Isoleucine and valine supplementation of a low-protein corn-wheat-soybean meal-based diet for piglets: growth performance and nitrogen balance

The effects of Ile and Val supplementation of a low-CP, corn-wheat-soybean meal-based piglet diet on growth performance, incidence of diarrhea, and N balance were studied using 60 Landrace × Duroc male piglets in a 4-wk experiment. The 60 individually caged piglets were divided into 5 dietary treatments, each consisting of 12 piglets. Diet 1 was a positive control diet (20% CP); diet 2 was a low-CP negative control diet (17% CP); diets 3, 4, and 5 were low-CP diets to which Ile, Val, or the combination of Ile and Val were added, respectively. All diets were supplemented with Lys, Met, Thr, and Trp to provide the required concentrations of these AA according to the 1998 NRC. Average daily gain and ADFI were similar among pigs fed the positive control, Val-added, and the Val plus Ileadded diets. On wk-2 and wk-4, fecal score was greater (softer feces) in piglets fed the 20% CP level compared with the remaining treatments (P < 0.01). Nitrogen intake was decreased (P < 0.0001) in pigs fed diets containing low levels of CP compared with pigs fed the 20% CP diet. Fecal N excretion (g/d) was decreased (P < 0.05) in piglets fed low-CP diets at wk 1 and wk 4 of feeding, and in urine at wk 4 of feeding. Crude protein levels or AA supplementation had no effect on N retention efficiencies. These results indicate that the supplementation of Val alone, or in combination with Ile, to a low-CP piglet diet with adequate levels of Lys, Met, Thr, and Trp is necessary to achieve maximum performance in pigs consuming corn-wheat-soybean meal-based diets

Metabolic stability and metabolite profiling of emerging synthetic cathinones

We thank Fundação para a Ciência e a Tecnologia (FCT), Portugal, for financial support through projects UIDB/QUI/00100/2020 and UIDP/00100/2020 (to CQE), LA/P/0056/2020 (to IMS), UIDB/04046/2020 and UIDP/04046/2020 (to BioISIBiosystems & Integrative Sciences Institute), UIDB/04292/2020 and UIDP/04292/2020 (to MARE-Marine and Environmental Sciences Centre). FCT is also acknowledged for the PhD grant 2022.04738. PTDC to RPL. Joint funding from FCT and the COMPETE Program through grant RNEMLISBOA-01-0145-FEDER-022125 funding are also gratefully acknowledged.Synthetic cathinones constitute the second largest groups of new psychoactive substances (NPS), which are especially popular among adolescents and young adults. Due to their potential toxicity, the recreational use of these NPS constitute a serious worldwide public health problem. However, their fast appearance in the market renders the continuous updating of NPS information highly challenging for forensic authorities. The unavailability of pharmacokinetic data for emerging NPS is critical for forensic and clinical verifications. With the ultimate goal of having a proactive approach towards the NPS issue, high resolution mass spectrometry was used in the current work to assess preliminary pharmacokinetic data for 8 selected cathinones: 4 reported substances (4-CIC, 3-CMC, 4-CMC and 4-MEAP) and 4 previously unreported ones (3-CIC, 4-MDMB, 4-MNEB and 4-MDMP) for which the emergence on the NSP market is expected to be eminent, were also included in this study. Based on the calculation of pharmacokinetic parameters, half-life and intrinsic clearance, 4-CMC and 4-MDMB are low and high clearance compounds, respectively, and all the remaining cathinones included in this study are intermediate clearance compounds. This fact anticipates the key role of metabolites as suitable biomarkers to extend detection windows beyond those provided by the parent cathinones. Reduction of the keto group and hydroxylation on the alkyl chains were the common metabolic pathways identified for all cathinones. However, the relative importance of these metabolic transformations is dependent on the cathinone substituents. The glucuronic acid conjugation to metabolites stemming for keto group reduction constituted the sole Phase II transformation identified. To our knowledge, this study constitutes the first metabolite profiling of the already reported synthetic cathinones 4-CIC, 3-CMC and 4-CMC. Noteworthy is the fact that 3-CMC accounts for almost a quarter of the quantity of powders seized during 2020. The analytical methods developed, and the metabolites characterized, are now available to be included in routine screening methods to attest the consumption of the 8 cathinones studied.info:eu-repo/semantics/publishedVersio

A Step Forward in Breast Cancer Research: Gold Nanoparticles as Photothermal Therapy Enhancers

Gold nanoparticles (AuNPs) have been widely used and characterized for multiple biomedical applications, including the enhancement of photothermal therapy (PTT). AuNPs present a particular plasmon resonance band and are able to convert the absorbed optical radiation into heat, which validates their use in PTT. Several production methods have already been proposed for the synthesis of AuNPs, allowing to optimize the particles' morphology, size and optical properties. However, the production methods commonly used are frequently associated with the use of toxic reagents such as Cetyltrimethylammonium bromide, which presents some concerns for clinical applications. Herein, it is proposed a novel AuNPs' core synthesis method using tetrachloroauric acid and a mixture of reducing agents, later on coated with a combination of hyaluronic and oleic acids. The coating here represents a potential improvement of AuNPs biocompatibility, biodegradability and lifetime, while simultaneously potentiating the attachment towards specific ligands, such as the CD44 receptor, to develop more localized and highly selective tools. The produced functionalized nanoparticles were characterized by Dynamic Light Scattering, Microscopy Techniques and Spectroscopy, showing diameter sizes under 350 nm, polydispersity index smaller than 0.4 and enhanced absorbance in the Near Infrared (NIR, 650 to 900 nm) range. Moreover, the AuNPs safety and efficacy were preliminarily assessed in vitro using breast cancer cell lines. No toxicity was observed by MTT assay, both in breast cancer cell lines, and red blood cells. The irradiation process was proved to be safe; however, when combined with the AuNPs administration, it resulted in a significant reduction of cell viability for some of the breast cell lines tested. Thus, the results highlight the potential of the proposed system for some type of tumors, even though further tests are required to better understand the mechanisms behind the obtained results

Methimazole associated eosinophilic pleural effusion: a case report

© The Author(s). 2017 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver(http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Adverse reactions associated to anti-thyroid drugs include fever, rash, arthralgia, agranulocytosis and hepatitis that are thought to be hypersensitivity reactions. Five cases of pleural effusion associated to thionamides have also been reported, two with propylthiouracil and three with carbimazole. Case presentation: We report here a case of a 75-year-old man admitted because of unilateral pleural effusion. The patient had a recent diagnosis of hyperthyroidism and 6 days after starting methimazole complained of pleuritic chest pain. He had elevated C-reactive protein and erythrocyte sedimentation rate and normal white blood cell count and liver enzymes. Chest radiography showed a moderate right pleural effusion and the ultrasound revealed a loculated effusion that was shown to be an eosinophilic exudate. Conclusions: The temporal relationship between methimazole intake and the development of pleural effusion combined with the extensive exclusion of alternative causes, namely infectious, neoplastic and primary auto-immune diseases, led to the diagnosis of hypersensitivity reaction to methimazole. The thionamide was stopped and corticosteroid was started with complete resolution of the pleural effusion in 3 months. Awareness of this rare adverse reaction of anti-thyroid drugs is important and methimazole can be added to the list of possible etiologies of drug-induced eosinophilic pleural effusion.info:eu-repo/semantics/publishedVersio

The Role of Rosmarinic Acid on the Bioproduction of Gold Nanoparticles as Part of a Photothermal Approach for Breast Cancer Treatment.

Breast cancer is a high-burden malignancy for society, whose impact boosts a continuous search for novel diagnostic and therapeutic tools. Among the recent therapeutic approaches, photothermal therapy (PTT), which causes tumor cell death by hyperthermia after being irradiated with a light source, represents a high-potential strategy. Furthermore, the effectiveness of PTT can be improved by combining near infrared (NIR) irradiation with gold nanoparticles (AuNPs) as photothermal enhancers. Herein, an alternative synthetic method using rosmarinic acid (RA) for synthesizing AuNPs is reported. The RA concentration was varied and its impact on the AuNPs physicochemical and optical features was assessed. Results showed that RA concentration plays an active role on AuNPs features, allowing the optimization of mean size and maximum absorbance peak. Moreover, the synthetic method explored here allowed us to obtain negatively charged AuNPs with sizes favoring the local particle accumulation at tumor site and maximum absorbance peaks within the NIR region. In addition, AuNPs were safe both in vitro and in vivo. In conclusion, the synthesized AuNPs present favorable properties to be applied as part of a PTT system combining AuNPs with a NIR laser for the treatment of breast cancer

Effects of recent minimum temperature and water deficit increases on Pinus pinaster radial growth and wood density in southern Portugal

Western Iberia has recently shown increasing frequency of drought conditions coupled with heatwave events, leading to exacerbated limiting climatic conditions for plant growth. It is not clear to what extent wood growth and density of agroforestry species have suffered from such changes or recent extreme climate events. To address this question, tree-ring width and density chronologies were built for a Pinus pinaster stand in southern Portugal and correlated with climate variables, including the minimum, mean and maximum temperatures and the number of cold days. Monthly and maximum daily precipitations were also analyzed as well as dry spells. The drought effect was assessed using the standardized precipitation-evapotranspiration (SPEI) multi-scalar drought index, between 1 to 24-months. The climate-growth/density relationships were evaluated for the period 1958-2011. We show that both wood radial growth and density highly benefit from the strong decay of cold days and the increase of minimum temperature. Yet the benefits are hindered by long-term water deficit, which results in different levels of impact on wood radial growth and density. Despite of the intensification of long-term water deficit, tree-ring width appears to benefit from the minimum temperature increase, whereas the effects of long-term droughts significantly prevail on tree-ring density. Our results further highlight the dependency of the species on deep water sources after the juvenile stage. The impact of climate changes on longterm droughts and their repercussion on the shallow groundwater table and P. pinaster’s vulnerability are also discussed. This work provides relevant information for forest management in the semi-arid area of the Alentejo region of Portugal. It should ease the elaboration of mitigation strategies to assure P. pinaster’s production capacity and quality in response to more arid conditions in the near future in the regioninfo:eu-repo/semantics/publishedVersio

Hesperidin improves the follicular development in 3D culture of isolated preantral ovarian follicles of mice

In vitro follicular culture systems provide optimal culture models for research about the physiology of the ovary and support the clinical practices to achieve competent mature oocytes for in vitro fertilization. In vitro maturation of preantral follicles makes it possible to study the effects of therapeutic agents on various conditions or disorders of the ovary. Nowadays, preventive bioflavonoids against cancer, hypercholesterolemia, fatty liver, or a variety of toxic agents are in focus. The aim of this study was to design and investigate the impacts of different concentrations of hesperidin, a glycoside flavonoid, on the in vitro preantral follicle growth and maturation in the three-dimensional (3D) culture system which was made with sodium alginate. Preantral follicles (n = 1363) were mechanically isolated from immature mice ovaries, then, after capsulating, they were randomly divided into four groups: the control group received no concentration of hesperidin, and three experimental groups were supplemented with 10, 22.5, and 50 µmol/L of hesperidin. All groups were cultured for 12 days. At the end of the culture period, the percentage of survival rate, antrum formation, obtained metaphase II oocytes, and the secretion of 17β-estradiol and progesterone were significantly higher in the group Hesp 50 (50 µmol/L hesperidin). Moreover, the mean average of follicular diameter cultured in the group Hesp 50 was also increased and the mRNA expression levels of PCNA, FSH-R, and Bcl-2 genes were higher, while Bax mRNA expression was significantly reduced compared with the other groups. Follicles cultured in the presence of 50 µmol/L of hesperidin had a higher fertilization rate and embryo development. Adding hesperidin at the concentration of 50 µmol/L to the culture medium resulted in higher follicular growth and maturation and increased the rate of in vitro fertilization and embryo development. Impact statement: It has been stated that hesperidin has many pharmacological effects, such as anti-inflammatory and antioxidant effects, antimicrobial activity, and anti-carcinogenic activity; but hesperidin and its derivatives have been under investigation as anti-fertility factors for a very long time. However, our results show that hesperidin can improve mice follicular growth and maturation during in vitro 3D culture. Hesperidin as an antioxidant factor could enhance the mRNA expression levels of two important genes involved in folliculogenesis, PCNA, and FSH-R. Our results prove for the first time that hesperidin not only has deleterious effects on follicular development but can also increase rates of in vitro fertilization and embryo development. © 2019 by the Society for Experimental Biology and Medicine

Measurement of the Bs0→J/ψKS0B_s^0\to J/\psi K_S^0 branching fraction

The $B_s^0\to J/\psi K_S^0$ branching fraction is measured in a data sample corresponding to 0.41$fb^{-1}$ of integrated luminosity collected with the LHCb detector at the LHC. This channel is sensitive to the penguin contributions affecting the sin2$\beta$ measurement from $B^0\to J/\psi K_S^0$ The time-integrated branching fraction is measured to be $BF(B_s^0\to J/\psi K_S^0)=(1.83\pm0.28)\times10^{-5}$. This is the most precise measurement to date