Influence of SiO2 or h-BN substrate on the room-temperature electronic transport in chemically derived single layer graphene

The substrate effect on the electronic transport of graphene with a density of defects of about 0.5% (^0.5%G) is studied. Devices composed of monolayer ^0.5%G, partially deposited on SiO₂ and h-BN were used for transport measurements. We find that the ^0.5%G on h-BN exhibits ambipolar transfer behaviours under ambient conditions, in comparison to unipolar p-type characters on SiO₂ for the same flake. While intrinsic defects in graphene cause scattering, the use of h-BN as a substrate reduces p-doping.

Defects in graphene cause scattering and basal plane interactions shift the Dirac-point.

Wet-chemically prepared graphene from graphite can be stabilized in solution by covalently bound oxo-groups using established oxidation protocols.^1–3 In general, the materials obtained are termed graphene oxide (GO). However, the chemical structure varies and the carbon lattice may even be amorphous due to the evolution of CO₂ during synthesis.⁴ Thus, in this study we use oxo-functionalized graphene (oxo-G), a type of GO with a more defined structure, as proven in our previous work.³ The oxygen-containing groups on the graphene basal plane and rims of flakes and holes make GO a p-type semiconductor with a typical resistance of 10¹⁰–10¹³ Ω sq^−1 5,6 and a band gap of about 2.2 eV.^7,8 The reductive defunctionalization of GO leads to a certain type of graphene (G), often named reduced GO (r-GO).^4,9 Removal of oxo-groups from the surface can be achieved by chemical reduction,^9,10 electrochemical methods,^11,12 electron beam treatment¹³ and was observed in situ by transmission electron microscopy.¹³ Thermal processing of GO instead leads to a disproportionation reaction forming carbon with additional vacancy defects and CO₂.¹⁴ In general, the reduction of GO turns r-GO from a semi-conductive material to a semi-metal. Mobility values were determined in field effect transistor (FET) devices.^15,16 Generally, the quality of graphene strongly depends on the integrity of the hexagonal carbon lattice. Thus, mobility values of 10⁻³ and up to 10³ cm² V⁻¹ s⁻¹ were reported,^3,17,18 with the resistance fluctuating between 10³ and 10⁶ Ω sq⁻¹.^19–21 We reported on the highest mobility values of chemically reduced oxo-G (with about 0.02% of lattice defects) of 1000 cm² V⁻¹ s⁻¹,³ determined by Hall-bar measurements at 1.6 K.Hexagonal boron nitride (h-BN) has been proved to be an excellent substrate for matching graphene-based materials owing to its atomic flatness, chemical inertness and electronic insulation due to a bandgap of ∼5.5 eV.²² Up to now, most studies with graphene deposited on h-BN were restricted to measurements with virtually defect-free graphene.²³ To the best of the authors knowledge, no studies reported transport measurements based on single layers of GO or oxo-G on h-BN substrates. No studies are reported with graphene derived from GO or oxo-G on single-layer level. Recently, we found that chemical reactions can be selectively conducted close to the rims of defects.²⁴ However, before functionalized devices can be studied, the lack of knowledge on the ambient environment device performances of graphene with defects and the influence of substrates must be addressed. Therefore, we fabricated the devices composed of ^0.5%G, partially deposited on SiO₂ (SiO₂/^0.5%G) and h-BN (h-BN/^0.5%G) (Fig. 1). Areas of the same flake on both materials are used to ensure reliable measurements and to prove that the results stem from the influence of the substrate rather than from the difference between devices. Thereby, the ^0.5%G exhibits an I_D/I_G ratio of about 3–4, corresponding to 0.5% of defects, according to the model introduced by Lucchese and Cançado.^25–28 Our results demonstrate that the h-BN layer is responsible for a downshift of the Dirac point and a more narrow hysteresis, resulting in ambipolar transfer behaviours in h-BN/^0.5%G.Open in a separate windowFig. 1(a) Optical image of the fabricated h-BN/^0.5%G heterostructure on SiO₂. (b) The h-BN/^0.5%G heterostructure device. Electrodes 1 and 2 define the SiO₂/^0.5%G FET device. Electrodes 1 and 3 define the ^0.5%G on overlapped SiO₂/h-BN hetero-substrate device. Electrodes 3 and 4 define the h-BN/^0.5%G FET device. Distance between the electrodes 1–2 and 3–4 is 1.5 μm and 3 μm, respectively. (c) 3D illustration of the h-BN/^0.5%G transistor device.     

REHABILITATION SETTINGS DURING AND AFTER COVID-19: AN OVERVIEW OF RECOMMENDATIONS

ObjectiveThe aim of this review is to identify the best evidence to define rehabilitative approaches to acute and post-acute phases of coronavirus 2019 (COVID-19) disease.MethodsA literature search (of PubMed, Google Scholar, PEDro and Cochrane databases) was performed for relevant publications from January to April 2020.ResultsA total of 2,835 articles were retrieved, and the search resulted in a final total 31 published articles. A narrative synthesis of the selected articles was then performed. Some studies examine the effect of the pandemic on rehabilitation services and provide suggestions for a new reorganization of these services. Other studies focus on COVID-19 sequelae, formulating recommendations for rehabilitative interventions.ConclusionFor COVID-19 patients, an integrated rehabilitative process is recommended, involving a multidisciplinary and multi-professional team providing neuromuscular, cardiac, respiratory, and swallowing interventions, and psychological support, in order to improve patients’ quality of life. The intervention of a physician expert in rehabilitation should assess the patient, and a dedicated intervention set up after thorough assessment of the patient’s clinical condition, in collaboration with all rehabilitation team professionals.LAY ABSTRACTRehabilitation, in a multidisciplinary and multi-professional setting, plays a pivotal role in the management of Covid-19 patients, focusing on respiratory and motor functions and it is therefore crucial to establish treatment strategies to guarantee an optimal recovery of these patients. We performed a review of the scientific literature. All the studies concerning respiratory rehabilitation treatments for Covid-19 patients were included. Respiratory rehabilitation has the goal of improve respiratory symptoms, preserve function and reduce complications and disability; it also has positive effects on the psychological sphere, reducing anxiety and depression that can frequently develop in this context.Key words: rehabilitation, COVID-19, recommendation

In late December 2019, coronavirus 2019 (COVID-19) emerged in Wuhan, the capital city of Hubei province, China, and spread rapidly throughout the world, causing a large global outbreak and becoming a major health concern (1). In March 2020, the World Health Organization (WHO) declared COVID-19 a global pandemic and public health emergency (2).The causative agent is the newly identified severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), initially named 2019 novel coronavirus (2019-nCoV) (3). It is a non-segmented, enveloped, positive-sense single-strand RNA β-coronavirus (4), which may have been transmitted to humans from a potential reservoir in bats, through as-yet unknown intermediate hosts (5). Human-to-human transmission of COVID-19 occurs mainly through the respiratory tract, by inhalation of infected droplets (from symptomatic, but also asymptomatic people) and through direct contact (6, 7). The estimated incubation period is 1–14 days, mainly in the range 3–7 days (8).COVID-19 infection displays a prevalence of respiratory involvement, being responsible for interstitial pneumonia, the major manifestation of the disease, which first led to identification of the pathogen (3, 9). It causes various degrees of illness, with a clinical picture ranging from asymptomatic cases to acute respiratory distress syndrome (ARDS) and multi-organ failure (10).Symptoms include fever and dry cough (dominant manifestations), anosmia, sore throat, upper airway congestion, fatigue, headache, muscle ache, shortness of breath, and other signs of upper respiratory tract infection. Progression to pneumonia (mainly occurring in the second or third week of a symptomatic infection) (10, 11) is associated with a reduction in oxygen saturation, reduction in arterial blood gas exchange, extreme increase in inflammatory markers, and lymphopaenia (10). The clinical picture also correlates with bilateral ground glass opacities and patchy consolidations, seen on chest computed tomography (CT) (12, 13).Diagnosis of COVID-19 infection can be made only through nucleic acid detection by real-time polymerase chain reaction (RT-PCR) in respiratory tract samples.Since there is currently no approved treatment for COVID-19, management of the disease is based on symptomatic and supportive treatments, mainly targeted at preserving hydration and nutrition and controlling fever and respiratory symptoms. Oxygen or non-invasive ventilation are necessary for hypoxic patients. In most severe cases mechanical ventilation is required, and even extra-corporeal membrane oxygen (ECMO), which is recommended by the WHO for patients with refractory hypoxaemia (14). Elderly people and patients with underlying comorbidities are more susceptible to developing complications, including ARDS, acute kidney injury, arrhythmias, cardiac injury, and liver dysfunction (15, 16).Patients may undergo prolonged bed rest, leading to immobilization syndrome (17) associated with respiratory dysfunction, both of which might require rehabilitation interventions. Prolonged immobilization leads to muscle weakness, motor deconditioning, balance and postural impairment, and joint stiffness, pain and limitation, which have a strong impact on patients’ general condition (17, 18).Post-intensive care syndrome (PICS) refers to a new or worsening impairment of patient’s physical, cognitive, or mental health status arising during stay in the intensive care unit (ICU) and persisting beyond ICU discharge or hospital discharge. These patients undergo various degrees of respiratory, physical and psychological distress (19, 20). It is essential that any rehabilitative intervention is customized to the specific condition of each patient, and that this should take into account, as already observed in SARS-CoV and MERS-CoV, that SARS-CoV-2 may also have a neurotropic effect, leading to neurological involvement, which may be partially responsible for acute respiratory failure in COVID-19 patients (21).Indeed, it has recently been observed that SARSCoV-2 is involved in neurological manifestations (22) in COVID-19 patients, including in the central nervous system (CNS) (e.g. dizziness, headache, impaired consciousness, acute cerebrovascular disease, ataxia, and seizure), peripheral nervous system (PNS) (e.g. impairments of taste, smell and vision, and nerve pain), and skeletal muscle injury (23). Cases of viral encephalitis and infectious toxic encephalopathy have been reported (24). Patients who had cerebrovascular disease were older, developed severe COVID-19 and underlying disorders, an increased inflammatory response, and a hypercoagulable state (25, 26). Neurological manifestations, apart from cerebrovascular disease and impairment of consciousness, have been reported early in the illness prior to the onset of COVID-19-related symptoms (23). Hence it is important to evaluate patients who present with neurological symptoms, to assess risk factors (25) and underlying disorders that indicate an early diagnosis of COVID-19 (23), enabling the recognition and management of complications and improving the prognosis (24).The ongoing COVID-19 pandemic is placing great stress on healthcare systems, especially acute care departments, and is already having an impact on the rehabilitation community (17, 18, 27). In a multidisciplinary and multi-professional setting, rehabilitation plays a pivotal role in the management of patients with COVID-19, focusing on respiratory and motor functions. It is therefore crucial to establish rehabilitation treatment strategies that enable optimal recovery of these patients.The aim of this study was to review the literature on COVID-19, in order to identify best evidence to define rehabilitative approaches to acute and post-acute phases of the disease.     

E–Z isomerization of 3-benzylidene-indolin-2-ones using a microfluidic photo-reactor

Here, we report controlled E–Z isomeric motion of the functionalized 3-benzylidene-indolin-2-ones under various solvents, temperature, light sources, and most importantly effective enhancement of light irradiance in microfluidic photoreactor conditions. Stabilization of the E–Z isomeric motion is failed in batch process, which might be due to the exponential decay of light intensity, variable irradiation, low mixing, low heat exchange, low photon flux etc. This photo-μ-flow light driven motion is further extended to the establishment of a photostationary state under solar light irradiation.

(E)-3-Benzylidene-indolin-2-ones were efficiently converted to their corresponding (Z) -isomers at low temperature in the presence of light.

Functionalized 3-benzylidene-indolin-2-ones are an important structural motif in organic chemistry and are embedded in many naturally occurring compounds.¹ They found wide applications in molecular-motors,² energy harvesting dyes,³ pharmaceutical chemistry (sunitinib, tenidap),⁴ protein kinase inhibitors,⁵ pesticides,⁶ flavors,⁷ and the fragrance industry.⁸ In the last few decades, numerous protocols have been developed for the synthesis of novel indolin-2-ones. For instance, palladium (Pd)-catalysed intramolecular hydroarylation of N-arylpropiolamides,⁹ Knoevenagel condensation of oxindole and aldehyde,¹⁰ two-step protocols such as Ni-catalyzed CO₂ insertion followed by coupling reaction,¹¹ Pd-catalysed C–H functionalization/intramolecular alkenylation,¹² Pd(0)/monophosphine-promoted ring–forming reaction of 2-(alkynyl)aryl isocyanates with organoboron compound, and others.¹³Knoevenagel condensation is one of the best methods for the preparation of 3-benzylidene-indolin-2-ones, but often it gives mixture of E/Z isomeric products. Otherwise, noble metal-catalysed protocols received enormous interest. However, the limited availability, high price, and toxicity of these metals diminished their usage in industrial applications. Therefore, several research groups have been engaged in search of an alternative greener and cleaner approach under metal-free conditions. To address the diastereoisomeric issue, Tacconi et al. reported a thermal (300–310 °C) isomerization reaction of 3-arylidene-1,3-dihydroindol-2-ones,¹⁴ which suffers from poor reaction efficiency and E/Z selectivity. Therefore, transformations controlling E/Z ratio of 3-benzylidene-indolin-2-ones remains a challenging task and highly desirable (Scheme 1).Open in a separate windowScheme 1Functionalized 3-benzylidene-indolin-2-ones and alkenes in bioactive compounds and the accessible methods.On the other hand, selective E/Z stereo-isomerization of alkenes has been well established using various methods in the presence of light stimuli,^15a cations,^15b halogens or elemental selenium,¹⁶ palladium-hydride catalyst,¹⁰ cobalt-catalyst,¹⁷ Ir-catalyst,¹⁸ organo-catalysts.¹⁹ Among these, light-induced photostationary E/Z stereoisomerization is very attractive, due to its close proximity towards the natural process. In recent years, several light-driven molecular motors (controlled motion at the molecular level), molecular propellers,²⁰ switches,²¹ brakes,²² turnstiles,²³ shuttles,²⁴ scissors,²⁵ elevators,²⁶ rotating modules,²⁷ muscles,²⁸ rotors,²⁹ ratchets,³⁰ and catalytic self-propelled objects have been developed.³¹ Further, equipment''s relying on molecular mechanics were rapidly developed, particularly in the area of health care.Till date, controlled photo-isomerization of functionalized 3-benzylidene-indolin-2-ones is one of the puzzling problems to the scientific community. Photochemical reactions in batch process have serious drawbacks with limited hot-spot zone due to inefficient light penetration with increasing light path distance through the absorbing media, and the situation becomes poorer when the reactor size increases.^32,33 In contrast, the capillary microreactor platform has emerged as an efficient the artificial tool with impressive advantages, such as excellent photon flux, uniform irradiation, compatibility with multi-step syntheses, excellent mass and heat transfer, which lead to significant decrease the reaction time with improved yield or selectivity over batch reactors.^33a,34 To address the aforementioned challenges, it is essential to develop a highly efficient photo-microchemical flow approach for the controlled isomerization of functionalized 3-benzylidene-indolin-2-ones in catalyst-free and an environment friendly manner.     

Preparation of Ni-microsphere and Cu-MOF using aspartic acid as coordinating ligand and study of their catalytic properties in Stille and sulfoxidation reactions

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies. The Ni-microsphere and Cu-MOF with aspartic acid, as the coordinating ligand, were prepared via a solvothermal method. The morphology and porosity of the obtained Ni microsphere and Cu-MOF were characterized by XRD, FTIR, TGA, DSC, BET and SEM techniques. The catalytic activity of the Ni-microsphere and Cu-MOF was examined in Stille and sulfoxidation reactions. The Ni microsphere and Cu-MOF were easily isolated from the reaction mixtures by simple filtration and then recycled four times without any reduction of catalytic efficiency.

In this study, the thermal and catalytic behavior of Ni-microsphere and Cu-MOF were investigated with aspartic acid as the coordinating ligand with different morphologies.

Cross-coupling reaction is one of the most significant methods to create carbon–carbon bonds in organic synthesis. There are many approaches, including, Suzuki, Stille, and Sonogashira cross-coupling reactions, which are well recognized and highly applicable in organic synthesis. Among them, the Stille reaction, which is an increasingly versatile tool for the formation of carbon–carbon bonds, involves the coupling of aryl halides with organotin reagents.¹ However, these reactions generally require expensive transition metal catalysts such as Pd.² Therefore, it is necessary to develop a new economic, green, and efficient methodology to reduce the environmental impact of the reaction. They are also important intermediates in organic chemistry and have been widely used as ligands in catalysis. The direct oxidation of sulfides is an important method in organic chemistry. Besides, they are also valuable synthetic intermediates for the construction of chemically and biologically important molecules, which usually synthesized by transition metal complexes.³ In this regard, different transition metal complexes of mercury(ii) oxide/iodine,⁴ oxo(salen) chromium(v),⁵ rhenium(v) oxo,⁶ H₅IO₆/FeCl₃,⁷ Na₂WO₄/C₆H₅PO₃H₂,⁸ chlorites and bromites,⁹ NBS¹⁰etc. have been introduced as catalysts. However, these catalysts have several drawbacks; including, separation problems from the reaction medium, harsh reaction conditions, and generating a lot of waste. In order to solve these drawbacks, of separation and isolation of expensive homogeneous catalysts is the heterogenization of homogeneous catalysts and generation of a new heterogeneous catalytic system. Metal–organic frameworks (MOFs) are a class of porous crystalline materials, which show great advantages, i.e. their enormous structural and chemical diversity in terms of high surface area,^11,12 pore volumes,¹³ high thermal,¹⁴ and chemical stabilities,¹⁵ various pore dimensions/topologies, and capabilities to be designed and modified after preparation.¹⁶ In this sense, it is worth mentioning that these features would result in viewing these solids as suitable heterogeneous catalysts for organic transformations.^17–22 MOFs materials are prepared using metal ions (or clusters) and organic ligands in solutions (i.e. solvothermal or hydrothermal synthesis). MOF structures are affected by metal and organic ligands, leading to have more than 20 000 different MOFs with the largest pore aperture (98 Å) and lowest density (0.13 g cm⁻³).²³ Generally, surface area and pore properties of MOFs seem quite dependent on their metal and ligand type as well as synthesis conditions and the applied post-synthesis modifications. The largest surface area was measured in Al-MOF (1323.67 m² g⁻¹)^24,25 followed by ZIF-8-MOF (1039.09 m² g⁻¹),²⁶ while the lowest value was with Zn-MOF (0.86 m² g⁻¹),²⁷ followed by γ-CD-MOF (1.18 m² g⁻¹)²⁸ and Fe₃O(BDC)₃ (7.6 m² g⁻¹).²⁹ Microspheres are either microcapsule or monolithic particles, with diameters in the range (typically from 1 μm to 1000 μm),²⁹ depending on the encapsulation of active drug moieties. In this regard, there are two types of microspheres: microcapsules, defined, as spherical particles in the size range of about 50 nm to 2 mm and micro matrices.³⁰ Microsphere structures have recently attracted much attention due to their unique properties, such as large surface area,³¹ which make them suitable for tissue regenerative medicine,³²i.e. as cell culture scaffolds,³³ drug-controlled release carriers³⁴ and heterogeneous catalysis.³⁵ Many chemical synthetic methods has been developed for their synthesis, including seed swelling,³⁶ hydrothermal or solvothermal methods,³⁶ polymerization,³⁷ spray drying³⁸ and phase separation.³⁹ Among these methods, the solvothermal synthesis has been used as the most suitable methodology to prepare a variety of nanostructural materials, such as wire, rod,⁴⁰ fiber,⁴¹ mof⁴² and microsphere.⁴³ In this sense, the synthesis process involves the use of a solvent under unusual conditions of high pressure and high temperature.⁴⁴ The properties of microspheres are highly dependent on the number of pores, pore diameter and structure of pore.⁴⁵ The degree of porosity depends on various factors such as temperature, pH, stirring speed, type, and concentration of porogen, polymer, and its concentration.⁴⁶ There have been numerous studies to investigate the coordination behavior of a ligand with different metals under the same conditions.^47–49 Herein, we aim at comparing the catalytic behavior of Ni-microsphere and Cu-MOF with aspartic acid as the coordinating ligand in Stille and sulfoxidation reactions (Scheme 1).Open in a separate windowScheme 1(a) Schematic synthesis of Ni microsphere and Cu-MOF and their application as catalyst (b) topological structure of Cu-MOF (c) topological of Ni microsphere.     

Nanozyme-based catalytic theranostics

Nanozymes, a type of nanomaterial with intrinsic enzyme-like activities, have emerged as a promising tool for disease theranostics. As a type of artificial enzyme mimic, nanozymes can overcome the shortcomings of natural enzymes, including high cost, low stability, and difficulty in storage when they are used in disease diagnosis. Moreover, the multi-enzymatic activity of nanozymes can regulate the level of reactive oxygen species (ROS) in various cells. For example, superoxide dismutase (SOD) and catalase (CAT) activity can be used to scavenge ROS, and peroxidase (POD) and oxidase (OXD) activity can be used to generate ROS. In this review, we summarize recent progress on the strategies and applications of nanozyme-based disease theranostics. In addition, we address the opportunities and challenges of nanozyme-based catalytic theranostics in the near future.

With its diverse physical–chemical properties and highly efficient enzyme-like activities, nanozymes have been widely used in various theranostics.

A nanozyme is a type of nanomaterial (1–100 nm) with enzyme-like activities.^1,2 It can catalyze the reaction of enzyme substrates under physiological conditions, and it has similar catalytic efficiency and enzymatic abilities to natural enzymes. Our previous work found that Fe₃O₄ nanoparticles (NPs) possess an intrinsic peroxidase (POD)-like activity.³ Since then, numerous nanomaterials have been discovered to have POD-, catalase (CAT)-, superoxide dismutase (SOD)-, or oxidase (OXD)-like catalytic activities.⁴ A nanozyme may have more than one type of catalytic activity.⁵ Nowadays, more than 540 nanozymes from 49 elements have been reported from 350 laboratories in 30 countries.^6,7 Among these, iron oxide nanoparticles,⁸ CeO₂,⁹ graphene oxide,¹⁰ carbon nanozymes¹¹ and gold nanoparticles¹² are widely studied and applied.Nanozymes can simulate the catalytic processes of natural enzymes and regulate the redox level of cells, especially on reactive oxygen species (ROS). ROS are intermediate products which emerge in the process of oxygen metabolism, mainly including superoxide anion (O₂˙⁻), hydroxyl radical (·OH), and hydrogen peroxide (H₂O₂).¹³ An abnormal rise in ROS level will destroy the homeostasis of redox in vivo and cause oxidative stress. Nanozymes typically exhibit multiple enzymatic activities. On the one hand, the catalase and superoxide dismutase activity of nanozymes are mainly used to regulate the intracellular ROS level, which plays an important role in protecting cells. On the other hand, the oxidase and peroxidase activity of nanozymes induce ROS production and promote apoptosis, such as in cancer cells.With advantages such as high catalytic efficiency, high stability, biosafety, low cost and easy preparation,¹⁴ nanozymes have been widely used in industrial, medical, and biological fields and in environmental remediation.^2,15,16 Currently, a variety of nanozyme-based biomedical applications have been extensively explored, including biosensors,¹⁷in vitro texts,¹⁸ and antimicrobial¹⁹ and disease treatments, such as cancer therapy, bone marrow therapy and wound healing.²⁰ Here, we summarize the biomedical applications of nanozymes in vivo, as well as addressing the opportunities and challenges of nanozyme-based catalytic disease theranostics in the near future.     

ASSESSMENT OF REHABILITATION NEEDS IN PATIENTS DURING AND AFTER COVID-19: DEVELOPMENT OF THE COVID-19-REHABILITATION NEEDS SURVEY

ObjectiveCOVID-19 can result in a broad spectrum of dysfunctions, some of which may persist for long periods, requiring long-term rehabilitation. A comprehensive screening tool is therefore necessary to identify these needs. To date, no data exist on satisfaction with medical and therapeutic interventions for COVID-19 in terms of quality and quantity. The aim of this study is to develop a survey for use with COVID-19 patients during and after the end of the acute phase of the disease.MethodsFollowing the definition of dimensions by a group of experts, and a literature search, proven survey instruments were searched for suitable items. In addition, specific questions were developed based on symptoms, and answer options were created with regard to to the complexity of the questions.ResultsThe COVID-19 Rehabilitation Needs Survey (C19-RehabNeS) consists of the established 36- item Short Form Survey (SF-36) together with the newly developed COVID-19-Rehabilitation Needs Questionnaire (C19-RehabNeQ) (11 further dimensions, respectively 57 items).ConclusionC19-RehabNeS is a comprehensive survey to assess functional limitations and rehabilitation needs during and after infection with SARS-CoV-2 (COVID-19). The strength of this survey is that it combines the assessment of important rehabilitation needs with assessment of satisfaction with the health services, treatment and therapy during the pandemic (C19-RehabNeQ) and assessment of patients’ quality of life (SF-36). The C19-RehabNeS survey also enables collection of systematic information on patients with Post-COVID-19 syndrome (Long-COVID-19).LAY ABSTRACTCOVID-19 can cause a wide range of problems that affect several organ systems, resulting in long-term rehabilitation needs. A comprehensive screening instrument, that can identify these needs, is therefore necessary. The aim of this study is to develop a survey questionnaire for COVID-19 patients. A literature search was performed to identify current assessments concerning previously defined dimensions. A group of experts decided on the useful composition of possible questions. The resulting questionnaire (COVID-19 Rehabilitation Needs Survey; C19-RehabNeS) combines the 36-item Short Form (SF-36) with the newly developed COVID-19 Rehabilitation Needs Quesionnaire (C19-RehabNeQ) (with 11 dimensions and 57 items). The C19-RehabNeS is a comprehensive questionnaire for assessment of functional limitations during and after infection with SARS-CoV-2. The strength of the survey lies in the combination of assessment of 2 important issues: (i) rehabilitation needs and satisfaction with health services; and (ii) treatment and therapy during the pandemic. The C19-RehabNeS also enables collection of systematic information regarding rehabilitation and other treatments.Key words: survey method, health service administration, physical and rehabilitation medicine, questionnaire design, Covid-19, SARS-CoV2

The outbreak of COVID-19 in Wuhan, China, in December 2019 quickly developed into a global pandemic. There is increasing evidence that infection with the virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causes COVID-19 can result in a wide range of dysfunctions in several organ systems (1). In addition to primary pulmonary restrictions, which are divided into different stages and may lead to pulmonary fibrosis (2–4), many studies show that there can also be damage to the cardiovascular (5, 6), gastrointestinal (7, 8), nervous (9, 10) and musculoskeletal systems (11). Effects on mental health, such as increased fatigue and mood-related disorders (12), as well as dermatological (13) and ophthalmological symptoms (14), should not be underestimated. In addition to the wide and variable range of symptoms, the possible long-term health consequences of SARS-CoV-2 infection are not fully understood at this stage. However, current knowledge indicates the possible development of Post-COVID-19 syndrome (Long-COVID-19), with restrictions lasting for months (15). COVID-19 infection reduces performance, quality of life and participation, in both vocational and personal life (16).The wide range of possible symptoms leads to a necessity for multi-professional rehabilitation interventions in order to treat these functional deficits starting in the acute phase (17, 18). In addition to acute care rehabilitation, many patients will also require longterm and multidimensional treatment (19, 20). This is a core task of physical and rehabilitative medicine (21).A few studies (22, 23) have investigated healthrelated quality of life (using the 36-item Short Form survey; SF-36) of COVID-19 patients, and the results support the need for far-reaching rehabilitative therapies.For the full assessment of patients, a comprehensive screening instrument is required to identify their rehabilitation needs, and to serve as a basis for the development of treatment concepts. However, there are currently only a few survey instruments that ask about the effects of a SARS-CoV-2 infection. A recently developed questionnaire can be conducted as a telephone interview (24). This tool comprises 19 questions on the biopsychosocial effects of COVID-19 and corresponding limitations in functioning (24). However, there are currently no other assessment tools known to the authors that specifically address the rehabilitation needs of COVID-19 patients. No study has yet been published that assesses these needs from a broader perspective.The aim of this study was therefore to develop a multidimensional assessment tool for surveying the rehabilitation needs of patients during and after SARS-CoV-2 infection. It is important that the survey also records long-term symptoms that persist beyond the acute infection, referred to as Post-COVID-19-syndrome resp. Long-COVID-19 (15, 25–27).     

Synthesis of novel 1,2,4-thiadiazinane 1,1-dioxides via three component SuFEx type reaction

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors. The β-aminoethane sulfonamides were obtained through sequential Michael addition of amines to α,β-unsaturated ethenesulfonyl fluorides followed by further DBU mediated sulfur(vi) fluoride exchange (SuFEx) reaction with amines at the S–F bond.

Herein, we report the preparation of 1,2,4-thiadiazinane 1,1-dioxides from reaction of β-aminoethane sulfonamides with dichloromethane, dibromomethane and formaldehyde as methylene donors.

The 1,2,4-thiadiazinane 1,1-dioxide motif can be found in many biologically active compounds for vastly different medical conditions. For example, verubecestat (1) has been in phase III clinical trials as a β-amyloid precursor protein cleaving enzyme (BACE 1) inhibitor to treat moderate and prodromal Alzheimer''s disease.¹ Ribizzi et al. have shown that taurolidine (2) displays cytotoxic activity against certain human tumour cells,² but primarily it is used as an antibacterial agent.³ In addition, benzothiadiazines (3) are patented as ATP-sensitive potassium channel modulators for the treatment of respiratory, central nervous, and endocrine system disorders.⁴ 1,2,4-Thiadiazinane 1,1-dioxides of this type may be formed by various methods;^5–13 most closely related to the present work is the [2 + 2 + 2] sulfa Staudinger cycloaddition of sulfonylchlorides and imines, in which case β-sultams may also be formed through the corresponding [2 + 2] cycloaddition.^14,15 α,β-Unsaturated sulfonyl fluorides 4 are so far rarely encountered as starting materials for organic synthesis.^16–18 The literature on this reagent describe it as a connector molecule,¹⁹ and a warhead in chemical biology.^20–22 There are only four publications that, so far, have reported the use of α,β-unsaturated sulfonyl fluoride based compounds as starting materials in organic synthesis.^23–26 Based on our earlier experience with the reactivity of aryl α,β-unsaturated sulfonyl fluoride towards various amine nucleophiles¹⁷ (Scheme 1), we hypothesized that an α,β-unsaturated sulfonyl fluoride of type 4 can possibly be explored for the synthesis of thiadiazinanes. This hypothesis was based on observation of low amounts of the six-membered product was formed along with the major β-sultam product 5 when p-nitrophenylethenesulfonyl fluoride was subjected to excess methyl amine in methylene chloride as a solvent and triethylamine as additional base at room temperature (Scheme 1).Open in a separate windowScheme 1Formation of 1,2,4-thiadiazinane 1,1-dioxides, along with β-sultams, when aryl ethenesulfonyl fluorides are subjected to large excess of primary amines in DCM as solvent and DBU as catalyst.The reactivity of dichloromethane (DCM) as a methylene donor was unfamiliar to us at the time, but a literature survey quickly revealed that organic solvents (DMF,²⁷ DMSO,^28–30 CHCl₃ (ref. 31 and 32) and CH₂Cl₂ (ref. 33 and 34)) have proved to be more than solvents. DCM has indeed been reported to act as a bis-electrophilic methylene donor in the presence of strong bases and nucleophiles³³ (e.g. carboxylic acids,³⁵ thiols,³⁶ amines, etc.). DCM may also form hydrochloride salts,³⁷ aminals,³⁸ and quaternary salts³⁹ when reacted with tertiary and secondary amines. These reactions were reviewed by Mills et al.⁴⁰ and the kinetics of the reaction of DCM with pyridine was documented by Rudine et al.⁴¹ Liu and co-workers reported formation of methylene-bridged 3,3′-bis-(oxazolidin-2-one) through reaction of oxazolidin-2-ones with DCM and sodium hydride.⁴² Cui et al. reported the synthesis of bispidine with the utilisation of DCM as a C1 unit.⁴³ Dipyrrolidylmethane CH₂(pyr)₂ and dipiperidylmethane, CH₂(pip)₂ were synthesized via the condensation of the secondary amine precursors and DCM at room temperature in the absence of light.⁴⁴ Another reaction of amines with methylene chloride yielded aminals rapidly.⁴⁵ Matsumoto et al. reported the reaction of DCM with ketones or esters in the presence of secondary amines at high pressure whereby DCM was used as methylene bridge in forming both C–C and C–N bonds.⁴⁶ Zhang and co-workers also published the formation of simultaneous carbon–carbon bond and carbon-nitrogen bonds whereby DCM acted as a synthon in the presence of 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) and a copper catalyst.⁴⁷     

TEMPORAL EVOLUTION AND PREDICTORS OF SUBJECTIVE COGNITIVE COMPLAINTS UP TO 4 YEARS AFTER STROKE

ObjectiveTo examine the temporal evolution of subjective cognitive complaints in the long-term after stroke, and to identify predictors of long-term subjective cognitive complaints.MethodsProspective cohort study including 395 stroke patients. Subjective cognitive complaints were assessed at 2 months, 6 months and 4 years post-stroke, using the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24). The temporal evolution of subjective cognitive complaints was described using multilevel growth modelling. Associations between CLCE-24 cognition score at 4 years post-stroke and baseline characteristics, depression, anxiety, cognitive test performance, and adaptive and maladaptive psychological factors were examined. Significant predictors were entered in a multivariate multilevel model.ResultsA significant increase in subjective cognitive complaints from 2 months up to 4 years (mean 3.7 years, standard deviation (SD) 0.6 years) post-stroke was observed (p≤0.001). Two months post-stroke, 76% of patients reported at least one cognitive complaint, 72% at 6 months, and 89% at 4 years post-stroke. A higher level of subjective cognitive complaints at 2 months and lower scores on adaptive and maladaptive psychological factors were significant independent predictors of a higher level of subjective cognitive complaints at 4 years post-stroke.ConclusionPost-stroke subjective cognitive complaints increase over time and can be predicted by the extent of subjective cognitive complaints and the presence of adaptive and maladaptive psychological factors in the early phases after stroke.LAY ABSTRACTMany people suffer a stroke in the brain leading to consequences in different areas of functioning. Complaints in the domain of thinking (memory, attention, planning and organization) are frequent post-stroke. This study investigated the occurrence and type of complaints experienced in the first years after a stroke. The study found that these complaints increase over time. Longterm complaints are found in those people who already have problems early after stroke.Key words: stroke, rehabilitation, cognition, cognitive complaints

Subjective cognitive complaints (SCC) are common after stroke, with prevalence rates varying between 28.6% (1) and 90.2%, (2), depending on stroke characteristics, time since stroke, SCC definitions and the instruments used. The most commonly reported complaints are mental slowness (in 46–80% of patients) and difficulties in concentration and memory (in 38–68% and 38–94% of patients, respectively) (3). Previous cross-sectional studies showed that SCC are present in both the early stages after stroke (1–6 months after stroke) (4–6), and in the long-term (> 1 year after stroke) (1, 7, 8). To date only a few studies have examined the temporal evolution of SCC. Tinson & Lincoln observed an increase in SCC between 1 and 7 months post-stroke (n = 95) (9). The authors used the Everyday Memory Questionnaire (10), focusing on memory-related complaints. Wilz & Barskova also found an increase in SCC over time after stroke (3 vs 15 months post-stroke, n = 81) (11). SCC were measured with the Patient Competency Rating Scale cognition subscale (12). Van Rijsbergen et al., who used the Checklist for Cognitive and Emotional consequences following stroke (CLCE-24) (13), recently found that SCC remained stable between 3 and 12 months after stroke (n = 155) (14). Long-term results on the course of post-stroke SCC are lacking. Since SCC were found to be independently related to lower quality of life in patients with mild cognitive impairment (15), and patients with subarachnoid haemorrhage (16), it is important to assess SCC after stroke. Furthermore, earlier research showed that SCC were most strongly associated with participation after stroke, compared with cognitive tests in a neuropsychological test battery, and the Montreal Cognitive Assessment (MoCA) (17, 18). Hence, in order to improve participation and integration in society after stroke, it is important to take the patients’ perspective into account, rather than only determining objective cognitive measures.The presence and severity of SCC is expected to be a direct reflection of the presence and severity of cognitive deficits. However, previous studies investigating the relationship between SCC and cognitive performance in stroke patients have shown conflicting results (1–4, 7, 8, 13, 19, 20). Other factors have shown to be related to SCC, in particular psychological factors, such as depressive symptoms (2, 4, 6, 7, 21), anxiety (21, 22), perceived stress (14), personality traits (7, 22), and coping style (23). To date, only one study on SCC used a longitudinal design (14), which prevents conclusions on the temporal evolution of SCC in stroke patients in the long term. Since more stroke patients survive, recover well and are discharged home nowadays, it is important to address predictors of SCC in the early phases after stroke, in order to identify patients who need more intensive monitoring at follow-up. Once identified, it is possible to investigate whether the patients will benefit from more focused rehabilitation programmes.The aim of this longitudinal study was to examine the temporal evolution of SCC, from 2 months until 4 years post-stroke. Furthermore, the study assessed which factors are predictive of SCC at 4 years post-stroke, taking into account demographic and stroke-related characteristics at baseline, and cognitive deficits and psychological factors measured at 2 months post-stroke.     

Three-dimensional macroporous graphene monoliths with entrapped MoS2 nanoflakes from single-step synthesis for high-performance sodium-ion batteries

Layered metal sulfides (MoS₂, WS₂, SnS₂, and SnS) offer high potential as advanced anode materials in sodium ion batteries upon integration with highly-conductive graphene materials. However, in addition to being costly and time-consuming, existing strategies for synthesizing sulfides/graphene composites often involve complicated procedures. It is therefore essential to develop a simple yet scalable pathway to construct sulfide/graphene composites for practical applications. Here, we highlight a one-step, template-free, high-throughput “self-bubbling” method for producing MoS₂/graphene composites, which is suitable for large-scale production of sulfide/graphene composites. The final product featured MoS₂ nanoflakes distributed in three-dimensional macroporous monolithic graphene. Moreover, this unique MoS₂/graphene composite achieved remarkable electrochemical performance when being applied to Na-ion battery anodes; namely, excellent cycling stability (474 mA h g⁻¹ at 0.1 A g⁻¹ after 100 cycles) and high rate capability (406 mA h g⁻¹ at 0.25 A g⁻¹ and 359 mA h g⁻¹ at 0.5 A g⁻¹). This self-bubbling approach should be applicable to delivering other graphene-based composites for emerging applications such as energy storage, catalysis, and sensing.

A single-step, template-free, high-throughput synthesis method is developed to produce graphene/MoS₂ composites for improved performances in sodium-ion batteries.

Sodium-ion batteries (NIBs) have been proposed as promising alternatives to lithium-ion batteries (LIBs) in the megawatt- and kilowatt-scale energy storage scenarios (i.e.; electric vehicles, stationary grids) for their high cost-effectiveness, sustainability, and environmental benignity.¹ Since the operation chemistry of NIBs is very similar to that of LIBs, knowledge gained from developing LIB technology can be mostly applied to NIBs with the exception of electrode materials.^2,3 In particular, the larger ionic radius of Na⁺ (0.102 nm) than that of Li⁺ (0.076 nm) makes graphite, the most commonly used anode in LIBs, unable to accommodate sodium ions in a satisfactory regime.⁴ Inspired by the findings on LIBs, scientists have tested carbonaceous materials,^5,6 alloy materials (Sn, Sb),^7,8 and metal oxides (Fe₂O₃, CuO, TiO₂)^9–11 as anode materials for NIBs. Unfortunately, due to the large volume change and/or the sluggish kinetics during charge/discharge cycles, these materials delivered either low reversible capacity or poor cyclability.¹² Consequently, layered metal sulfides (MoS₂, WS₂, SnS₂ and SnS) have also been explored as anode materials in NIBs due to their unique structural characteristics.¹³ For example, molybdenum sulfide (MoS₂), stemming from its large interlayer spacing (0.62 nm, compared to 0.34 nm for graphite) and high capacity for hosting foreign species, has been recently highlighted as a possible candidate for anode material in NIBs.^14–19 According to the intercalation and conversion reaction between one MoS₂ molecule and four Na⁺, the theoretical capacity of MoS₂ is as high as 670 mA h g⁻¹.²⁰However, there are two major issues when using MoS₂ as anodes in large-scale applications: poor electronic conductivity and drastic volume expansion upon conversion reaction from MoS₂ to Mo and Na₂S.^18,20–27 One effective approach to address the problems and thus improve the electrochemical performance of MoS₂ in NIBs is by supporting MoS₂ with conductive scaffolds to create porous composites, so as to simultaneously improve its conductivity as well as buffer the volumetric variation.¹² In this regard, carbon materials, especially graphene, have been repeatedly confirmed to be an efficient conductive additive in electrode materials in resolving the above issues.^28,29 Some examples of such effective treatment on electrode materials include sulfur/graphene cathode in lithium–sulfur batteries,³⁰ lithium metal phosphates/carbon cathode materials in LIBs,^31–34 and various metal oxides/graphene anode materials in LIBs.³⁵To improve the electrical conductivity and enhance the structural integrity of MoS₂ anode, MoS₂/graphene composites have been synthesized via several methods and applied in NIBs.^{17,18,21,23,26,36–41} For instance, David et al. prepared MoS₂/graphene composite paper through vacuum filtration of homogeneous dispersions consisting of exfoliated MoS₂ and graphene oxide sheets, followed by thermal reduction at elevated temperatures.¹⁸ Wang et al. and Xie et al. also synthesized MoS₂/graphene composites via hydrothermal reactions plus thermal annealing, respectively.^23,26 In spite of the significant synthetic achievements made, the existing strategies for synthesizing MoS₂/graphene composites present a few shortcomings as these methods often involve complicated procedures (graphene oxide preparation, MoS₂ preparation, compositing or mixing step, thermal treatments, etc.) in addition to be costly and time-consuming.²⁸ Another issue with existing MoS₂/graphene compositing methods is that some of them do not ensure the intimate contact between MoS₂/graphene interfaces, an unfavorable condition for electrochemical applications (charge-transfer process).²⁶ Finally, most of the present MoS₂/graphene compositing methods are faced with the issue of low yield, ranging from several tens to hundreds milligrams of powders under laboratory conditions.Herein, we report a single-step, template-free, high-throughput “self-bubbling” method for synthesizing MoS₂/graphene composite. Our method is cost-effective, simple and scalable. The synthesis utilizes the thermal decomposition of solid precursor to generate MoS₂; meanwhile, the released gas from the decomposition reaction blows premixed, melted glucose into crowded bubbles, which then evolve into graphene structures during annealing. The final product is microscopically featured as highly crystalline MoS₂ nanoflakes distributed in three-dimensional (3D) macroporous monolithic graphene. With the additional assistance of intimate interfacial contacts between MoS₂ and graphene, our composite demonstrates considerably improved electrochemical performance when compared with those of conventional MoS₂/graphene composite upon application in NIBs. It is expected that such a unique MoS₂/graphene composite should hold potential in promoting the development of practical MoS₂ anode in NIBs, while the straightforward self-bubbling method could offer the opportunity in producing MoS₂/graphene composites in industrial scale as well as synthesizing other advanced graphene-based composites.     

Organocatalytic sulfa-Michael/aldol cascade: constructing functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter

A practical sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylates has been developed, which allows efficient access to functionalized 2,5-dihydrothiophenes bearing a quaternary carbon stereocenter in moderate to good yields with high enantioselectivities.

A sulfa-Michael/aldol cascade reaction of 1,4-dithiane-2,5-diol and α-aryl-β-nitroacrylate has been developed, which allows access to 2,5-dihydrothiophenes bearing a quaternary carbon center in moderate to good yields with high enantioselectivities.

Among the various classes of heterocycles, members of the thiophene family have received particular attention from the chemical community because of their widespread occurrence as ubiquitous motifs in natural products, pharmaceuticals, agrochemicals as well as materials.¹ In this context, the 2,5-dihydrothiophene ring is a common structural feature of many bioactive compounds and a potential intermediate for various synthetic applications.² Over the decades, only a few examples of the assembly of optically active 2,5-dihydrothiophenes have been documented.³ For instance, the Spino^3b group successfully prepared non-racemic dihydrothiophenes using an efficient chiral auxiliary. The first gold-catalyzed cycloisomerization of α-hydroxyallenes to 2,5-dihydrothiophenes was reported by Krause^3c and co-workers. Then in 2010, the Xu^3e group developed a highly stereoselective domino thia-Michael/aldol reaction between 1,4-dithiane-2,5-diol and α,β-unsaturated aldehyde catalyzed by a chiral diphenylprolino TMS ether, which provided a new avenue for the synthesis of functionalized 2,5-dihydrothiophenes.Quaternary carbon stereocenters are often contained in natural products and pharmaceuticals.⁴ Compared with the chiral pool synthesis,⁵ the procedure of chiral materials or catalysts to construct such sterically congested stereogenic centers is more challenging because of the difficulty of orbital overlap.⁶ To date, a lot of progresses have been made in the construction of chiral quaternary carbon centers in cyclic compounds,⁷ which are greatly accelerated by the advancement of transition metal catalysis,⁸ and organocatalysis,⁹ including methods beyond radical initiation.¹⁰ However, only few examples are about the construction of a quaternary carbon in 2,5-dihydrothiophene ring.¹¹ Inspired by the previous work of the Xu group,^3e we describe herein an elegant organocatalytic asymmetric cascade sulfa-Michael/aldol reaction, providing a convenient way for the synthesis of 2,5-dihydrothiophenes bearing a chiral quaternary cabon center.     

Yield stress fluids and fundamental particle statistics

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers. Probability distribution functions are determined for canonical ensembles of volumes displaced at the incipient motion in three representative states (single, double, and multiple occupancies). The statistical average points out an effective solid fraction by which the yield stress behavior is satisfactorily described in a number of aqueous (Si₃N₄, Ca₃(PO₄)₂, ZrO₂, and TiO₂) and non-aqueous (Al₂O₃/decalin and MWCNT/PC) disperse systems. Interestingly, the only two model coefficients (maximum packing fraction and stiffness parameter) turn out to be correlated with the relevant suspension quantities. The latter relates linearly with (Young’s and bulk) mechanical moduli, whereas the former, once represented versus the Hamaker constant of two particles in a medium, returns a good linear extrapolation of the packing fraction for the simple cubic cell, here recovered within a relative error ≈ 1.3%.

Yield stress in complex fluids is described by resorting to fundamental statistical mechanics for clusters with different particle occupancy numbers.

Yield stress fluids form a particular state of matter,¹ displaying non-linear and novel visco-plasto-elastic flow dynamics upon different boundary conditions. As their name says, they don’t flow until a certain load, the so-called yield stress (or point, τ₀), is applied. This value may be generally interpreted as a shear stress threshold for the breakage of interparticle connectivity.² Furthermore, as it initiates motion in the system, it is connected to mechanical inertia³ and particle settling, i.e. it is a terse summary of buoyancy, dynamic pressure, weight, viscous and yield stress resistances.⁴ For prototype systems such as colloids dispersed in a liquid, yield points sensibly depend on the mechanism by which the solid phase tends to interact or aggregate.^5–8 The macroscopic constitutive equations they obey, such as the Herschel–Bulkley model, were shown to correspond, over a four-decade range of shear rates, to the local rheological response.⁹From the side of an experimenter, however, unambiguously defining a yield stress may not always be straightforward. It can be affected by the experimental procedure adopted, always considering a measurement or some extrapolation technique with the limit of zero shear. Conversely, unyielded domains may be defined by areas where the shear stress second invariant falls below the yield value, plus some small semi-heuristic constant.¹⁰ In addition, theoretically, the meaning of notions like τ₀ and rheological yielding were questioned to be only qualitative or even to stand for an apparent quantity.¹¹ The dependence they generally show on timescales characteristic of the applied (mechanical) disturbance, also suggested an intimate relationship¹² between yield stress and dispersion thixotropy.¹³ On the other hand, assigning a hydrodynamic or mechanical state below the yield point to a material that is not flowing seems not to be scientifically sound. Experimental values are normally obtained by extrapolation of limited data, whereas careful measurements below the yield point would actually imply that flow takes place.¹⁴At any rate, the analysis of properly defined τ₀ concepts forms the subject of interesting investigations and is still a powerful tool in many applications, including macromolecular suspensions,¹⁵ gels, colloidal gels and organogels,^16–18 foams, emulsions and soft glassy materials.¹⁹ It allows for effective comparisons between the resistances which fluids initially oppose to the shear perturbation, somehow specifying a measure of the particle aggregation states taking place in a given dispersant. Electrorheological materials, for instance, exhibit a transition from liquid-like to solid-like behaviors, which is often examined by a yield stress investigation upon a given fluid model (e.g. the Bingham model or the Casson model).^20,21 The combination of yield stress measurements with AFM techniques can be used to well-characterize the nature of weak particle attractions and surface forces at nN scales.⁸ Further issues of a more geometrical nature, which naturally connect to τ₀, are rheological percolation²² and its differences from other connectivity phenomena, such as the onset of electric²³ or elastic percolation.^24,25 In granular fluids, it relates with the theory of jammed states,²⁶ originally pioneered by Edwards.²⁷In nanoscience as well, the stability control and characterization in single and mixed dispersions or melts is an important and complex step.^28,29 Carbon nanotube suspensions,³⁰ for example, can be prepared in association with other molecular systems, like surfactants and polymers^31–33 or by (either covalent or non-covalent) functionalization of their walls with reactive groups, which increases the chemical affinity with dispersing agents.³⁴ As a consequence of large molecular aspect ratios and significant van der Waals’s attractions, the nanotube aggregation is highly enhanced, giving rise to strongly anisotropic systems of crystalline ropes and entangled network bundles, which are difficult to exfoliate, suspend or even characterize.³⁵ Stable CNT dispersions of controlled molecular mass may also exhibit polymeric behavior, and be quantitatively studied by equations taken from the well-established science of macromolecules.^36,37This paper puts forward a basic approach, mostly focused on equilibrium arguments, to devise a yield stress law connected with particle statistics. By conjecturing an ensemble of effective volumes ‘displaced’ at the incipient state of motion, a statistical mechanics picture of τ₀ is proposed. This affords a phenomenological hypothesis that can be developed with reasonable simplicity. The derived relations are applied to typical disperse systems in colloid science and soft matter, such as aqueous and nonaqueous suspensions of ceramic/metal oxides and nanoparticles.     

ARM IMPAIRMENT AND WALKING SPEED EXPLAIN REAL-LIFE ACTIVITY OF THE AFFECTED ARM AND LEG AFTER STROKE

ObjectiveTo determine to what extent accelerometer-based arm, leg and trunk activity is associated with sensorimotor impairments, walking capacity and other factors in subacute stroke.DesignCross-sectional study.PatientsTwenty-six individuals with stroke (mean age 55.4 years, severe to mild motor impairment).MethodsData on daytime activity were collected over a period of 4 days from accelerometers placed on the wrists, ankles and trunk. A forward stepwise linear regression was used to determine associations between free-living activity, clinical and demographic variables.ResultsArm motor impairment (Fugl-Meyer Assessment) and walking speed explained more than 60% of the variance in daytime activity of the more-affected arm, while walking speed alone explained 60% of the more-affected leg activity. Activity of the less-affected arm and leg was associated with arm motor impairment (R² = 0.40) and independence in walking (R² = 0.59). Arm activity ratio was associated with arm impairment (R² = 0.63) and leg activity ratio with leg impairment (R² = 0.38) and walking speed (R² = 0.27). Walking-related variables explained approximately 30% of the variance in trunk activity.ConclusionAccelerometer-based free-living activity is dependent on motor impairment and walking capacity. The most relevant activity data were obtained from more-affected limbs. Motor impairment and walking speed can provide some information about real-life daytime activity levels.LAY ABSTRACTActivity data from accelerometers can help clinicians to better understand factors limiting physical activity levels. This study aimed to determine to what degree arm, leg and trunk activity, measured with accelerometers, is associated with sensorimotor impairments, walking and other factors in people with stroke in the subacute stage of recovery. Real-life activity, measured by accelerometers, was primarily associated with motor impairment and walking speed. Spasticity, dependency in walking, and disability level also showed association with real-life activity, although to a lesser degree. Accelerometers, placed on the more-affected wrist and ankle, provided most relevant clinical information and are therefore recommended for research and clinical practice. The strong associations observed in this study suggest that when accelerometers are not available, clinical assessments of arm motor function and walking speed can provide some information on real-life activity levels in people with stroke.Key words: stroke, accelerometry, clinical research, rehabilitation, ambulatory monitoring, wearable technology, outcome assessment (healthcare), outcome measures

Individuals with stroke spend approximately 70–80% of their daytime in sedentary activities, and, when active, their activity level seldom reaches moderate-to-vigorous levels of intensity (1–3). To better understand which factors limit activity levels, wearable devices for movement monitoring, such as accelerometers, can be used effectively (4–6). Interest in using wearable technology for quantification of activity and motor function in real-life activities after stroke is increasing within the field of neurorehabilitation (7–9), although application in clinical practice is sparse (7, 10, 11).The Fugl-Meyer Assessment (FMA) is one of the most widely used clinical scales to assess sensorimotor function after stroke. The FMA has excellent psychometric properties (12, 13) and is commonly used as reference when validating new instruments. In addition to motor impairment, sensory function, spasticity, walking ability and speed are commonly assessed in clinical practice after stroke. In general, clinical assessments rely on therapists’ observational skills, and the scoring is limited to predefined categories of the scale. Traditional clinical assessments provide a snapshot of how the patient is functioning at the time of testing, which does not always overlap with the real-life functioning in daily activities (7, 8). Here accelerometers can offer several advantages, by measuring movements and activity continuously over a defined period of time in free-living conditions, and providing an objective measure of motor functioning (9, 14). Such measurements are complicated by the fact that there are numerous different accelerometer devices available, the placement of devices differs, and the metrics obtained are diverse. To overcome this limitation, the use and reporting of accelerometer data in acceleration metrics (m/s²) is advocated to allow comparison between systems, studies and conditions (10). Even though the number of studies using accelerometers is increasing, the validation of the obtained measures is critical for meaningful use in clinical research and practice (14, 15).Moderate-to-strong correlations have been reported between accelerometer-based activity measures and FMA scores (16, 17) as well as Action Research Arm Test (18) among stroke-survivors at different phases of recovery after stroke. Accelerometer-based arm ratio (i.e. the ratio between more-affected and less-affected arm) showed strong correlation with FMA, after controlling for cofactors, such as age, sex, time since stroke, sensory deficit, neglect, apraxia or lower extremity function (17). Knowledge is, however, limited regarding how different relevant cofactors might be associated with real-life activity in people with stroke in a multifactor model. Such knowledge is necessary to advance the routine use of technology-based assessment in clinical practice (19–21).The aim of this study was to determine to what degree arm, leg and trunk activity, measured with accelerometers, is associated with sensorimotor impairments and activity limitations as well as clinical and demographic characteristics in individuals with subacute stroke.     

EFFECTS OF VIRTUAL REALITY-BASED NECK-SPECIFIC SENSORIMOTORTRAINING IN PATIENTS WITH CHRONIC NECK PAIN: A RANDOMIZED CONTROLLED PILOT TRIAL

ObjectiveTo evaluate the effects of neck-specific sensorimotor training using a virtual reality device compared with 2 standard rehabilitation programmes: with, and without general sensorimotor training, in patients with non-traumatic chronic neck pain.DesignPilot randomized control study.Patients and methodsA total of 51 participants were randomly assigned to 1 of 3 groups: 1: control group; 2: sensorimotor group; 3: virtual reality group. All 3 groups received the clinic’s standard rehabilitation programme. Group 2 also received “general sensorimotor training” in the form of group therapy, for a total of 120 min. Group 3 received additional virtual reality-based “neck-specific sensorimotor training” for a total of 120 min. Participants’ neck pain, headaches, active cervical range of motion, and Neck Disability Index were determined before and after 3 weeks of intervention.ResultsCompared with the control group, the virtual reality group showed significant (p < 0.05) advantages in relief of headaches, and active cervical range of motion in flexion and extension. Compared with the sensorimotor group, the virtual reality group showed significant improvements in cervical extension.ConclusionVirtual reality-based sensorimotor training may increase the effects of a standard rehabilitation programme for patients with non-traumatic chronic neck pain, especially active cervical range of motion in extension.LAY ABSTRACTThe aim of this study was to evaluate the effectiveness of neck-specific coordination training using a virtual reality device, in comparison with general coordination training and a standard exercise programme as part of inpatient rehabilitation for patients with chronic neck pain. Pain, disability and mobility of the neck were determined before and after 3 weeks of training intervention in 51 patients. The virtual reality training group exhibited greater effects in relief of headaches, and bending the neck forwards and backwards compared with the standard exercise group, and an increased ability to bend the neck backwards compared with the coordination training group. The results suggest that neck-specific coordination training using a virtual reality device increases the benefits of standard inpatient rehabilitation in patients with chronic neck pain, particularly in bending the neck backwards.Key words: neck pain, rehabilitation, virtual reality, kinematics

Neck pain is a widespread problem; 60–80% of individuals develop neck pain during their life-time, with 30–50% of the general population reporting neck pain annually (1–3). Many patients experience neck pain as a complex biopsychosocial disorder, with problematic physical and psychological symptoms (3), such as reduced cervical range of motion, headaches, lack of concentration, emotional and cognitive disorders (4, 5). Aside from the decreased quality of life, these complaints are a major cause of inability to work (6, 7) and lead to considerable economic damage (8). Hence, the demand for an effective treatment is indisputable.According to a recently published review (9), the strongest treatment effects for neck pain are those associated with exercise. However, the evidence for this claim is only of moderate quality. Since there is no data available at present to show that any one form of exercise is evidentially more effective than another, multimodal care is concordantly recommended by leading experts (3, 9).Sensorimotor training methods are a current trend in exercise therapy, and for the first time they take into account the special function of the neck, by including connections between the perceptions of sensory organs located in the head and neck muscles (10–14). Alterations of sensorimotor control have been identified in many patients with neck pain, and are thought to play an important role in the aetiology and maintenance of associated disorders (14, 15).To date, there are only a few sensorimotor training concepts that have been specially developed for the neck region. Initial studies found that patients undergoing these training methods experienced reduced neck pain, as well as improvements in cervical range of motion, self-reported disability, and general health (11, 13, 14, 16). However, a systematic review from 2014 (17) revealed very little evidence for eye-neck coordination and proprioceptive exercises. Furthermore, a randomized controlled trial (RCT) found that neck coordination exercises did not produce a larger effect than strength training and massages (18).Application of a virtual reality (VR) device is a novel and promising option for training cervical kinematics (10, 12, 19). In theory, this technique provides several advantages: distracting attention and therefore reducing pain and kinesiophobia (20, 21), engaging and motivating physical activities, and improving the effectiveness of exercise (22, 23).To date, only one RCT has compared the effects of VR-based training with conventional kinematic training using laser beams in patients with chronic neck pain (12). The VR group exhibited significant improvements in motion velocity, pain intensity, health status, and accuracy of neck motion.Due to the conflicting evidence and lack of research, there is a need for more studies that consider the effectiveness of VR-based sensorimotor training concepts, especially in combination with other effective therapeutic exercises or as part of individually tailored programmes (12).The aim of this study was therefore to evaluate the effects of neck-specific sensorimotor training using a VR device, in comparison with standard rehabilitation programmes, both with and without general sensorimotor training, in patients with non-traumatic chronic neck pain.     

Nano-Fe3O4@walnut shell/Cu(ii) as a highly effective environmentally friendly catalyst for the one-pot pseudo three-component synthesis of 1,3-oxazine derivatives under solvent-free conditions

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium. A series of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines were synthesized by the one-pot pseudo three-component reaction of β-naphthol, formaldehyde and various amines using nano-Fe₃O₄@walnut shell/Cu(ii) at 60 °C under solvent-free conditions. The catalyst was removed from the reaction mixture by an external magnet and was reusable several times without any considerable loss of its activity. This protocol has several advantages such as excellent yields, short reaction times, clean and convenient procedure, easy work-up and use of an eco-friendly catalyst.

Fe₃O₄@walnut shell/Cu(ii) as an eco-friendly bio-based magnetic nano-catalyst was prepared by adding CuCl₂ to Fe₃O₄@walnut shell in alkaline medium.

Biopolymers, especially cellulose and its derivatives, have some unparalleled properties, which make them attractive alternatives for ordinary organic or inorganic supports for catalytic applications.¹ Cellulose is the most abundant natural material in the world and it can play an important role as a biocompatible, renewable resource and biodegradable polymer containing OH groups.² Walnut shell is a natural, cheap, and readily available source of cellulose. Fe₃O₄ nanoparticles are coated with various materials such as surfactants,³ polymers,^4,5 silica,⁶ cellulose⁷ and carbon⁸ to form core–shell structures. Magnetic nanoparticles as heterogeneous supports have many advantages such as high dispersion in reaction media and easy recovery by an external magnet.⁹ Cu(ii) as a safe and ecofriendly cation is a good Lewis acid and can activate the carbonyl group for nucleophilic addition reactions.¹⁰1,3-Oxazines moiety has gained great attention from many organic and pharmaceutical chemists due to their broad range of biological activities such as anticancer,¹¹ anti-bacterial,¹² anti-tumor¹³ and anti-Parkinson''s disease.¹⁴Owing to the biological importance of benzo-fused 1,3-oxazines, various methods have been developed for the synthesis of these compounds. Some shown protocols for the synthesis of various 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazines via a Mannich type condensation between a 2-naphthol, formaldehyde and a primary amine were reported. This protocol has been catalyzed by KAl(SO₄)₂·12H₂O (alum),¹⁵ ZrOCl₂,¹⁶ polyethylene glycol (PEG),¹⁷ thiamine hydrochloride (VB₁)¹⁸ and CCl₃COOH.¹⁹ Other methods of synthesis of oxazines are aza-acetalizations of aromatic aldehydes with 2-(N-substituted aminomethyl) phenols in the presence of an acid as catalyst²⁰ and electrooxidative cyclization of hydroxyamino compounds.²¹However, some of these catalysts have limitations such as inefficient separation of the catalyst from reaction mixtures, unrecyclable and environmental limitations. Therefore, the development of green and clean methodology for the preparation of 2-aryl/alkyl-2,3-dihydro-1H-naphtho[1,2-e][1,3]oxazine derivatives is still an interesting challenge.Herein, we wish to report the preparation of Fe₃O₄@nano-walnut shell/Cu(ii) as a new and bio-based magnetic nanocatalyst and its using for one-pot synthesis of 1,3-oxazine derivatives via condensation of β-naphthol, primary amine and formaldehyde.     

COGNITIVE FUNCTION AND PERFORMANCE OF EVERYDAY ACTIVITIES IN ADULTS WITH SPINA BIFIDA

Background and objectiveIndividuals with spina bifida often have cognitive impairments leading to difficulties in education and daily activities. The aims of this study were to explore cognitive impairments in adults with spina bifida and to consider associations between impairments, educational outcome and performance of daily activities, comparing individuals with and without intellectual disability.MethodsData were collected on 35 adults with spina bifida via cognitive tests and Assessment of Motor and Process Skills (AMPS). Participants were divided into 3 groups: individuals without intellectual disability who completed compulsory education (NID-C); those without intellectual disability, who failed to successfully pass compulsory education (NID-F); and those with intellectual disability failed to successfully pass compulsory education (ID-F).ResultsAll individuals with intellectual disability failed to successfully pass compulsory education (group ID-F) and had poorer scores across almost all measures than group NID-F and significantly poorer scores than group NID-C. All except 6 individuals scored below cut-off levels for effort and safety on both AMPS motor and process scales; more significant associations were seen between the cognitive tests and the motor rather than process scale.ConclusionCognitive impairments, irrespective of intellectual disability, impact on the performance of everyday activities and on educational achievement, and thus need to be considered in assessments and interventions to improve outcomes and promote independence in people with spina bifida.LAY ABSTRACTIndividuals with spina bifida often have cognitive impairments, resulting in difficulties in performing their everyday life activities at home, in education, training and social life. These difficulties are often not recognized, and the individuals do not receive the support they need from society. This study investigated the relationship between cognitive impairments, school achievements and performance of daily life activities of 35 adults with spina bifida. The study examined whether individuals had an intellectual disability, and whether they had completed compulsory education, and compared this with their cognitive function and performance in everyday activities. The results confirm that individuals with cognitive impairments, even those without intellectual disabilities, often have considerable difficulties in school achievements, and performance of daily life activities, reducing their ability to live independently.Key words: disability evaluation, intellectual disability, cognitive function, activities of daily living, spina bifida

Spina bifida (SB) is caused by the incomplete closing of the embryonic neural tube, which can affect brain development, with consequent sensory and motor difficulties (1, 2). Hydrocephalus is present at birth in 80–85% of individuals with SB (3), and by adulthood 63% are estimated to have hydrocephalus (4). Hydrocephalus leads to structural anomalies in the brain (1), which seem to contribute to a cognitive phenotype with relative strengths and weaknesses (5) and differing degrees of cognitive impairments amongst individuals with SB (6). One in 5 individuals with SB and hydrocephalus are reported to have an intellectual disability (ID) (intelligence quotient (IQ) < 70) (7). Furthermore, according to several studies many other individuals with SB show impaired executive functions (EF)¹, which become more evident when performing more complex activities (5). Impaired working memory (9), a part of EF (8), and prospective memory (10) are also common, as well as attention disorders (11), impaired processing speed, timing deficits (5), problems with time management (12) and with getting things done (13). Impaired visuospatial function is also common (11). In general, individuals with SB have no limitations in reading, vocabulary, grammar, and sentence structure, but may have difficulties in understanding the underlying meaning of words and in drawing conclusions (5). Reduced reading comprehension and reduced numeracy are also common (5). Learning capacity is often unaffected, but individuals may have difficulties in processing and retrieving information (5). These cognitive impairments can be observed in childhood and become more evident during adolescence and adulthood, when activities of daily living (especially taking care of your own household), education, work and relations put increased demands on the person (14). Several studies found that cognitive impairments in individuals with SB do not decrease with maturity, but persist into adulthood (9, 14). Furthermore, impairments in prospective memory have also been shown to increase for persons over 32 years of age (10). Few studies have examined the effects of ageing on cognitive function in individuals with SB (9).Cognitive impairments are associated with quality of life (15) and affect performance of daily activities negatively for adults with SB (16), with potential impact on health and wellbeing (4, 17). Impaired EF may limit young adults in achieving milestones of independence in life, like education, work, relationships and assuming responsibility for their own household (18). Many individuals with SB do not reach secondary education and have difficulties in obtaining a job (19). Further challenges may appear in adulthood with the need to manage contacts with authorities regarding special transportation services, housing, and community-based support services, etc. (20). Moreover, management of personal hygiene and medication due to complex SB-related disabilities put additional demands on EF (20). Consequently, impaired EF increases risks for complications, such as pressure ulcers, urinary infections, incontinence, and constipation (21). However, individuals with SB are often highly verbal, giving the impression of managing everyday life well (22). Thus, healthcare professionals and others not specialized in the field seldom recognize these cognitive limitations (23). The need for support may go unrecognized, and interventions may be insufficient or even fail (24).In order to provide appropriate support, there is a need for assessments to recognize the range of cognitive impairments in individuals with SB and to consider how these impact on educational outcomes (completion of compulsory education²) and performance of daily activities (especially household activities). The aims of the current study were to explore cognitive impairments in adults with SB and to consider associations between these impairments, educational outcome, and performance of daily activities, comparing individuals with and without intellectual disabilities (ID).     

ASSOCIATION BETWEEN PRE-STROKE PHYSICAL ACTIVITY AND MOBILITY AND WALKING ABILITY IN THE EARLY SUBACUTE PHASE: A REGISTRY-BASED STUDY

ObjectiveTo investigate associations between prestroke physical activity and mobility, walking ability, and self-perceived upper extremity function during stroke unit care.DesignA longitudinal, registry-based study with a consecutively collected cohort.Subjects/patientsA total of 1,092 adults with stroke admitted to 3 Swedish stroke units between 2017 and 2018.MethodsLogistic mixed effects regression models were performed to investigate associations (adjusted for age and sex). Pre-stroke physical activity was assessed with Saltin-Grimby Physical Activity Level Scale on admission. Mobility, walking ability, and self-perceived upper extremity function were assessed at admission and discharge from the stroke units and compared between pre-stroke physically active (45%) and inactive (55%) groups.ResultsAll groups of patients showed improvements in mobility (p < 0.001), walking ability (p < 0.001), and upper extremity function (p < 0.001). The changes over time tended to differ between the physically inactive and active groups for mobility (p < 0.062) and walking ability (p < 0.056), but the differences were not significant.ConclusionPre-stroke physically active people showed a tendency to be more independent in physical functioning early after stroke. Regardless of prestroke physical activity, all patients showed improvements in mobility, walking ability, and self-perceived upper extremity function during inpatient care.LAY ABSTRACTTo be physically active prior to a stroke may improve the post-stroke recovery process. Therefore, we hypothesized that pre-stroke physical activity might reduce the consequences of a stroke. This study investigated associations between pre-stroke physical activity and post-stroke recovery of mobility, walking ability, and arm and hand function. A total of 1,092 patients were examined; 44% were women, 89% had ischaemic stroke, and 55% were physically inactive before the stroke. All patients showed improvements during care at the stroke units, regardless of their previous physical activity level. At hospital discharge, 71% of patients showed independent mobility, 68% could walk independently, and 55% reported self-perceived arm and hand impairments. Patients with higher pre-stroke physical activity levels had a tendency of being more independent in mobility and walking compared with inactive patients. However, the frequencies of self-perceived arm and hand impairments were similar between the physically active and physically inactive groups. To be physically active prior to a stroke may improve the post-stroke recovery process.Key words: prestroke, stroke, exercise, physical activity, mobility, transfers, walking, upper extremity

The number of people living with the consequences of a stroke has increased over time (1), which has substantially increased the global burden of adult disability (2). The overall goal of stroke rehabilitation is to regain independence (2), but it has been shown that 43% have remaining disability one month after stroke, and 39% after 5 years (3). Recovery can be defined as an improvement over time, evaluated as the return to pre-stroke functions and activities, or alternatively, evaluated in terms of the underlying mechanisms (4). Agreed definitions of phases in stroke recovery are acute (1–7 days), early (7 days to 3 months), and late (3–6 months) subacute, and chronic (more than 6 months) (4). Improvements mainly occur in the early subacute phase after a stroke (4), and care at a stroke unit is important for positive outcomes (5). Stroke-unit care and rehabilitation increases the probability that patients will survive, return to their own homes, and regain independence (5) at one year post-stroke (6). In stroke rehabilitation research, stroke-related impairments (sensorimotor deficiencies, quality of life, and global disability) should be evaluated with measures capturing mobility, walking, and motor function (7). According to the International Classification of Functioning, Disability, and Health (ICF) (8), mobility and walking ability are categorized as “activities and participation”, and upper extremity (UE) function is included in the category of “body structures”.Pre-stroke physical activity may promote neuroprotective mechanisms, such as angiogenesis, and neuroplasticity, in both human and animal subjects (9). This could contribute to better motor function, and motor recovery (9). Previous studies have shown that physical activity could reduce the risk of stroke by 25–30% (10). Physical activity is defined as any bodily movement produced by skeletal muscles that requires energy expenditure (11). Different types of physical activity can be categorized as occupational, sports, conditioning, household, or other activities (11). Exercise, which is a subcategory of physical activity, is planned, structured, and repetitive, and its purpose is to improve or maintain physical fitness (11). Pre-stroke physical activity was previously related to a reduction in the size of a cerebral infarction (12), less severe acute stroke symptoms (12–15), less post-stroke disability (12, 15, 16), and improved performance in activities of daily living (ADL) (15, 17, 18). Previous studies on disability after stroke often included a mobility assessment, but, typically, mobility was not measured separately from other abilities. Moreover, few studies have focused on associations between pre-stroke physical activity and post-stroke physical functioning (19) (i.e. mobility, walking ability, and UE function). However, 3 small studies showed that pre-stroke physical activity was positively related to post-stroke improvements in balance, walking speed (17), independent gait (20), and walking frequency (21). No studies have investigated the association between pre-stroke physical activity and UE function. Overall, little evidence is available on associations between pre-stroke physical activity and different post-stroke consequences, and the published results are conflicting (19, 22). The current study aimed to investigate associations between pre-stroke physical activity and post-stroke mobility, walking ability, and self-perceived UE function during inpatient stroke unit care.     

Synthesis of novel benzopyran-connected pyrimidine and pyrazole derivatives via a green method using Cu(ii)-tyrosinase enzyme catalyst as potential larvicidal,antifeedant activities

A series of benzopyran-connected pyrimidine (1a–g) and benzopyran-connected pyrazole (2a–i) derivatives were synthesized via Biginelli reaction using a green chemistry approach. Cu(ii)-tyrosinase was used as a catalyst in the synthesis of compounds 1a–g and 2a–ivia the Biginelli reaction. The as-synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectroscopy, and elemental analysis. The as-synthesized compounds were screened for larvicidal and antifeedant activities. The larvicidal activity was evaluated using the mosquito species Culex quinquefasciatus, and the antifeedant activity was evaluated using the fishes of Oreochromis mossambicus. The compounds 2a–i demonstrated lethal effects, killing 50% of second instar mosquito larvae when their LD₅₀ values were 44.17, 34.96, 45.29, 45.28, 75.96, and 28.99 μg mL⁻¹, respectively. Molecular docking studies were used for analysis based on the binding ability of an odorant binding protein (OBP) of Culex quinquefasciatus with compound 2h (binding energy = −6.12 kcal mol⁻¹) and compound 1g (binding energy = −5.79 kcal mol⁻¹). Therefore, the proposed target compounds were synthesized via a green method using Cu(ii)-enzyme as a catalyst to give high yield (94%). In biological screening, benzopyran-connected pyrazole (2h) was highly active compared with benzopyran-connected pyrimidine (1a–g) series in terms of larivicidal activity.

Cu(ii)-tyrosinase catalytic help with the synthesis of benzopyran-connected pyrimidine and pyrazole derivatives and their larvicidal activity.

Benzopyrans (coumarins) are an important group of naturally occurring compounds widely distributed in the plant kingdom and have been produced synthetically for many years for commercial uses.¹ In addition, these core compounds are used as fragrant additives in food and cosmetics.² The commercial applications of coumarins include dispersed fluorescent brightening agents and as dyes for tuning lasers.³ Some important biologically active natural benzopyran (coumarin) derivatives are shown in Fig. 1. Mosquitoes are the vectors for a large number of human pathogens compared to other groups of arthropods.⁴ Their uncontrollable breeding poses a serious threat to the modern humanity. Every year, more than 500 million people are severely affected by malaria. The mosquito larvicide is an insecticide that is specially targeted against the larval life stage of a mosquito. Particularly, the compound bergapten (Fig. 1), which shows the standard of larivicidal activity,⁵ is commercially available, and it was used as a control in this study for larvicidal screening. Moreover, the antifeedant screening defense mechanism makes it a potential candidate for the development of eco-friendly ichthyocides. Coumarin derivatives exhibit a remarkably broad spectrum of biological activities, including antibacterial,^6,7 antifungal,^8–10 anticoagulant,¹¹ anti-inflammatory,¹² antitumor,^13,14 and anti-HIV.¹⁵Open in a separate windowFig. 1Biologically active natural benzopyran compound.Coumarin and its derivatives can be synthesized by various methods, which include the Perkin,¹⁶ Knoevenagel,¹⁷ Wittig,¹⁸ Pechmann,¹⁹ and Reformatsky reactions.Among these reactions, the Pechmann reaction is the most widely used method for the preparation of substituted coumarins since it proceeds from very simple starting materials and gives good yields of variously substituted coumarins. For example, coumarins can be prepared by using various reagents, such as H₂SO₄, POCl₃,²⁰ AlCl₃,²¹ cation exchange resins, trifluoroacetic acid,²² montmorillonite clay,²³ solid acid catalysts,²⁴ W/ZrO₂ solid acid catalyst,²⁵ chloroaluminate ionic liquid,²⁶ and Nafion-H catalyst.²⁷Keeping the above literature observations, coumarin derivatives 1a–g and 2a–i are usually prepared with the conventional method involving CuCl₂·2H₂O catalysis with using HCl additive. This reduces the yield and also increases the reaction time. To overcome this drawback, we used mushroom tyrosinase as a catalyst without any additive, a reaction condition not reported previously. The as-synthesized compounds were used for the biological screening of larvicidal and antifeedant activities (marine fish). In addition, in this study, we considered the molecular docking studies study based on previous studies for performing the binding ability of hydroxy-2-methyl-4H-pyran-4-one (the root extract of Senecio laetus Edgew) with the odorant binding protein (OBP) of Culex quinquefasciatus.²⁸     

INCREASED SATELLITE CELL APOPTOSIS IN VASTUS LATERALIS MUSCLE AFTER ANTERIOR CRUCIATE LIGAMENT RECONSTRUCTION

ObjectiveRecovery of the quadriceps femoris muscle after anterior ligament reconstruction is impaired. The aim of this study was to investigate satellite cell content and function of the vastus lateralis muscle after anterior ligament reconstruction.MethodsBiopsies were obtained from the vastus lateralis muscle of 16 recreational athletes immediately before and again 12 weeks after anterior ligament reconstruction. Total satellite cell number (Pax7⁺), activated (Pax7⁺/MyoD⁺), differentiating (Pax7^–/MyoD⁺), and apoptotic (Pax7⁺/TUNEL⁺) satellite cells, myofibers expressing myosin heavy chain (MHC) I and II, and neonatal MHC (MHCneo) were determined immunohistochemically.ResultsAfter anterior ligament reconstruction, the number of apoptotic satellite cells was significantly (p = 0.019) increased, concomitant with a significant (p < 0.001) decrease in total satellite cell number, with no change in activated and differentiating satellite cell number. MHCneo⁺ myofibers tended towards an increase.CONCLUSIONSatellite cell apoptosis and the reduction in the satellite cell pool might provide an explanation for prolonged quadriceps muscle atrophy after anterior ligament reconstruction.LAY ABSTRACTProtracted muscle atrophy is common after anterior ligament reconstruction, even if athletes adhere to a structured rehabilitation programme. Satellite cells, the stem cells of skeletal muscle, play an important role in recovery of an atrophied muscle. Exercise can activate satellite cells, induce their proliferation, and probably also differentiation of these stem cells. The current study evaluated satellite cell content and function in biopsies from the vastus lateralis muscle of 16 recreational athletes immediately before and 12 weeks after anterior ligament reconstruction. After anterior ligament reconstruction, an increased number of satellite cells showed signs of apoptosis (cell death). Furthermore, total satellite cell number was decreased, with no change in the numbers of activated and differentiating satellite cells. The number of regenerating myofibers expressing neonatal myosin tended to increase. In conclusion, satellite cell apoptosis and the reduced satellite cell number might provide an explanation for the impaired muscle recovery after anterior ligament reconstruction.Key words: satellite cells, apoptosis, muscle regeneration, developmental myosin heavy chain, muscular atrophy, quadriceps muscle

Protracted atrophy and weakness of the quadriceps muscle are common after anterior cruciate ligament (ACL) injury and/or anterior cruciate ligament reconstruction (ACL-R), even if the patients undergo guided rehabilitation programmes (1–4). Muscle recovery is compromised due to negative changes in the knee extensor muscles, most likely due to impaired neuromuscular function (5), post-surgery inflammation (6) and immobilization (7). After ACL injury, fibrogenic alterations were observed in biopsies obtained from the vastus lateralis muscle of the injured leg (8, 9). Satellite cell (SC) abundance was also reduced compared with biopsies taken from the vastus lateralis muscle of the uninjured leg (8, 10). Furthermore, there was a surprising lack of increase in SC number after regular rehabilitation training (10), as well as after 12 weeks of supervised quadriceps strength training during rehabilitation after ACL-R (3).SCs play an important role in skeletal muscle growth and regeneration (11, 12). Increases in SC number occur after 11–12 weeks of quadriceps strength training in healthy subjects (13–15). The role of SCs in atrophy of human skeletal muscle, however, has scarcely been investigated. In the very few studies on the role of SCs in atrophy of human skeletal muscle (8, 10, 16), loss of SCs with atrophy is not a consistent finding. However, there is some evidence that a particularly severe atrophic environment, as is found, for example, after severe burn injury, has a negative impact on SC number and SC function and can induce SC apoptosis (17). With regard to findings in animal studies, it has been hypothesized that muscle wasting in old age (sarcopaenia) could at least partly be explained by SC dysfunction with increased SC apoptosis due to chronic low-grade systemic inflammation (18). The significantly reduced SC number in biopsies from the vastus lateralis muscle after ACL injury (8, 10) and the lack of increase in SC number after resumption of muscular training after ACL-R (3, 10) suggest that ACL injury and/or ACL-R with quadriceps tendon or semitendinosus tendon autografts, respectively, might generate a severe atrophic environment with negative effects on SC number and function.The primary aim of this study was to further investigate the effects of ACL-R on SCs and to determine whether the previously described reduction in SC number might be due to SC apoptosis. The study analysed muscle biopsies from the vastus lateralis muscle of recreational athletes immediately before ACL surgery and again after 12 weeks of early rehabilitation.     

Challenges and opportunities in the recovery of gold from electronic waste

Rapid global technological development has led to the rising production of electronic waste that presents both challenges and opportunities in its recycling. In this review, we highlight the value of metal resources in the printed circuit boards (PCBs) commonly found in end-of-life electronics, the differences between primary (ore) mining applications and secondary (‘urban’) mining, and the variety of metallurgical separations, in particular those that have the potential to selectively and sustainably recover gold from waste PCBs.

Rapid global technological development has led to the rising production of electronic waste that presents both challenges and opportunities in its recycling.

The rapid global rise in technology, tied in with consumer pressures for upgrades in functionality and design, has generated advanced electrical and electronic equipment with short lifespans. A consequence of this is the production of electronic waste (e-waste) which, in 2018 amounted to 50 million tonnes,^1,2 with a projected annual growth of 3–5%, three times more than for other waste streams.³ Reports on recycling rates vary, with estimates of around 20–30%.^1,4 It is estimated that more than 70% of globally produced waste electronics and electrical equipment (WEEE) enter China, Africa and India for reprocessing, much of it illegally, and often using crude, hazardous and inefficient processes.^5,6 Dumping and incinerating large amounts of WEEE has severe impact on human life and the environment,⁷ as it leads to the release of toxic heavy elements such as lead, mercury, chromium, nickel, beryllium, arsenic and antimony into the air, soil and water cycles.⁸An end-of-life printed circuit board (PCB) may contain up to 60 different chemical elements,⁹ and have a metal content as high as 40% by weight,¹⁰ so should be viewed as a valuable secondary source of precious and base metals. The metal content of a PCB is typically ten to a hundred times higher than that of conventionally mined ores.¹¹ It is estimated that recycling one ton of mobile phones could produce on average 130 kg of copper, 3.5 kg of silver, 0.34 kg of gold and 0.14 kg of Pd.¹² On this basis, the global e-waste management market is projected to produce an annual revenue of USD 62.5 billion by the end of 2020.^2,13 With an estimated 97% of the world population owning a mobile phone,¹⁴ it can be viewed as a plentiful feedstock for a recycling process. As such, the treatment of e-waste not only helps minimise the environmental impact of our technology-driven society by reducing pollution and energy demands compared to conventional mining practice,¹⁵ it also presents economic drivers for wealth creation and circular economies.^16–21In this review, we outline some of the latest chemical approaches that have been reported for the recovery of gold from discarded mobile phones and other WEEE.^22,23 Gold is the most valuable component of e-waste, with estimates for its consumption to fuel our technology-driven society at 263.3 MT per year.^7,24 We provide an overview of metal concentrations that are present in waste PCBs from end-of-life mobile phones, analyse the different pre-treatment steps that can be used to separate the metallic and non-metallic components of PCBs, and highlight various metallurgical methods for the extraction of gold from waste PCBs. For this latter aspect, we focus on methods in the primary research literature for which an understanding of the chemical mode of action has been developed; as such, a detailed analysis of the patent literature is not in the scope of this review.