β3-Adrenoceptors mediate several functions in rodents that could be beneficial for the treatment of obesity and type 2 diabetes. This includes promotion of insulin release from the pancreas, of cellular glucose uptake, of lipolysis, and of thermogenesis in brown adipose tissue. In combination, they lead to a reduction of body weight in several rodent models including ob/ob mice and Zucker diabetic fatty rats. These findings stimulated drug development programs in various pharmaceutical companies, and at least nine β3-adrenoceptor agonists have been tested in clinical trials. However, all of these projects were discontinued due to lack of clinically relevant changes of body weight. Following a concise historical account of discoveries leading to such drug development programs we discuss species differences that explain why β3-adrenoceptors are not a meaningful drug target for the treatment of obesity and type 2 diabetes in humans.

Background: This study aimed to evaluate whether measles vaccine uptake can be predicted directly or indirectly by parental perceptions about the availability of measles vaccine services with parental hesitancy towards the measles vaccine as a potential mediator. Methods: This was a community-based cross-sectional study conducted at Omdurman locality in Khartoum state, Sudan in February 2019. The study population included parents/ guardians having at least one child aged 2 -3 years old. Mediation analysis was conducted using two models, the ordinary least squares path analysis and multiple logistic regression. Results: a total of 495 responded and the mean age of the mothers who participated in the study was 31.1 (SD=5.73). A half of the respondents (50.1%) completed university education and nearly three-quarters of the respondents (74.7%) were housewives. After controlling for the other factors, including the mother’s age and the number of children, parental perception about the accessibility and availability of the measles vaccine influences the uptake of the measles vaccine indirectly through the mediation effect of measles vaccine hesitancy. Conclusions: We suggest that intervening in measles vaccine hesitancy in addition to measles vaccination access issues will have positive impact on the uptake and coverage of the measles vaccine in Sudan.

Most smallscale farmers still use the traditional way of agricultural crop farming, and relay mostly use of chemical fertilizers (CF). Recently CF have become expensive and could in some way have a negative impact on soil quality after long term application. However, co-application of biogas slurry (BGS) with CF could help reduce farming costs while improving dry matter yields, grain yields, primary macronutrient uptake of (Nitrogen) N, (Phosphorus) P, (Potasium) K, (Calcium) Ca and (Magnesium) Mg and soil concentration of pH, (organic carbon) OC, N, P, K, Ca and Mg after crop harvest. The study was a field experiment conducted in 2016-2017 and 2017-2018 growing seasons. The field experiment was arranged in a randomized complete block design with four replicates. The treatments were based on percentages of recommended N rates of 120 kg N ha-1 for maize production. The BGS/CF treatments were (i) 0/0, (ii) 0/120, (iii) 24/96, (iv) 48/72, (v) 72/48, (vi) 96/24, (vii) 120/0 kg N ha-1. The spreading of the combination of BGS/CF treatments was performed by hand and incorporated into the top soil (0-10 cm) in each experimental plots. BGS/CF (48/72) treatment resulted into higher dry matter yield in 2016-2017, which was higher than all other treatment combinations, while in the 2017-2018 season, treatment of (0/120) resulted into higher dry matter than all other treatment combinations. The 48/72 and 0/120 treatments resulted into similar grain yield in 2016-2017 season which were higher than all other treatments. Treatments of 48/72, 72/48 and 120/0 had higher N, P, K, Ca and Mg uptake than 0/0, 0/120, 24/96 and 96/24 treatments in both seasons. Soil pH, total N, K, and Mg were high from the treatment of (120/0) than all other treatments in 2016-2017 while in the 2017-2018 season, treatment of (48/72) had higher OC, P and K after maize harvest. The findings of his study show that co-application of BGS/CF at 48/72 and 72/48 have maize yield benefits compared to the two resources, BGS/CF (120/0) and BGS/CF (0/120), applied separately in soil especially in the arid and semi-arid regions.

Thermal fluctuations in two-dimensional (2D) isotropy systems at non zero finite temperatures can destroy the long-range (LR) magnetic order due to Mermin-Wanger theory. Interestingly, the magnetic anisotropy related to spin-orbit coupling (SOC) could stabilize magnetic order in 2D systems. Recently, 2D FexGeTe2 (3≤x≤7) with high curie temperature (TC), as a typical 2D van der Waals metallic ferromagnet, has not only made significant progress in synthetic methods and controlling ferromagnetism (FM), but also actively explored many device applications. In this Review, we introduce six experimental methods, ten ferromagnetic modulation strategies, and three spintronic devices of 2D FexGeTe2 materials. Overall, we have outlined the challenges and potential research directions in this field.

In metal continuous casting process is important to estimate the temperature evolution of casted section along machine from meniscus (point in which liquid metal is poured) to cutting machine where product is cut at commercial length. Particularly in the case of large sections, a convenient approximated model to achieve this goal with a feasible computational effort, is the so called travelling slice: the transversal section of casted product is subjected to different thermal boundary conditions (e.g. thermal flux, radiation, convection) that are found during the movement at constant speed from meniscus to the end of machine. In the case of an axisymmetric section, a comparison with the exact solution can be easily achieved. The article will show pros and cons of both, namely the far lower computational cost of travelling slice model without losing precision. Results confirm the validity of the travelling slice approach also at low casting speed and huge dimensions.

Among the thermophysical properties, the surface / interfacial tension, viscosity and density / molar volume of liquid alloys are the key properties for the modelling of microstructural evolution during solidification. Therefore, only reliable input data can yield accurate predictions preventing the error propagation in numerical simulations of solidification related processes. Due to experimental difficulties related to reactivity of metallic melts at high temperatures, the measured data are often unreliable or even lacking. The application of containerless processing techniques either leads to a significant improvement of the accuracy or makes the measurement possible at all. On the other side, accurate model predicted property values could be used to compensate the missing data; otherwise, the experimental data are useful for the validation of theoretical models. The choice of models is particularly important for the surface, transport and structural properties of liquid alloys representing the two limiting cases of mixing, i.e. ordered and phase separating alloy systems. To this aim, the thermophysical properties of the Fe-Si and Cu-Pb systems were analysed and the connections with the peculiarities of their mixing behaviours are highlighted.

The spectra currently emerging from modern ground- and space-based astronomical instruments are of exceptionally high quality and resolution. To meaningfully analyse these spectra researchers utilise complex modelling codes to replicate the observations. The main inputs to these codes are atomic data such as excitation and photoionisation cross sections as well as radiative transition probabilities, energy levels and line strengths. In this publication the current capabilities of the numerical methods and computer packages used in the generation of these data are discussed. Particular emphasis is given to Fe-peak species and the heavy systems of tungsten and molybdenum. Some of the results presented to highlight certain issues and/or advances have already been published in the literature, while other sections present, for the first time, new recently evaluated atomic data.

The present work investigates primarily the morphology evolution of the body-centered-cubic (BCC)/B2 phases in AlxNiCoFeCr high-entropy alloys (HEAs) with increasing Al content, which has been neglected so far. There exist two types of microscopic morphologies of BCC and B2 phases in this HEA series: one is the weave-like morphology induced by the spinodal decomposition, and the other is the microstructure of a spherical disordered BCC precipitation on the ordered B2 matrix that appears in HEAs with a much higher Al content. The shape of coherent precipitates is found to be closely related to the lattice misfit between BCC and B2 phases, which is sensitive to Al. The mechanical properties, including the compressive yielding strength and microhardness of the AlxNiCoFeCr HEAs, are also discussed in light of the concept of the valence electron concentration (VEC).

Ever since the tremendous success of the rapid vaccine development against COVID‑19, its availa-bility, distribution, and deployment have been a significant concern; however, evidence suggests that vaccine hesitancy has become a greater problem. Therefore, trust in vaccines is crucial and critically dependent on regimes' ability to communicate the benefits of immunization. This study investigated ideas on ways to reduce barriers to COVID-19 vaccination uptake. It explores methods to overcome COVID-19 vaccine barriers through qualitative research: interviews and group discussions involving healthcare providers, administration personnel, teachers, and individuals with chronic conditions across urban (Mombasa) and rural (Kilifi) Kenya. Audio-recorded discussions were transcribed and thematically analyzed across locations. Five themes emerged in our results regarding how to reduce barriers to the COVID vaccine in the context of Kenya, including awareness campaigns, engaging diverse stakeholders, using various communication techniques, capacity building to increase vac-cination centers and trained staff, and lastly, revising relevant government health policies and guidelines. These results indicate the importance of adopting multiple approaches, as no single strategy could boost vaccine acceptance. Moreover, this study provides recommendations for con-ceiving actionable interventions to potentially boost vaccine demand and maintain routine immun-ization in Kenya.

As the use of microbial inoculants in agriculture rises, it becomes important to understand how the environment may influence microbial ability to promote plant growth. This work examines whether there are light dependencies in the biological functions of Azospirillum brasilense, a commercialized prolific grass-root colonizer. Though classically defined as non-phototrophic, A. brasilense possesses photoreceptors that could perceive light conducted through its host’s roots. Evidence for light dependency of four microbial processes were examined and noted: biological nitrogen fixation (BNF), auxin biosynthesis, ATP biosynthesis, and iron and manganese uptake. Functional mutants of A. brasilense were leveraged and studied in light and dark environments: HM053 (high BNF and auxin production), ipdC (capable of BNF, deficient in auxin production), and FP10 (capable of auxin production, deficient in BNF). HM053 exhibited the highest rate of nitrogenase activity with the greatest light dependency comparing iterations in light and dark environments. The ipdC mutant showed similar behavior with relatively lower nitrogenase activity observed, while FP10 did not show a light dependency. Auxin biosynthesis showed strong light dependencies in HM053 and FP10 strains, but not for ipdC. Iron is involved in the BNF biological process, and light dependency was observed for microbial 59Fe2+ uptake in HM053 and ipdC, but not FP10. Surprisingly, a light dependency for 52Mn2+ uptake was only observed in ipdC. Finally, ATP biosynthesis was sensitive to light across all three mutants favoring blue light over red light compared to darkness with observed ATP levels in descending order for HM053 > ipdC > FP10.

We aimed to provide a comprehensive assessment of exercise physiology of adult Fontan patients (FP) and factors limiting functional capacity (FC). A prospective single-centre study of 37 FP aged ≥16years and 19 healthy-controls (HC), who underwent CPET on cycle-ergometer in February-March 2022. Lung function was impaired in FP, mostly mild restrictive pattern (56.8%). Mean peakVO2 was 21±5.4ml/kg/min, 55% predicted. Morphologically left-single ventricle showed higher peakVO2%predicted (57.4±14.4% vs 43.4±8.1%, p=0.045). A lower peakVO2%predicted was observed in patients with an early flattened and/or descending O2 pulse at maximal exertion (52±14% vs 62±12.5, p=0.04 and 47.6±9% vs 60±14 respectively, p=0.018) and chronotropic insufficiency (53±12% vs 69.8±20%, p=0.008). Strong positive correlation was observed between %OUES and peakVO2%predicted (r=0.726, p>0.001). PeakVO2%predicted was progressively higher as the level of physical activity increased (low-level 49.5±14%, moderate-level 55±12%, intense-level 69±20%). FP showed lower inspiratory muscle strength compared to HC but it was no statistically associated with either peakVO2 or VE/VCO2 slope. In FP OUES is a useful submaximal parameter in those who fail to reach maximal exertion. Chronotropic insufficiency and early flattened or descending oxygen pulse slope were factors associated with low peakVO2. Regular intense physical activity improves FC. Although FP have inspiratory muscle weakness, its impact on FC is unclear.

In the last 20 years, an increasing number of studies have been reported on membrane active peptides, which exert their biological activity by interacting with the cell membrane either to disrupt it and lead to cell lysis or to translocate through it to deliver cargos into the cell and reach their target. These peptides are attractive alternatives to currently used pharmaceuticals. Antimicrobial peptides (AMPs) and peptides designed for drug and gene delivery currently in the drug pipeline suggest that these membrane active peptides will soon constitute a significant percentage of the drug market. Here, we focus on two most prominent classes of membrane active peptides; AMPs and cell-penetrating peptides (CPPs). AMPs are a group of membrane active peptides that disrupt the membrane integrity or inhibit the cellular functions of bacteria, virus and fungi. CPPs are another group of membrane active peptides that mainly function as cargo-carriers even though they may also show antimicrobial activity to some extent. Biophysical techniques to understand how they interact with the membrane have shed light on the peptide–membrane interaction at various levels of detail. Structural investigation of membrane active peptides in the presence of the membrane provides important clues on the effect of the membrane environment on peptide conformations. Advances in live imaging techniques have allowed examination of peptide action at a single cell or single molecule level. In addition to these experimental biophysical techniques, molecular dynamics simulations provided clues on the peptide-lipid interactions and dynamics of the cell entry process at atomic detail. In this review, we summarize the recent advances in experimental and computational investigation of membrane active peptides with particular emphasis on two amphipathic membrane active peptides, the AMP melittin and the CPP pVEC.

In this study, we evaluated the antibacterial effect against Staphylococcus aureus and Salmonella Typhimurium in fried fish paste using floating electrode-dielectric barrier discharge (FE-DBD) plasma (1.1 kV, 43 kHz, N2 1.5 m/s, 1-60 min). In addition, quality evaluation (pH, VBN) of fried fish paste was conducted after FE-DBD plasma treatment. When FE-DBD plasma was treated for 1, 5, 10, 20, 30 and 60 min, S. aureus decreased by 0.16-1.13 log10 CFU/g, and S. Typhimurium decreased 0.25-1.13 log10 CFU/g. Both decreased > log10 CFU/g at 60 min. The D-value was 58.92 and R2 was 0.97 for S. aureus using first-order kinetics, and the D-value was 43.60 and R2 was 0.97 for S. Typhimurium using the Weibull model. There was no significant difference in pH after FE-DBD plasma treatment (p > 0.05). However, volatile basic nitrogen (VBN) significantly decreased as the treatment time increased (p < 0.05), and it was the lowest at 60 min to 3.46. Therefore, FE-DBD plasma treatment could be considered as a technology for preserving the quality of processed foods.

: This article reports on polymer (PLLA, poly(L-lactic acid)) nanosheets incorporated with Fe-ion nanoparticles, aiming at using the latter nanoparticles as source to release Fe ions to facilitate burn wound healing when such nanosheets are applied on skin as biomedical tissue. Laser ablation in liquid phase was used to produce Fe-containing nanoparticles that after incorporation into PLLA nanosheets would release Fe ions when in immersed in water. Such nanoparticles prepared in chloroform are shown by XPS to be based on iron chloride and oxide phases. After incorporation into PLLA nanosheets, the ion –release test demonstrated that Fe ions could be released successfully into water at pH 7.4, which implies that such polymer nanosheets show promise for biomedical applications as potential patches for healing burn wounds. Incorporation with two different metal ions (Fe and Zn) is shown to be efficient and both types of ions were demonstrated to be released simultaneously and with comparable release rates.

: The article examines the regularities of structure formation of ultrafine fibers based on poly-3-hydroxybutyrat under the influence of technological (electrical conductivity, viscosity), molecular (molecular weight), and external factors (low-molecular and nanodispersed substances of different chemical nature). Systems with polar substances are characterized by the presence of intermolecular interactions and the formation of a more perfect crystalline fiber structure. Changes in technological and molecular characteristics affect the fiber formation process, resulting in alterations in the morphology of the non-woven fabric, fiber geometry, and supramolecular fiber structure. Polymer molecular weight, electrical conductivity, and solution viscosity influence fiber formation and fiber diameter. The fiber structure is heterogeneous, consisting of both crystalline and non-equilibrium amorphous phases. This is significant in the development of matrix-fibrillar systems for drug delivery, bioactive substances, antiseptics, tissue engineering constructs, tissue engineering scaffolds, artificial biodegradable implants, sorbents, and other applications.

Abstract Purpose Despite a considerable amount of literature on dual-energy-CT(DECT) iodine uptake of the head and neck, the physiologic iodine uptake of this region has not been defined yet. This study aims to establish reference values for the iodine uptake of healthy organs to facilitate clinical application. Material and Methods: Consecutive venous DECT scans of head and neck were reviewed, and unremarkable exams were included (n=617). 35 region of interest measurements were performed in 16 anatomical regions. Iodine uptake was compared among different organs/tissues and subgroup analysis was performed (male [n=403] vs female [n=214]; young [n=207] vs middle-aged [n=206] vs old [n=204]; normal weight [n=314] vs overweight [n=196] vs obese [n=107]]). Results: Overall mean iodine uptake values ranged between 0.5 and 9.4mg/ml. Women showed higher iodine concentration in the cervical vessels and higher uptake for the parotid gland, masseter muscle, submandibular glands, sublingual glands, palatine tonsils, tongue body, thyroid gland, and the sternocleidomastoid muscle than men (p0.04). With increasing age, intravascular iodine concentrations increased as well as iodine uptake for cerebellum and thyroid gland, while values for tongue and palatine tonsils were lower compared to younger subjects (p0.03). Iodine concentrations for parotid glands and sternocleidomastoid muscles decreased with higher BMI (p0.004), while normal-weighted patients showed higher iodine values inside the jugular veins, other cervical glands, and tonsils versus patients with higher BMI (p0.04). Conclusion: Physiologic iodine uptake values of cervical organs and tissues show gender-, age-, and BMI-related differences, which should be considered in clinical routine of head and neck DECT.

The concrete sector is known for its significant contribution to the CO2 emissions. There are two main contributing factors for this situation: the large amount of concrete consumed per year on the planet and the high CO2 released from Portland cement manufacture, the key binding agent in concrete. To face the consequent sustainability issues, diverse strategies have been explored on the carbon capture and storage potential of cementitious materials. This paper addresses the potential of storing CO2 in concrete during the curing stage, applied to the precast Portuguese industry. To this purpose, it was assumed that CO2 will become a waste that will require an outlet in the future, considering that carbon capture will become mandatory in many industries. This work concluded that the net benefit in terms of carbon retention is positive for the process of storing carbon in concrete during the curing stage. More specifically, it was demonstrated that the additional emissions from the introduction of this new operation are only 10% of the stored amount, returning a storage potential of 76 000 tonnes of CO2 yearly. Moreover, the overall net reduction in the concrete life cycle averages 9.4% and 8.8% for precast elements and only non-structural elements, respectively. When a low cement dosage strategy is coupled with carbonation curing technology, the overall carbon net reduction is estimated to be 45%.

Diesel contamination of farming soils is of great concern because hydrocarbons are toxic to all forms of life and can potentially enter the food web through crops or plants used for remediation. Data on plant ability to uptake, translocate and accumulate diesel-derived compounds are controversial not only due to the probable diverse attitude of plant species but also because of the lack of a reliable method to distinguish petrogenic from biogenic compounds in plant tissues. The purpose of this study was to set up a GC-MS-based protocol enabling the determination of diesel-derived hydrocarbons in plants grown in contaminated soil for assessing human and ecological risks, predicting phytoremediation effectiveness and biomass disposal. To this aim two plant species Vicia sativa L. and Secale cereale L., belonging to two diverse vascular plant families, were used as plant models. They were grown in soil spiked with increasing concentrations of diesel fuel and the produced biomass was used to set up the hydrocarbon extraction and GC-MSD analysis. The developed protocol was also applied to the analysis of Typha latifolia L. plants, belonging to a different botanical family and grown in a long-time and highly contaminated natural soil. Results showed the possibility of distinguishing diesel-derived compounds from biogenic hydrocarbons in most terrestrial vascular plants, just considering the total diesel compounds in the n-alkanes carbon range C10-C26, where the interference of biogenic compounds is negligible. Diesel hydrocarbons quantification in plant tissues was strongly correlated (0.92<r2<0.99) to the concentration of diesel in spiked soils, suggesting a general ability of the considered plant species to adsorb and translocate relative low amounts of diesel hydrocarbons and the reliability of the developed protocol.

Key elements of Blue-Green Infrastructure are vegetation and stormwater storage. A combination of a bioretention cell with an underlying trench (BC-T) serving as a tree pit is often used in dense urban environments. An adequate ratio of drained area to bioretention cell area is a crucial design parameter. The ratio is derived from the hydrological balance; however, input data are often difficult to obtain or uncertain. The goal is to study the sensitivity of such data (tree water uptake and water holding capacities of soil filter and trench substrate) in the BC-T design. Sensitivity analysis is performed for the setup of a BC-T used in Prague, Czech Republic. A 10-year rainfall series (1 hour resolution) is used as an input. Data that are subject to the sensitivity analysis are changed for different trench exfiltration rates, and the effect on the size of the drained area is studied. At low trench exfiltration rates (1.8 mm.h-1), both the water holding capacity of the trench substrate and potential tree water uptake have a significant influence (more than a 20% change in the size of the drained area) and cannot be neglected. At good exfiltration rates (more than 18 mm.h-1) or when the trench is equipped with an underdrain, all studied parameters can be neglected. However, it is recommended to reduce the size of the drained area by 10-20%.

Inflammation mediators enhance the activity of connexin (Cx) hemichannels especially in the epithelial and endothelial tissues. As potential release route for injury signals like (oligo)nucleotides, Cx hemichannels may contribute to long lasting inflammation. Specific inhibition of Cx hemichannels may therefore be a mode of prevention and treatment of long lasting, chronic sterile inflammation. The activity of Cx hemichannels was analysed in N2A and HeLa cells transfected with human Cx26 and Cx46 as well as in Calu-3 cells using the dye uptake as functional assay. Moreover, possible impact of the bioactive phenolic agents CVB2-61 and CVB4-57 on the barrier function of epithelial cells was analysed using Calu-3 cells. Both agents inhibited the dye uptake in N2A cells expressing Cx26 (> 5 µM) and Cx46 (> 20 µM). In Calu-3 cells, CVB2-61 and CVB4-57 reversible inhibited the dye uptake at concentrations as low as 5 µM, without affecting the gap junction communication and barrier function, even at concentrations of 20 µM. While CVB2-61 or CVB4-57 maintained a reduced dye uptake in Calu-3 cells, an enhancement of the dye uptake in response to stimulation of adenosine signaling was still observed after removal of the agents. The report shows that CVB2-61 and CVB4-57 reversible block Cx hemichannels. Deciphering the interaction mechanisms with Cx hemichannels could allow further development of phenolic compounds to target Cx hemichannels for a better and safer use in treatment of pathologies that involve Cx hemichannels.

Concern over potential antimony mediated toxicity from mining and smelting activities has instigated novel concepts toward removing aqueous antimony ions. The iron based adsorbent Fe3O4/HCO was found to be efficient for treating antimony-containing wastewater However, ineffective methodology for preparation limited its effective adsorption capacity and thus wider application. In this study, a new type of HCO-doped-(Fe3O4)x adsorbent was prepared by co-precipitation method for doping Fe3O4 into HCO sludge (HCO), thereby improving adsorption performance for Sb(III) and Sb(V) ions, with the maximum adsorbing capacity being 44.46 mg/g and 47.91 mg/g, respectively. According to the results of BET, SEM-EDS, XRD and XPS, it were confirmed that the FeOOH and X≡Fe-OH were formed during the preparation process, bring about the increased the surface area, thus resulting in further increase of surface area, hydroxyl groups and the net negative ionic charge. Moreover, the adsorption kinetics followed the pseudo-second-order kinetic model which indicated that adsorption process of Sb(III)/Sb(V) by HCO-doped-(Fe3O4)x adsorbent was controlled by chemical reaction. The main adsorption mechanism is that antimony ion and amorphous iron oxide X≡Fe-OH undergo coordination exchange reaction and complexation reaction with CeO2 or Ce2O3. Furthermore, HCO-doped-(Fe3O4)x could adapt to wide pH and had stable adsorption ability after regeneration. The good adsorption performance of HCO-doped-(Fe3O4)x makes it a potential applications of adsorbent for removal of antimony.

In vitro glucose uptake in yeast cell facilitated by Abelmoschus esculentus L. (okra seed) for management of type 2 diabetes was studied. Plant material was collected, identified, processed, and stored for further use. 80% methanol was employed for extraction and sonicated to release antidiabetic-bioactive component in solution and was filtered, concentrated, freeze-dried, and fractionated using standard techniques. Glucose uptake at an initial concentration of 5mM/L and 10mM/L by the crude extract was consistent to that of the known standard drug while at 25mM/L glucose concentration was equivalent with the crude extract. Also, at 0.625 mg/mL the linear equations, and R2 demonstrations that the crude extract was higher in dose predictability than the standard drug as presented by the equation; y = 35.754x - 57.822, and R² = 0.9502 (95%). The extract-fractions were employed to evaluate the ability of yeast cell line culture to take up glucose from the system through DPPH, FRAP, lipid peroxidation and anti-diabetes effect of extract-fraction assays. Extract-fractions were found to poses antioxidant activity high enough to inhibit stress-related diseases. The extract fractions were active as drug candidates both at low and high concentrations and were better compared with the standard drug and standard antioxidant was comparable. The high bioactive extract fractions require encapsulation with a nanoparticle as a drug candidate for type 2 diabetes patients. And an animal trial of the drug candidate may be necessary to monitor the in vivo performances of the extract fractions and subsequent human volunteered trial.

We recently developed a novel hyperspectral excitation-resolved near-infrared fluorescence imaging system (HER-NIRF) based on a continuous-wave wavelength-swept laser. In this study, this technique is applied for measuring the distribution of the therapeutic agent dimethyl sulfoxide (DMSO) by utilizing solvatochromic shift in the spectral profile of albumin-bound Indocyanine green (ICG). Using wide-field imaging in turbid media, complex dynamics of albumin-bound ICG is measured in mixtures of dimethyl sulfoxide (DMSO) and water. Phantom experiments are conducted to evaluate the performance of the HER-NIRF system. The results show that the distribution of DMSO can be visualized in the wide-field reflection geometry. One of the main purposes of the DMSO is to act as a carrier for other drugs, enhancing their effects by facilitating skin penetration. Understanding solubility and permeability of drugs in vivo is very important in drug discovery and development. Hence, this HER-NIRF technique has a great potential to advance the utilization of the therapeutic agent DMSO by mapping its distribution via solvatochromic shift of ICG. By customizing the operational wavelength range, this system can be applied to any other fluorophores in the near infrared region and utilized for a wide variety of drug delivery studies.

The use of swine manure as a source of plant nutrients is one alternative to synthetic fertilizers. However, conventional manure application with >90% water and a low C:N ratio results in soil C loss to the atmosphere. Our hypothesis was to use biochar as a manure nutrient stabilizer that would slowly release nutrients to plants upon biochar-swine manure mixture application to soil. The objectives were to evaluate the impact of biochar-treated swine manure on soil total C, N, and plant-available macro and micronutrients in greenhouse-cultivated corn (Zea mays L.) and soybean (Glycine max (L.) Merr.). Neutral pH red oak (RO), highly alkaline autothermal corn stover (HAP), and mild acidic Fe-treated autothermal corn stover (HAPE) biomass were pyrolyzed to prepare biochars. Each biochar was surface-applied to swine manure at a 1:4 (biochar wt/manure wt) ratio to generate mixtures of manure and respective biochars (MRO, MHAP, and MHAPE). Conventional manure (M) control and manure-biochar mixtures were then applied to the soil at a recommended rate. Corn and soybean were grown under these controls and treatments (S, M, MRO, MHAP, and MHAPE) to evaluate the manure-biochar impact on soil quality, plant biomass yield, and nutrient uptake. Soil OM significantly (<0.05) increased in all manure-biochar treatments; however, no change in soil pH or N was observed under any treatment. No difference in soil ammonium between treatments was identified. There was a significant decrease in soil M3-P and soil NO₃^- for all manure-biochar treatments compared to the conventional M. However, the plant biomass nutrient concentrations were not significantly different from control manure. Moreover, an increasing trend of N and decreasing trend of P in the plant under all biochar-manure treatments than the controls were noted. This observation suggests that the presence of biochar is capable of influencing the soil N and P in such a way as not to lose those nutrients at the early growth stages of the plant. In general, no statistical difference in corn or soybean biomass yield and plant nutrient uptake for N, P, and K was observed. Interestingly, manure-biochar application to soil significantly diluted the M3-extractable soil Cu and Zn concentrations. The results attribute that manure-biochar has the potential to be a better soil amendment than conventional manure application to the soil.

Our environment has been significantly impacted by man-made pollutants, primarily due to industries make substantial use of synthetic chemicals, resulting in significant environmental consequences. In this research investigation, the co-precipitation approach was employed for the synthesis of cellulose-based ferric oxide (Fe₂O₃/cellulose) and copper oxide nanoparticles (CuOx-NPs). Scanning electron microscopy (SEM) analyses were conducted to determine the properties of the newly synthesised nanoparticles. Furthermore, the synthesized nanoparticles were employed for eliminating chromium from aqueous media under various conditions, including temperature, contact time, adsorbent concentration, adsorbate concentration, and pH. Additionally, the synthesised materials were used to recover Cr(VI) ions from real samples, including tap water, seawater, and industrial water, and the adsorptive capacity of both materials evaluated under optimal conditions. The synthesis of Fe₂O₃/cellulose and CuOx-NPs proved to be effective, as indicated by the outcomes of the study.

Parkinson’s Disease (PD) is a neurodegenerative and progressive disease that impacts the nerve cells in the brain and varies from person to person. The exact cause of PD is still unknown, and the diagnosis of PD does not include a specific objective test with certainty. Although deep learning has made great progress in medical neuroimaging analysis, these methods are very susceptible to biases present in neuroimaging datasets. An innovative decorrelated deep learning technique is introduced to mitigate class bias and scanner bias while simultaneously focusing on finding distinguishing characteristics in resting-state functional MRI (rs-fMRI) data, which assist in recognizing the PD with good accuracy. The decorrelation function reduces the non-linear correlation between features and bias in order to learn bias-invariant features. The Parkinson’s Progression Markers Initiative (PPMI) dataset, referred to as a single scanner imbalanced dataset in this study used to validate our method. The imbalanced dataset problem affects the performance of the deep learning framework by overfitting to the majority class. To resolve this problem, we propose a new Decorrelated Convolutional Neural Networks (DcCNN) framework by applying decorrelation-based optimization to Convolutional Neural Networks(CNN). An analysis of evaluation metrics comparisons shows that integrating the decorrelation function boosts the performance of PD recognition by removing class bias. Specifically, our DcCNN model performs significantly better than existing traditional approaches to tackle the imbalance problem. Finally, the same framework can be extended to create scanner invariant features without significantly impacting the performance of a model. The obtained dataset is a multi-scanner dataset which leads to scanner bias due to the differences in acquisition protocols and scanners. The multi-scanner dataset is a combination of two datasets, namely PPMI and FTLDNI - frontotemporal lobar degeneration neuroimaging initiative (NIFD) dataset. The results of t-distributed stochastic neighbor embedding (t-SNE) and scanner classification accuracy of our proposed Feature Extraction-DcCNN (FE-DcCNN) model validated the effective removal of scanner bias. Our method achieves an average accuracy of 77.80% on a multi-scanner dataset for differentiating PD from healthy control, which is superior to the DcCNN model trained on a single scanner imbalanced dataset.

Keywords: Wall-like RC columns; Strengthening; FRP; NSM rebars; Steel plates; Testing; FE modeling; Preloading.

The responses of the aromatic and medicinal plant Salvia sclarea (clary sage) to 900 µM Zn exposure for 8 days in a hydroponic culture were investigated. The tolerance mechanisms under excess Zn exposure were assessed by changes in nutrient uptake, photosynthetic characteristics and leaf structure. The uptake and the distribution of Zn, as well as some essential nutrient elements such as: Ca, Mg, Fe, Mn and Cu, were examined by inductively coupled plasma mass spectrometry (ICP-MS). The results revealed that Salvia sclarea is a Zn accumulator plant that tolerates significantly high toxic levels of Zn in the leaves by increasing the leaf content of Fe, Ca and Mn ions to protect the photosynthetic function and even stimulate photosystem I (PSI) and photosystem II (PSII) activities. Additionally, the leaf photosynthetic pigments and the total phenolic and anthocyanin content were also studied. Data showed that the exposure to excess Zn significantly increases the synthesis of phenolic compounds in the leaves which plays an important role in the Zn detoxification and protection against oxidative stress. Lipid peroxidation and electrolyte leakage in leaves used as clear indicators for heavy metal damage were slightly increased. All these data highlight that Salvia sclarea is an economically interesting plant for phytoextraction and/or phytostabilization of Zn contaminated soils.

In this study, we evaluated chlorophyll fluorescence (CF) under two extreme illumination conditions at plant scale with a passive spectroradiometer. Fluorescence (F) was estimated by reading directly from radiance spectra of a variety of plants illuminated with light-emitting diode (LED) grow lights in the laboratory. Solar-induced fluorescence (SIF) was estimated from spectral measurements of the same plants under sunlight using the Fraunhofer Line Depth (FLD) method. Chlorophyll fluorescence yield (F_yield) and solar-induced fluorescence yield (SIF_yield) were calculated by normalizing F and SIF with absorbed photosynthetically active radiation (APAR). Two approaches to estimating APAR were compared: utilizing white reference spectra and reflected spectra versus white reference spectra combined with the fraction of absorbed photosynthetically active radiation (fPAR) derived from literature. Average F and SIF were different by a factor of approximately twenty-four (F = 0.110 ± 0.038 Wm⁻²μm⁻¹sr⁻¹ versus SIF = 2.60 ± 1.87 Wm⁻²μm⁻¹sr⁻¹). In contrast, the average normalized values F_yield and SIF_yield were within the margin of error of one another (F_yield = 0.022 ± 0.008 μm⁻¹sr⁻¹ and SIF_yield = 0.030 ± 0.020 μm⁻¹sr⁻¹). This study highlights the influence of APAR on CF and the importance of properly accounting for it when estimating yield and demonstrates the ability of two simple and portable experimental setups with a passive instrument to obtain fluorescence metrics.

Fire is a significant threat to human life and civil infrastructures. Builders and architects are hankering for safer and sustainable alternatives of concrete that do not compromise with their design intent or fire safety requirements. The aim of the present work is to improve the residual compressive performance of concrete in the post-fire exposure, by incorporating by-products from urban residues. Based on sustainability and circular economy motivations, the attention is focused on rubber tire fly ash, aged brick powder, and plastic (PET) bottle residuals used as partial sand replacement. The selected by-products from urban residues are used for the preparation of Cement-Based Composites (CBCs) in two different proportions (10 % and 15 %). The thermal CBC behaviour is thus investigated under realistic fire scenarios (i.e., Direct Flame (DF) for 1 hour (1h)), by following the ISO 834 standard provisions, but necessarily resulting in non-uniform thermal exposure for the cubic specimens. The actual thermal exposure is further explored with a Finite Element (FE) model, giving evidence of thermal boundaries effects. The post-fire residual compressive strength of heated concrete and CBC samples is hence experimentally derived, and compared to unheated specimens in ambient conditions. From the experimental study, the enhanced post-fire performance of CBCs with PET bottle residual is generally found superior to other CBCs or concrete. The structure-property relation is also established, with the support of Scanning Electron Microscopy (SEM) micrographs. Based on existing empirical models of literature for the prediction of the compressive or residual compressive strength of standard concrete, newly developed empirical relations for both concrete and CBCs are assessed.

The process of anaerobic digestion used for methane production can be enhanced by incorporating stimulating materials. The effects of these materials are dependent on various factors including the processed substrate, process conditions, and the type and amount of the stimulating material used. As part of the study, three different stimulating materials - iron powder, lime, and milled porous ceramic - were added to the 30-day anaerobic digestion of the brewer's spent grain to improve its performance. Different doses ranging from 0.2 to 2.3 gTS×L-1 were tested, and methane production kinetics were determined using the first-order model. The results showed that the methane yield ranged from 281.4±8.0 to 326.1±9.3 ml×gVS-1, while substrate biodegradation ranged from 56.0±1.6 to 68.1±0.7%. The addition of lime reduced methane yield at almost all doses by -6.7% to -3.3%, while the addition of iron powder increased methane yield from 0.8% to 9.8%. The addition of ceramic powder resulted in a methane yield change ranging from -2.6% to 4.6%. These findings suggest that the use of stimulating materials should be approached with caution, as even slight changes in the amount used can impact methane production.

Objective: Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) are often overlapping conditions. We aimed to determine whether 18F-fluorodeoxyglucose (FDG) positron emission tomography-computed tomography (PET-CT) is useful in identifying PMR in the setting of large vessel vasculitis (LVV)-GCA. Methods: Patients diagnosed with LVV-GCA by PET-CT at a tertiary referral hospital for a population of 450,000 people over a two-year period were reviewed. Scoring was performed based on potential significant FDG uptake at up to 16 sites in nine different extravascular areas (SCORE 16). Differences in extravascular sites of significant FDG uptake were evaluated between LVV-GCA with a clinical diagnosis of PMR or not. Results: Fifty-four patients were diagnosed with LVV-GCA by 18F-FDG-PET-CT. Of them, 21 (38.8%) were clinically diagnosed with PMR. Significant extravascular FDG uptake was more frequently observed in those with a clinical diagnosis of PMR. In this sense, the SCORE 16 was higher in those with clinical PMR (5.10 ± 4.05 versus 1.73 ± 2.31 in those without a clinical diagnosis of PMR; p< 0.001). A SCORE 16 involving more than 4 sites of significant FDG uptake yielded a sensitivity of 52% and a specificity of 91% for establishing a clinical diagnosis of PMR associated with LVV-GCA. The best areas of significant FDG uptake to clinically identify PMR in patients with LVV were the shoulder, the greater trochanter and the lumbar interspinous regions with an area under the ROC curve of 0.810 (0.691-0.930). Conclusion: Significant extravascular 18F-FDG-PET-CT uptake may help establish a clinical diagnosis of PMR in patients with LVV-GCA. These patients are more commonly diagnosed with PMR if they have significant FDG uptake in the shoulder, greater trochanter, and lumbar interspinous areas.

Background: Since 2000, vaccine coverage in Sub-Saharan Africa (SSA) has surpassed multiple milestones. Its contribution to global health, especially in low-middle-income countries is one of the achievements in global governance of modern medicine, averting 2-3 million child deaths every year. However, in Nigeria, vaccine-preventable-diseases still account for one in eight child deaths before their fifth-year birthday and remains one of the ten countries where 4.3 million children under five are without complete immunization. The reasons for declining childhood vaccine demand are unclear. Therefore, the goal of this contribution is to shed light on the reasons to set a foundation for future interventions. Methods: Four focus group discussions were conducted. The primary targets were mothers of children 0 – 12 months old in Nigeria. A simplified quota sampling approach was used to select mothers in four geographical clusters of Nigeria’s Federal Capital Territory. At least six mothers from each cluster were randomly included, giving a total of 24 participants. An interview guide developed from the 5C psychological antecedence model was used (assessing confidence, complacency, calculation, constraints, collective responsibility); two additional variables were included that had proved meaningful in previous work (religion and masculinity). The data were analyzed using meta-aggregation approach such as framework synthesis, which summarized data in a stepwise fashion. Results: The sample was generally relatively positive towards vaccination. Still, mothers reported low trust in vaccine safety and the healthcare system (confidence). Yet, they had great interest in seeking additional information during antenatal visits (calculation), difficulties in prioritizing vaccination over other equally competing priorities (constraints) and were aware that vaccination translates into overall community health and wellbeing (collective responsibility). They had a bias towards God as ultimate giver of good health (religion) and reported that their husbands played a dominant role in vaccination decision-making (masculinity). Mothers perceived their children vulnerable to disease outbreaks, which motivated them to get them vaccinated (complacency). Conclusion: The 5C model and the added determinants provided a useful qualitative tool for understanding mothers’ vaccination decision-making in low resources settings.

Buckling defect will appear on the outer surface of the deformed ring during constrained ring rolling (CRR) of aluminum alloy thin wall conical ring with inner high ribs (AATWCRIHR), if the geometrical dimension of the ribs doesn't match the wall thickness. To avoid the buckling defect, a quantitative method for characterizing the degree of the buckling defect is proposed using the area of buckling profile. Then an orthogonal experimental scheme was designed taking the width of the middle rib, thickness of wall, and height of the middle rib as design variables and defining the area of buckling profile as optimization objective. Subsequently, a quadratic polynomial response surface model was established by combining the optimization algorithm with the finite element method (FEM), and the geometrical dimension of the middle ribs of the deformed AATWCRIHR is optimized. Also the optimal parameter combination to minimize the area of buckling profile is obtained and verified using FE simulation. Results show that the AATWCRIHR after optimization doesn’t generate the buckling defect during constrained ring rolling, and it is proved that the quantitative buckling defect representation method and the optimization design method based on the response surface model and the finite element simulation results are feasible for the constrained ring rolling process of the AATWCRIHR.

The dynamic behaviour of a machine tool (MT) directly influences the machining performances. The adoption of lightweight structures may reduce the effects of undesired vibrations and increasing the workpiece quality. This paper aims to present and compare a set of hybrid materials that may be excellent candidate to fabricate the MT moving parts. The selected materials have high dynamic characteristics and capacity to damp mechanical vibrations. In this way, starting by the kinematic model of a milling machine that highlights the main critical factors, this study paper evaluates a number of prototypes made of Al Foam sandwiches (AFS), Al Corrugated sandwiches (ACS) and materials reinforced by carbon fibres (CFRP). A set of prototypes has been fabricated, represented the Z-axis ram of a commercial milling machine. The static and dynamical properties have been evaluated by using both FE simulations and experimental tests. The obtained results show that the proposed structures may be a valid alternative to the conventional materials of MT moving parts, increasing machining performances. In particular, the AFS prototype highlighted a damping coefficient that is 20 times greater than a conventional ram (e.g. steel). The CFRP structure is able to satisfy the machining requirements with a reduced weight of 48.5%, while the ACS prototype showed a good trade-off between stiffness and damping.

Varunaivibrio sulfuroxidans type strain TC8T is a mesophilic, facultatively anaerobic, facultatively chemolithoautotrophic alphaproteobacterium, isolated from a sulfidic shallow-water marine gas vent located at Tor Caldara, Tyrrhenian Sea, Italy. V. sulfuroxidans belongs to the family Thalassospiraceae within the Alphaproteobacteria, with Magnetovibrio blakemorei as its closest relative. The genome of V. sulfuroxidans encodes the genes involved in sulfur, thiosulfate and sulfide oxidation, as well as nitrate and oxygen respiration. The genome encodes the genes involved in carbon fixation via Calvin-Benson-Bassham cycle, in addition to genes involved in glycolysis and TCA cycle, indicating a mixotrophic lifestyle. Genes involved in the detoxification of mercury and arsenate are also present. The genome also encodes a complete flagellar complex, one intact prophage and one CRISPR, as well as a putative DNA uptake mechanism mediated by the type IVc (aka Tad pilus) secretion system. Overall, the genome of Varunaivibrio sulfuroxidans indicates that the bacterium is metabolically versatile and well-adapted to the dynamic environmental conditions of sulfidic gas vents.

Myr47 lipopeptide consisting of hepatitis B virus (HBV) pre-S1 domain (myristoylated 2-48 peptide) is a commercialized effective anti-HBV drug, preventing the interaction of HBV with sodium taurocholate cotransporting polypeptide (NTCP) on human hepatocytes, of which the activity requires both N-myristoylation residue and specific amino acid sequence. Meanwhile, we recently reported that Myr47 reduces the cellular uptake of HBV surface antigen (HBsAg, subviral particle of HBV) in the absence of NTCP expression (Somiya; et al. Virology 2016, 497, 23–32). In this study, we analyzed how Myr47 reduces the cellular uptake of lipid nanoparticles (including liposomes (LPs) and HBsAg) without NTCP expression. By using Myr47 mutants lacking the HBV infection inhibitory activity, they could reduce the cellular uptake of LPs in an N-myristoylation-dependent manner whereas in an amino acid sequence-independent manner. Moreover, Myr47 and its mutants could reduce the interaction of LPs with apolipoprotein E3 (ApoE3) in an N-myristoylation-dependent manner regardless of their amino acid sequences. From these results, N-myristoyl residue of lipopeptides generally could interfere the LPs/HBsAg-ApoE3 complex formation, thereby reducing the cellular uptake of LPs/HBsAg. When lipid nanoparticles are used as a DDS (drug delivery system) nanocarrier, the surface modification with lipopeptides may be a new method to inhibit unwanted cellular uptake of DDS nanocarriers by non-target cells.

Tailoring treatment in patients with Hodgkin lymphoma (HL) is paramount to maximize outcomes while avoiding unnecessary toxicity. We aimed to compare the performance of SUVmax reduction (ΔSUVmax%) versus Deauville score (DS) in assessing chemotherapy response in pediatric HL patients undergoing 18F-FDG PET-CT. Fifty-two patients with biopsy-proven HL (age 8-16 years) were enrolled at baseline, interim (after the 2nd or 3rd chemotherapy round), and post-therapy (upon completion of first-line chemotherapy) 18F-FDG PET-CT. Interim and post-therapy DS and ΔSUVmax% were compared as response predictors. Patients were classified as responders and non-responders based on 24-month clinical follow-up. Interim DS showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and diagnostic accuracy of 100%, 80.4%, 100%, 40% and 82.7%, respectively in predicting response. Post-therapy DS showed a sensitivity, specificity, PPV, NPV and accuracy of 66.7%, 97.8%, 95.7%, 80% and 94.2%. Interim ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 82.6%, 97.4%, 38.5% and 82.7%, with a 56.3% cutoff. Post-therapy ΔSUVmax% showed a sensitivity, specificity, PPV, NPV and accuracy of 83.3%, 84.8%, 97.5%, 41.7% and 84.6%, with a 76.8% cutoff. Sensitivity, specificity (p<0.05) and NPV (p<0.01) were significantly higher using DS than ΔSUVmax%. In conclusion, DS can predict chemotherapy response better than ΔSUVmax% in pediatric HL patients.

Quantitative biomarkers derived from positron-emission tomography/computed tomography (PET/CT) have been suggested as prognostic variables in immune-checkpoint inhibitor (ICI) treated non-small cell lung cancer (NSCLC). As such data for first-line ICI therapy and especially for chemotherapy-ICI combinations are still scarce, we retrospectively evaluated baseline 18F-FDG-PET/CT of 85 consecutive patients receiving first-line pembrolizumab with chemotherapy (n=70) or as monotherapy (n=15). Maximum and mean standardized uptake value, metabolic tumor volume (MTV), total lesion glycolysis and bone marrow-/ spleen to liver ratio (BLR/SLR) were calculated. Kaplan-Meier analyses and Cox-regression models were used to assess progression-free/overall survival (PFS/OS) and their determinant variables. Multivariate selection for PFS/OS revealed MTV as most relevant PET/CT biomarker (p<0.001). Median PFS/OS were significantly longer in patients with MTV≤70mL versus >70mL (PFS: 10 months (M; 95% confidence interval 4-16) vs. 4M (3-5), p=0.001; OS: not reached vs. 10M (5-15), p=0.004). Disease control rate was 81% vs. 53% for MTV≤/>70mL (p=0.007). BLR ≤1.06 versus >1.06 was associated with better outcomes (PFS: 8M (4-13) vs. 4M (3-6), p=0.034; OS: 19M (12-/) vs. 6M (4-12), p=0.005). In patients with MTV>70mL, concomitant BLR≤1.06 indicated a better prognosis. Higher MTV is associated with inferior PFS/OS in first-line ICI treated NSCLC, with BLR allowing additional risk stratification.

Background: Obesity among pregnant women is common, and their offspring are predisposed to obesity, insulin resistance, and diabetes. Circulating metabolites that are related to insulin resistance and are associated with this decreased tissue-specific uptake are unknown. Here, we assessed metabolite profiles in elderly women and who were either female offspring from obese mothers (OOM) or offspring of lean mothers (OLM). Metabolic changes were tested for associations with metrics for insulin resistance. Methods: 37 elderly women were separated into an elderly offspring from obese mothers (OOM; n = 17) and elderly offspring from lean/normal weight mothers (OLM; n = 20) groups. We measured plasma metabolites using 1H-NMR and also insulin-dependent tissue specific glucose uptake in skeletal muscle were assessed. Associations were made between metabolites and glucose uptake. Results: Compared to the OLM group, we found that the 22:6 docosahexaenoic acid percentage of the total long chain n-3 fatty acids (DHA/FA) was significantly lower in OOM (P = 0.015). DHA/FA associated significantly to skeletal muscle GU (P = 0.031) and M-value in the OLM group only (P = 0.050). Conclusions: DHA/FA is associated with insulin-dependent skeletal muscle glucose uptake and that this association is significantly weakened in the offspring of obese mothers.

: Broad-spectrum antifungal drug deployed for topical therapy, specific for onychomycosis, Itraconazole was used as the active pharmaceutical ingredient in a nail lacquer formulation1. The objective of the study was to optimize an antifungal nail lacquer, which when applied topically onto the dorsal surface of the nail plate would facilitate the transungual penetration of the drug. Itraconazole hydrochloride was synthesized to aid the formulation of the lacquers. The optimization involved comparing four different formulations of 1%w/w Itraconazole nail lacquers containing combinations of penetration enhancers (Urea, Salicylic acid, and Papain) based on their ability to facilitate diffusion of the drug through the nail plate over five days. The drug uptake was quantified by extracting the drug from the nail clippings and analyzing it. The tests conducted to account for the quality of the optimized formulation were drug content, spreadability, check for precipitation, and accelerated stability. The results demonstrated that the optimized 1%w/w Itraconazole nail lacquer contained 5%w/w Salicylic acid, 5 %w/w Papain, and 2.8% w/w Urea. The drug uptake from nail clippings was higher than the MIC90 for T. Rubrum strain, and the quality of the optimized lacquer was not compromised throughout three weeks2. The hypothesis stated that the inclusion of Salicylic acid, Papain, and Urea in an Itraconazole (1%w/w) nail lacquer would have the highest transungual penetration on application to the nail plate. In conclusion, the hypothesis was accepted, and the optimized lacquer passed the drug uptake evaluation and all quality control tests.

Cisplatin (CDDP), carboplatin (CP), and oxaliplatin (OXP) are three platinating agents clinically approved worldwide for use against a variety of cancers. They are canonically known as DNA damage inducers; however, that is only one of their mechanisms of cytotoxicity. CDDP mediates its effects through DNA damage-induced transcription inhibition and apoptotic signalling. In addition, CDDP targets the endoplasmic reticulum (ER) to induce ER-stress, the mitochondria via mitochondrial DNA damage leading to ROS production, and the plasma membrane and cytoskeletal components. CP acts in a similar fashion to CDDP by inducing DNA damage, mitochondrial damage, and ER stress. Additionally, CP is also able to upregulate micro-RNA activity, enhancing intrinsic apoptosis. OXP, on the other hand, at first induces damage to all the same targets as CDDP and CP, yet it is also capable of inducing immunogenic cell death via ER stress and can decrease ribosome biogenesis through its nucleolar effects. In this comprehensive review, we provide detailed mechanisms of action for the three platinating agents, going beyond their nuclear effects to include their cytoplasmic impact within cancer cells. In addition, we cover their current clinical use and limitations, including side effects and mechanisms of resistance.