Search

8 pags., 2 figs., 2 tabs., Keratolytic properties of urea 40% have long time used for the treatment of onychomycosis. Fractional ablative lasers enhance the delivery of topically applied photosensitizers improving photodynamic therapy (PDT) efficacy. The aim of this study was to compare the short- and medium-term efficacy of a pretreatment with urea 40% and fractional Er:YAG (Fr Er:YAG) laser radiation before PDT mediated by methylene blue (MB) for moderate toenail onychomycosis. Twenty-first-toe toenails were randomized to receive either urea 40% (Group I) or Fr Er:YAG laser (Group II) pretreatment and 9 sessions of MB/PDT over the course of 16 weeks. At baseline, 28- and 40-week follow-ups, clinical efficacy was assessed by digital photographs [allowing determination of the onychomycosis severity index (OSI)], whereas mycological efficacy was assessed by histological examination and fungal culture. Details of the side effects and patients' satisfaction were also recorded. In both groups, a significant decrease in OSI values was observed at the 28-week follow-up and a slight rebound at the 40-week follow-up. The percentage of nail involvement decreased significantly in both groups at the 28-week follow-up, to continue declining gently in Group I at 40 weeks, in contrast to the rebound observed during this period in Group II. The mycological cure rate was 20% and 30% at 28-week follow-up and 70% and 40% at 40-week follow-up, in Group I and II, respectively. Patients reported being fairly satisfied, and no side effects were detected in any groups. Although both pretreatments favor the action of PDT for the treatment of onychomycosis, the use of urea at 40% is more effective in the medium term., This research was supported by a grant from the Eugenio Rodríguez Pascual Foundation (Madrid, Spain) and by the Spanish Research Project MICINN (Ref.:PiD2020-114755GB-C31). Open Access funding provided thanks to the CRUE-CSIC agreement with Springer Nature.

During the last decade, the treatment for many cancer indications has evolved due to intensive clinical research into anti-tumor agents' combination. In most instances, new combination treatments consist of an add-on to the standard of care (SOC), which then demonstrate a substantial gain in efficacy and no detrimental effect in tolerability. In the era of targeted therapies, for which maximum tolerated dose (MTD)-based dosing strategies are no longer applicable, early stage studies exploring new combinations are often conducted in the population of interest, expediting the collection of preliminary safety data, to be promptly expanded to collect preliminary efficacy data. Nevertheless, rule-based dose-finding studies are still a prevailing approach for early stage cancer, especially for chemotherapy (CT)-containing combinations. Pharmacokinetic (PK) assessments play a key role throughout the clinical development of drug combinations, informing potential PK interactions. But most importantly, they allow the development of innovative exposure-response (E-R) models aimed at exploring the contribution of each agent to the overall effect of the combination therapy. This review identifies 81 new drug combinations approved by the United States Food and Drug Administration (FDA) for hemato-oncology during the 2011-2021 period and summarizes the main design features of clinical trials and the role of PK assessments.

Inferring the functional capabilities of bacteria from metagenome-assembled genomes (MAGs) is becoming a central process in microbiology. Here we show that the completeness of genomes has a significant impact on the recovered functional signal, spanning all domains of metabolic functions. We identify factors that affect this relationship between genome completeness and function fullness, and provide baseline knowledge to guide efforts to correct for this overlooked bias in metagenomic functional inference.

Background Understanding the complex structures and interactions of the bacterial communities inhabiting the upper (URT) and lower (LRT) respiratory tract of pigs is at an early stage. The objective of this study was to characterize the bacterial topography of three URT (nostrils, choana, and tonsils) and LRT (proximal trachea, left caudal lobe and secondary bronchi) sites in pigs. Thirty-six post-mortem samples from six pigs were analysed by 16S rRNA gene quantification and sequencing, and the microbiota in nostrils and trachea was additionally profiled by shotgun sequencing. Results The bacterial composition obtained by the two methods was congruent, although metagenomics recovered only a fraction of the diversity (32 metagenome-assembled genomes) due to the high proportion (85–98%) of host DNA. The highest abundance of 16S rRNA copies was observed in nostrils, followed by tonsils, trachea, bronchi, choana and lung. Bacterial richness and diversity were lower in the LRT compared to the URT. Overall, Firmicutes and Proteobacteria were identified as predominant taxa in all sample types. Glasserella (15.7%), Streptococcus (14.6%) and Clostridium (10.1%) were the most abundant genera but differences in microbiota composition were observed between the two tracts as well as between sampling sites within the same tract. Clear-cut differences were observed between nasal and tonsillar microbiomes (R-values 0.85–0.93), whereas bacterial communities inhabiting trachea and lung were similar (R-values 0.10–0.17). Moraxella and Streptococcus were more common in bronchial mucosal scraping than in lavage, probably because of mucosal adherence. The bacterial microbiota of the choana was less diverse than that of the nostrils and similar to the tracheal microbiota (R-value 0.24), suggesting that the posterior nasal cavity serves as the primary source of bacteria for the LRT. Conclusion We provide new knowledge on microbiota composition and species abundance in distinct ecological niches of the pig respiratory tract. Our results shed light on the distribution of opportunistic bacterial pathogens across the respiratory tract and support the hypothesis that bacteria present in the lungs originate from the posterior nasal cavity. Due to the high abundance of host DNA, high-resolution profiling of the pig respiratory microbiota by shotgun sequencing requires methods for host DNA depletion.

Research on animal-microbiota interactions has become a central topic in biological sciences because of its relevance to basic eco-evolutionary processes and applied questions in agriculture and health. However, animal hosts and their associated microbial communities are still seldom studied in a systemic fashion. Hologenomics, the integrated study of the genetic features of a eukaryotic host alongside that of its associated microbes, is becoming a feasible - yet still underexploited - approach that overcomes this limitation. Acknowledging the biological and genetic properties of both hosts and microbes, along with the advantages and disadvantages of implemented techniques, is essential for designing optimal studies that enable some of the major questions in biology to be addressed.

Proboscideans were keystone Cenozoic megaherbivores and present a highly relevant case study to frame the timing and magnitude of recent megafauna extinctions against long-term macroevolutionary patterns. By surveying the entire proboscidean fossil history using model-based approaches, we show that the dramatic Miocene explosion of proboscidean functional diversity was triggered by their biogeographical expansion beyond Africa. Ecomorphological innovations drove niche differentia- tion; communities that accommodated several disparate proboscidean species in sympatry became commonplace. The first burst of extinctions took place in the late Miocene, approximately 7 million years ago (Ma). Importantly, this and subsequent extinction trends showed high ecomorphological selectivity and went hand in hand with palaeoclimate dynamics. The global extirpation of proboscideans began escalating from 3 Ma with further extinctions in Eurasia and then a dramatic increase in African extinctions at 2.4 Ma. Overhunting by humans may have served as a final double jeopardy in the late Pleistocene after climate-triggered extinction trends that began long before hominins evolved suitable hunting capabilities., This work was supported by the Talent Attraction Program of the Madrid Government (no. 2017-T1/AMB5298), the German Research Foundation (AOBJ no. 637491) and the Academy of Finland (post-doctoral research fund no. 315691).

The possibility of exploiting the human immune response to glycan α-Gal for the control of multiple infectious diseases has been the objective of recent investigations. In this field of research, the strain of Escherichia coli O86:B7 has been at the forefront, but this Gram-negative microorganism presents a safety concern and therefore cannot be considered as a probiotic. To address this challenge, this study explored the identification of novel lactic acid bacteria with a safe history of use, producing α-Gal and having probiotic potential. The lactic acid bacteria were isolated from different traditionally fermented foods (kununn-zaki, kindirmo, and pulque) and were screened for the production of α-Gal and some specific probiotic potential indicators. The results showed that Ten (10) out of forty (40) [25%] of the tested lactic acid bacteria (LAB) produced α-Gal and were identified as Limosilactobacillus fermentum, Levilactobacillus brevis, Agrilactobacillus composti, Lacticaseibacillus paracasei, Leuconostoc mesenteroides and Weissella confusa. Four (4) LAB strains with highest levels of α-Gal were further selected for in vivo study using a mouse model (α1,3GT KO mice) to elucidate the immunological response to α-Gal. The level of anti-α-Gal IgG observed were not significant while the level of anti-α-Gal IgM was lower in comparison to the level elicited by E. coli O86:B7. We concluded that the lactic acid bacteria in this study producing α-Gal have potential probiotic capacity and can be further explored in α-Gal-focused research for both the prevention and treatment of various infectious diseases and probiotic development., Research on α-Gal has been partially supported by Ministerio de Ciencia e Innovación/Agencia Estatal de Investigación MCIN/AEI/10.13039/501100011033, Spain and EU-FEDER (Grant BIOGAL PID2020-116761 GB-I00). BT was supported by The World Academy of Sciences, Italy (FR number_3240306342) and the Department of Biotechnology, Government of India (BT/AB/03/04/2002Timothy).

Wire and arc additive manufacturing (WAAM) technology is growing in interest in the last years. The technology enables the manufacturing of real geometries by overlapping weld beads and is well suited for metallic parts with high buy-to-fly ratio. Manufacturing costs and time are critical issues which determine the business case. Therefore, it is necessary to develop strategies that minimise the production time while meeting quality requirements. In this regard, cooling conditions are a key factor to reduce time and determine mechanical properties and resulting microstructure. This study aims at investigating the effect of interpass cooling conditions on resulting mechanical properties and microstructure of Ti-6Al-4V alloy. The influence of dwell time between successive deposition of layers is investigated both for air and forced interpass cooling. Forced cooling is done by using water-cooled anvil under base plate. The goal is to find a minimum dwell time to maximise arc-on time and deposition rate while avoiding wall collapse, widening, oxidation and the need to apply post building heat treatment. Obtained mechanical properties are compared with standards for products manufactured by conventional manufacturing. Additionally, microstructure, surface finishing and part accuracy of WAAM samples are characterised.

Currently, gastric cancer (GC) and gallbladder cancer (GBC) constitute important causes of human deaths related to cancer worldwide. In the last years, several researches are focused on the role of dietary compounds in preventing cancers. The consumption of fruits with high antioxidants, mainly anthocyanins, represents a good option to reduce the risk of chronic human diseases. Calafate (Berberis microphylla G. Forst.) berries, recognized by their remarkable antioxidant properties and high content of anthocyanins, appear as a new alternative to treat degenerative diseases of public interest. The present work was aimed to evaluate the impact of crude and anthocyanin-rich extracts from Calafate fruits on in vitro cell viability and migration capacity of gastric (AGC) and gallbladder (G415) human cancer cell lines, as related with their antioxidant properties. Crude and anthocyanin-rich extracts were obtained from fruits of Calafate grown under field conditions in the south of Chile. Antioxidants, phenols, anthocyanins, and anthocyanidins were determined. In vitro cell viability and migration of AGS and G415 human cancer cell lines at different concentrations of extracts (25–800 μg mL−1) were determined. Anthocyanin-rich extracts of Calafate berries showed comparable antioxidant activity (up to 1200 μg Trolox eq. g−1DW), slightly lower total phenolic content (12%), but higher total anthocyanin content (25%) compared to the crude extract. The major anthocyanidin molecule detected in both extracts was delphinidin, followed by malvidin, and low concentrations of petunidin, cyanidin, and peonidin. As expected, all of these compounds were detected in higher levels in anthocyanin-rich extracts (up to 2-fold). Noteworthy, our study revealed that Calafate fruit extracts strongly decrease in vitro viability and migration capacity of gastric carcinoma (AGC model) and gallbladder carcinoma (G415 model) human cell lines; however, the anthocyanin-rich extract displayed higher inhibitory effects (up to 70%) compared to crude extracts. These findings allow suggesting that the in vitro antiproliferative potential of Calafate fruit extract is strongly related to the anthocyanin concentration, especially delphinidin.

In the present study, single and mixture effects of cadmium (Cd) and zinc (Zn) on Lemna gibba were analyzed and compared using growth parameters, based on frond number and fresh weight, and biochemical parameters, such as pigment, protein content and activity of antioxidant enzymes. Plants were exposed for 7 days to these metals in nutrient solution. Single and mixture exposures affected plant growth and the biomarkers of the antioxidant response. Considering the growth parameters, Cd was found to be much more toxic than Zn. IC50-7d, based on growth rate calculated on frond number, were 17.8 and 76.73 mg/L, and on fresh weight were 1.08 and 76.93 mg/L, for Cd and Zn respectively. For Cd, LOEC values were obtained at 2.06 and 1.03 mg/L, for frond number and fresh weight respectively; while for Zn, at 20.1 and 74.6 mg/L. A high toxicity effect, considering the same response variables, was observed in plants exposed to the mixtures. Three fixed ratios, based on toxic units (TU) were assayed, ratio 1: 2/3 Cd-1/3 Zn, ratio 2: 1/2 Cd-1/2 Zn and ratio 3: 1/3 Cd-2/3 Zn. Ratio 3 (where Zn was added in higher proportion) was the less toxic. All concentrations of Ratio 1 and 2 significantly inhibited plant growth, showing a 100% inhibition of growth rate at the highest concentrations when based on frond number. Catalase (CAT; EC 1.11.1.6), ascorbate peroxidase (APOX; EC 1.11.1.11) and guaiacol peroxidase (GPOX; EC 1.11.1.7) activities in single metals assays were higher than controls. In mixture tests, the activity of APOX and GPOX was significantly stimulated in plants exposed to all evaluated combinations, while CAT was mainly stimulated in Ratio 3. It was observed that the activity of the enzymes was increased in the mixtures compared with similar concentrations evaluated individually. APOX activity was observed to fit the CA model and following a concentration-response pattern. The response of this antioxidant enzyme could serve as a sensitive stressor biomarker for Cd-Zn interactions. Frond number in Cd-Zn mixtures was not well predicted from dissolved metal concentration in solution using concentration addition (CA) as reference model, as results showed that toxicity was more than additive, with an average of ΣTU = 0.75. This synergistic effect was observed up to 50 mg Zn/L in the mixture, but when it was present in higher concentrations a less than additive effect was observed, indicating a protective effect of Zn. A synergistic and dose-ratio deviations from CA model were also observed.

Manganese (Mn) is an essential micronutrient for plants; however, in excess, it can have negative effects on their physiological and biochemical characteristics. We evaluate photosynthetic performance, antioxidant activity, and organic acid exudations to clarify the mechanisms involved in highbush blueberry (Vaccinium corymbosum L.) under Mn excess. One-year-old plants of V. corymbosum cultivars (Legacy, Brigitta, and Bluegold) were grown in hydroponic solution with 2, 10, 50, 250, 500, and 1000 μM of Mn treatments for 25 days. Plant growth as shoot and root biomass, Mn content, photosynthetic performance [photochemical efficiency of PSII, CO2 assimilation, and stomatal conductance (gs)], lipid peroxidation, radical scavenging activity, superoxide dismutase activity, and organic acid exudations were analyzed. Mn excess triggered detrimental effects in terms of plant growth, photochemical efficiency, and CO2 assimilation, as well as in biochemical features in V. corymbosum cultivars. Despite Legacy decreasing its photosynthesis, plant growth was maintained throughout the experiment; by contrast, Brigitta maintained photosynthesis and growth despite the decrease in stomatal conductance (gs). Meanwhile, Bluegold presented the lowest level in net photosynthesis and photochemical processes and an increase in lipid peroxidation. Oxalate and citrate were the most important organic acid anions in Legacy and Brigitta, gradually increasing their concentration with the enhancement of Mn doses. Our study demonstrated that Mn excess negatively and differently affects the physiological and biochemical features of V. corymbosum cultivars, with Legacy and Brigitta being Mn-resistant and Bluegold Mn-sensitive.

Vitamin D status may play a role in the development of atopic diseases due to its action on lung development and immune system development and function.Our objective was to assess whether 25-hydroxyvitamin D (25OHD) levels in maternal blood in pregnancy were associated with atopy in children.We analysed 279 mother-child pairs from the ROLO study conducted in Dublin, Ireland. Serum 25OHD was measured at 13 and 28 weeks of pregnancy. Development of childhood atopy was self-reported by mothers at follow-up appointments at 6 months, 2 years or 5 years. Logistic regression analysis was used to evaluate associations between maternal 25OHD status and development of atopy.The mean (SD) 25OHD levels in early and late pregnancy were 41.9 (19.2) nmol/L and 40.2 (21.6) nmol/L, respectively. Maternal 25OHD status in early pregnancy, but not in late pregnancy, was associated with a reduced risk of atopy at 2 years (OR 0.972, CI 0.946-0.999). In early pregnancy, those with serum 25OHD levels 30 nmol/L compared with those with 25OHD 50 nmol/L had significantly greater risk of developing atopy at 2 years (OR 4.76, CI 1.38-16.47).The development of childhood atopy may be associated with maternal vitamin D deficiency in early pregnancy among a cohort of women at risk of vitamin D deficiency. Further research is required to explore the relationship between vitamin D and atopy, particularly among women with poor vitamin D status, and whether supplementation should be prioritised in early pregnancy to reduce childhood atopy.

Methyl jasmonate (MeJA) protective effect on photosynthetic performance and its association with antioxidants in two highbush blueberry (Vaccinium corymbosum L.) cultivars with contrasting aluminum (Al) resistance under Al toxicity was determined. Legacy (Al-resistant) and Bluegold (Al-sensitive) cultivars were subjected to control, MeJA, Al, and their combination (Al+MeJA) for 0, 24, and 48 h under greenhouse conditions. Al concentration, oxidative damage (malondialdehyde (MDA) and H2O2 concentrations), antioxidant activity (AA), superoxide dismutase (SOD) and catalase (CAT) activities, total polyphenols (TPP), chlorogenic acid, and in vivo photosynthetic performance were determined. The exposure to Al toxicity increased the Al concentration (up to 15-fold) and oxidative damage (up to 5.5-fold) compared to the control at 48 h, despite the antioxidant responses (SOD and CAT activities) were increased (up to 4-fold), mainly in the Al-sensitive cultivar at 48 h. Concomitantly, the photosynthetic performance was strongly reduced in the Al-sensitive cultivar (1.6-fold), while the Al-resistant cultivar was more stable during the experiment. However, when cultivars were exposed to Al+MeJA, the Al accumulation and oxidative damage strongly decreased (7-fold and 1.6-fold, respectively), increasing AA, SOD and CAT activities, and TPP in both cultivars during the first hours of Al exposure. The MeJA application decreased Al uptake and stimulated antioxidant pathways, which may counteract the toxic Al effects, protecting the photosynthetic apparatus in both cultivars, being more evident in the Al-sensitive cultivar.

The design of periodic elastoplastic microstructures for maximum energy dissipation is carried out using topology optimization. While the topology optimization of elastic microstructures has been performed in numerous studies, microstructural design considering inelastic behavior is relatively untouched due to a number of reasons which are addressed in this study. An RVE-based multiscale model is employed for computational homogenization with periodic boundary constraints, satisfying the Hill-Mandel principle. The plastic anisotropy which may be prevalent in materials fabricated through additive manufacturing processes is considered by modeling the constitutive behavior at the microscale with Hoffman plasticity. Discretization is done using enhanced assumed strain elements to avoid locking from incompressible plastic flow under plane strain conditions and a Lagrange multiplier approach is used to enforce periodic boundary constraints in the discrete system. The design problem is formulated using a density-based parameterization in conjunction with a SIMP-like material interpolation scheme. Attention is devoted to issues such as dependence on initial design and enforcement of microstructural connectivity, and a number of optimized microstructural designs are obtained under different prescribed deformation modes.

Breastfeeding rates in Ireland are among the lowest worldwide. A feasibility study of a breastfeeding-support intervention explored maternal characteristics associated with antenatal breastfeeding self-efficacy and with infant-feeding mode at 6 weeks postpartum among women giving birth in Ireland. We conducted a prospective study across two sites, urban and rural: The National Maternity Hospital (NMH), Dublin and Wexford General Hospital (WGH), Wexford. Nulliparous, pregnant women were recruited at approximately 32 weeks gestation from the hospitals’ antenatal out-patient departments. Participants attended an antenatal class with a support partner, received a one-to-one session with a lactation consultant after delivery and had access to a breastfeeding-support clinic and telephone advice postpartum. Our aim was to understand maternal variables associated with breastfeeding self-efficacy and infant-feeding mode. We explored associations between continuous and categorical variables and any breastfeeding and exclusive breastfeeding using t tests and Chi-squared analyses. One hundred mothers provided baseline data; 64 provided follow-up data. Lower maternal age and non-Irish nationality were associated with higher antenatal breastfeeding self-efficacy. At the rural unit, mothers with tertiary education were more likely to be exclusively breastfeeding than those with secondary education. Though not statistically significant, more normal-weight mothers from the urban unit were exclusively breastfeeding at 6 weeks than overweight/obese mothers. Breastfeeding outcomes differed by maternal education. Future interventions should target mothers with lower education and possibly also overweight and obese mothers. Increasing breastfeeding self-efficacy, particularly among older and Irish-born mothers, may be a mechanism for improving breastfeeding outcomes.

Because shrub cover is related to many forest ecosystem functions, it is one of the most relevant variables for describing these communities. Nevertheless, a harmonized indicator of shrub cover for large-scale reporting is lacking. The aims of the study were threefold: to define a shrub indicator that can be used by European countries for harmonized shrub cover estimation using data from their respective national forest inventories (NFIs); to quantify the effects of using different NFI field cover scales; and to establish bridges to facilitate harmonized estimation. Data for shrub species cover from the Third Spanish NFI together with scales for cover assessment from 16 European NFIs were used. The indicator, mean species cover (MSC), was defined for each species and each European forest category. Estimates of MSC calculated using species covers recorded for field plots, with 1% interval widths (MSCobs), were compared with the MSC values that would be obtained for the same data with the different European cover scales (MSCpred). Residuals calculated as differences between MSCobs and MSCpred were analyzed, and a linear mixed model was used as bridging function to adjust predictions and thus further harmonize estimates. Scales with only two or three intervals produced the greatest residuals, while all the other analyzed scales had residuals less than 5%. Most scales, except those most similar to Braun-Blanquet, displayed a tendency to be unreliable for larger covers. The proposed mean species cover indicator provides comparable estimates for shrub communities at large scales. The linear models improved the harmonization of MSC for the scales having two and three intervals.

An isogeometric analysis (IGA) framework is presented to construct and solve dispersion relations for generating the band structure of periodic materials with complicated geometries representing phononic crystals and elastic metamaterials. As the dispersive properties depend on the microstructural geometry, an accurate representation of microstructural geometrical features is paramount. To this end, the ability of isogeometric analysis to exactly model complex curved geometries is exploited, and wave propagation in infinitely periodic solids is combined with isogeometric analysis. The benefits of IGA are demonstrated by comparing the results to those obtained using standard finite element analysis (FEA). It is shown that the IGA solutions can reach the same level of accuracy as FEA while using significantly fewer degrees of freedom. IGA is applied to phononic crystals and elastic metamaterials and the band structure for a variety of unit cells with complex microstructural geometries is investigated to illustrate the desirable dispersive effects in these metamaterials.