of the most prolific and valuable ecosystems on the planet, offering a wide range of benefits to both the local and wider communities. A limited number of research on this topic have been carried out in various wetlands in coastal hilsa, but none have been located in the northeastern region of Bangladesh. Thus, the goal of this study was to better understand the most commercially relevant species (anadromous hilsa) in northeastern Bangladesh as well as to assess the wetland ecosystem services more thoroughly with the contribution of their fish genetic resources. In addition to laboratory studies, fieldwork was done in the fishing settlements along the Surma River, Hakaluki Haor, and Tanguar Haor. The study classified 77 fish species into 21 subcategories of ecosystem services, of which 56% were not threatened, 17% were vulnerable, and 10% were highly endangered. The species Hilsa was found to be the most economically significant, accounting for 1% of the GDP overall. The study determined if the hilsa stock of the examined wetlands maintains a single or several subpopulations in comparison to other parts of the country when they migrate from saline water to northeastern Bangladesh (freshwater). But when compared to other groups, the FST score was between 0.000 to 0.017, indicating that the populations are identical and that there is genetic material sharing between them. Additionally, these statistics imply that the Sylhet haor and adjacent river systems contain a single stock of Hilsa fish. Nevertheless, a number of stresses and risks, including overexploitation, illicit and destructive fishing, siltation, and natural disasters like flash floods, have been linked to changes in the supply of hilsa and other ecosystem services. This study also emphasizes the necessity of policy attention and research to address the concerns.

In this paper, we introduce a specialized, fully automated experimental arrangement designed for assessing the effectiveness of augmented and virtual reality technologies in healthcare setting and explore its design principles focusing on depth sensor characterization. The main goal of this project is to establish a robust benchtop platform for the quantitative evaluation of extended reality technologies in a controlled environment, emphasizing the practical assessment of augmented reality head-mounted devices. We outline a design concept and considerations for an experimental configuration aimed at creating a realistic testing environment. This apparatus comprises an observation platform mounted on a three-degree-of-freedom motorized system and a test phantom stage. Focusing on real-case scenarios, we utilized a range of sensors, including readily available range-sensing cameras and commercial augmented reality headsets, such as the Intel RealSense L515 LiDAR camera, mounted on the motion control system. The setup enabled automated data collection and facilitates controlled assessments and validation of various facets of augmented reality technologies, including object, hand, and head tracking, as well as static and dynamic image registration. This paper describes the system architecture, the process of automated data collection, and presents several evaluation studies conducted with this setup, providing insights into the quality and temporal noise associated with static or moving objects or observers in augmented reality applications.

To conduct high-precision and high-resolution numerical simulation of complex flow structures in turbomachinery, a high-order finite volume weighted essentially non-oscillatory (WENO) scheme for the large eddy simulation (LES) is improved and embedded into the three-dimensional viscous unsteady CFD solver NUAA-Turbo. Firstly, the spectral characteristics and unsteady convergence of the improved WENO scheme are studied. Compared with the classical WENO scheme, the improved WENO scheme has better dissipation and dispersion characteristics and faster convergence speed. Then, the coefficient CW of the Wall-Adapting Local Eddy-viscosity (WALE) model is calibrated by decaying homogeneous isotropic turbulence (DHIT) test case. Finally, the scheme is applied to conduct high-precision LES calculations of turbulent boundary layer flow, supersonic compression corner flow, and low-pressure turbine cascade separation flow. The numerical simulation results show that this WENO scheme has excellent shock wave capture ability and turbulence resolution and can capture more flow field details with less mesh size, greatly reducing the computational cost and laying a foundation for large-scale engineering application of LES.

To secure logic circuits against the illegal copying the insertion of the so-called key bit inputs using XOR/XNOR gates has been proposed in . The inserted gates modify (lock) the behavior of the original circuit and only the correct choice of the secret key bits guarantees the equivalent behaviour of the locked circuit to the original circuit. To break this kind of security, i.e. to find the secret key bits, there was a SAT solver based attack proposed in . The aim of this work is to experimentally verify this attack on several locked circuits with various number of primary inputs and outputs and with various number of gates. Except for the random placement of the key gates we evaluate also the positioning with chaining elimination. The obtained and presented results show that we were able to unlock 10 of 11 circuits within few minutes on a common PC.

Intermetallic compounds are increasingly being expected to utilize in tribological environments, but to date the works are hindered by insufficient ductility at low and medium temperature. This paper presents a novel multiphase intermetallic alloy with the chemical composition of Mo-40Ni-13Si (at.%). Microstructure characterization reveals that a certain amount of ductile Mo phases formed during the solidification process of ternary Mo-Ni-Si alloy melt, which is undoubtedly beneficial to the ductility improvement of intermetallic alloy. Tribological properties of the designed alloy, including wear resistance, friction coefficient and metallic tribological compatibility, were evaluated under dry sliding wear test conditions at room temperature. Results suggested that the multiphase alloy possesses an excellent property for room-temperature wear applications, which is attributed to the unique microstructural features and thereby good combination in hardness and ductility. The corresponding wear mechanism is also reported by observing the worn surface, subsurface and wear debris of alloy, which to be found is soft abrasive wear.

With the integrated development of the Internet, wireless sensor technology, cloud computing, and mobile Internet, there has been a lot of attention given to research about and applications of the Internet of Things. A Wireless Sensor Network (WSN) is one of the important information technologies in the Internet of Things; it integrates multi-technology to detect and gather information in a network environment by mutual cooperation, using a variety of methods to process and analyze data, implement awareness, and perform tests. This paper mainly researches the localization algorithm of sensor nodes in a wireless sensor network. Firstly, a multi-granularity region partition is proposed to divide the location region. In the range-based method, the RSSI (Received Signal Strength indicator, RSSI) is used to estimate distance. The optimal RSSI value is computed by the Gaussian fitting method. Furthermore, a Voronoi diagram is characterized by the use of dividing region. Rach anchor node is regarded as the center of each region; the whole position region is divided into several regions and the sub-region of neighboring nodes is combined into triangles while the unknown node is locked in the ultimate area. Secondly, the multi-granularity regional division and Lagrange multiplier method are used to calculate the final coordinates. Because nodes are influenced by many factors in the practical application, two kinds of positioning methods are designed: the unknown node is in the positioning unit or not. When the unknown node is on the side of the positioning unit, we use the method of vector similarity. Moreover, we use the centroid algorithm to calculate the ultimate coordinates of unknown node. When the unknown node is not on the side of the positioning unit, we establish a Lagrange equation containing the constraint condition to calculate the first coordinates. Furthermore, we use the Taylor expansion formula to correct the coordinates of the unknown node. In addition, this localization method has been validated by establishing the real environment.