Novel Bidentate Amine Ligand and the Interplay between Pd(II) and Pt(II) Coordination and Biological Activity.

Pt(II) and Pd(II) coordinating N-donor ligands have been extensively studied as anticancer agents after the success of cisplatin. In this work, a novel bidentate N-donor ligand, the N-[[4-(phenylmethoxy)phenyl]methyl]-2-pyridinemethanamine, was designed to explore the antiparasitic, antiviral and antitumor activity of its Pt(II) and Pd(II) complexes. Chemical and spectroscopic characterization confirm the formation of [MLCl2 ] complexes, where M=Pt(II) and Pd(II). Single crystal X-ray diffraction confirmed a square-planar geometry for the Pd(II) complex. Spectroscopic characterization of the Pt(II) complex suggests a similar structure. 1 H NMR, 195 Pt NMR and HR-ESI-MS(+) analysis of DMSO solution of complexes indicated that both compounds exchange the chloride trans to the pyridine for a solvent molecule with different reaction rates. The ligand and the two complexes were tested for in vitro antitumoral, antileishmanial, and antiviral activity. The Pt(II) complex resulted in a GI50 of 10.5 µM against the NCI/ADR-RES (multidrug-resistant ovarian carcinoma) cell line. The ligand and the Pd(II) complex showed good anti-SARS-CoV-2 activity with around 65 % reduction in viral replication at a concentration of 50 µM.

Adaptive Skills of Individuals with Angelman Syndrome Assessed Using the Vineland Adaptive Behavior Scales, 2nd Edition.

In the current study, we examined adaptive skills and trajectories over time in 257 individuals with Angelman syndrome (AS) using the Vineland Adaptive Behavior Scales, 2nd Edition. Multilevel linear models were used to examine differences between molecular subtypes over time, from one year to 13 years of age, in the adaptive domains of communication, daily living skills, socialization and motor skills. Individuals with non-deletion subtypes typically demonstrated a higher level of adaptive skills compared to those with deletion subtypes. Statistically significant growth was observed in all adaptive domains through at least early adolescence. Individuals with AS should continue to receive developmental services and educational supports through adolescence and into adulthood given the slow rates of growth being observed across adaptive domains.

Universal redirection of CAR T cells against solid tumours via membrane-inserted ligands for the CAR.

The effectiveness of chimaeric antigen receptor (CAR) T cell therapies for solid tumours is hindered by difficulties in the selection of an effective target antigen, owing to the heterogeneous expression of tumour antigens and to target antigen expression in healthy tissues. Here we show that T cells with a CAR specific for fluorescein isothiocyanate (FITC) can be directed against solid tumours via the intratumoural administration of a FITC-conjugated lipid-poly(ethylene)-glycol amphiphile that inserts itself into cell membranes. In syngeneic and human tumour xenografts in mice, 'amphiphile tagging' of tumour cells drove tumour regression via the proliferation and accumulation of FITC-specific CAR T cells in the tumours. In syngeneic tumours, the therapy induced the infiltration of host T cells, elicited endogenous tumour-specific T cell priming and led to activity against distal untreated tumours and to protection against tumour rechallenge. Membrane-inserting ligands for specific CARs may facilitate the development of adoptive cell therapies that work independently of antigen expression and of tissue of origin.

Long-acting injectable progesterone treatment prior to puberty induction in gilts.

Progesterone (P4) has a pivotal role on female puberty attainment in most farm animals. However, there are no studies evaluating the effect of P4 treatment previously to boar exposure for puberty induction in gilts. Therefore, serum P4 concentration, estrus expression and reproductive performance after boar stimuli were evaluated in gilts intramuscularly treated with long-acting P4 before boar exposure. In Experiment I, prepubertal gilts received either 1 mL of saline (control) or intramuscular (I.M.) P4 treatment (150 mg, 300 mg or 600 mg; n = 6 per treatment). Serum P4 concentration for P4-treated gilts was greater than for control gilts for at least 8 d for P4300 and P4600 groups (P < 0.05), but greater until after 16 d only for those treated with 600 mg (P < 0.05). In Experiments II (prepubertal) and III (peripubertal), gilts received either saline (control) or 300 mg P4 I.M. and those showing estrus signs were artificially inseminated (AI), whereas gilts without estrus expression were culled. In prepubertal gilts (Exp. II), estrus expression rate did not differ (P < 0.05) for control (79.1%; n = 110) and P4-treated gilts (81.5%; n = 108). In peripubertal gilts (Exp. III), although estrus expression did not differ between control (77.6%; n = 106) and P4-treated (69.6%; n = 102) gilts (P > 0.05), P4-treated gilts presented longer (23.1 ± 1.4 days) interval from treatment to estrus expression than control gilts (17.1 ± 1.3 days; P < 0.05). In Experiments II and III, the proportion of culled gilts with ovarian structures consistent with normal estrous cycles, farrowing rate, and litter size did not differ between treatments (P > 0.05). In conclusion, I.M. treatment with 300 or 600 mg of long-acting P4 was efficient in maintaining high P4 concentrations in prepubertal gilts for at least 8 days. However, P4 treatment over this time interval did not benefit the reproductive performance of prepubertal and peripubertal gilts.

Structural and biochemical characterization of Leptospira interrogans Lsa45 reveals a penicillin-binding protein with esterase activity.

Leptospirosis is a bacterial disease that affects humans and animals and is caused by Leptospira. The recommended treatment for leptospirosis is antibiotic therapy, which should be given early in the course of the disease. Despite the use of these antibiotics, their role during the course of the disease is still not completely clear because of the lack of effective clinical trials, particularly for severe cases of the disease. Here, we present the characterization of L. interrogans Lsa45 protein by gel filtration, protein crystallography, SAXS, fluorescence and enzymatic assays. The oligomeric studies revealed that Lsa45 is monomeric in solution. The crystal structure of Lsa45 revealed the presence of two subdomains: a large α/ß subdomain and a small α-helical subdomain. The large subdomain contains the amino acids Ser122, Lys125, and Tyr217, which correspond to the catalytic triad that is essential for ß-lactamase or serine hydrolase activity in similar enzymes. Additionally, we also confirmed the bifunctional promiscuity of Lsa45, in hydrolyzing both the 4-nitrophenyl acetate (p-NPA) and nitrocefin ß-lactam antibiotic. Therefore, this study provides novel insights into the structure and function of enzymes from L. interrogans, which furthers our understanding of this bacterium and the development of new therapies for the prevention and treatment of leptospirosis.

Conformal Volumetric Grayscale Metamaterials.

Conformal artificial electromagnetic media that feature tailorable responses as a function of incidence wavelength and angle represent universal components for optical engineering. Conformal grayscale metamaterials are introduced as a new class of volumetric electromagnetic media capable of supporting highly multiplexed responses and arbitrary, curvilinear form factors. Subwavelength-scale voxels based on irregular shapes are designed to accommodate a continuum of dielectric values, enabling the freeform design process to reliably converge to exceptionally high figures of merit (FOMs) for a given multi-objective design problem. Through additive manufacturing of ceramic-polymer composites, microwave metamaterials, designed for the radio-frequency range of 8-12 GHz, are experimentally fabricated and devices with extreme dispersion profiles, an airfoil-shaped beam-steering device, and a broadband, broad-angle conformal carpet cloak, are demonstrated. It is anticipated that conformal volumetric metamaterials will lead to new classes of compact and multifunctional imaging, sensing, and communications systems.

Cytoprotective effect of Fridericia chica (Bonpl.) L.G. Lohmann extract associated with geranylgeraniol enriched-fraction from Bixa orellana L. on epithelial cells treated with bisphosphonate.

Bisphosphonates are drugs used to treat bone disorders. The chronic use of bisphosphonates is associated with the occurrence of medication-related osteonecrosis of the jaw (MRONJ). Previous data reported the positive effects of Geranylgeraniol on different cell types treated with Bisphosphonates. Foregoing work done by our research group demonstrated the wound healing capacity of Fridericia chica (Bonpl.) L.G.Lohmann standardized ethanol extract. Herein in vitro cytoprotective synergistic effect of the association of F. chica extract associated with an enriched geranylgeraniol fraction on keratinocytes exposed to zoledronic acid is reported. An association of F. chica at 1 and 5 µg/mL with geranylgeraniol at 15 µg/mL, increased cell viability by 73.5% and 71.1%, respectively. This treatment did not increase tumor cells viability; whereas the clonogenic potential assessment showed that, the association with F. chica (5 µg/mL) reversed the effects of zoledronic acid on the cells. This study provides data for a potential treatment for MRONJ.

Developmental Skills of Individuals with Angelman Syndrome Assessed Using the Bayley-III.

We describe the development of 236 children with Angelman syndrome (AS) using the Bayley Scales of Infant and Toddler Development, Third Edition. Multilevel linear mixed modeling approaches were used to explore differences between molecular subtypes and over time. Individuals with AS continue to make slow gains in development through at least age 12 years of age at about 1-2 months/year based on age equivalent score and 1-16 growth score points/year depending on molecular subtype and domain. Children with a deletion have lower scores at baseline and slower rate of gaining skills while children with UBE3A variant subtype demonstrated higher scores as well as greater rates of skill attainment in all domains. The developmental profiles of UPD and ImpD were similar.

Intermittent Soft-Tissue Tumor Enlargement in Episodic Angioedema With Eosinophilia Syndrome.

ABSTRACT: Episodic hypereosinophilia and angioedema syndrome, also known as Gleich syndrome, is a rare entity characterized by recurrent episodes of eosinophilia, angioedema, urticaria, fever and weight gain with spontaneous resolution. It is classified as an idiopathic hypereosinophilic syndrome. Unlike other hypereosinophilic syndromes, it has a low risk for internal organ damage. We report the case of a 42-year-old male with a 28-year history of recurrent erythematous wheals and plaques and persistent hypereosinophilia. Physical examination revealed a well-defined subcutaneous nodule on his right lower limb that increased in size with each episode of angioedema. Histopathology evidenced a lipoma with intense eosinophil infiltration within the mature adipose tissue, while the specimen of the wheal revealed scarce perivascular and interstitial eosinophilic inflammatory infiltrate. Diagnosis of episodic angioedema with eosinophilia syndrome was made based on clinical and laboratory findings.

Attention deficits in Brazilian health care workers with chronic pain.

The impact of COVID-19 on chronic pain (CP) in non-infected vulnerable South American subjects is unknown. Healthcare workers (HCWs) are at increased risk for CP. During the pandemic, many HCWs with CP kept working. Knowing how cognition is affected by CP in these subjects is an important subject for work safety. The attention domain has a pivotal role in cognition. Previously, the Continuous Visual Attention Test (CVAT) was applied to detect specific attention deficits in fibromyalgia patients. The present investigation described CP prevalence in non-infected Brazilian HCWs during the pandemic and assessed HCWs' attentional performance with the aid of the CVAT. This study was carried out at a reference University Hospital in Rio de Janeiro, Brazil. HCWs of both sexes, aged 20 or older, were interviewed from August to December 2020. A 90-second version of the CVAT was performed. The average reaction time to correct responses and the respective intraindividual reaction time variability for correct responses to target (VRT) was determined. Omission and commission errors were also calculated. Then, for each participant we calculated the Z-scores of the CVAT variables based on the distribution of CVAT performance of 211 healthy subjects (reference-comparison group). HCWs with Z-scores > 1.64 were classified as significantly impaired. From the 154 selected HCWs, 72 reported CP during the pandemic (prevalence = 47%). Post hoc ANCOVAs showed that the average correct VRT was significantly higher in the CP group than in the non-CP group (F = 4.99, df = 1/150, p = 0.027, η2 = 0.032). The percentage of participants with impaired VRT performance was 30% (n = 21) in the CP group and 16% (n = 13) in the non-CP group. The difference between these two propositions reached significance (χ2 = 3.96, df = 1, p = 0.047). As VRT is associated with the sustained-attention subdomain, our data suggest that this subdomain is disrupted in the CP group.

Cytotoxicity, antinociceptive and gastroproiltective potential of the Abuta selloana Eichler: a fruit plant from Catarinense flora, Brazil.

This study evaluated some biological activities of extracts from Abuta selloana. The gastroprotective potential was determined against ethanol/HCl- and indomethacin-induced gastric ulcers, whereas the antinociceptive effect was evaluated by acetic acid-induced abdominal contortions in mice. The cytotoxicity activity was measured against human cancer cell lines: U251 (glioma), MCF-7 (breast cancer) and NCI-H460 (lung cancer). The radical scavenger potential was verified; and preliminary phytochemical analyses were performed. The phytochemical screening revealed higher levels of phenolic compounds in all extracts. Moreover, the methanolic extract from pulp fruit (MEPu), peel fruit (MEPe), branches (MEB) and leaves (MEL) scavenged the DPPH radical at 100 µg/mL. Besides, only MEL presented GI50 < 30 µg/mL in all tested cells. Besides, MEPu, MEPe, MEB or MEL at 10 mg/kg (i.p) reduced the abdominal contortions at 47.22%, 63.31%, 84.59% and 37.76%, respectively. The MEPu, MEPe, MEB and MEL reduced the ethanol/HCl- and indomethacin- induced ulcer at 250 mg/kg (p.o). In conclusion, A. selloana had interesting biological activities; presenting the leaves as a promising source for compounds with cytotoxic potential, however, further studies should be performed to confirm its antitumoral activity. Besides, the whole plant can be an important source of bioactive compounds associated with gastroprotective and antinociceptive properties.

Moisture content monitoring in industrial-scale composting systems using low-cost sensor-based machine learning techniques.

Moisture is a key aspect for proper composting, allowing greater efficiency and lower environmental impact. Low-cost real-time moisture determination methods are still a challenge in industrial composting processes. The aim of this study was to design a model of hardware and software that would allow self-adjustment of a low-cost capacitive moisture sensor. Samples of organic composts with distinct waste composition and from different composting stages were used. Machine learning techniques were applied for self-adjustment of the sensor. To validate the model, results obtained in a laboratory by the gravimetric method were used. The proposed model proved to be efficient and reliable in measuring moisture in compost, reaching a correlation coefficient of 0.9939 between the moisture content verified by gravimetric analysis and the prediction obtained by the Sensor Node.

Biosynthesis, Gene Expression, and Pharmacological Properties of Triterpenoids of Ganoderma Species (Agaricomycetes): A Review.

For more than 6 millennia, Ganoderma species have been used in traditional Asian medicine due to their health benefits. Ganoderma synthesizes several compounds with biological activity, including lanostane-type triterpenoids like ganoderic acids (GAs), lucidones, and colosolactones. These triterpenoids have been investigated for their antiviral, hypoglycemic, and anticancer effects. GAs are highly oxygenated triterpenoids with different functional groups attached to lanostane skeleton. Their great chemical diversity makes GAs prospects for the development of new drugs to treat multiple illnesses such as cancer. The effect of GAs against cancer cells has been associated with their capability to inhibit specific targets such as STAT3, to induce apoptosis and cell cycle blockage, and to increase natural killer cell activity. Due to the biological activity of these molecules, novel strategies are being developed for Ganoderma production mainly by liquid cultivation, gene overexpression (HMGR, SQS, LS) by elicitors, and modified growing conditions (carbon and nitrogen sources, pH, temperature), which induce reactive oxygen species production, key compounds for secondary metabolism. In addition, some transcription factors are mainly expressed under stress conditions, such as cytochrome P450 genes, which participate in the regulation of triterpenoid synthesis. The fermentation process has been scaled up to a 300-L bioreactor, which shows good GA production. This article reviews current knowledge on bioactive triterpenoids of Ganoderma and their production, biosynthesis, and pharmacological properties, emphasizing gene expression in liquid culture. It also discusses the lack of information regarding other species with high potential.