Dosage of botulinum toxin in patients undergoing treatment for hemifacial spasm: is there modification during follow-up?

Background:  The movement disorder known as hemifacial spasm is characterized by involuntary contractions of the muscles that are innervated by the facial nerve. The treatment of choice for this condition is botulinum toxin injections.

Objective:  To analyze the botulinum toxin dosage in patients undergoing treatment for hemifacial spasm during a 14-year period.

MoA Studies of the TEAD P-Site Binding Ligand MSC-4106 and Its Optimization to TEAD1-Selective Amide M3686.

Taking the structural information into account, we were able to tune the TEAD selectivity for a specific chemotype. However, different TEAD selectivity profiles did not affect the compound potency or efficacy in the NCI-H226 viability assay. Amides based on or analogues showed improved viability efficacy compared with the corresponding acids.

Coaxial Helices in Chiral Supramolecular Aggregates from Highly Hindered Chiral Allenes.

Chiral allenes self-assembly following a cooperative mechanism into a supramolecular chiral aggregate consisting of two coaxial helices: the internal helix described by the allene stack and the external helix which consist in a 4-helix described by the four allene substituents. More precisely, this supramolecular aggregate possesses six axially chiral elements within its structure-the allene, the allene stack (internal helix) and the stacks of the four allene substituents (external 4-helix)-. Interestingly, slight variations in the magnitude of the tilting degree while keeping its P- or M- orientation (internal helix) can vary the orientation of the 4-axial motifs at the external helix.

SMARTER-database: a tool to integrate SNP array datasets for sheep and goat breeds.

Unlabelled: Underutilized sheep and goat breeds can adapt to challenging environments due to their genetics. Integrating publicly available genomic datasets with new data will facilitate genetic diversity analyses; however, this process is complicated by data discrepancies, such as outdated assembly versions or different data formats. Here, we present the SMARTER-database, a collection of tools and scripts to standardize genomic data and metadata, mainly from SNP chip arrays on global small ruminant populations, with a focus on reproducibility.

Optical and Chiroptical Stimuli-Responsive Chiral AgNPs@H-Leu-Poly(phenylacetylene) Nanocomposites in Water.

Dynamic macroscopically chiral nanocomposites are prepared by combining silver nanoparticles (AgNPs) and dynamic helical poly(phenylacetylene)s (PPAs) bearing pendants functionalized with amino groups. These amino groups provide the nanocomposite with the ability to disperse in water along with high stability due to the interaction between the ammonium group and the AgNP. Moreover, the equilibrium between NH/NH produces a "blinking" contact between the PPA and the AgNPs, which allows total control of the dynamic helical behavior of the polymer.

Discovery of reversible and covalent TEAD 1 selective inhibitors MSC-1254 and MSC-5046 based on one scaffold.

The Transcriptional Enhanced Associated Domain (TEAD) family of transcription factors are key components of the Hippo signalling family which play a crucial role in the regulation of cell proliferation, differentiation and apoptosis. The identification of inhibitors of the TEAD transcription factors are an attractive strategy for the development of novel anticancer therapies. A HTS campaign identified hit 1, which was optimised using structure-based drug design, to deliver potent TEAD1 selective inhibitors with both a reversible and covalent mode of inhibition.

Ulva lactuca blooms through the eyes of fishers: Threats to vulnerable coastal communities.

Eutrophication intensifies Harmful Macroalgae Blooms (HMBs) in coastal environments, reducing habitat suitability for organisms and creating significant challenges for small-scale artisanal fishers. Leveraging fishers' memories, we analyzed over 20 years of data on Ulva lactuca blooms and their effects on fishing activities and fish resources in a tropical semi-arid region of Brazil. We estimated the timing, seasonality, and impacts of these bloom episodes on fish catches, fishing gears, and fishery revenues.

Toward the apoplast metabolome: Establishing a leaf apoplast collection approach suitable for metabolomics analysis.

The leaf apoplast contains several compounds that play important roles in the regulation of different physiological processes in plants. However, this compartment has been neglected in several experimental and modelling studies, which is mostly associated to the difficulty to collect apoplast washing fluid (AWF) in sufficient amount for metabolomics analysis and as free as possible from symplastic contamination. Here, we established an approach based in an infiltration-centrifugation technique that use little leaf material but allows sufficient AWF collection for gas chromatography mass spectrometry (GC-MS)-based metabolomics analysis in both tobacco and Arabidopsis.

Effects of a 217-km mountain ultramarathon on the gut microbiota of an obese runner: A case report.

Obesity is characterized by specific changes in the composition of the gut microbiota (GM). Exercise can contribute to the modulation of GM. This is the first case study to analyze the composition and metabolism of the GM of an obese runner in a single-stage mountain ultramarathon (MUM) with a mileage of 217 km.

Structural insights of an LCP protein-LytR-from through biophysical and methods.

The rise of antibiotic-resistant bacterial strains has become a critical health concern. According to the World Health Organization, the market introduction of new antibiotics is alarmingly sparse, underscoring the need for novel therapeutic targets. The LytR-CpsA-Psr (LCP) family of proteins, which facilitate the insertion of cell wall glycopolymers (CWGPs) like teichoic acids into peptidoglycan, has emerged as a promising target for antibiotic development.

Identifying selection strategies based on the practices and preferences of small ruminant farmers to improve the sustainability of their breeding systems.

Small ruminant farming is of socio-economic and environmental importance to many rural communities around the world. The SMARTER H2020 project aims to redefine genetic selection criteria to increase the sustainability of the sector. The objective of this study was to analyse the selection and breeding management practices of small ruminant producers and breeders, linked with socio-technical elements that shape them.

Estimation and probabilistic projection of age- and sex-specific mortality rates across Brazilian municipalities between 2010 and 2030.

Background: Mortality rate estimation in small areas can be difficult due the low number of events/exposure (i.e. stochastic error).

Size Control of Chiral Nanospheres Obtained via Nanoprecipitation of Helical Poly(phenylacetylene)s in the Absence of Surfactants.

Nanostructuration of dynamic helical polymers such as poly(phenylacetylene)s (PPAs) depends on the secondary structure adopted by the polymer and the functional group used to connect the chiral pendant to the PPA backbone. Thus, while PPAs with dynamic and flexible scaffolds (para- and meta-substituted, ω<165°) generate by nanoprecipitation low polydisperse nanospheres with controllable size at different acetone/water mixtures, those with a quasi-static behavior and the presence of an extended, almost planar structure (ortho-substituted, ω>165°), aggregate into a mixture of spherical and oval nanostructures whose size is not controlled. Photostability studies show that poly(phenylacetylene) particles are more stable to light irradiation than when dissolved macromolecularly.

Central and mixed apneas in children with obstructive sleep apnea: effect of adenotonsillectomy.

Purpose: Investigate the effect of adenotonsillectomy on mixed apnea index (MAI) and central apnea index (CAI) in children with moderate-to-severe obstructive sleep apnea syndrome (OSAS).

Methods: Observational retrospective analysis of polysomnographic data in children diagnosed with moderate-to-severe OSAS and without comorbidity, submitted to adenotonsillectomy.

Results: Data were available for 80 children, 55 boys and 25 girls, with a median age of 3.

Metallo-Supramolecular Helical Fibres from Chiral Phenylacetylene Monomers: Cation Induced Self-Assembly.

Chiral metallo-supramolecular fibres can be easily obtained by mixing a chloroform solution of a phenylacetylene monomer (PA) that bears a chiral sulfoxide group as pendant, with different equivalents of a methanolic solution of AgClO . Thus, while the PA is found molecularly dissolved in chloroform, the addition of Ag ions induce its aggregation through the formation of an axially chiral metallo-supramolecular aggregate with high thermal stable properties. In this case, the ability of the metal ion to coordinate the PA triple bond, combined with the argentophilicity of the metal ion and the planarity of the phenylacetylene drives to the formation of a helical coordination polymer, whose P or M axial chirality is determined by the chirality of the sulfoxide used as substituent of the PA.

Macromolecular Switch Based on Conformational Control Exerted by an Achiral Side Chain within an Axially Chiral Locked Pendant.

Molecular switches, supramolecular chemistry, and polymers can be combined to create stimuli-responsive multichiral materials. Therefore, by acting on the extended/bent conformational composition of an achiral arm, it is possible to create a macromolecular gear, where different supramolecular interactions can be activated/deactivated to control the helical sense of a polymer containing up to five different chiral axial motifs. For this, a chiral allene with a flexible achiral arm was introduced as a pendant in poly(phenylacetylene).

Stimuli-responsive synthetic helical polymers.

Synthetic dynamic helical polymers (supramolecular and covalent) and foldamers share the helix as a structural motif. Although the materials are different, these systems also share many structural properties, such as helix induction or conformational communication mechanisms. The introduction of stimuli responsive building blocks or monomer repeating units in these materials triggers conformational or structural changes, due to the presence/absence of the external stimulus, which are transmitted to the helix resulting in different effects, such as assymetry amplification, helix inversion or even changes in the helical scaffold (elongation, J/H helical aggregates).

Life cycle assessment of pharmaceutical packaging addressing end-of-life alternatives.

Pharmaceutical packaging waste has increased due to a higher global demand for pharmaceutical products, leading to more waste generation and associated environmental impacts. The main goal of this article is to present a cradle-to-grave life cycle assessment of pharmaceutical packaging, evaluating end-of-life (EoL) alternatives, aiming to identify hotspots and opportunities for improvement. A life cycle model was implemented for three types of pharmaceutical packaging (blisters, sachets, bottles; 23 packaging).

Biomass and carbon balance in a dry tropical forest area in northeast Brazil.

Forest ecosystems play an important role in mitigating the concentration increase of carbon dioxide (CO2) in the atmosphere through carbon sequestration by plants and its storage in biomass and soil. The objective was to determine the aerial biomass carbon stock in a dry tropical forest in Brazil. It was developed between 2012 to 2015, in an area with an advanced regeneration stage (50 years) in the semi-arid region of Pernambuco and it was used 40 permanent plots (400 m²) distant 80 m apart, with 50 m from the border, totaling 1.

Extract2Chip-Bypassing Protein Purification in Drug Discovery Using Surface Plasmon Resonance.

Modern drug discovery relies on combinatorial screening campaigns to find drug molecules targeting specific disease-associated proteins. The success of such campaigns often relies on functional and structural information of the selected therapeutic target, only achievable once its purification is mastered. With the aim of bypassing the protein purification process to gain insights on the druggability, ligand binding, and/or characterization of protein-protein interactions, herein, we describe the Extract2Chip method.

RETINAL DEPOSITS OF TRIAMCINOLONE-MOXIFLOXACIN AFTER DROPLESS CATARACT SURGERY.

Purpose: To report a case of epiretinal crystalline deposits observed on fundus examination and optical coherence tomography 2 years after transzonular intravitreal injection of triamcinolone-moxifloxacin (TriMoxi) during "dropless" cataract surgery.

Methods: Observational case report with literature review of toxic effects of intravitreal triamcinolone and differential diagnosis of retinal crystalline deposits.

Results: A 37-year-old asymptomatic pseudophakic man presented with refractile crystalline retinal deposits that had prompted an extensive systemic embolic workup.

Single-Layer Graphene/Germanium Interface Representing a Schottky Junction Studied by Photoelectron Spectroscopy.

We investigated the interfacial electronic structure of the bidimensional interface of single-layer graphene on a germanium substrate. The procedure followed a well-established approach using ultraviolet (UPS) and X-ray (XPS) photoelectron spectroscopy. The direct synthesis of the single-layer graphene on the surface of (110) undoped Ge substrates was conducted via chemical vapor deposition (CVD).

Unveiling the dark side of guard cell metabolism.

Evidence suggests that guard cells have higher rate of phosphoenolpyruvate carboxylase (PEPc)-mediated dark CO assimilation than mesophyll cells. However, it is unknown which metabolic pathways are activated following dark CO assimilation in guard cells. Furthermore, it remains unclear how the metabolic fluxes throughout the tricarboxylic acid (TCA) cycle and associated pathways are regulated in illuminated guard cells.