Nickel(ii)-catalyzed tandem C(sp2)–H bond activation and annulation of arenes with gem-dibromoalkenes

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold. Attractive features of this system include its low cost, ease of operation, and its ability to access a wide range of isoindolinones.

A nickel(ii)/silver(i)-catalyzed tandem C(sp²)–H activation and intramolecular annulation of arenes with dibromoalkenes has been successfully achieved, which offers an efficient approach to the 3-methyleneisoindolin-1-one scaffold.

Over the past years, the transition-metal-catalyzed oxidative C–H/C–H cross-coupling reaction has emerged as a useful, atom- and step-economic synthetic protocol to construct a series of important N-heterocycles.¹ In this context, the synthesis of isoindolinones has attracted considerable attention owing to their interesting biological and pharmaceutical properties,² as well as their usefulness as precursors for the synthesis of structurally diverse and complex molecules (Scheme 1).^2c,3 Several methods have successfully been developed toward isoindolinone synthesis based on Pd,⁴ Cu,⁵ Ru,⁶ and Rh⁷ salts. Among these reactions, the oxidative coupling reactions of benzamides with alkenes^4b,6,7a,f,g or alkynes^5a,5d exhibit high atom economy and the application of this strategy to simple arenes is still largely underdeveloped.⁸ For instance, in 2015, Zhang''s group⁹ revealed cobalt-catalyzed oxidative alkynylation and cyclization of simple arenes and terminal alkynes with silver-cocatalyst via 2-fold C–H bond and N–H bond cleavage and C–C bond and C–N bond formation. In 2016, Song''s group¹⁰ developed a method of a cobalt(ii)-catalyzed decarboxylative C–H activation/annulation of benzamides and alkynyl carboxylic acids and nickel(ii)-catalyzed C(sp²)–H alkynylation/annulation cascade with terminal alkynes to synthesize 3-methyleneiso-indolin-1-ones. Zhang also reported a nickel-catalyzed oxidative alkynylation with amides and terminal acetylenes.^10c In addition, from an environmentally point of view, in 2015, wei''s group¹¹ described an operationally simple, Pd-catalyzed C–H functionalization for the synthesis of important and useful isoindolinones from readily available carboxamides and carboxylic acids or anhydrides. The protocol avoided the use of excess oxidants including benzoquinone, Cu(OAc)₂, or Ag₂CO₃ of previous all the reactions, thus generating stoichiometric amounts of undesired wastes.Open in a separate windowScheme 1Representative isoindolinones with biological and pharmaceutical.To our knowledge, the synthesis of alkynes is among the most fundamental and important synthetic transformations due to the unique reactivity of alkynes including addition, oxidation, reduction, and in particular cyclization.¹² However, the lack of reactivity of alkynes, more electron-deficient than the corresponding alkenes, makes it harder to couple them with heteroarenes. As a consequence, terminal alkyne precursors have been developed to facilitate acetylene exchange.¹³ Halogenoalkynes,¹⁴ hypervalent alkynyliodoniums,¹⁵acetylenic sulfones,¹⁶ copper acetylides¹⁷ and α,β-ynoic acids¹⁸ allowed the generation of more activated alkyne moieties thus broadening the applications of direct alkynylation reactions to heterocycles. Among these alternatives, gem-dihaloalkenes emerged as more efficient coupling partners than the corresponding monohalogenated alkynes along with being inexpensive and readily-available.¹⁹ Indeed, the two geminal halogen atoms on the alkenyl carbon enhance the reactivity of metal complexes thus facilitating cross coupling reactions.²⁰ Stable and readily-available 1,1-dibromo-1-alkenes and our interests in the C–H activation²¹ led us to consider using these reagents in the C–H functionalization to construct the valuable isoindolinones. We can envision that the abundance and structural diversity of the aldehydes (used the preparation of gem-dibromoethylenes via wittig reaction) as well as the merits of C–H functionalization would make the synthetic methods desirable and attractive. Herein, we wish to disclose the nickel(ii)/silver(i)-mediated tandem transformation involving sequential C(sp²)–H/C(sp²)–H alkynylation and intramolecular annulation of unactivated arenes with dibromoethylenes with the assistance of 8-aminoquinoline (Scheme 2). These features of this approach operational simplicity, a wide-ranging substrate scope, and tolerance of various synthetically useful functional groups.Open in a separate windowScheme 2Nickel(ii)/silver(i)-catalyzed alkynylation/annulation of arenes with dibromoalkenes.     

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.     

Correction: Porous conducting polymer and reduced graphene oxide nanocomposites for room temperature gas detection

Correction for ‘Porous conducting polymer and reduced graphene oxide nanocomposites for room temperature gas detection’ by Yajie Yang et al., RSC Adv., 2014, 4, 42546–42553.

The authors wish to draw the reader’s attention to their previous related study, published in ACS Applied Materials & Interfaces,¹ which was not cited in this RSC Advances paper. The RSC Advances paper is a valuable and necessary supplement to the publication in ACS Applied Materials & Interfaces and focused on the reduced gas sensing performance of the devices instead of film characterization and film conductive performance.The authors regret not giving correct attribution to Fig. 1–6 which duplicate data from ref. 1 and therefore should be attributed to that paper. Additionally, there are portions of overlapping text in the discussion of these figures and the Introduction and Conclusion sections of the RSC Advances paper, which should be attributed to ref. 1.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

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     

REHABILITATION IN PATIENTS WITH LYMPHOMA: AN OVERVIEW OF SYSTEMATIC REVIEWS

ObjectiveTo evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation interventions in patients with lymphoma.Data sourcesA comprehensive literature search was conducted using medical/health science databases up to 1 October 2020. Bibliographies of pertinent articles, journals and grey literature were searched.Data extraction and synthesisTwo reviewers independently selected and reviewed potential reviews for methodological quality and graded the quality of evidence for outcomes using validated tools. Any discrepancies were resolved by final group consensus.ResultsTwelve systematic reviews (n = 101 studies, 87,132 patients with lymphoma) evaluated 3 broad categories of rehabilitation interventions (physical modalities, nutrition and complementary medicine). Most reviews were of moderate-to-low methodological quality. The findings suggest: moderate-quality evidence for exercise programmes for improved fatigue and sleep disturbance; low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and an inverse association between sunlight/ultraviolet radiation exposure and incidence of non-Hodgkin’s lymphoma; and very low-quality evidence for beneficial effects of yoga for sleep disturbances. Association between physical activity and lymphoma risk is indistinct.ConclusionDespite a range of rehabilitation modalities used for patients with lymphoma, high-quality evidence for many is sparse. Beneficial effects of exercise programmes were noted for fatigue, psychological symptoms and quality of life. More research with robust study design is required to determine the effective rehabilitation approaches.LAY ABSTRACTLymphoma and its treatment cause significant disability and morbidity, often requiring comprehensive rehabilitation. Currently, a range of rehabilitation interventions are applied in patients with lymphoma. This review systematically evaluated evidence from published systematic reviews of clinical trials to determine the effectiveness of rehabilitation interventions in patients with lymphoma. The findings suggest that there is moderate-quality evidence for exercise programmes in improving fatigue and sleep disturbance. There was low-quality evidence for exercise therapy alone and qigong/tai chi for improved symptoms and overall quality of life, and very low-quality evidence for beneficial effects of yoga for sleep disturbances. The evidence for association of vitamin D or physical activity and lymphoma risk is limited.Key words: lymphoma, rehabilitation, systematic review, critical appraisal

Lymphomas are a heterogeneous group of malignant neoplasms of the haematopoietic system, characterized by the aberrant proliferation of mature lymphoid cells or their precursors (1). Traditionally lymphoma is classified broadly into 2 major groups: non-Hodgkin’s lymphoma (NHL, 90%) and Hodgkin’s lymphoma (HL) (1); however, lymphomas can also be stratified by cell of origin, as in the World Health Organization (WHO) classification (B-cell, T-cell/natural killer-cell (T/NK) and HL), or clinical behaviour (aggressive or indolent) (2, 3). An estimated 590,000 new cases of lymphoma (3.2% of all cancers) were diagnosed worldwide in 2018, the majority being NHLs (509,590 cases, 2.8% of all cancers) (4). NHL is a leading cause of death amongst the haematological malignancies globally, estimated to cause over 248,000 deaths (2.6% of all cancers) in 2018 (4). The incidence of lymphoma is increasing, with total worldwide incidence projected to reach approximately 919,000 by 2040 (5).The total global economic burden of lymphoma is unknown; however, treatments and supportive care requirements are resource-intensive and associated with significant financial costs for patients/families and healthcare systems. Productivity losses arise from disease and treatment-associated morbidity and premature mortality (6). In 2018, the mean monthly healthcare and utilization costs per patient for diffuse large B-cell lymphoma (DLBCL) and follicular lymphoma (FL) in the USA were approximately US$11,890 and $10,460, respectively (6). In Spain, in 2017 lymphoma represented 45.4% of productivity losses due to haematological malignancies, resulting in €121 million in losses due to premature mortality (7).Current therapeutic advances and cancer detection/diagnosis have improved survival rates for patients with lymphoma (PwL). The age-standardized 5-year net survival of lymphoid malignancies in adults ranges from 40% to 70% globally in 2010–14, with a 5–10% increase in trend for the period 2000–04 (8). The 5-year survival rate in the US in 2010–16 was estimated to be 72.7% for NHL and 87.4% for HL (9). As the incidence of NHL is strongly associated with increasing age, improved supportive care and availability of reduced intensity chemotherapy regimens (such as prednisone, etoposide, procarbazine, and cyclophosphamide – ‘PEP-C’; rituximab, doxorubicin, cyclophosphamide, vincristine, and prednisone – ‘R-miniCHOP’, rituximab, cyclophosphamide, vincristine, prednisolone – ‘R-CVP’) are critical to facilitate deliverable therapy to older patients. Despite these factors, certain lymphomas and their treatment are associated with short- and medium-term residual neurological deficits, leading to physical, cognitive, psychosocial and behavioural impairments, limiting activities of daily living (ADL) and participation (10–13). Treatment procedures can be extensive (e.g., radiotherapy, chemotherapy and/or surgery), and associated with a range of side-effects/complications, such as neuropathy, cardiotoxicity, cachexia, fatigue, deconditioning, myopathy, etc. (14–16). Furthermore, in the transitional period, various adjustment issues are reported, such as increased care needs, inability to drive and return to work, financial constraints, relationship stress, and limitation in societal participation (11, 14, 17, 18). Distressing symptoms, such as fatigue, is a major complaint, reported in 60–100% of patients during or after cancer treatment, which persists for several years after treatment (19–21). Therefore, patients require routine surveillance to monitor complications and relapse and integrated longer-term management, including rehabilitation (22–24).Rehabilitation is an integral part of any cancer management, and there is evidence suggesting the beneficial effect of comprehensive rehabilitation (25–31). Furthermore, a major limitation of delivery of chemotherapy and predictor of inferior outcome is poor performance status (32). As the incidence of older patients treated for lymphoma requiring rehabilitation before or after anti-lymphoma therapy increases, effective evidence-based rehabilitation strategies are expected to play critical and expanding roles in best practice. Currently, a range of rehabilitation interventions are trialled in the management of lymphoma pre-treatment, during adjuvant therapies, and late phases of care, and, for the longer-term, care continuum in the community. The aim is to maximize patient function, promote independence and participation, and improve psychological well-being and quality of life (QoL) (28, 29). Reports suggest that patients with haematological malignancies, including lymphomas, can make functional gains in inpatient rehabilitation settings (31). Maximal exercise capacity seems to decrease before treatment in PwL, especially in patients with advanced disease, and tends to return to close to normal during and/or after treatment (33). Furthermore, comprehensive exercise programmes were found to be effective in reducing disability and symptoms (depression, anxiety, fatigue, pain, etc.), improving functional capacity, muscular strength and QoL (19, 31, 34, 35). One systematic review reported that NHL survivors who met public health exercise guidelines defined by the American College of Sports Medicine (i.e. engaging in >30 min/day of at least moderate physical activity (PA) on ≥ 5 days/week, or > 150 min a week) reported a clinically important better health-related quality of life (HRQoL) than their counterparts who did not meet exercise guidelines (11). Aerobic exercise training interventions were associated with positive effects on cardiorespiratory fitness, fatigue and self-reported physical functioning, and were feasible and safe in PwL (33). Other complementary and alternative therapies, such as mindfulness-based cognitive therapy, meditation, yoga, and tai chi, have shown improvement in cognitive function and QoL (36–38). Another recent systematic review reported that a combination of PA together with mental exercise may be more beneficial to PwL (39). There remains, however, an unmet need in the cancer population, and only a limited number of survivors receive the appropriate rehabilitation intervention that they need (40, 41). Furthermore, despite acknowledging rehabilitation as an integral component of the management of cancer patients, rehabilitation-specific guidelines for many cancer groups are limited, and many general cancer guidelines do not incorporate recommendations for specific rehabilitation interventions (42–44).As mentioned above, various systematic reviews have evaluated the current evidence regarding the effectiveness and safety of different rehabilitation interventions in PwL. However, these published reviews vary in scope, methodology and quality, with diverse, and occasionally discordant, conclusions. The heterogeneity of the lymphoma rehabilitation literature warrants a comprehensive review, with a focus on the evidence for efficacy and potential harm of various rehabilitative strategies. A systematic review of systematic reviews is a new approach to synthesize current evidence across the same or similar interventions, to summarize treatment effect in a much broader concept (45). This approach allows comparison of results from multiple reviews, thereby providing a comprehensive evidence-based summary (45, 46). To our knowledge, systematic reviews of rehabilitation strategies for PwL have not been thoroughly and qualitatively appraised to date. Therefore, this review aimed to systematically evaluate existing evidence from published systematic reviews for the effectiveness of rehabilitation strategies for improved function, impairments and participation in PwL. Specific questions addressed include: Are rehabilitation interventions effective in minimizing impairment, activity limitation, participation restriction and treatment-related complications in PwL?, and: What specific types of rehabilitation interventions are effective in PwL, and in which setting?     

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.     

LONGITUDINAL GOAL ATTAINMENT WITH INTEGRATED UPPER LIMB SPASTICITY MANAGEMENT INCLUDING REPEAT INJECTIONS OF BOTULINUM TOXIN A: FINDINGS FROM THE PROSPECTIVE,OBSERVATIONAL UPPER LIMB INTERNATIONAL SPASTICITY (ULIS-III) COHORT STUDY

ObjectiveTo assess the longitudinal effects of integrated spasticity management incorporating repeated cycles of botulinum toxin A type A (BoNT-A) over 2 years.MethodsThe Upper Limb International Spasticity study was a prospective, observational, cohort study following adult patients over 2 years of integrated upper-limb spasticity management including repeat botulinum toxin (BoNT-A) treatment (any commercially-available product).ResultsA total of 1,004 participants from 14 countries were enrolled, of which 953 underwent ≥ 1 BoNT-A injection cycle (median 4 cycles) and had ≥ 1 goal attainment scaling assessment. Most participants (55.9–64.6% across cycles 1–6) saw a therapist after BoNT-A treatment; the most frequent therapy intervention was passive stretch (70.1–79.8% across cycles 1–6). Patients achieved their goals as expected over repeated cycles; mean cumulated goal attainment scaling T-score at 2 years was 49.5 (49.1, 49.9). Mean goal attainment scaling change scores of ≥ 10 were maintained across up to 7 cycles. Higher rates of goal achievement were seen for primary goals related to passive vs active function (86.6% vs 71.4% achievement). Standardized measures of spasticity, pain, involuntary movements, active and passive function improved significantly over the study.CONCLUSIONThis large, international study provides evidence for benefit of repeated cycles of BoNT-A, over 2 years captured through person-centred goal attainment and standardized measures.LAY ABSTRACTThis paper presents the primary efficacy results from the Upper Limb International Spasticity (ULIS-III) study, a large international longitudinal study that explored real-life clinical practice in the integrated management of upper-limb spasticity, using botulinum toxin-A (BoNT-A) in conjunction with physical therapies. The study provides evidence for the sustained functional benefit of repeated cycles of BoNT-A. In particular, those patients who continued to receive repeated injections for up to 7 cycles in 2 years showed relevant goal attainment. Standard outcome measures generally supported the rates of goal achievement; ratings of pain, involuntary movements, active and passive function all improved significantly over each treatment cycle. The successful results from ULIS-III highlight the importance of accurate and clear goal-setting during BoNT-A treatment to help target clinical intervention and the use of focused outcome measurement.Key words: botulinum toxin A, goal attainment scaling, physical therapies, post-stroke spasticity, stroke rehabilitation

Spasticity is a common feature of upper motor neurone syndrome, which typically follows damage to the central nervous system. Botulinum toxin type A (BoNT-A) is shown in controlled studies to be a safe and effective focal intervention for reduction of spasticity (1-3), which is now recommended for use in routine clinical practice by national and international guidelines (4–6). However, while changes at the level of impairment are readily seen, changes at the level of function or activity have been more difficult to demonstrate (7–9). This is partly due to the wide heterogeneity of patient presentation and the diversity of individual expectations and goals for treatment (10).Goal attainment scaling (GAS) (11) is increasingly accepted as a person-centred outcome measure for evaluating the attainment of individual goals for treatment and is now used to assess the effectiveness of rehabilitation in the areas that matter most to the patients and their caregivers (9, 10, 12). GAS has been shown to be sensitive to changes that occur following treatment of focal spasticity using BoNT-A (13–15), but a criticism of GAS is the theoretical lack of comparability in the data produced (16). Moreover, spasticity is a long-term condition, often requiring repeated treatment, and most of the studies to date have evaluated outcomes from just 1 or 2 injection cycles, mainly following stroke.The Upper Limb International Spasticity (ULIS) study programme is a series of international observational studies designed to describe real-life clinical practice in the use of BoNT-A to manage upper limb spasticity (17). The first 2 studies (ULIS-I (18) and ULIS-II (19)) documented current practice and confirmed the feasibility of a common international dataset to collect prospective data incorporating GAS to capture outcomes across a range of goal areas, which included passive and active function, as well as pain and mobility. The third study (ULIS-III) describes the effects of integrated spasticity management incorporating repeated cycles of BoNT-A over 2 years in patients with spasticity of any aetiology. It introduces novel methods to: (i) systematically capture integrated approaches to spasticity management, including multidisciplinary therapy inputs; and (ii) the Upper Limb Spasticity Index, which combines GAS with targeted standardized measures (selected according to the patient’s priority goals for treatment) to provide comparability between different populations and practices.This article presents the first primary effectiveness findings from the ULIS-III longitudinal study, reporting the population level recorded at each cycle. In addition, our previously-reported analysis of baseline and first cycle data identified significantly different injection intervals between the various BoNT-A products (20), and a secondary aim was to explore in more detail the longevity of these observations.     

Correction: An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent

Correction for ‘An efficient multicomponent synthesis of 2,4,5-trisubstituted and 1,2,4,5-tetrasubstituted imidazoles catalyzed by a magnetic nanoparticle supported Lewis acidic deep eutectic solvent’ by Thanh Thi Nguyen et al., RSC Adv., 2019, 9, 38148–38153, DOI: 10.1039/C9RA08074K.

The authors apologise that a related reference, given here as ref. 1–5, was not cited in the original article. On page 38148, in the first paragraph of the Introduction, a citation to the reference should be added at the end of the sentence beginning “Among them, Lewis acidic…”. The paragraph should be changed as follows “In past decade, deep eutectic solvents (DESs) have attracted much attention in both reaction media and catalysts due to their unique properties such as wide liquid range, biodegradability, excellent thermal stability, and negligible vapor pressure.^1,2 Among them, Lewis acidic deep eutectic solvents (LADESs) have been intensively studied as efficient media for organic syntheses.^3–5”.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

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     

Correction: Nano N-TiO2 mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes

Correction for ‘Nano N-TiO₂ mediated selective photocatalytic synthesis of quinaldines from nitrobenzenes’ by Kaliyamoorthy Selvam et al., RSC Adv., 2012, 2, 2848–2855, DOI: 10.1039/C2RA01178F.

The authors regret omitting citations of their related papers in Journal of Molecular Catalysis A: Chemical and Applied Catalysis A: General: ‘Cost effective one-pot photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂’ (DOI: 10.1016/j.molcata.2011.09.014)¹ and ‘Mesoporous nitrogen doped nano titania—A green photocatalyst for the effective reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol’ (DOI: 10.1016/j.apcata.2011.11.011).² The citations should have appeared in the following places as ref. 36 (ref. 1, in the reference list here) and ref. 37 (ref. 2, in the reference list here):In the sentence starting on line 5 of paragraph 5 in the introduction:‘Photocatalytic synthesis of quinolone derivatives from nitrobenzene using TiO₂, metal doped TiO₂ and others had been reported earlier.^1,23–25’At the end of Section 3.12 with the addition of the following sentence:‘This catalyst was also found to be effective for the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles in methanol.²’The authors regret that it was not clear in the original article that the bare TiO₂ and N-TiO₂ characterisation data had been reproduced from their related Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 Although the Catalysis Communications article was cited as ref. 25 (ref. 3, in the reference list here) in the original article, it was not made clear that some of the data was reproduced from this article. The appropriate figure captions have been updated to reflect this.Fig. 2: Diffuse reflectance spectra of (a) bare TiO₂, (b) N-TiO₂ and (c) TiO₂-P25. The bare TiO₂ data in Fig. 2a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 2b have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 3: Photoluminescence spectra of (a) bare TiO₂, (b) TiO₂-P25 and (c) N-TiO₂. The bare TiO₂ data in Fig. 3a have been reproduced with permission from ref. 1. Copyright 2011 Elsevier. The N-TiO₂ data in Fig. 3c have been reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 4: HR-TEM analysis: (a and b) images at two different regions of N-TiO₂, (c) SAED pattern of N-TiO₂, (d) lattice fringes of N-TiO₂ and (e) particle size distribution of N-TiO₂. Fig. 4 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 5: X-ray photoelectron spectra of N-TiO₂: (a) survey spectrum, (b) Ti 2p peak, (c) O 1s peak, (d) N 1s peak and (e) C peak. Fig. 5 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 6: (a) N₂ adsorption–desorption isotherms of N-TiO₂ and (b) its pore size distribution. Fig. 6 has been entirely reproduced with permission from ref. 2. Copyright 2012 Elsevier.Fig. 8: GC-MS chromatograms at different reaction times for the photocatalytic conversion of nitrobenzene with N-TiO₂. Fig. 8 has been entirely reproduced with permission from ref. 3. Copyright 2011 Elsevier.The authors also wish to remove Fig. 1 from the original article due to similarities between two of the spectra and the raw data no longer being available. This does not affect the conclusions as the presence of nitrogen was confirmed by other techniques.The authors also wish to clarify the differences between this RSC Advances paper and the Journal of Molecular Catalysis A: Chemical, Applied Catalysis A: General and Catalysis Communications papers.^1–3 The Journal of Molecular Catalysis A: Chemical paper discusses the photocatalytic synthesis of quinaldines from nitroarenes by silver loaded TiO₂.¹ The Applied Catalysis A: General paper reports the reductive cleavage of azoxybenzenes to amines or 2-phenyl indazoles using mesoporous nitrogen doped nano titania.² The Catalysis Communications paper, ref. 25 in the original article, discusses the synthesis of quinaldines from nitroarenes with gold loaded TiO₂ nanoparticles.³ The original RSC Advances paper discusses the catalytic ability of N-TiO₂ in the synthesis of quinaldines from nitrobenzenes. In each paper, either a different catalyst was used or a different synthetic reaction was investigated.     

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.     

PREDICTORS FOR SELF-REPORTED FEELING OF DEPRESSION THREE MONTHS AFTER STROKE: A LONGITUDINAL COHORT STUDY

ObjectiveDepression and impaired cognition are common consequences of stroke. The aim of this study was to determine whether cognitive impairment 36–48 h post-stroke could predict self-reported feeling of depression 3 months post-stroke.DesignA longitudinal, cohort study.PatientsPatients aged ≥ 18 years at stroke onset.MethodsCognition was screened using the Montreal Cognitive Assessment, 36–48 h after admission to the stroke unit at Sahlgrenska University Hospital. Information about self-reported feeling of depression 3 months post-stroke was retrieved from Riksstroke (the national quality register for stroke in Sweden). Bootstrapped binary logistic regression analyses were performed.ResultsOf 305 patients, 42% were female, median age was 70 years, and 65% had mild stroke. Three months post-stroke, 56% of patients had self-reported feeling of depression; of these, 65% were female. Impaired cognition at baseline could not predict self-reported feeling of depression 3 months later. The odds for self-reported feeling of depression were twice as high in female patients (odds ratio 2.01; 95% confidence interval, 0.20–1.22; p < 0.01).ConclusionImpaired cognition early after stroke could not predict self-reported feeling of depression 3 months post-stroke. Compared with male patients, female patients had twice the odds of self-reported feeling of depressionLAY ABSTRACTDepression and impaired cognition are common consequences of stroke. This study investigated whether screening for cognitive function 36–48 h after stroke could predict self-reported feeling of depression 3 months later. Of the 305 patients with mild stroke, 56% had self-reported feeling of depression. Cognitive impairment could not predict self-reported feeling of depression. Therefore, cognitive screening within the first 2 days after stroke might be too early to predict self-reported feeling of depression 3 months after stroke. However, the high proportion of patients with self-reported feeling of depression indicates the severity of the problem that needs to be addressed.Key words: stroke, cognition, assessment, depression, selfperceived, prediction, bootstrapping

Post-stroke depression (PSD) is a common condition identified in up to 40% of patients, 3 months after stroke (1–3). Since approximately only 17% of patients with PSD have a previous history of depression, PSD can primarily be considered a consequence of stroke (4). A previous study showed a high number of patients developing PSD in the first month after stroke (5). The prevalence of depression in the acute phase after stroke was 25%, with a slight increase of to 31% after 3 months (5). PSD is associated with increased mortality, decreased quality of life, physical disability, and poor functional outcomes after stroke (6). Therefore, timely detection of depression is important (1), but can be hindered by various factors, such as short duration of hospitalization, insufficient healthcare resources, and poor communication between healthcare facilities (7). Thus, the availability of other information gathered early after stroke that can help predict PSD will be of clinical value.The mechanisms underlying PSD are complex and associated with multiple factors; including patients’ pre-stroke characteristics, stroke-related risk factors, and post-stroke conditions (8). Impaired cognition has been linked to PSD (9, 10). Executive dysfunction, language impairment, and orientation deficits were also related to PSD (11). However, the cause–effect relationship between cognition and depression is unclear. Neurobiological pathways, such as vascular depression and neuroinflammation can cause PSD (12, 13). Nevertheless, none of these can be considered more dominant or the leading cause of PSD. However, these pathways could still be possible causes of PSD, together with cognitive impairment.Unlike cognitive function, female sex is a well-known predictor of PSD (14, 15). Female patients are also more likely to be widowed before stroke, have a high mean age, more severe stroke, and a higher level of post-stroke disability (14). However, the results regarding patients’ age and risk of PSD are conflicting, indicating that both young and old patients have a high risk of PSD 3–12 months after stroke (14, 16, 17). Furthermore, patients younger than 70 years have a high risk of PSD (16, 18). Other well-known predictors of PSD are severe stroke, stroke localization, high dependency level, and social isolation post-stroke (15, 16).The predictive value of cognitive function for PSD remains unclear. Moreover, no studies were found that assessed the association between screening of cognition very early post-stroke and self-reported feeling of depression (SRFD) 3 months after stroke, when the first post-stroke follow-up is commonly done. Thus, the primary aim of this study was to explore the association between cognitive function screened very early after stroke and SRFD 3 months later. The secondary aims were to study the influences of sex and age on cognition and SRFD 3 months post-stroke.     

EFFECTIVENESS OF EXERCISE INTERVENTIONS FOR CHILDREN WITH CEREBRAL PALSY: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

ObjectiveThe results of previous research into exercise interventions for children with cerebral palsy are inconsistent. The aim of this study is to assess the effectiveness of such exercise interventions.DesignSystematic review and meta-analysis.MethodsSystematic searches of the PubMed, Embase and Cochrane Library databases for randomized controlled trials involving exercise interventions for children with cerebral palsy, from inception to January 2020, were performed. Pooled weighted mean differences (WMDs) with 95% confidence intervals (95% CI) for gross motor function, gait speed, and muscle strength were calculated using random-effects models.ResultsA final total of 27 trials, including 834 children with cerebral palsy, were selected for quantitative analysis. Exercise interventions had no significant effect on the level of gross motor function (WMD 1.19; 95% CI −1.07 to 3.46; p = 0.302). However, exercise interventions were associated with higher levels of gait speed (WMD 0.05; 95% CI 0.00–0.10; p = 0.032) and muscle strength (WMD 0.92; 95% CI 0.19–1.64; p = 0.013).ConclusionThese results suggest that exercise interventions may have beneficial effects on gait speed and muscle strength, but no significant effect on gross motor function in children with cerebral palsy.LAY ABSTRACTCerebral palsy is the most common cause of physical impairment in children. This study evaluated the effectiveness of exercise interventions for children with cerebral palsy. Exercise interventions were significantly associated with increased gait speed and muscle strength, while gross motor function was not affected. Exercise interventions should therefore be used for children with cerebral palsy.Key words: cerebral palsy, child, exercise, meta-analysis, systematic review

Cerebral palsy is the most common cause of physical impairment in children and is characterized by gait abnormalities (1–3). The characteristics of cerebral palsy are associated with damage to the immature brain, which causes subsequent primary impairments, including decreased muscle tone, loss of selective motor control, and impaired balance. Secondary impairments include muscle shortening or weakness and decreased range of motion (4, 5). The prevalence of cerebral palsy is approximately 2.1 in every 1,000 births, and children account for 74% of cases worldwide (6, 7). Children with cerebral palsy are significantly affected by epilepsy and by disorders in motor function, sensation, perception, communication, and behaviour, which significantly affect quality of life and result in huge economic and psychological burdens (8–11).Currently, the primary therapeutic goals for cerebral palsy are aimed at improving mobility and upper limb function (12). Exercise interventions may also play an important role in improving muscle strength, endurance, and cardiorespiratory fitness. Several systematic reviews and meta-analyses have illustrated the potential role of exercise interventions for children with cerebral palsy; however, results regarding gross motor function, gait speed, and muscle strength are inconsistent (13–15). Exercise programmes usually include resistance and/ or aerobic training. Children with cerebral palsy have reduced muscle strength, and resistance exercise can maintain or increase muscle performance (16, 17), while aerobic training can improve cardiorespiratory fitness. Studies have found that muscle stretching can increase range of motion (18, 19). It is important to clarify the effectiveness of exercise interventions for treatment of cerebral palsy in children, and to determine the role of the type of training for children with cerebral palsy. A meta-analysis of randomized controlled trials (RCTs) of exercise interventions for children with cerebral palsy was therefore performed in order to assess the effectiveness of this treatment.     

Retraction: Olefin epoxidation with chiral salen Mn(iii) immobilized on ZnPS-PVPA upon alkyldiamine

Retraction of ‘Olefin epoxidation with chiral salen Mn(iii) immobilized on ZnPS-PVPA upon alkyldiamine’ by J. Huang et al., RSC Adv., 2016, 6, 19507–19514, DOI: 10.1039/C6RA00002A.

The Royal Society of Chemistry, with the agreement of the authors, hereby wholly retracts this RSC Advances article due to extensive overlap with other published articles by these authors, including the text, data and figures published in ref. 1, which was not cited in this article. Although there are sections of original work, there are significant portions of text overlap, particularly in the Results and discussion section. Fig. 1, 3, 4 and 5, Tables 1 and 2 and Schemes 1 and 2 in the RSC Advances article have also been reproduced from ref. 1.Signed: J. Huang, D. W. Qi, J. L. Cai and X. H. ChenDate: 19^th November 2020Retraction endorsed by Laura Fisher, Executive Editor, RSC Advances     

Correction: Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance

Correction for ‘Direct electrodeposition of cationic pillar[6]arene-modified graphene oxide composite films and their host–guest inclusions for enhanced electrochemical performance’ by Qunpeng Duan et al., RSC Adv., 2020, 10, 21954–21962, DOI: 10.1039/D0RA03138K.

The authors regret omitting a citation of their related paper published in Frontiers in Chemistry: ‘Facile one-step electrodeposition preparation of cationic pillar[6]arene-modified graphene films on glassy carbon electrodes for enhanced electrochemical performance’ (DOI: 10.3389/fchem.2020.00430) shown as ref. 1 here. The citation should appear as ref. 58 in the original article.¹The authors regret that it was not clear in the original article that the ErGO-CP6/GCE film had been previously reported by them in their related Frontiers in Chemistry paper¹ and therefore the sentence at the start of paragraph 3 on page 2 ‘In this work, we report for the first time preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1).’ should be ‘In this work, we report the preparation of CP6 functionalized graphene films on glassy carbon electrode (GCE) directly from GO-CP6 dispersions by facile one-step pulsed electrodeposition technique (Scheme 1), which was previously reported by us.⁵⁸’.The authors also wish to clarify the differences between this RSC Advances paper and the Frontiers in Chemistry paper.¹ The papers use different guests molecules and different optimum pulse electrodeposition parameters and the RSC Advances paper reports an improvement in electrochemical performance with additional characterisation, stability studies and the analysis of real samples which are not reported in the Frontiers in Chemistry paper.¹The appropriate figure captions have been updated to reflect the data reproduced from the Frontiers in Chemistry paper.¹Scheme 1 Schematic illustration for the pulsed electrodeposition preparation of ErGO and ErGO-CP6 films on the surface of GCE and sensing the guest molecules by an electrochemical strategy. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 1 Characterization of materials. FTIR spectra (A), UV-vis absorption spectra (B), TGA curves of CP6, GO-CP6, and GO (C), and XPS survey spectra of GO and GO-CP6 (D). The data in (a, c and d) have been reproduced with permission from ref. 1. Copyright 2020 Frontiers.Fig. 4 (A) Raman spectra of GO and ErGO. (B) Raman spectra of GOCP6 and ErGO-CP6. Reproduced with permission from ref. 1. Copyright 2020 Frontiers.     

Correction: Directed evolution of mevalonate kinase in Escherichia coli by random mutagenesis for improved lycopene

Correction for ‘Directed evolution of mevalonate kinase in Escherichia coli by random mutagenesis for improved lycopene’ by Hailin Chen et al., RSC Adv., 2018, 8, 15021–15028.

The authors wish to draw the readers’ attention to their closely related paper, published in Microbial Cell Factories,¹ which should have been cited in this RSC Advances paper.The authors regret that there is unattributed overlap in text between this RSC Advances paper and ref. 1. The authors confirm that new data has been reported in this RSC Advances article.Two different rate-limiting enzymes in the lycopene synthetic pathway were studied using the same methods, mevalonate kinase (MK) in this paper and isopentenyl diphosphate isomerase (IDI) in ref. 1. In the RSC Advances paper, a directed evolution strategy was used to optimize the activity of MK to enhance the tolerance for farnesyldiphosphate (FPP) and geranylgeranyldiphosphate (GGPP), to enhance the affinity of mevalonate and MK, and to improve lycopene production. The catalytic mechanisms of both enzymes are very different; however improving their activities can improve lycopene production.The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

Correction: Homo-condensation of acetophenones toward imidazothiones

Correction for ‘Homo-condensation of acetophenones toward imidazothiones’ by Phuc Hoang Pham et al., RSC Adv., 2020, 10, 40225–40228, DOI: 10.1039/D0RA03047C.

The authors regret the omission of two references, shown below as ref. 1(a) and (b), which should have appeared as ref. 7(a) and (b).On page 40227, at the end of the paragraph which starts “With the results in hand, we proposed a possible mechanism for the annulation (Scheme 5)…” the following sentence should have been added:“It should be noted that Asinger and co-workers reported a similar transformation using ammonia, instead of ammonium acetate, that occurred in methanol solvent.¹ For that reason, an alternative mechanism should not be excluded.”The Royal Society of Chemistry apologises for these errors and any consequent inconvenience to authors and readers.     

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.