Laboratory Studies Research Articles

Effects of Conditioned Media From Human Umbilical Cord-Derived Mesenchymal Stem Cells on Tenocytes From Degenerative Rotator Cuff Tears in an Interleukin 1β-Induced Tendinopathic Condition.

Evidence suggests that mesenchymal stem cells (MSCs) are safe for treating different tendinopathies. Synovial fluid is a pooled environment of biomarkers from the inflammatory and degenerative joint cavity. Understanding the effects of synovial fluid on MSCs is important, as it is the first microenvironment that administered MSCs encounter. Several studies have reported that exposure to osteoarthritic synovial fluid-activated MSCs increased the release of soluble factors; however, the paracrine effects of shoulder synovial fluid-stimulated umbilical cord-derived MSCs (SF-UC-MSCs) on tendinopathy have yet to be investigated. To assess the effects of the conditioned media from SF-UC-MSCs on tenocytes from degenerative rotator cuff tears in an interleukin-1β (IL-1β)-induced tendinopathic condition. Controlled laboratory study. UC-MSCs were isolated and cultured from healthy, full-term deliveries by cesarean section. Tenocytes were isolated and cultured from patients with degenerative rotator cuff tears. Conditioned media were obtained from UC-MSCs stimulated with synovial fluid. To evaluate the gene expression of proinflammatory and anti-inflammatory cytokines, enzymes and their inhibitors, matrix molecules, and growth factors, the tenocytes were cultured with IL-1β and 50% of the conditioned media from the SF-UC-MSCs; quantitative, real-time, reverse transcriptase polymerase chain reaction was also performed. A prostaglandin E2 (PGE2) assay was performed to investigate the PGE2 level secreted by the tenocytes. Western blotting was performed to examine protein synthesis of collagen type I and III. Cell viability, senescence, and apoptosis assays were also performed. The conditioned media from the SF-UC-MSCs interfered with the inflammatory gene expression on tenocytes induced by IL-1β, but it increased the gene expression of tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-3. Meanwhile, the conditioned media decreased the PGE2 level on cells induced by IL-1β. It did increase the type I/III ratio of gene expression and protein synthesis, mainly through the induction of type I collagen. Conditioned media of SF-UC-MSCs reversed senescence and apoptosis induced by IL-1β. Study findings indicated that the conditioned media from SF-UC-MSCs had anti-inflammatory effects and cytoprotective effects on IL-1β-treated tenocytes from degenerative rotator cuff tears. UC-MSCs have useful potential for the treatment of tendinopathy in practice.

Enhancing accuracy and reproducibility in asphalt VOCs qualitative and quantitative analysis: Insights from laboratory studies on emission characteristics

Asphalt pavement will emit Volatile Organic Compounds (VOCs) during life cycle, posing environmental and health risks. Precise understanding of the emission characteristics of asphalt VOCs will facilitate the formulation of targeted measures for reducing emissions. Simulating the emission characteristics of VOCs from asphalt under laboratory conditions is an effective method for predicting asphalt VOCs pollution and implementing effective control measures. In this study, a quality control method for qualitative and quantitative detection of asphalt VOCs in laboratory settings was established based on sample storage time, asphalt sources, and temperature sensor positions. Furthermore, the study investigated the influence of mixing speed and sampling pump speed during asphalt VOCs generation on the emission characteristics. The results demonstrate that the quality control methods exhibit excellent reproducibility and reliability, making them valuable for future research and emission control strategies. Furthermore, the total concentration of asphalt VOCs increases with higher mixing speeds, but stabilizes when the mixing speed reaches 750–1250 r/min. As mixing speed increases, the proportion of alkane groups significantly decreases, while the proportion of aldehydes markedly increases, with the overall proportion remaining relatively stable. Decreasing sampling pump speed leads to a gradual increase in asphalt VOCs concentration. At lower pump speeds, a nonlinear increase in concentration occurs due to VOCs enrichment effects. Asphalt VOCs concentrations exhibit a proportional increase with sampling pump speeds exceeding 1000 ml/min. Finally, based on the results of the three-level analysis of "total concentration-group-substance" and taking into account the energy consumption, it is recommended that the mixing speed be set at 1000 r/min and the sampling pump speed be set at 1000 ml/min for the generation and collection of asphalt-related VOCs. This study can provide a reliable method for generating and collecting asphalt-related VOCs and offer critical insights for optimizing VOCs emission reduction strategies.

Antibacterial and mineralising properties of copper tetraamine fluoride on dentine caries: A laboratory study

ObjectiveTo investigate the antibacterial, mineralising, and discolouring properties of copper tetraamine fluoride (CTF) on artificial dentine caries. MethodDemineralised human dentine blocks were treated with CTF, silver diamine fluoride (SDF, positive control) and water (negative control) before they were subjected to cariogenic challenge with Streptococcus mutans biofilm. The morphology, viability, and growth kinetics of the biofilm were assessed by scanning electron microscopy (SEM), confocal laser scanning microscopy (CLSM), and colony-forming unit (CFU) counting. The lesion depths, mineral loss, chemical structure, and crystal characteristics were measured using micro-computed tomography, Fourier transform infrared (FTIR), and X-ray diffraction (XRD). The discolouring property on demineralised dentine was assessed by spectrophotometry. One-way analysis of variance with the Bonferroni post hoc test was performed to assess and compare the data. ResultsSEM revealed confluent bacterial growth covering the surface of dentine treated with Water but not CTF and SDF. CLSM showed the dead-to-live ratio of the biofilm treated with CTF, SDF and Water were 0.7 ± 0.1, 0.8 ± 0.1 and 0.5 ± 0.1 (p < 0.001, CTF, SDF>Water). The Log10 CFU values of the biofilm treated with CTF, SDF and Water were 7.8 ± 0.1, 7.8 ± 0.1 and 8.1 ± 0.2 (p < 0.001, CTF, SDF<Water). Micro-computed tomography showed the Δlesion-depth (μm) of dentine treated with CTF, SDF and water were 33 ± 5, 40 ± 7 and 169 ± 17 (p < 0.001, CTF, SDF<Water). The Δmineral loss (gHApcm−3) of dentine treated with CTF, SDF and Water were 0.19 ± 0.04, 0.18 ± 0.04 and 0.30 ± 0.04 (p < 0.001, CTF, SDF<Water). FTIR showed the amide I-to-hydrogen phosphate ratios of dentine treated with CTF, SDF and Water were 0.23 ± 0.02, 0.24 ± 0.05, and 0.44 ± 0.06 (p < 0.001, CTF, SDF<Water). XRD revealed well-crystallised hydroxyapatite in the CTF and SDF groups. Spectrophotometry showed the ΔE values of the CTF, SDF and Water groups were 6 ± 4, 49 ± 3 and 10 ± 3 (p < 0.001, CTF, water<SDF). ConclusionCTF inhibited Streptococcus mutans. It mineralised but not discoloured artificial dentine caries. Clinical significanceIf CTF is successfully translated into clinical application, it may be a non-discolouring anti-caries agent for clinicians to arrest dentine caries.

Rinse aid with bischofite: prevention of caries and gingivitis in adolescents

The frequency of using liquid complementary hygiene products has been increasing significantly in recent years. This trend is typical not only for adults, but also for children. The ease of use of rinses, foams, suspensions largely contributes to the growth of their popularity. As substances having a complex effect, researchers have long been interested in mineral complexes, among which calciumand magnesium-containing compounds are of particular importance [2, 3]. Such natural minerals as carnalite, kieserite, and bischofite are of particular interest. The effectiveness of the anti-carious, anti-plaque and anti-inflammatory effects of preventive drugs was evaluated: irrigator liquid + mouthwash WATERDENT Anti-caries and baby foam for the oral cavity WATERDENT Happy Smile during the rehabilitation period in children with permanent bite. Materials and methods. An open comparative study of the effectiveness of the use of liquid for the irrigator + mouthwash WATERDENT «Anticaries» and baby foam for the oral cavity WATERDENT Happy Smile was conducted. To assess the effectiveness of the hygiene products used, the following clinical indicators were selected: the caries intensity index (KPI), the Green – Vermillion simplified index (IG-U), the PMA index and the Mulleman – Cowell index. Clinical parameters were determined before and after the use of the compared hygiene products in groups after 1 month. During the study, laboratory saliva parameters were monitored: saliva pH, total protein, determination of saliva Ca and Md. 3 groups of participants were recruited from among those who applied for help at the UMMU dental clinic. All volunteers were somatically healthy children aged 12–18 years with different caries activity and catarrhal gingivitis, randomly distributed by gender and age. Statistical data processing was carried out in Microsoft Excel and Statist programs. Results. The evaluation of clinical tests in the groups showed a significant change in the indices of PMA and Grinn – Vermilion (р ≤0,05) in patients of the main group and a statistically significant improvement in the index of Grinn – Vermilion (р ≤ 0,05) in patients using foam (comparison group), while in the control group there were no dynamics of statistically significant changes in clinical indicators. An increase in the level of calcium in saliva in patients who used Irrigator Liquid + mouthwash WATERDENT Anti-caries from 2.30 to 2.95 characterizes the high mineralizing potential of bischofite, which is part of its composition, and its karyoprophylactic property. An assessment of laboratory data in the main and comparison groups at the beginning of the experiment and after 1 month showed a significant change in total protein values from 2.94 to 2.26 and 2.72 to 2.09 g/l, respectively, for these groups (p &lt;0.05), which shows the positive effect of these products on hygiene, on changes in saliva properties and karyoprophylactic potential. Conclusions. Clinical and laboratory studies of the use of Liquid for irrigator + rinse WATERDENT Anti-caries and baby Foam for the oral cavity Waterdent Happy Smile confirm the claimed consumer properties of these products: anti-carious, anti-plaque and anti-inflammatory effects and can be recommended in comprehensive individual hygienic oral care for children.

Formulasi dan Evaluasi Ekstrak Aseton Kulit Putih Semangka Merah Non Biji (Citrullus Vulgaris S) dengan Niacinamide sebagai Gel Pelembab Kulit dengan Uji Kelembapan

This research was carried out with the aim of identifying the content of phytochemical compounds of alkaloids, flavonoids, tannins and saponins in the acetone extract of seedless red watermelon rind (Citrullus vulgaris), knowing the results of evaluating the physical properties of the acetone extract gel of seedless red watermelon rind (Citrullus vulgaris) with niacinamide against various concentrations of moisturizing gel preparations, and comparing the best moisture test concentration on acetone extract gel preparations of seedless red watermelon rind (Citrullus vulgaris) in providing optimal results. This research is a laboratory study of the experimental formulation of acetone extract of seedless red watermelon rind (Citrullus vulgaris) to determine the formulation and concentration of the best extract produced. The research results showed that acetone extract from the white skin of red seedless watermelon (Citrullus vulgaris) contained phytochemical compounds alkaloids, flavonoids, and polyphenol as well as lycopene in the white skin of red seedless watermelon (Citrullus vulgaris). The results of the evaluation of the physical properties of the acetone extract gel of seedless red watermelon rind (Citrullus vulgaris) in the negative control, 2.5% concentration, 5% concentration, and 7.5% concentration met the test requirements but did not meet the spreadability test requirements. And the best concentration of water content test in the acetone extract gel preparation of seedless red watermelon rind (Citrullus vulgaris) in providing optimal results is found in the gel preparation with a concentration of 7.5%.

Moderate Intensity Interval Training (MIIT) and High Intensity Interval Training (HIIT) exercise therapy against irisin levels in obesity

Obesity can cause physiological disorders. These physiological disturbances cannot be separated from the roles of irisin. Exercising with the right measure, measurable, and regularly is a strategy for dealing with obesity. The aims of this study were (1) to determine the effect of irisin levels on exercise with the Moderate Intensity Interval Training (MIIT) and High Intensity Interval Training (HIIT) levels models in obese rats. This research is a true experimental laboratory study with a pretest-posttest control group design. This research was conducted at the Bioscience Laboratory of Brawijaya University, Malang. The research sample used 27 obese male Wistar rats divided into 9 MIIT group rats, 9 HIIT rats, and 9 control rats. Exercise intervention is given for 6 weeks at a frequency of 4 times per week. The intensity of MIIT (60–80% of base line ability), HIIT (90–100% of base line ability), irisin levels are obtained from blood tests using enzyme-linked immunosorbent assay (ELISA). Data analysis used the Anova test and post hoc Tukey analysis with a significance level of 0.01. The results showed that there was no significant difference in irisin levels (p = 0.507). The HIIT irisin difference was lower than MIIT (p = 0.932) and Control (p = 0.491), and there was no difference in irisin value between the MIIT and Control groups (p = 0.708).

The relationship between knee joint effusion and quadriceps strength and activation after anterior cruciate ligament (ACL) injury and reconstruction.

Knee joint effusion and quadriceps strength and activation deficits are common consequences of anterior cruciate ligament (ACL) injury and reconstruction. The presence of an effusion may initiate or worsen the quadriceps dysfunction present after ACL trauma. In simulated effusion studies, evidence indicates an inverse relationship between effusion size and quadriceps dysfunction. While this relationship was not found in patients after ACL injury, prior research was limited by a subjective clinical assessment of effusion grade. The purpose of this study was to determine if the size of the knee joint effusion, measured via ultrasound, after ACL injury and reconstruction influences quadriceps strength and activation. Descriptive Laboratory Study. Research Laboratory. 41 individuals (23 females, age=21.8±7.5years, height =171.7±7.9cm, 15 mass =72.3±14.2kg), with an ACL injury reported for 2 sessions [one before 16 reconstruction and one ∽16 weeks after ACL reconstruction]. Three ultrasound images of the suprapatellar pouch and three trials of quadriceps strength and activation using the interpolated twitch technique were gathered from the ACL knee. Effusion cross-sectional area was measured using ImageJ, averaged and inputted into linear regression models to predict muscle strength and interpolated twitch activation. Analyses were considered significant at p≤0.05. No relationship was found between effusion size and strength (R2 = 0.086) or activation (R2=0.056) after ACL injury (p>0.05). After reconstruction, however, there was a small negative relationship between effusion size 24 and activation (R2=0.122; Standardized β=-0.349; p=0.025), while no relationship was found for effusion size and strength (R2=0.000; p≤0.05). The size of the effusion after ACL injury does not influence strength or activation. However, after ACL reconstruction, effusion size does have a small influence on quadriceps activation, with a larger effusion being related to lower activation. Prior research using simulated effusions appear to overestimate the effects of effusion on quadriceps function.

Variation In Response to Limb Loading Instruction on Knee Mechanics During Squatting in Early Recovery Following Anterior Cruciate Ligament Reconstruction.

On average, individuals in early recovery following anterior cruciate ligament reconstruction (ACLr) improve limb loading symmetry (LLS) with instruction to equalize weight distribution between limbs during squats. However, the extent to which these instructions improve knee extensor loading symmetry (KLS) or reduce intra-limb compensations is not known. Determine how limb loading instructions influence knee and intra-limb loading in individuals 3-4 months post-ACLr and to explore variations in responses across individuals. Controlled Laboratory study. Research Laboratory. Individuals 109.4 days (18.2 days) post-ACLr (n=20) and healthy matched controls (CTRL; n=19). Participants performed double limb squats in natural (N; no instruction) and instructed (IN; instruction to evenly distribute weight between limbs) conditions. Between limb and knee loading symmetry were calculated as the ratio of vertical ground reaction force and knee extensor moment impulse, between surgical(Sx):matched and non-surgical(NSx):matched limbs (ACLr:control), respectively. Intra- limb hip/knee (H/K) extensor loading distribution was calculated in Sx:matched limbs. LLS (N: 0.86; IN: 0.93, P < 0.001; ES:0.83) and KLS (N: 0.54; IN: 0.62, P=0.007; ES:0.67) improved with instruction in the ACLr group with no change in CTRL. H/K ratio did not change for either group. K-means clustering, considering natural and change (natural- instructed) in LLS, KLS, and H/K ratio, described response to instruction across three clusters: 1) ACLr: n=3; CTRL: n=9, were symmetrical in both conditions, 2) ACLr: n=14, showed some improvement in symmetry, 3) ACLr: n=3, only improved LLS. Average data suggests that weightbearing instruction improved LLS to within 7%, but a 38% knee loading deficit remained, and intra-limb compensation did not improve. Data- driven clusters indicate that three ACLr subjects were similar to controls, fourteen improved LLS, KLS and H/K distribution, and three only improved LLS with worsening KLS and H/K.

Paraneoplastic Resolution Holds Prognostic Utility in Patients with Metastatic Renal Cell Carcinoma.

Background/Objectives: The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). Methods: We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022. Patients with the necessary laboratory studies available within 90 days before and by one year after surgery were included for study. PNS resolution was defined as an abnormal value compared to established laboratory cutoffs by one year after surgery. Multiple PNS in one patient was allowed, and resolution of each PNS was measured separately. OS and CSS were assessed using Kaplan-Meier curves and Cox proportional hazards models. Results: A total of 253 patients met inclusion criteria. A total of 177 patients (70.0%) met criteria for at least one PNS resolution by one year. Five-year OS and CSS rates were 15.7% and 36.2% for no PNS resolved, 24.5% and 31.6% for 1 PNS resolved, and 43.0% and 58.2% for ≥2 PNS resolved, respectively (p < 0.001). On multivariable analysis, no PNS resolution was associated with worse OS (HR 2.75, p < 0.001) and CSS (HR 2.62, p < 0.001) compared to ≥2 PNS resolved. Conclusions: Resolution of preoperative PNS abnormalities by one year following surgery is associated with improved OS and CSS in patients with mRCC.

In vivo and Laboratory Studies of Tetracycline Prevention of Foulbrood disease of Apis cerana indica Fab. and its Effects on Honey

Laboratory and field studies were carried out to assess the efficacy of the antibiotic tetracycline in preventing and managing American foulbrood (AFB) and European foulbrood (EFB) diseases in honey bees. Experiments with immature worker bees in the laboratory demonstrated that honey bee larvae could endure a broad range of antibiotic doses in their diet. The recommended dose of tetracycline (100 μg/ml) effectively protected young larvae from infection. However, once the dose exceeded this recommended level, it reached a point where it became lethal.

Investigating the Response Mechanism of Vertical Concrete Structures to Alternating Horizontal and Lateral Loads

The improper performance of columns in concrete buildings designed and built in the past years has caused concern and attention to their vulnerability to collapse. The investigation of the damages caused to the structures after various earthquakes and the research conducted during these years have caused changes in the design practices to achieve ductile behavior in the columns. Most of the efforts have been made in these years to improve the design criteria, but the effect of the axial force or the loss of the axial capacity of the columns in the existing buildings built in the past years is still unknown. Most of these columns have transverse reinforcements with large distances, which provide little lateral resistance for the longitudinal reinforcements and also little confinement for the concrete in seismic loads. Many of these columns are not accepted according to the rules of today's regulations. In these columns, not only determining the shear capacity but also the ability of the column to withstand the axial force after the shearing is of great importance. The failure of such columns is due to shear deformations that lead to shear failure and then axial failure. At first, a comprehensive review is done of the studies of other researchers. In this review, we try to collect the analytical and laboratory studies available in the technical literature. These studies are related to the testing of concrete columns until the time of gravitational collapse and the behavior models of the columns until this limit state. Then, according to the collected information and their analysis, several columns will be designed and built for laboratory study. These columns are designed to represent the condition of columns in old concrete buildings. The comparison between the analytical and laboratory results of the 6 tested column samples shows a good agreement between them. As a result, the proposed method has sufficient accuracy and efficiency to determine the effective stiffness of columns.

Positive reinforcement-based magnet training permits social housing in catheterized squirrel monkeys

BackgroundNon-human primates play a critical role in neuroscience research. Though they are social animals, laboratory study requirements can sometimes require single housing and thereby prevent social housing. New MethodTo eliminate single housing and promote well-being within our squirrel monkey colony, we used positive reinforcement training in combination with magnetic/mechanical clasps and custom jackets to permit pair housing of catheterized squirrel monkeys used in behavioral studies. ResultsAdult Saimiri boliviensis boliviensis monkeys (n = 7) readily progressed through a six-stage training procedure for cooperative handling and transport from the home cage to the experimental testing rooms.Comparison with existing methods and conclusions: Given the evidence of isolation induced stress and neurobiological consequences in multiple species, and consistent with an increased regulatory emphasis on social housing of non-human primates, the methods presented herein provide a method for handling squirrel monkeys in behavioral studies that is compatible with social housing.

Uranium in groundwaters of North Kazakhstan

Relevance. The need to dentify the characteristics of the distribution of radioactive elements in the groundwater of Northern Kazakhstan. Aim. Generalization of available data on the geochemistry of groundwater and uranium and radon distribution in them using the example of the northern regions of the Republic of Kazakhstan. Methods. Generalization of long-term hydrogeochemical research and compilation of an electronic data bank on the territory of Northern Kazakhstan. A laboratory study of the chemical composition of groundwater was carried out at the Research Laboratory of Hydrogeochemistry of the School of Natural Resources Engineering of Tomsk Polytechnic University. Measurements of 222Rn contents in waters were carried out using the Alfarad Plus complex in the Laboratory of Hydrogeology of Sedimentary Basins of Siberia, Institute of Geology and Geography, Siberian Branch, Russian Academy of Sciences. Results. The groundwater of aquifers of different ages, distributed in the territory of Northern Kazakhstan (North Kazakhstan uranium province), was studied. Two geochemical sets of groundwater were identified. The first is characterized by the dominance of HCO3– and Mg2+ in the water composition, and the second by Cl– and Na+. A change in composition and an increase in the value of total mineralization from 0,1 to 49 g/dm3, in the direction from north to south, indicate the development of continental salinization. In natural waters of the first group, uranium content varies from 0.065 to 16000 μg/dm3 and radon activity from 4 to 3885 Bq/dm3. For sodium chloride waters of the second set, concentrations can reach 32500 μg/dm3, and radon activity is 6–59 Bq/dm3, since the emanating reservoir (granitoids) is located to the north – at a distance of 80–100 km. Naturally, granitoid massifs of the studied region are sources of uranium. Their drainage by the river network leads to its removal and concentration on geochemical barriers in the groundwater of the Neogene-Quaternary aquifer. This distribution of radioactive elements is associated with the high migration ability of uranium in solution in the form of uranyl ion in oxidizing geochemical conditions.

Sublethal fungicide-insecticide co-exposure affects nest recognition and parental investment in a solitary bee

Fungicides may interact synergistically with insecticides. However, our understanding of the impacts of sublethal insecticide-fungicide combinations on solitary bees is mostly restricted to laboratory studies, providing no information about potential consequences on behavior and reproductive success. We analyzed the effects of a fungicide application, alone and in combination with sublethal levels of an insecticide, on the nesting behavior and reproductive output of the solitary bee Osmia cornuta. We released individually-marked females into oilseed rape field cages, and subsequently sprayed the plants with four treatments: control (water), fungicide (tebuconazole), insecticide (acetamiprid at a sublethal concentration), and mixture (fungicide + insecticide). We recorded nesting activity before and after the sprays and assessed post-spray individual reproductive success. Bees of the single pesticide treatments were unaffected by the sprays and did not differ from control bees in any of the parameters measured. The longevity of bees of the mixture treatment was unaffected. However, these bees showed reduced foraging activity, shorter in-nest pollen-nectar deposition times, and increased difficulty recognizing their nesting cavity, leading to a decrease in provisioning rate, parental investment, and offspring production. Our study demonstrates that co-exposure to a fungicide with otherwise harmless levels of an insecticide caused behavioral effects with consequences on reproductive success. Because longevity was unaffected, these effects would not have been easily detected in a chronic laboratory test. Our results have important implications for bee risk assessment, which should account for exposure to multiple compounds and address behavioral effects and reproductive output under semi-field and/or field conditions.

Efficacy of a chewable tablet containing sarolaner, moxidectin and pyrantel for the treatment of generalised demodicosis in dogs.

Demodicosis is common in dogs and is caused by proliferation of commensal Demodex canis mites. To evaluate the efficacy of sarolaner in combination with moxidectin and pyrantel (SMP) for the treatment of generalised demodicosis in dogs. One hundred and thirty dogs with generalised demodicosis. In two separate randomised masked studies (laboratory and field studies), dogs received monthly oral SMP or afoxolaner + milbemycin oxime (AM). In the laboratory study, dogs received three monthly treatments with biweekly mite counts and clinical evaluations. In the field study, mite counts and clinical evaluations were performed monthly and treatments were administered until two consecutive skin scrapings were negative. Both products were tolerated well. In the laboratory study, mite counts for SMP were significantly (p < 0.001) reduced by 88.8% on Day (D)14, by 99.2% on D29, and no live mites were detected thereafter with no statistically significant difference (p = 0.96) between the two treatment groups. In the field study, SMP provided 92.4%, 98.1%, 100% and 100% reduction in arithmetic mean live mite counts on D30, D60, D90 and D120, and was non-inferior to the control product on D30 and D60. Clinical signs of demodicosis improved in all dogs. Monthly administration of SMP was effective for the treatment of generalised demodicosis in dogs as it eliminated Demodex mites after two monthly treatments in the laboratory study, and at most after three monthly treatments in the field study.

Scientific and Regulatory Lessons Learnt on Building a Chemistry, Manufacturing, and Controls (CMC) Package for COVID-19 Variant Vaccine Updates in the EU—A Regulator’s Perspective

During the COVID-19 pandemic, eight COVID-19 vaccines were authorised in the European Union (EU); as a result of emerging SARS-CoV-2 variants and waning immunity, some of these have been adapted to broaden the immunity against circulating variants. The pace at which variants emerge challenges the technical feasibility to make adapted vaccines available in a suitable timeframe and in sufficient quantities. Despite the current absence of a clear-cut seasonal spread for COVID-19, the EU regulatory approach thus far is a pragmatic approach following a pathway similar to that of seasonal influenza. This approach currently requires chemistry, manufacturing, and controls (CMC—the design, development and consistent manufacture of a specified medicinal product of good quality) and non-clinical data (from product laboratory and animal studies), as well as demonstrating that updated vaccines induce an immune response that can predict clinical efficacy and safety in humans. For CMC data, COVID-19 mRNA vaccine adaptations generally made use of the same formulation, control strategy, manufacturing process, and inclusion of registered manufacturing sites for the drug product; therefore assessment was generally streamlined. The experience gained from the vaccine adaptations, combined with a continuous early regulator-developer scientific discussion, permits increasingly greater predictability for timing and positive regulatory outcomes. Here, we review key aspects of the quality control and manufacture of updating COVID-19 vaccines to protect against new variants. Although most experience has been gained with mRNA vaccines, we note that investment in the streamlining of manufacturing processes for recombinant protein vaccines would facilitate future strain updates/adaptations thereby safeguarding availability of different COVID-19 vaccine types, which is considered of value for public health. We also reflect on the challenges and opportunities in establishing more predictable regulatory mechanisms for future COVID-19 vaccine adaptions and more widely for future vaccines containing rapidly evolving pathogens with the potential to cause health threats.

Linking the evolution of two prefrontal brain regions to social and foraging challenges in primates.

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively, involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints), and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

Linking the evolution of two prefrontal brain regions to social and foraging challenges in primates

The diversity of cognitive skills across primates remains both a fascinating and a controversial issue. Recent comparative studies provided conflicting results regarding the contribution of social vs ecological constraints to the evolution of cognition. Here, we used an interdisciplinary approach combining comparative cognitive neurosciences and behavioral ecology. Using brain imaging data from 16 primate species, we measured the size of two prefrontal brain regions, the frontal pole (FP) and the dorso-lateral prefrontal cortex (DLPFC), respectively, involved in metacognition and working memory, and examined their relation to a combination of socio-ecological variables. The size of these prefrontal regions, as well as the whole brain, was best explained by three variables: body mass, daily traveled distance (an index of ecological constraints), and population density (an index of social constraints). The strong influence of ecological constraints on FP and DLPFC volumes suggests that both metacognition and working memory are critical for foraging in primates. Interestingly, FP volume was much more sensitive to social constraints than DLPFC volume, in line with laboratory studies showing an implication of FP in complex social interactions. Thus, our data highlights the relative weight of social vs ecological constraints on the evolution of specific prefrontal brain regions and their associated cognitive operations in primates.

17O Destruction Rate in Stars

In recent years, several laboratory studies of CNO cycle-related nuclear reactions have been carried out. Nevertheless, extant models of stellar nucleosynthesis still adopt CNO reaction rates reported in old compilations, such as NACRE or CF88. In order to update these rates, we performed new calculations based on a Monte Carlo R-Matrix analysis. In more detail, a method was developed that is based on the collection of all the available data, including recent low-energy measurements obtained by the LUNA collaboration in the reduced background environment of the INFN-LNGS underground laboratory, on R-Matrix cross-section calculations with the AZURE2 code and on uncertainty evaluations with a Monte Carlo analysis. As a first scientific benchmark case, the reactions 17O(p,γ)18F and 17O(p,α)14N were investigated. Among the different stellar scenarios they can influence, the 16O/17O abundance ratio in RGB and AGB stars is the one that can be directly confirmed from spectroscopic measurements. The aim is to reduce the nuclear physics uncertainties, thus providing a useful tool to constrain deep mixing processes eventually taking place in these stars. In this work, we present the procedure we followed to calculate the 17O(p,γ)18F and the 17O(p,α)14N reaction stellar rates and preliminary comparisons with similar rates reported in widely used nuclear physics libraries are discussed.

Complex additive for improving the strength properties of heavy concrete based on industrial waste

The article presents the results of using a complex modified additive to improve concrete's physical and mechanical properties. The complex additive includes industrial production wastes: metallurgical slag and alcohol production wastes (post-alcohol bard). To stabilize the hydrogen index the alkali KON is included in the composition of the additive. A set of laboratory studies was carried out to measure the strength, absorption, and frost resistance of test specimens to assess the effect of the additive on the properties of concrete. A comparison of physical and mechanical properties was made for samples of different concentrations of slag. The ratio of slag components to cement was from 5 to 25% by the total mass of the binder, a multiple of 5%. The optimal composition of the mixture, with maximum strength values, corresponds to the percentage of slag 15%, post-alcohol bard 22.5 liters, and alkali 150 grams. In general, the results obtained from data points of the compared parameters showed consistent results with minimal variation in the data. The results obtained are of practical value related to the reduction of the cost of production of structural concrete with an increase in its strength indicators.