A Suzuki Coupling Based Route to 2,2'-Bis(2-indenyl)biphenyl Derivatives

Because of the promising performance in olefin polymerization of 2,2'-bis(2-indenyldiyl)biphenyl zirconium dichloride, we developed a new and broadly applicable route to 2,2'-bis(2-indenyl)biphenyl derivatives. Reaction of the known 2,2'-diiodobiphenyl with the new 2-indenyl boronic acid did not result in the desired 2,2'-bis(2-indenyl)biphenyl (10); instead an isomer thereof, (spiro-1,1-(2,2'-biphenyl)-2-(2-indenyl)indane), was obtained. It was found that compound 10 could be made via a palladium-catalyzed reaction of 2,2-biphenyldiboronic acid with 2-bromoindene under standard Suzuki reaction conditions. However, the yield of this reaction was low at low palladium catalyst loadings, due to a competitive hydrolysis reaction of 2,2-biphenyldiboronic acid. HTE techniques were used to find an economically viable protocol. Thus, use of the commercially available 1.0 molar solution of (n-Bu)4NOH in methanol with cosolvent toluene led to precipitation of the pure product in a fast and clean reaction, using only 0.7 mol % (0.35 mol % per C-C) of the expensive palladium catalyst.

Nonsense mutations in alpha-II spectrin in three families with juvenile onset hereditary motor neuropathy

Distal hereditary motor neuropathies are a rare subgroup of inherited peripheral neuropathies hallmarked by a length-dependent axonal degeneration of lower motor neurons without significant involvement of sensory neurons. We identified patients with heterozygous nonsense mutations in the alpha II-spectrin gene, SPTAN1, in three separate dominant hereditary motor neuropathy families via next-generation sequencing. Variable penetrance was noted for these mutations in two of three families, and phenotype severity differs greatly between patients. The mutant mRNA containing nonsense mutations is broken down by nonsense-mediated decay and leads to reduced protein levels in patient cells. Previously, dominant-negative alpha II-spectrin gene mutations were described as causal in a spectrum of epilepsy phenotypes

Safe and sustainable by design:A computer-based approach to redesign chemicals for reduced environmental hazards

Persistency of chemicals in the environment is seen a pressing issue as it results in accumulation of chemicals over time. Persistent chemicals can be an asset in a well-functioning circular economy where products are more durable and can be reused or recycled. This objective can however not always be fulfilled as release of chemicals from products into the environment can be inherently coupled to their use. In these situations, chemicals should be designed for degradation. In this study, a systematic and computer-aided workflow was developed to facilitate the chemical redesign for reduced persistency. The approach includes elements of Essential Use, Alternatives Assessment and Green and Circular Chemistry and ties into goals recently formulated in the context of the EU Green Deal. The organophosphate chemical triisobutylphosphate (TiBP) was used as a case study for exploration of the approach, as its emission to the environment was expected to be inevitable when used as a flame retardant. Over 6.3 million alternative structures were created in silico and filtered based on QSAR outputs to remove potentially non-readily biodegradable structures. With a multi-criteria analysis based on predicted properties and synthesizability a top 500 of most desirable structures was identified. The target structure (di-n-butyl (2-hydroxyethyl) phosphate) was manually selected and synthesized. The approach can be expanded and further verified to reach its full potential in the mitigation of chemical pollution and to help enable a safe circular economy

Concepts and characteristics of the 'COST Reference Microplasma Jet'

Biomedical applications of non-equilibrium atmospheric pressure plasmas have attracted intense interest in the past few years. Many plasma sources of diverse design have been proposed for these applications, but the relationship between source characteristics and application performance is not well-understood, and indeed many sources are poorly characterized. This circumstance is an impediment to progress in application development. A reference source with well-understood and highly reproducible characteristics may be an important tool in this context. Researchers around the world should be able to compare the characteristics of their own sources and also their results with this device. In this paper, we describe such a reference source, developed from the simple and robust micro-scaled atmospheric pressure plasma jet (μ-APPJ) concept. This development occurred under the auspices of COST Action MP1101 'Biomedical Applications of Atmospheric Pressure Plasmas'. Gas contamination and power measurement are shown to be major causes of irreproducible results in earlier source designs. These problems are resolved in the reference source by refinement of the mechanical and electrical design and by specifying an operating protocol. These measures are shown to be absolutely necessary for reproducible operation. They include the integration of current and voltage probes into the jet. The usual combination of matching unit and power supply is replaced by an integrated LC power coupling circuit and a 5 W single frequency generator. The design specification and operating protocol for the reference source are being made freely available

Format zorgpad Voeding bij kanker

Het zorgpad ‘Voeding bij kanker’ beschrijft het (logistiek) pad dat de oncologische patiënt doorloopt binnen de voedingszorg vanaf het moment dat screening op behoefte aan voedingszorg plaatsvindt en verwijzing naar de diëtist tot en met follow-up of palliatieve fase. Hierbij zijn het format en de indeling aangehouden van de IKNL-formats van (niet-)tumorspecifieke zorgpade

The relationship between exercise-induced muscle fatigue, arterial blood flow and muscle perfusion after 56 days of muscle unloading

In the light of the dynamic nature of habitual plantar flexor activity, we utilized an incremental isokinetic exercise test (IIET) to assess the work-related power deficit (WoRPD) as a measure for exercise-induced muscle fatigue before and after prolonged calf muscle unloading and in relation to arterial blood flow and muscle perfusion. Eleven male subjects (31 ± 6 years) wore the HEPHAISTOS unloading orthosis unilaterally for 56 days. It allows habitual ambulation while greatly reducing plantar flexor activity and torque production. Endpoint measurements encompassed arterial blood flow, measured in the femoral artery using Doppler ultrasound, oxygenation of the soleus muscle assessed by near-infrared spectroscopy, lactate concentrations determined in capillary blood and muscle activity using soleus muscle surface electromyography. Furthermore, soleus muscle biopsies were taken to investigate morphological muscle changes. After the intervention, maximal isokinetic torque was reduced by 23·4 ± 8·2% (P<0·001) and soleus fibre size was reduced by 8·5 ± 13% (P = 0·016). However, WoRPD remained unaffected as indicated by an unchanged loss of relative plantar flexor power between pre- and postexperiments (P = 0·88). Blood flow, tissue oxygenation, lactate concentrations and EMG median frequency kinematics during the exercise test were comparable before and after the intervention, whereas the increase of RMS in response to IIET was less following the intervention (P = 0·03). In conclusion, following submaximal isokinetic muscle work exercise-induced muscle fatigue is unaffected after prolonged local muscle unloading. The observation that arterial blood flow was maintained may underlie the unchanged fatigability

Psychological distress and lower health-related quality of life are associated with need for dietary support among colorectal cancer survivors with overweight or obesity

Objective: Two-third of colorectal cancer (CRC) survivors are overweight or obese. Psychological distress and low health-related quality of life (HRQoL) may be barriers to improving diet. We aimed to assess associations between psychological distress and HRQoL and the need for dietary support in CRC survivors with overweight or obesity. Methods: All alive individuals diagnosed with CRC between 2000 and 2009, as registered by the Dutch population-based Eindhoven Cancer Registry, were eligible for participation and received a questionnaire. Multivariable logistic regression analyses were conducted to assess associations between HRQoL (EORTC QLQ-C30), symptoms of anxiety and depression (HADS), and self-reported need for dietary support (single-item). Results: A total of 1458 completed the questionnaire (response rate 82%), and 756 (43%) had a BMI of 25.0 or higher and complete data on “need for dietary support” and were included for analyses. BMI ranged between 25.0 and 60.6 (mean, 28.9; SD, 3.6). The majority (71.7%) was overweight (BMI ≥ 25), and 28.3% obese (BMI ≥ 30). Twenty-one percent reported a need for dietary support which was associated with more psychological distress and lower HRQoL. Those who experienced symptoms of anxiety or depression were more likely to report a need for dietary support (27.6% and 28.7%) than those who did not experience symptoms of anxiety (12.3%; OR 2.02; 95% CI 1.22–3.35) or depression (13.5%; OR 1.96; 95% CI 1.19–3.22). Conclusions: Results suggest that psychological distress and lower HRQoL should be taken into account while promoting a healthy diet in overweight or obese CRC survivors since these factors may hinder adherence to a healthy diet.</p