Rapid Synthesis of the Spiroketal Subunit of Neaumycin B: Stereochemical Aspects of Singly Anomeric Spiroketals and Proposal for a Stereocenter Reassignment.

Neaumycin B is a complex polyketide that shows phenomenal cytotoxicity against U87 glioblastoma cells. The singly anomeric spiroketal core is a notable subunit in the natural product's structure. We report a rapid and convergent approach to the spiroketal group, resulting in the formation of two isomeric singly anomeric spiroketals.

Development and Preliminary Testing of the Staffordshire Questionnaire for Adolescent Idiopathic Scoliosis (SQ-AIS): Content and Face Validity.

Introduction: Adolescent Idiopathic Scoliosis (AIS) is a structural spinal deformity with implications for health-related quality of life (HR-QoL). The Scoliosis Research Society-22 revised (SRS-22r) questionnaire is the standard for HR-QoL assessment. However, studies have identified limitations with the SRS-22r, including content and face validity issues, reliability concerns, and language appropriateness.

Allopolyploidy expanded gene content but not pangenomic variation in the hexaploid oilseed Camelina sativa.

Ancient whole-genome duplications (WGDs) are believed to facilitate novelty and adaptation by providing the raw fuel for new genes. However, it is unclear how recent WGDs may contribute to evolvability within recent polyploids. Hybridization accompanying some WGDs may combine divergent gene content among diploid species.

Development of polymer-encapsulated microparticles of a lipophilic API-IL and its lipid based formulations for enhanced solubilisation.

Active Pharmaceutical Ingredient-Ionic liquids (API-ILs) have the potential to improve the bioavailability of BCS Class IV Drugs. However, the problematic physical handling properties of room temperature API-ILs have impaired clinical and commercial exploitation to date. Lipid-based formulations (LBFs) are used to improve the absorption of drugs with limited bioavailability.

Maximising the Quality of Stroke Care: Reporting of Data Collection Methods and Resourcing in National Stroke Registries: A Systematic Review.

Stroke registries are tools for improving care and advancing research. We aim to describe the methodology and resourcing of existing national stroke registries. We conducted a systematic search of the published, peer-reviewed literature and grey literature examining descriptions of data collection methods and resourcing of national stroke registries published from 2012 to 2023.

An Enantioselective Decarboxylative Glycolate Aldol Reaction.

Herein, we report the application of a benzyloxy-functionalized malonic acid half thioester as an activated ester equivalent in a highly enantioselective decarboxylative glycolate aldol reaction. This robust method operates at ambient temperature, tolerates air and moisture, and generates CO as the only byproduct. The synthetic applicability of the method is demonstrated by the large-scale enantiodivergent synthesis of α-benzyloxy-β-hydroxybutyric acid thioester and its subsequent conversion to diverse polyoxygenated building blocks, deoxy-sugars, and (-)-angiopterlactone B.

Application of shadowgraph imaging (SGI) particle characterisation data to interpret the impact of varying test conditions on powder dissolution and to develop an automated agglomeration identification method (AIM) in the USP flow-through apparatus.

The aims of this work were 1) to explore the application of shadowgraph imaging (SGI) as a real time monitoring tool to characterize ibuprofen particle behaviour during dissolution testing under various conditions in the USP 4 flow-through apparatus and 2) to investigate the potential to develop an SGI-based automated agglomeration identification method (AIM) for real time agglomerate detection during dissolution testing. The effect of surfactant addition, changes in the drug mass and flow rate, the use of sieved and un-sieved powder fractions, and the use of different drug crystal habits were investigated. Videos at every sampling time point during dissolution were taken and analysed by SGI.

A Dual Role for the -Perfluorobutanesulfinamide Auxiliary in an Asymmetric Decarboxylative Mannich Reaction.

Herein, we demonstrate that the enhanced electrophilicity of -perfluorobutanesulfinamide auxiliary-derived imines enables a highly selective decarboxylative Mannich reaction under mild conditions. The molecular sieves-mediated transformation tolerates a broad substrate scope and produces chiral β-amino thioesters in high yield. Additionally, we demonstrate that the -perfluoroalkyl sulfinyl group can function as a phase tag for fluorous purification, thus enabling the rapid isolation of the chiral amine products by solid-phase extraction.

Development of inhaled moxifloxacin-metformin formulation as an alternative for pulmonary tuberculosis treatment.

Resistant M. tuberculosis strains threaten pulmonary tuberculosis (P-TB) control since they limit drug options. Drug repositioning and new development strategies are urgently required to overcome resistance.

Quantitative proteomic analysis reveals Ga(III) polypyridyl catecholate complexes disrupt Aspergillus fumigatus mitochondrial function.

Infections caused by the airborne fungal pathogen, Aspergillus fumigatus, are increasing in severity due to growing numbers of immunocompromised individuals and the increasing incidence of antifungal drug resistance, exacerbating treatment challenges. Gallium has proven to be a strong candidate in the fight against microbial pathogens due to its iron-mimicking capability and substitution of Ga(III) in place of Fe(III), disrupting iron-dependent pathways. Since the antimicrobial properties of 2,2'-bipyridine and derivatives have been previously reported, we assessed the in vitro activity and proteomic effects of a recently reported heteroleptic Ga(III) polypyridyl catecholate compound against A.

-to- Acyl Transfer as an Enabling Strategy in Asymmetric and Chemoenzymatic Synthesis.

The observation of thioester-mediated acyl transfer processes in nature has inspired the development of novel protein synthesis and functionalization methodologies. The chemoselective transfer of an acyl group from -to- is the basis of several powerful ligation strategies. In this work, we sought to apply the reverse process, the transfer of an acyl group from -to-, as a method to convert stable chiral amides into more reactive thioesters.

Effectiveness of a universal, school-based, online programme for the prevention of anxiety, depression, and substance misuse among adolescents in Australia: 72-month outcomes from a cluster-randomised controlled trial.

Background: The CSC study found that the universal delivery of a school-based, online programme for the prevention of mental health and substance use disorders among adolescents resulted in improvements in mental health and substance use outcomes at 30-month follow-up. We aimed to compare the long-term effects of four interventions-Climate Schools Combined (CSC) mental health and substance use, Climate Schools Substance Use (CSSU) alone, Climate Schools Mental Health (CSMH) alone, and standard health education-on mental health and substance use outcomes among adolescents at 72-month follow-up into early adulthood.

Methods: This long-term study followed up adolescents from a multicentre, cluster-randomised trial conducted across three states in Australia (New South Wales, Queensland, and Western Australia) enrolled between Sept 1, 2013, and Feb 28, 2014, for up to 72 months after baseline assessment.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors for a wide range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed "DrugMap," an atlas of cysteine ligandability compiled across 416 cancer cell lines.

The challenge of downstream processing of spray dried amorphous solid dispersions into minitablets designed for the paediatric population - A sustainable product development approach.

Poorly water-soluble drugs present a significant challenge in the development of oral solid dosage forms (OSDs). In formulation development the appropriate use of excipients to adjust solubility, and the choice of manufacturing method and pharmaceutical processes to obtain a dosage form to meet the needs of the patient group, is crucial. Preparing an amorphous solid dispersion (ASD) is a well-established method for solubility enhancement, and spray drying (SD) a common manufacturing method.

Core requirements of frailty screening in the emergency department: an international Delphi consensus study.

Introduction: Frailty is associated with adverse outcomes among patients attending emergency departments (EDs). While multiple frailty screens are available, little is known about which variables are important to incorporate and how best to facilitate accurate, yet prompt ED screening. To understand the core requirements of frailty screening in ED, we conducted an international, modified, electronic two-round Delphi consensus study.

The national profile of the prosthetic and orthotic workforce in the UK: Sociodemographics and employment characteristics.

Background: Prosthetists and orthotists (POs) are essential members of the health care workforce and one of the United Kingdom's (UK's) allied health professions. There is a paucity of information on their demographics, which is essential for the development of the profession. To fill this void, this study has attempted to comprehensively explore the sociodemographics and work-related characteristics of the entire workforce.

The UK prosthetic and orthotic workforce: current status and implications for the future.

Background: Prosthetists and orthotists (POs) are the smallest of the 14 allied health profession (AHP) workforces within NHS England. Obtaining data on the workforce has always been challenging due to this information being held across different organisations. An understanding of the prosthetic and orthotic (P&O) workforce is essential to ensure that it is adequately equipped to meet the evolving needs of users of P&O services.

Astronaut Candidate, Candidate-Like, and Undergraduate Subjects Compared on Retention and Transfer.

The present study examined long-term retention and transfer of knowledge and skills, as well as the effect of cognitive load on retention and transfer, using a sample of astronaut candidates and two comparison groups. The first comparison group, recruited from Johnson Space Center, was similar in age, education, and general health to the astronaut candidate group; the second comparison group included university undergraduate students.This study employed two different tasks-a simple perceptual-motor task involving data entry and a complex memory updating task requiring both prospective and retrospective memory.

Capsular pneumatosis: A rare radiographic sign for internal breast implant capsule violation in trauma.

Breast augmentation is considered one of the most commonly performed procedures by aesthetic plastic surgeons, representing 16 % of all global plastic surgery procedures in 2020. Given the fact that thoracic trauma comprises over 20 % of trauma worldwide, it is unsurprising that there is potential for overlap between these two patient populations. Here, we present the case of a 59-year-old patient who had undergone bilateral breast augmentation over 10 years prior to presentation.

Co-Delivery of a High Dose of Amphotericin B and Itraconazole by Means of a Dry Powder Inhaler Formulation for the Treatment of Severe Fungal Pulmonary Infections.

Over the past few decades, there has been a considerable rise in the incidence and prevalence of pulmonary fungal infections, creating a global health problem due to a lack of antifungal therapies specifically designed for pulmonary administration. Amphotericin B (AmB) and itraconazole (ITR) are two antifungal drugs with different mechanisms of action that have been widely employed in antimycotic therapy. In this work, microparticles containing a high dose of AmB and ITR (20, 30, and 40% total antifungal drug loading) were engineered for use in dry powder inhalers (DPIs) with an aim to improve the pharmacological effect, thereby enhancing the existing off-label choices for pulmonary administration.

DrugMap: A quantitative pan-cancer analysis of cysteine ligandability.

Cysteine-focused chemical proteomic platforms have accelerated the clinical development of covalent inhibitors of a wide-range of targets in cancer. However, how different oncogenic contexts influence cysteine targeting remains unknown. To address this question, we have developed , an atlas of cysteine ligandability compiled across 416 cancer cell lines.

Non-Invasive Assessment of Back Surface Topography: Technologies, Techniques and Clinical Utility.

(1) Background: Frequent exposure to ionising radiation is often used to determine the diagnosis of adolescent idiopathic scoliosis (AIS), a lateral curvature of the spine in those aged between 10 and 18 years, and a treatment plan according to Cobb angle. This narrative review outlines the clinical utility of surface topography (ST), a radiation-free imaging modality. (2) Methods: Publicly available databases were searched to yield literature related to ST.