An Exploration of Wearable Device Features Used in UK Hospital Parkinson Disease Care: Scoping Review.

BACKGROUND: The prevalence of Parkinson disease (PD) is becoming an increasing concern owing to the aging population in the United Kingdom. Wearable devices have the potential to improve the clinical care of patients with PD while reducing health care costs. Consequently, exploring the features of these wearable devices is important to identify the limitations and further areas of investigation of how wearable devices are currently used in clinical care in the United Kingdom. OBJECTIVE: In this scoping review, we aimed to explore the features of wearable devices used for PD in hospitals in the United Kingdom. METHODS: A scoping review of the current research was undertaken and reported according to the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) guidelines. The literature search was undertaken on June 6, 2022, and publications were obtained from MEDLINE or PubMed, Embase, and the Cochrane Library. Eligible publications were initially screened by their titles and abstracts. Publications that passed the initial screening underwent a full review. The study characteristics were extracted from the final publications, and the evidence was synthesized using a narrative approach. Any queries were reviewed by the first and second authors. RESULTS: Of the 4543 publications identified, 39 (0.86%) publications underwent a full review, and 20 (0.44%) publications were included in the scoping review. Most studies (11/20, 55%) were conducted at the Newcastle upon Tyne Hospitals NHS Foundation Trust, with sample sizes ranging from 10 to 418. Most study participants were male individuals with a mean age ranging from 57.7 to 78.0 years. The AX3 was the most popular device brand used, and it was commercially manufactured by Axivity. Common wearable device types included body-worn sensors, inertial measurement units, and smartwatches that used accelerometers and gyroscopes to measure the clinical features of PD. Most wearable device primary measures involved the measured gait, bradykinesia, and dyskinesia. The most common wearable device placements were the lumbar region, head, and wrist. Furthermore, 65% (13/20) of the studies used artificial intelligence or machine learning to support PD data analysis. CONCLUSIONS: This study demonstrated that wearable devices could help provide a more detailed analysis of PD symptoms during the assessment phase and personalize treatment. Using machine learning, wearable devices could differentiate PD from other neurodegenerative diseases. The identified evidence gaps include the lack of analysis of wearable device cybersecurity and data management. The lack of cost-effectiveness analysis and large-scale participation in studies resulted in uncertainty regarding the feasibility of the widespread use of wearable devices. The uncertainty around the identified research gaps was further exacerbated by the lack of medical regulation of wearable devices for PD, particularly in the United Kingdom where regulations were changing due to the political landscape.

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes.

This review presents a comprehensive overview of transition-metal-catalyzed domino reactions of strained bicyclic alkenes, including both homo- and heterobicyclic alkenes. These compounds are important synthons in organic synthesis, providing an important platform for the construction of biologically/medicinally significant compounds which bear multiple stereocenters. The review has been divided according to the metal used in the reaction. An overview of the substrate scope, reaction conditions, and their potential applications in organic synthesis is discussed. A comprehensive outlook on the reactivity paradigms of homo- and heterobicyclic alkenes is discussed and should shed light on future directions for further development in this field.

Erratum: Cold snare polypectomy of colorectal polyps ≤ 10 mm on clopidogrel: Australian and New Zealand randomized controlled trial.

[This corrects the article DOI: 10.1055/a-1813-1019.].

Iridium-catalyzed hydroacylation reactions of C1-substituted oxabenzonorbornadienes with salicylaldehyde: an experimental and computational study.

An experimental and theoretical investigation on the iridium-catalyzed hydroacylation of C1-substituted oxabenzonorbornadienes with salicylaldehyde is reported. Utilizing commercially available [Ir(COD)Cl]2 in the presence of 5 M KOH in dioxane at 65 °C, provided a variety of hydroacylated bicyclic adducts in up to a 95% yield with complete stereo- and regioselectivity. The mechanism and origins of selectivity in the iridium-catalyzed hydroacylation reaction has been examined at the M06/Def2TZVP level of theory. The catalytic cycle consists of three key steps including oxidative addition into the aldehyde C-H bond, insertion of the olefin into the iridium hydride, and C-C bond-forming reductive elimination. Computational results indicate the origin of regioselectivity is involved in the reductive elimination step.

Iron-catalyzed domino coupling reactions of π-systems.

The development of environmentally benign, inexpensive, and earth-abundant metal catalysts is desirable from both an ecological and economic standpoint. Certainly, in the past couple decades, iron has become a key player in the development of sustainable coupling chemistry and has become an indispensable tool in organic synthesis. Over the last ten years, organic chemistry has witnessed substantial improvements in efficient synthesis because of domino reactions. These protocols are more atom-economic, produce less waste, and demand less time compared to a classical stepwise reaction. Although iron-catalyzed domino reactions require a mindset that differs from the more routine noble-metal, homogenous iron catalysis they bear the chance to enable coupling reactions that rival that of noble-metal-catalysis. This review provides an overview of iron-catalyzed domino coupling reactions of π-systems. The classifications and reactivity paradigms examined should assist readers and provide guidance for the design of novel domino reactions.

Ruthenium-Catalyzed [2 + 2] versus Homo Diels-Alder [2 + 2 + 2] Cycloadditions of Norbornadiene and Disubstituted Alkynes: A DFT Study.

The ruthenium-catalyzed [2 + 2] and homo Diels-Alder [2 + 2 + 2] cycloadditions of norbornadiene with disubstituted alkynes are investigated using density functional theory (DFT). These DFT calculations provide a mechanistic explanation for observed reactivity trends with different functional groups. Alkynyl phosphonates and norbornadiene form the [2 + 2 + 2] cycloadduct, while other functionalized alkynes afford the respective [2 + 2] cycloadduct, in excellent agreement with experimental results. The computational studies on the potential energy profiles of the cycloadditions show that the rate-determining step for the [2 + 2] cycloaddition is the final reductive elimination step, but the overall rate for the [2 + 2 + 2] cycloaddition is controlled by the initial oxidative cyclization. Two distinct mechanistic pathways for the [2 + 2 + 2] cycloaddition, cationic and neutral, are characterized and reveal that Cp*RuCl(COD) energetically prefers the cationic pathway.

Chemistry of Unsymmetrical C1-Substituted Oxabenzonorbornadienes.

Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate, which can be readily activated by transition metal complexes with great face selectivity due to its dual-faced nature and intrinsic angle strain on the alkene. To date, the understanding of transition-metal catalyzed reactions of OBD itself has burgeoned; however, this has not been the case for unsymmetrical OBDs. Throughout the development of these reactions, the nature of C1-substituent has proven to have a profound effect on both the reactivity and selectivity of the outcome of the reaction. Upon substitution, different modes of reactivity arise, contributing to the possibility of multiple stereo-, regio-, and in extreme cases, constitutional isomers, which can provide unique means of constructing a variety of synthetically useful cyclic frameworks. To maximize selectivity, an understanding of bridgehead substituent effects is crucial. To that end, this review outlines hitherto reported examples of bridgehead substituent effects on the chemistry of unsymmetrical C1-substituted OBDs.

Intramolecular Palladium-Catalyzed Ring Opening of Oxabenzonorbornadienes with C1-Tethered Aryl Halides.

The novel intramolecular ring opening of oxabenzonorbornadienes with C1-tethered aryl halides was investigated using palladium catalysts to form fused tetracyclic frameworks. The reaction was generally found to synthesize 1,2-dihydronaphthalen-1-ol products with mild selectivity but was capable of synthesizing dehydrated naphthalene products in excellent yield and selectivity. Substituent effects on oxabenzonorbornadiene and on the iodoarene were explored along with the effects of varying tether length, where an efficient reaction was observed in nearly all cases. A total of 16 examples are reported with yields ranging from 0 to 96%.

Avocado-derived polyols for use as novel co-surfactants in low energy self-emulsifying microemulsions.

Avocado (Persea americana Mill.; Lauraceae) seed-derived polyhydroxylated fatty alcohols (PFAs) or polyols (i.e., avocadene and avocadyne) are metabolic modulators that selectively induce apoptosis of leukemia stem cells and reverse pathologies associated with diet-induced obesity. Delivery systems containing avocado polyols have not been described. Herein, natural surface active properties of these polyols are characterized and incorporated into self-emulsifying drug delivery systems (SEDDS) that rely on molecular self-assembly to form fine, transparent, oil-in-water (O/W) microemulsions as small as 20 nanometers in diameter. Mechanistically, a 1:1 molar ratio of avocadene and avocadyne (i.e., avocatin B or AVO was shown to be a eutectic mixture which can be employed as a novel, bioactive, co-surfactant that significantly reduces droplet size of medium-chain triglyceride O/W emulsions stabilized with polysorbate 80. In vitro cytotoxicity of avocado polyol-SEDDS in acute myeloid leukemia cell lines indicated significant increases in potency and bioactivity compared to conventional cell culture delivery systems. A pilot pharmacokinetic evaluation of AVO SEDDS in C57BL/6J mice revealed appreciable accumulation in whole blood and biodistribution in key target tissues. Lastly, incorporation of AVO in SEDDS significantly improved encapsulation of the poorly water-soluble drugs naproxen and curcumin.

12,15-Dimethyl-8-oxa-tetra-cyclo-[8.8.0.02,7.011,16]octa-deca-1(18),2,4,6,11(16),12,14-heptaen-10-ol.

In the title compound, C19H18O2, the pyran ring is in a half-chair conformation. The fused ring system comprising the benzene and cyclo-hexene rings is essentially planar (r.m.s. deviation = 0.053 Å) and forms a dihedral angle of 27.95 (6)° with the other benzene ring. In the crystal, O-H⋯O hydrogen bonds connect the mol-ecules into chains propagating along [001].

1,2,3,5-Tetra-hydro-naphtho-[2,1-c]oxepine.

In the title compound, C14H14O, the seven-membered ring is in a pseudo-chair conformation. In the crystal, mol-ecules are linked by weak C-H⋯O hydrogen bonds forming layers parallel to (010). In addition, there are weak π-π stacking inter-actions between inversion-related naphthalene ring systems, with a ring centroid-ring centroid distance of 3.518 (5) Å.

12-Ethyl-6a,10a-di-hydro-5H-6-oxachrysene.

In the title compound, C19H16O, the pyran ring is in a half-chair conformation. The essentially planar naphthalene ring system (r.m.s. deviation = 0.020 Å) forms a dihedral angle of 14.37 (5)° with the fused benzene ring. In the crystal, pairs of mol-ecules are connected into inversion dimers by weak C-H⋯O hydrogen bonds to generate R 2 2(6) loops.

[(1R*,3S*,4S*)-3-(2-Hy-droxy-benzo-yl)-1,2,3,4-tetra-hydro-1,4-ep-oxy-naphthalen-1-yl]methyl 4-nitro-benzoate.

The relative stereo- and regiochemistry of the racemic title compound, C25H19NO7, were established from the crystal structure. The fused benzene ring forms dihedral angles of 77.3 (1) and 60.3 (1)° with the hy-droxy-substituted benzene ring and the nitro-substituted benzene ring, respectively. The dihedral angle between the hy-droxy-substituted benzene ring and the nitro-substituted benzene ring is 76.4 (1)°. An intra-molecular O-H⋯O hydrogen bond closes an S(6) ring. In the crystal, weak C-H⋯O hydrogen bonds connect the mol-ecules, forming layers parallel to (100). Within these layers, there are weak π-π stacking inter-actions with a ring centroid-ring centroid distance of 3.555 (1) Å.

Study design of endoscopic polypectomy on clopidogrel (EPOC): A randomised controlled trial.

Concurrent cardiovascular disease and antiplatelet use (clopidogrel, prasugrel and ticagrelor) use poses a significant peri-endoscopic management challenge with a paucity of high-quality evidence available. Antiplatelet temporary interruption places patients at risk of serious cardiovascular thrombotic events. Continuing these agents potentially increases the risk of procedure related bleeding however this risk could be sufficiently mitigated by cold snare polypectomy and endoscopic clipping to manage intraprocedural bleeding, making routine colonoscopy on continued antiplatelet agents safe. The EPOC trial will examine whether continuation of antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) as single or dual therapy with aspirin, is inferior or superior to temporary interruption of antiplatelet therapy, current standard of care, with regard to the use of endoscopic rescue clips or clinically significant post-polypectomy bleeding after cold snare polypectomy of polyps ≤10 mm. EPOC is a parallel group, proceduralist-blinded randomized controlled trial comparing recruiting patients on antiplatelet therapy undergoing elective colonoscopy. This trial is underway throughout Australia and New Zealand with a view to expanding to additional sites. 496 subjects in each arm are required for this study. EPOC is the first randomised controlled trial comparing temporary interruption with continuation of antiplatelet therapy in patients undergoing elective colonoscopy.

An international, multi-institution survey of the use of EUS in the diagnosis of pancreatic cystic lesions.

BACKGROUND AND OBJECTIVES: Currently, pancreatic cystic lesions (PCLs) are recognized with increasing frequency and have become a more common finding in clinical practice. EUS is challenging in the diagnosis of PCLs and evidence-based decisions are lacking in its application. This study aimed to develop strong recommendations for the use of EUS in the diagnosis of PCLs, based on the experience of experts in the field. METHODS: A survey regarding the practice of EUS in the evaluation of PCLs was drafted by the committee member of the International Society of EUS Task Force (ISEUS-TF). It was disseminated to experts of EUS who were also members of the ISEUS-TF. In some cases, percentage agreement with some statements was calculated; in others, the options with the greatest numbers of responses were summarized. RESULTS: Fifteen questions were extracted and disseminated among 60 experts for the survey. Fifty-three experts completed the survey within the specified time frame. The average volume of EUS cases at the experts' institutions is 988.5 cases per year. CONCLUSION: Despite the limitations of EUS alone in the morphologic diagnosis of PCLs, the results of the survey indicate that EUS-guided fine-needle aspiration is widely expected to become a more valuable method.

Palladium/Lewis Acid Cocatalyzed Ring-Opening Reactions of Unsymmetrical Oxabenzonobornadienes with Oximes.

The palladium/Lewis acid cocatalyzed ring-opening reaction of various C1-substituted unsymmetrical oxabenzonorbornadienes (OBD) with oxime nucleophiles was investigated. The effects of various C1 substituents were explored. Moderate to excellent yields and excellent regioselectivities were obtained for electron-withdrawing groups. The presence of electron-donating alkyl groups leads to isomerization of the corresponding OBD to afford the substituted naphthol derivatives. Additionally, a mechanism for the formation of C2 regioisomeric ring-opened products has been proposed.

Cationic Ruthenium-Catalyzed Bis-Homo-Diels-Alder Cycloaddition.

OBJECTIVE: The ruthenium-catalyzed Bis-Homo-Diels-Alder cycloaddition between 1,5- cyclooctadiene and alkynes was explored, and the use of commercially available cationic catalysts was investigated. It was noted that [CpRu(CH3CN)3]PF6 was effective at catalyzing this cycloaddition and yields of the desired tricyclo[4.2.2.02,5]dec-7-ene adduct ranging from 13 to 83% were achieved using this cationic catalyst. Several cycloadducts that were previously unobtainable with the use of the neutral (Cp*RuCl(COD) catalysts were also successfully made using [CpRu(CH3CN)3]PF6 albeit in low yields. METHODS: Commercially available, and previously synthesized alkynes were combined with 1,5-cyclooctadiene and treated with a ruthenium catalyst within a glovebox. The reaction mixture was stirred for 72h at temperatures ranging from 25 to 70oC. The desired cycloadduct was then isolated using flash column chromatography and analyzed and characterized using NMR, IR and MS. RESULTS: Several previously unattainable adducts were synthesized using the cationic [CpRu(CH3CN)3]PF6. When this catalyst was compared to the neutral Cp*RuCl(COD) greater yields were observed. CONCLUSION: The present study describes an improved method for the formation of the tricyclo[4.2.2.02,5]dec-7- ene framework using a commercially available cationic ruthenium catalyst. It was noted that the use of [CpRu(CH3CN)3]PF6 led to improved yields when compared to Cp*RuCl(COD).

Recent Advances in Transition Metal-Catalyzed Reactions of Oxabenzonorbornadiene.

BACKGROUND: Oxabenzonorbornadiene (OBD) is a useful synthetic intermediate capable of undergoing multiple types of transformations due to three key structural features: a free alkene, a bridged oxygen atom, and a highly strained ring system. Most notably, ring-opening reactions of OBD using transition metal catalysts and nucleophiles produce multiple stereocenters in a single step. The resulting dihydronaphthalene framework is found in many natural products, which have been shown to be biologically active. OBJECTIVE: This review will provide an overview of transition metal-catalyzed reactions from the past couple of years including cobalt, copper, iridium, nickel, palladium and rhodium- catalyzed reactions. In addition, the recent derivatization of OBD to cyclopropanated oxabenzonorbornadiene and its reactivity will be discussed. CONCLUSION: It can be seen from the review, that the work done on this topic has employed the use of many different transition metal catalysts, with many different nucleophiles, to perform various transformations on the OBD molecule. Additionally, depending on the catalyst and ligand used, the stereo and regioselectivity of the product can be controlled, with proposed mechanisms to support the understanding of such reactions. The use of palladium has also generated a cyclopropanated OBD, with reactivity similar to that of OBD. An additional reactive site exists at the distal cyclopropane carbon, giving rise to three types of ring-opened products.

Transition Metal-Catalyzed Reactions of Alkynyl Halides.

BACKGROUND: Transition metal-catalyzed reactions of alkynyl halides are a versatile means of synthesizing a wide array of products. Their use is of particular interest in cycloaddition reactions and in constructing new carbon-carbon and carbon-heteroatom bonds. Transition metal-catalyzed reactions of alkynyl halides have successfully been used in [4+2], [2+2], [2+2+2] and [3+2] cycloaddition reactions. Many carbon-carbon coupling reactions take advantage of metal-catalyzed reactions of alkynyl halides, including Cadiot-Chodkiewicz, Suzuki-Miyaura, Stille, Kumada-Corriu and Inverse Sonogashira reactions. All the methods of constructing carbon-nitrogen, carbon-oxygen, carbon-phosphorus, carbon-sulfur, carbon-silicon, carbon-selenium and carbon-tellurium bonds employed alkynyl halides. OBJECTIVE: The purpose of this review is to highlight and summarize research conducted in transition metalcatalyzed reactions of alkynyl halides in recent years. The focus will be placed on cycloaddition and coupling reactions, and their scope and applicability to the synthesis of biologically important and industrially relevant compounds will be discussed. CONCLUSION: It can be seen from the review that the work done on this topic has employed the use of many different transition metal catalysts to perform various cycloadditions, cyclizations, and couplings using alkynyl halides. The reactions involving alkynyl halides were efficient in generating both carbon-carbon and carbonheteroatom bonds. Proposed mechanisms were included to support the understanding of such reactions. Many of these reactions face retention of the halide moiety, allowing additional functionalization of the products, with some new products being inaccessible using their standard alkyne counterparts.