Experimental and computational evidence for a stabilising C–Cl(lone-pair)⋯π(chelate-ring) interaction

In addition to a variety of conventional non-covalent intermolecular interactions such as C–H…π(arene), C–H…Cl and π(arene)…π(chelate-ring) contacts, the molecular packing in the crystal of an organotin dithiocarbamate compound, [SnCl(4-ClC6H4)2{S2CN(i-Pr)2}], exhibits evidence for a C–Cl…π(chelate-ring) interaction. These interactions occur via a side-on approach of the chloride atom to the chelate-ring and therefore, are characterised as C–Cl(lone pair)…π(chelate-ring) interactions, are shown to be attractive by NCI plots and QTAIM analysis, and are apparent in the calculated Hirshfeld surfaces. Theory suggests the energy of association provided the C–Cl…π(chelate-ring) interactions to be about 3-4 kcal/mol, a value greater than for analogous C–Cl…π(arene) and C–H…π(arene) interactions. A survey of the literature of related structures suggests these interactions are not common. The newly described C–Cl(lone-pair)…π(chelate-ring) interactions add to the variety of intermolecular interactions able to be formed by chelate-rings in the supramolecular chemistry of metal complexes

Side chain variations radically alter the diffusion of poly(2-alkyl-2-oxazoline) functionalised nanoparticles through a mucosal barrier

Functionalised nanomaterials are gaining popularity for use as drug delivery vehicles and, in particular, mucus penetrating nanoparticles may improve drug bioavailability via the oral route. To date, few polymers have been investigated for their muco-penetration, and the effects of systematic structural changes to polymer architectures on the penetration and diffusion of functionalised nanomaterials through mucosal tissue have not been reported. We investigated the influence of poly(2-oxazoline) alkyl side chain length on nanoparticle diffusion; poly(2-methyl-2-oxazoline), poly(2-ethyl-2-oxazoline), and poly(2-n-propyl-2-oxazoline) were grafted onto the surface of thiolated silica nanoparticles and characterised by FT-IR, Raman and NMR spectroscopy, thermogravimetric analysis, and small angle neutron scattering. Diffusion coefficients were determined in water and in a mucin dispersion (using Nanoparticle Tracking Analysis), and penetration through a mucosal barrier was assessed using an ex vivo fluorescence technique. The addition of a single methylene group in the side chain significantly altered the penetration and diffusion of the materials in both mucin dispersions and mucosal tissue. Nanoparticles functionalised with poly(2-methyl-2-oxazoline) were significantly more diffusive than particles with poly(2-ethyl-2-oxazoline) while particles with poly(2-n-propyl-2-oxazoline) showed no significant increase compared to the unfunctionalised particles. These data show that variations in the polymer structure can radically alter their diffusive properties with clear implications for the future design of mucus penetrating systems

Benzotiazoles sustituidos y sus aplicaciones terapéuticas para el tratamiento de enfermedades humanas

La presente invención se refiere a una familia de benzotialoles diferentemente sustituidos que presentan actividad inhibitoria de la enzima caseína quinasa 1 (CK-1), por lo que son útiles para el tratamiento o prevención de enfermedades mediadas por esta enzima, especialmente, enfermedades relacionadas con el ritmo circadiano, enfermedades inflamatorias, autoinmunes, psiquiátricas, neurodegenerativas, neurológicas, oftalmológicas, así como para inducir regeneración celularPeer reviewedConsejo Superior de Investigaciones CientíficasB1 Patente sin examen previ

Project INTEGRATE: An Integrative Study of Brief Alcohol Interventions for College Students

This paper provides an overview of a study that synthesizes multiple, independently collected alcohol intervention studies for college students into a single, multisite longitudinal data set. This research embraced innovative analytic strategies (i.e., integrative data analysis or meta-analysis using individual participant-level data), with the overall goal of answering research questions that are difficult to address in individual studies such as moderation analysis, while providing a built-in replication for the reported efficacy of brief motivational interventions for college students. Data were pooled across 24 intervention studies, of which 21 included a comparison or control condition and all included one or more treatment conditions. This yielded a sample of 12,630 participants (42% men; 58% first-year or incoming students). The majority of the sample identified as White (74%), with 12% Asian, 7% Hispanic, 2% Black, and 5% other/mixed ethnic groups. Participants were assessed two or more times from baseline up to 12 months, with varying assessment schedules across studies. This paper describes how we combined individual participant-level data from multiple studies, and discusses the steps taken to develop commensurate measures across studies via harmonization and newly developed Markov chain Monte Carlo algorithms for two-parameter logistic item response theory models and a generalized partial credit model. This innovative approach has intriguing promises, but significant barriers exist. To lower the barriers, there is a need to increase overlap in measures and timing of follow-up assessments across studies, better define treatment and control groups, and improve transparency and documentation in future single, intervention studies

Combined spinal-epidural anesthesia for cesarean section in a patient with Moyamoya disease -A case report-

Moyamoya disease is a rare progressive occlusive disease of the internal carotid arteries. We report a case of combined spinal-epidural anesthesia in a patient with Moyamoya disease presenting for Cesarean section. Hypotension associated with spinal anesthesia for Cesarean section is the most common and serious adverse effect despite the use of uterine displacement and volume preload. We continuously infused phenylephrine and ephedrine to prevent hypotension. The intraoperative hemodynamic state was stable. The patient had no significant postoperative complications

A Phase 2a cohort expansion study to assess the safety, tolerability, and preliminary efficacy of CXD101 in patients with advanced solid-organ cancer expressing HR23B or lymphoma.

BACKGROUND: This Phase 2a dose expansion study was performed to assess the safety, tolerability and preliminary efficacy of the maximum tolerated dose of the oral histone de-acetylase (HDAC) inhibitor CXD101 in patients with relapsed / refractory lymphoma or advanced solid organ cancers and to assess HR23B protein expression by immunohistochemistry as a biomarker of HDAC inhibitor sensitivity. METHODS: Patients with advanced solid-organ cancers with high HR23B expression or lymphomas received CXD101 at the recommended phase 2 dose (RP2D). Key exclusions: corrected QT > 450 ms, neutrophils  1. Baseline HR23B expression was assessed by immunohistochemistry. RESULTS: Fifty-one patients enrolled between March 2014 and September 2019, 47 received CXD101 (19 solid-organ cancer, 28 lymphoma). Thirty-four patients received ≥80% RP2D. Baseline characteristics: median age 57.4 years, median prior lines 3, male sex 57%. The most common grade 3-4 adverse events were neutropenia (32%), thrombocytopenia (17%), anaemia (13%), and fatigue (9%) with no deaths on CXD101. No responses were seen in solid-organ cancers, with disease stabilisation in 36% or patients; the overall response rate in lymphoma was 17% with disease stabilisation in 52% of patients. Median progression-free survival was 1.2 months (95% confidence interval (CI) 1.2-5.4) in solid-organ cancers and 2.6 months (95%CI 1.2-5.6) in lymphomas. HR23B status did not predict response. CONCLUSIONS: CXD101 showed acceptable tolerability with efficacy seen in Hodgkin lymphoma, T-cell lymphoma and follicular lymphoma. Further studies assessing combination approaches are warranted. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT01977638 . Registered 07 November 2013

FingerTac - A Wearable Tactile Thimble for Mobile Haptic Augmented Reality Applications

ingerTac is a novel concept for a wearable augmented haptic thimble. It makes use of the limited spatial discrimination capabilities of vibrotactile stimuli at the skin and generates tactile feedback perceived at the bottom center of a fingertip by applying simultaneous vibrations at both sides of the finger. Since the bottom of the finger is thus kept free of obstruction, the device is well promising for augmented haptic applications, where real world interactions need to be enriched or amalgamated with virtual tactile feedback. To minimize its lateral dimension, the vibration actuators are placed on top of the device, and mechanical links transmit the vibrations to the skin. Two evaluation studies with N=10 participants investigate (i) the loss of vibration intensity through these mechanical links, and (ii) the effect of lateral displacement between stimulus and induced vibration. The results of both studies support the introduced concept of the FingerTac

A review on natural based deep eutectic solvents (NADESs): fundamentals and potential applications in removing heavy metals from soil

Natural based deep eutectic solvent (NADES) is a promising green solvent to replace the conventional soil washing solvent due to the environmental benign properties such as low toxicity, high biodegradability, high polarity or hydrophilicity, and low cost of fabrication process. The application of NADES is intensively studied in the extraction of organic compounds or natural products from vegetations or organic matters. Conversely, the use of the solvent in removing heavy metals from soil is severely lacking. This review focuses on the potential application of NADES as a soil washing agent to remove heavy metal contaminants. Hydrophilicity is an important feature of a NADES to be used as a soil washing solvent. In this context, choline chloride is often used as hydrogen bond acceptor (HBA) whereby choline chloride based NADESs showed excellent performance in the extraction of various solutes in the past studies. The nature of NADES along with its chemistry, preparation and designing methods as well as potential applications were comprehensively reviewed. Subsequently, related studies on choline chloride-based NADES in heavy metal polluted soil remediation were also reviewed. Potential applications in removing other soil contaminants as well as the limitations of NADES were discussed based on the current advancements of soil washing and future research directions were also proposed

Thermoresponsive UCST-Type Behavior of Interpolymer Complexes of Poly(ethylene glycol) and Poly(poly(ethylene glycol) methacrylate) Brushes with Poly(acrylic acid) in Isopropanol

Upper critical solution temperature (UCST)-type thermoresponsive behavior of poly(ethylene glycol)-poly(acrylic acid) (PEG-PAA) and poly(poly(ethylene glycol) methacrylate)-poly(acrylic acid) (PPEGMA-PAA) interpolymer complexes has been observed in isopropanol. For these investigations, PPEGMA and PAA with various average molecular weights have been synthesized by atom transfer radical polymerization. It has been found that both the PEG and PPEGMA have lower cloud point temperatures (Tcp) than its mixed polymer solutions with PAA, whereas PAA does not show such behavior in the investigated temperature range. These findings indicate the reversible formation of interpolymer complexes with variable structure and composition in the solutions of the polymer mixtures in isopropanol. Increasing the ethylene glycol/acrylic acid molar ratio or the molecular weight of either the PAA or the H-acceptor PEG component of the interpolymer complexes increases the UCST-type cloud point temperatures of these interpolymer systems. The polymer-polymer interactions by hydrogen bonds between PAA and PEG or PPEGMA and the correlations between Tcp and structural parameters of the components revealed in the course of these investigations may be utilized for exploring well-defined UCST-type material systems for various applications. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Biology of advanced uveal melanoma and next steps for clinical therapeutics.

Uveal melanoma is the most common intraocular malignancy although it is a rare subset of all melanomas. Uveal melanoma has distinct biology relative to cutaneous melanoma, with widely divergent patient outcomes. Patients diagnosed with a primary uveal melanoma can be stratified for risk of metastasis by cytogenetics or gene expression profiling, with approximately half of patients developing metastatic disease, predominately hepatic in location, over a 15-yr period. Historically, no systemic therapy has been associated with a clear clinical benefit for patients with advanced disease, and median survival remains poor. Here, as a joint effort between the Melanoma Research Foundation\u27s ocular melanoma initiative, CURE OM and the National Cancer Institute, the current understanding of the molecular and immunobiology of uveal melanoma is reviewed, and on-going laboratory research into the disease is highlighted. Finally, recent investigations relevant to clinical management via targeted and immunotherapies are reviewed, and next steps in the development of clinical therapeutics are discussed