Combined Physiotherapy and Cognitive Behavioral Therapy for Functional Movement Disorders: A Randomized Clinical Trial.

Importance: Functional movement disorders (FMDs) are frequent and disabling neurological disorders with a substantial socioeconomic impact. Few randomized studies have analyzed the effectiveness of combined physiotherapy and psychotherapy in patients' quality of life. Objective: To assess the efficacy of multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) in FMDs. Design, Setting, and Participants: This was a parallel, rater-blinded, single-center, randomized clinical trial. Recruitment took place from June 2022 to April 2023, and follow-up visits were performed at months 3 and 5, concluding in October 2023. Participants were recruited from a national referral center for movement disorders: the Movement Disorders Unit from the Hospital Universitario Virgen Rocio in Seville, Spain. Patients had to be 18 years or older with a confirmed FMD diagnosis and capable of giving consent to participate. Patients who did not meet eligibility criteria or refused to participate were excluded. Any uncontrolled psychiatric disorder was considered an exclusion criterion. Interventions: Patients were randomly assigned, in a ratio of 1:1 to multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy), or a control intervention (psychological support intervention). Main Outcomes and Measures: Primary outcomes: between-group differences in changes from baseline to month 3 and month 5 in patients' quality of life (EQ-5D-5L score: EQ Index and EQ visual analog scale [EQ VAS]; and 36-Item Short-Form Survey Physical Component Summary [SF-36 PCS] and SF-36 Mental Component Summary [MCS]). Linear mixed models were applied, controlling by baseline severity and applying Bonferroni correction. Results: Of 70 patients screened with an FMD, 40 were enrolled (mean [SD] age, 43.5 [12.8] years; age range, 18-66 years; 32 female [80%]; mean [SD] age at FMD onset, 38.4 [12.1] years), and 38 completed all the follow-up visits and were included in the analysis for primary outcomes. Multidisciplinary treatment improved SF-36 PCS with a mean between-group difference at 3 months of 4.23 points (95% CI, -0.9 to 9.4 points; P = .11) and a significant mean between-group difference at 5 months of 5.62 points (95% CI, 2.3-8.9 points; P < .001), after multiple-comparisons adjustment. There were no significant differences in other quality-of-life outcomes such as SF-36 MCS (mean between-group difference at 3 and 5 months: 0.72 points; 95% CI, -5.5 to 7.0 points; P = .82 and 0.69 points; 95% CI, 2.3-8.9 points; P = .83, respectively), EQ VAS (9.34 points; 95% CI, -0.6 to 19.3 points; P = .07 and 13.7 points; 95% CI, -1.7 to 29.0 points; P = .09, respectively) and EQ Index (0.001 point; 95% CI, -0.1 to 0.1 point; P = .98 and 0.08 points; 95% CI, 0-0.2 points; P = .13, respectively). At months 3 and 5, 42% and 47% of patients, respectively, in the multidisciplinary group reported improved health using the EQ-5D system, compared with 26% and 16% of patients, respectively, in the control group. Conclusions and Relevance: Results show that multidisciplinary treatment (physiotherapy plus cognitive behavioral therapy) effectively improves FMD symptoms and physical aspects of patients' quality of life. Further studies must be performed to evaluate the potential cost-effectiveness of this approach in FMD. Trial Registration: ClinicalTrials.gov Identifier: NCT05634486.

Impact of universal use of a hyperangulated videolaryngoscope as the first option for all intubations in the ICU: A prospective before-after study.

BACKGROUND: Tracheal intubation in ICU is associated with high incidence of difficult intubations. The study aimed to investigate whether the "universal" use of a hyperangulated videolaryngoscope would increase the frequency of "easy intubation" in ICU patients compared to direct laryngoscopy. METHODS: A prospective before-after study was conducted. The pre-interventional period (36 months) involved tracheal intubations using direct laryngoscopy as the first intubation option. In the interventional period (18 months) a hyperangulated videolaryngoscope was the first intubation option. The primary outcome was the percentage of patients with "easy intubation" defined as intubation on the first attempt and easy laryngoscopy (modified Cormack-Lehane glottic view of I-IIa). Secondary outcomes included difficult laryngoscopy, operator technical difficulty, and complications. RESULTS: We enrolled 407 patients, 273 in non-interventional period, and 134 in interventional period. Tracheal intubation in the interventional period was associated with higher incidence of "easy intubation" (92.5%) compared with the non-interventional period (75.8%); P < 0.001)). Glottic visualization improved in the interventional period, with a reduced incidence of difficult laryngoscopy (1.5% vs. 22.5%; P < 0.001). The proportion of first-success rate intubation was 92.5% in the interventional period, and 87.8% in the non-interventional period (P = 0.147). Moderate and severe technical difficulty of intubation reported decreased in the interventional period (6% vs. 17.6%; P < 0.001). There was no significant difference between both periods in the incidence of complications. CONCLUSION: "Universal" use of hyperangulated videolaryngoscopy for tracheal intubation in patients admitted in ICU improves the percentage of easy intubation compared to direct laryngoscopy.

Electronically and geometrically complementary perylenediimides for kinetically controlled supramolecular copolymers.

The synthesis of 3,4,9,10-benzo[d,e]isoquinolino[1,8-g,h]quinoline-tetracarboxylic diimide (BQQDI) 1 endowed with peripheral trialkoxybenzamide fragments is reported and its self-assembling features investigated. The peripheral benzamide moieties generate metastable monomeric species that afford a kinetically controlled supramolecular polymerization. The electron-withdrawing character of 1 in comparison with previously reported PDIs 2, together with the similar geometry, makes this dye an optimal candidate to perform seeded supramolecular copolymerization yielding four different supramolecular block copolymers. Whilst heteropolymers poly-1-co-2a, poly-2a-co-1 and poly-1-co-2b present an H-type arrangement of the monomeric units, heteropolymer poly-2b-co-1, prepared by seeding the chiral, metastable monomers of 2b with achiral seeds of 1, produces chiral, J-type aggregates. Interestingly, the monosignated CD signal of pristine poly-2b changes to a bisignated CD signal most probably due to the formation of columnar domains around the seeds of 1 which implies the blocky nature of the supramolecular copolymers formed.

Chiral supramolecular polymers.

As an active branch within the field of supramolecular polymers, chiral supramolecular polymers (SPs) are an excellent benchmark to generate helical structures that can clarify the origin of homochirality in Nature or help determine new exciting functionalities of organic materials. Herein, we highlight the most utilized strategies to build up chiral SPs by using chiral monomeric units or external stimuli. Selected examples of transfer of asymmetry, in which the point or axial chirality contained by the monomeric units is efficiently transferred to the supramolecular scaffold yielding enantioenriched helical structures, will be presented. The importance of the thermodynamics and kinetics associated with those processes is stressed, especially the influence that parameters such as the helix reversal and mismatch penalties exert on the achievement of amplification of asymmetry in co-assembled systems will also be considered. Remarkable examples of breaking symmetry, in which chiral supramolecular polymers can be attained from achiral self-assembling units by applying external stimuli like stirring, solvent or light, are highlighted. Finally, the specific and promising applications of chiral supramolecular polymers are presented with recent relevant examples.

Supramolecular Block Copolymers from Tricarboxamides. Biasing Co-assembly by the Incorporation of Pyridine Rings.

The synthesis of a series of triangular-shaped tricarboxamides endowed with three picoline or nicotine units (compounds 2 and 3, respectively) or just one nicotine unit (compound 4) is reported, and their self-assembling features investigated. The pyridine rings make compounds 2-4 electronically complementary with our previously reported oligo(phenylene ethynylene)tricarboxamides (OPE-TA) 1 to form supramolecular copolymers. C3 -symmetric tricarboxamide 2 forms highly stable intramolecular five-membered pseudocycles that impede its supramolecular polymerization into poly-2 and the co-assembly with 1 to yield copolymer poly-1-co-2. On the other hand, C3 -symmetric tricarboxamide 3 readily forms poly-3 with great stability but unable to form helical supramolecular polymers despite the presence of the peripheral chiral side chains. The copolymer poly-1-co-3 can only be obtained by a previous complete disassembly of the constitutive homopolymers in CHCl3 . Helical poly-1-co-3 arises in a process involving the transfer of the helicity from racemic poly-1 to poly-3, and the amplification of asymmetry from chiral poly-3 to poly-1. Importantly, C2v -symmetric 4, endowed with only one nicotinamide moiety and three chiral side chains, self-assembles into a P-type helical supramolecular polymer (poly-4) in a thermodynamically controlled cooperative process. The combination of poly-1 and poly-4 generates chiral supramolecular copolymer poly-1-co-4, whose blocky microstructure has been investigated by applying the previously reported supramolecular copolymerization model.

Silver nanoparticles and silver ions indistinguishably decrease sperm motility in Pacific oysters (Magallana gigas) after short-term direct exposure.

The present study aimed to evaluate the reprotoxicity of environmental (0.25 µg.L-1) and supra-environmental (25 µg.L-1 and 250 µg.L-1) levels of silver nanoparticles (Ag NP) on the Pacific oyster (Magallana gigas), by determining sperm quality. For that, we evaluated sperm motility, mitochondrial function and oxidative stress. To determine whether the Ag toxicity was related to the NP or its dissociation into Ag ions (Ag+), we tested the same concentrations of Ag+. We observed no dose-dependent responses for Ag NP and Ag+, and both impaired sperm motility indistinctly without affecting mitochondrial function or inducing membrane damage. We hypothesize that the toxicity of Ag NP is mainly due to adhesion to the sperm membrane. Blockade of membrane ion channels may also be a mechanism by which Ag NP and Ag+ induce toxicity. The presence of Ag in the marine ecosystem is of environmental concern as it may affect reproduction in oysters.

Effects from the Freezing of Either Whole or Crushed Grapes on the Volatile Compounds Contents in Muscat Wines.

The transfer of aromatic compounds from the grape skins to the musts has been studied using a process involving freezing whole bunches or crushed grapes for winemaking the Muscat of Alexandria variety (white wine). Subsequently, a prefermentative maceration has been applied to some of the samples. The aromatic profiles of the final wines have been determined using gas chromatography coupled to mass spectrophotometry (GC-MS). The results revealed that, in the trials in which whole grapes were frozen, the final wines had a higher aromatic concentration compared to that of wines obtained by either freezing crushed grapes or obtained with traditional winemaking techniques. Thus, the wines produced from frozen whole grapes were found to exhibit different characteristics from the rest of the wines. The compounds affected by the freezing either of the whole bunches or the crushed grapes were terpenes, acids, and esters. Lower differences were found for wines produced applying prefermentative maceration after the freezing process.

Changes in the Aromatic Compounds Content in the Muscat Wines as a Result of the Application of Ultrasound during Pre-Fermentative Maceration.

This research focuses on the aromatic composition of Muscat of Alexandria wines after the application of ultrasound for 40 or 80 min during a 4 h pre-fermentative maceration process. Two methods of ultrasound application were compared in this study: probe ultrasound and bath ultrasound, for periods of 10-20 min per hour. Increases of more than 200% were obtained for some of the compounds from the skins, such as two of its terpenes, citronellol and nerol. On the other hand, increases in alcohol and ester values were registered with the application of ultrasound for 40 min. However, a significant decrease in these compounds was recorded when the ultrasound process was extended. In fact, when ultrasound was applied for 80 min, content values were even lower than those registered for the wine produced without the application of ultrasound. At the sensory level, the effect resulting from probe and bath ultrasound application for different times were compared, where most of the judges successfully discriminated the wines resulting from the application of ultrasound bath. According to data, the wines resulting from the application of ultrasound bath for 80 min presented the most significant differences, which affected the aromas of white fruit, tropical fruit, stone fruit, flowers and citrus.

From starphenes to non-benzenoid linear conjugated polymers by substrate templating.

Combining on-surface synthetic methods with the power of scanning tunneling microscopy to characterize novel materials at the single molecule level, we show how to steer the reactivity of one anthracene-based precursor towards different product nanostructures. Whereas using a Au(111) surface with three-fold symmetry results in the dominant formation of a starphene derivative, the two-fold symmetry of a reconstructed Au(110) surface allows the selective growth of non-benzenoid linear conjugated polymers. We further assess the electronic properties of each of the observed product structures via tunneling spectroscopy and DFT calculations, altogether advancing the synthesis and characterization of molecular structures of notable scientific interest that have been only scarcely investigated to date, as applies both to starphenes and to non-benzenoid conjugated polymers.

Dodecacene Generated on Surface: Reopening of the Energy Gap.

The acene series represents a model system to investigate the intriguing electronic properties of extended π-electron structures in the one-dimensional limit, which are important for applications in electronics and spintronics and for the fundamental understanding of electronic transport. Here, we present the on-surface generation of the longest acene obtained so far: dodecacene. Scanning tunneling spectroscopy gives access to the energy position and spatial distribution of its electronic states on the Au(111) surface. We observe that, after a progressive closing of the gap and a stabilization to about 1 eV at the length of decacene and undecacene, the energy gap of dodecacene unexpectedly increases to 1.4 eV. Considering the acene series as an exemplary general case, we discuss the evolution with length of the single tunneling resonances in comparison with ionization energy, electronic affinity, and optical gap.

Exploring a Route to Cyclic Acenes by On-Surface Synthesis.

A route to generate cyclacenes by on-surface synthesis is explored. We started by synthesizing two tetraepoxycyclacenes by sequences of Diels-Alder cycloadditions. Subsequently, these molecules were deposited onto Cu(111) and scanning-tunneling-microscopy(STM)-based atom manipulation was employed to dissociate the oxygen atoms. Atomic force microscopy (AFM) with CO-functionalized tips enabled the detailed characterization of the reaction products and revealed that, at most, two oxygens per molecule could be removed. Importantly, our experimental results suggest that the generation of cyclacenes by the described route might be possible for larger epoxycyclacenes.

Electronic Resonances and Gap Stabilization of Higher Acenes on a Gold Surface.

On-surface synthesis provides a powerful method for the generation of long acene molecules, making possible the detailed investigation of the electronic properties of single higher acenes on a surface. By means of scanning tunneling microscopy and spectroscopy combined with theoretical considerations, we discuss the polyradical character of the ground state of higher acenes as a function of the number of linearly fused benzene rings. We present energy and spatial mapping of the tunneling resonances of hexacene, heptacene, and decacene, and discuss the role of molecular orbitals in the observed tunneling conductance maps. We show that the energy gap between the first electronic tunneling resonances below and above the Fermi energy stabilizes to a finite value, determined by a first diradical electronic perturbative contribution to the polyacene electronic ground state. Up to decacene, the main contributor to the ground state of acenes remains the lowest-energy closed-shell electronic configuration.

Efficacy, acceptability and tolerability of Zelesse® for the treatment of non-specific vulvovaginitis in paediatric patients: The NINESSE Study.

Objective To evaluate the efficacy, tolerability and acceptability of Zelesse®, an intimate hygiene wash solution, in the relief of the symptoms and signs of non-specific vulvovaginitis in paediatric patients. Methods The NINESSE Study was a prospective, observational, multicentre study involving females aged 2-8 years who attended paediatric offices with symptoms suggestive of non-specific vulvovaginitis. They were administered Zelesse® as a single treatment for 15 ± 5 days. Pruritus, burning, dysuria, erythema, leucorrhoea and oedema were evaluated before and after treatment. Results A total of 71 paediatric patients were enrolled in the study (mean ± SD age, 4.5 ± 1.9 years). The most significant effects were observed for pruritus and burning, where 98.4% (62 of 63) and 96.9% (63 of 65) of the patients improved after treatment, respectively. Zelesse® demonstrated a beneficial effect on dysuria, erythema, leucorrhoea and oedema. The effects on the symptoms and signs were observed within the first week of treatment; although 44.9% (31 of 69) of patients experienced improvements after 2-3 days. Zelesse® was well accepted and tolerated by most patients. No serious adverse events were reported. Conclusions Zelesse® was very effective for the relief of the symptoms and signs of non-specific vulvovaginitis, in particular pruritus, burning and erythema, in females aged 2-8 years.

Decacene: On-Surface Generation.

Acenes are intriguing molecules with unique electronic properties. The difficulties in their preparation owing to low stability under ambient conditions are apparent because successful syntheses of long unsubstituted acenes are still scarce, in spite of the great attention they have attracted. Only unsubstituted acenes up to heptacene have been isolated in bulk, with nonacene being the largest acene detected to date. Herein we use on-surface assisted reduction of tetraepoxy decacene precursors on Au(111) as the key step to generate unprecedented decacene which is visualized and its electronic resonances studied by scanning tunneling microscopy (STM) and spectroscopy (STS).

Dynamic covalent polymers.

This Highlight presents an overview of the rapidly growing field of dynamic covalent polymers. This class of polymers combines intrinsic reversibility with the robustness of covalent bonds, thus enabling formation of mechanically stable, polymer-based materials that are responsive to external stimuli. It will be discussed how the inherent dynamic nature of the dynamic covalent bonds on the molecular level can be translated to the macroscopic level of the polymer, giving access to a range of applications, such as stimuli-responsive or self-healing materials. A primary distinction will be made based on the type of dynamic covalent bond employed, while a secondary distinction will be based on the consideration whether the dynamic covalent bond is used in the main chain of the polymer or whether it is used to allow side chain modification of the polymer. Emphasis will be on the chemistry of the dynamic covalent bonds present in the polymer, in particular in relation to how the specific (dynamic) features of the bond impart functionality to the polymer material, and to the conditions under which this dynamic behavior is manifested. © 2016 The Authors. Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2016, 54, 3551-3577.

Transfer and amplification of chirality in Phe-based C3-symmetric non-ionic amphiphiles.

The synthesis of amphiphiles and endowed with three l- or d-Phe units is reported. The chiral features provided by the Phe fragment are transferred to the supramolecular level to yield enantiomerically enriched helices. Additionally, we report herein the first example of amplification of chirality demonstrated by MR performed with supramolecular polymers showing very low degree of cooperativity.

Helical supramolecular polymerization of C3-symmetric amides and retroamides: on the origin of cooperativity and handedness.

The cooperative supramolecular polymerization of 1 and 2 yields P- or M-type helical aggregates depending on the absolute configuration (S or R) of the stereogenic centres attached to the side chains. The connectivity of the amide group does not affect the handedness of the helical aggregates, but determines a larger cooperativity for retroamides 1.

Multi-responsive coordination polymers utilising metal-stabilised, dynamic covalent imine bonds.

We report how the combination of dynamic covalent imine bonds and coordination bonds in a single polymer material not only imparts enhanced stability to the final polymer, but also allows the material to be sensitive to a range of stimuli, offering more fine-grained control over its properties.

Two Novel Nanosized Radiolabeled Analogues of Somatostatin for Neuroendocrine Tumor Imaging.

The somatostatin receptors (SR), which are overexpressed in a majority of neuroendocrine tumors, are targets for radiopeptide-based imaging using for example the 99mTc-Tyr3-Octreotide peptide. Dendrimers are hyperbranched polymeric structures. The nanoscopic size and near-monodisperse nature properties give polyamidoamine (PAMAM) dendrimers an edge over linear polymers in the context of drug delivery. Gold nanoparticles (AuNPs) conjugated to peptides produces stable multimeric systems with target-specific molecular recognition. The aim of this research was to prepare two nanosized multimeric systems for neuroendocrine tumor imaging, 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr-Octreotide, and to compare their in vitro uptake in SR-positive AR42J cancer cells as well as their biodistribution profile in athymic mice bearing AR42J tumors. [Tyr3, Lys(Boc)5]-Octreotide was conjugated to the carboxylate groups of the PAMAM dendrimer (G3.5) with further Boc deprotection using TFA. 99mTc labeling was carried out by a direct method. 99mTc-Tyr3-Octreotide was conjugated to AuNPs (20 nm) by spontaneous reaction with the thiol group of cysteine. Radiochemical purity (RP) was determined by size-exclusion HPLC and ITLC-SG analyses. In vitro binding studies were carried out in AR42J cancer cells. Biodistribution studies were accomplished in athymic mice with AR42J-induced tumors with blocked and unblocked receptors. Elemental analysis demonstrated that 26 Tyr3-Octreotide molecules were successfully conjugated to one molecule of PAMAM. RP for both nanosized conjugates was > 94% and showed recognition for SR in AR42J cells. The tissue distribution of radioactivity 2 h after 99mTc-PAMAM-Tyr3-Octreotide administration in mice showed specific tumor uptake (4.12 ± 0.57% of injected dose/g) and high accumulation in the pancreas (15.08 ± 3.11% of injected dose/g) which expresses SR. No significant difference in the tumor uptake was found between 99mTc-PAMAM-Tyr3-Octreotide and 99mTc-AuNP-Tyr3-Octreotide. However, the dendrimer-peptide conjugate showed a significant renal excretion. Both radiopharmaceuticals demonstrated properties suitable for use as target-specific agents for molecular imaging of tumors that overexpressed SR.