Mg-driven selection of natural phosphatidic acids in primitive membranes.

Biological membranes are composed exclusively of phospholipids comprising glycerol-1-phosphate or glycerol-3-phosphate. By contrast, primitive membranes would have likely been composed of heterogeneous mixtures of phospholipids, including non-natural analogues comprising glycerol-2-phosphate, as delivered by prebiotic synthesis. Thus, it is not clear how the selection of natural phospholipids could have come about.

Non-surgical interventions for preventing contralateral tissue loss and amputation in dysvascular patients with a primary major lower limb amputation.

Rationale: Major lower limb amputation (LLA, above the ankle) is performed for people with intractable pain, life-threatening infections, or non-functional limbs. Of 7500 LLAs carried out in England between 2015 and 2018, the majority of these were performed in dysvascular patients. Dysvascularity is the absence of adequate blood supply to maintain a limb's usual function (ischaemia, usually caused by peripheral arterial disease or diabetes mellitus), ultimately leading to pain and tissue injury (ulcers, gangrene, sometimes referred to as tissue loss).

A cross sectional pilot study utilising STrain Analysis and Mapping of the Plantar Surface (STAMPS) to measure plantar load characteristics within a healthy population.

Background: No in-shoe systems, measuring both components of plantar load (plantar pressure and shear stress) are available for use in patients with diabetes. The STAMPS (STrain Analysis and Mapping of the Plantar Surface) system utilises digital image correlation (DIC) to determine the strain sustained by a deformable insole, providing a more complete understanding of plantar shear load at the foot-surface interface.

Research Questions: What is the normal range and pattern of strain at the foot-surface interface within a healthy population as measured by the STAMPS system? Is STAMPS a valid tool to measure the effects of plantar load?

Methods: A cross-sectional study of healthy participants was undertaken.

Variation in Systemic Antibiotic Treatment for Diabetic Foot Osteomyelitis in England and Wales: A Multi-Centre Case Review.

Diabetic foot osteomyelitis (DFO) is a major complication and can lead to significant morbidity and mortality. Systemic antibiotic therapy is often initiated first line to achieve quiescence of infection. To perform a multi-centre case review of systemic antibiotic intervention to treat adults with DFO in England and Wales and compare with national guidelines ''.

Clinical perspectives on sampling and processing approaches for the management of infection in diabetic foot ulceration: A qualitative study.

Diabetic foot ulcers (DFUs) often become infected and are treated with antimicrobials, with samples collected to inform care. Swab samples are easier than tissue sampling but report fewer organisms. Compared with culture and sensitivity (C&S) methods, molecular microbiology identifies more organisms.

Targeted photodynamic therapy for breast cancer: the potential of glyconanoparticles.

Photodynamic therapy (PDT) uses a non-toxic light sensitive molecule, a photosensitiser, that releases cytotoxic reactive oxygen species upon activation with light of a specific wavelength. Here, glycan-modified 16 nm gold nanoparticles (glycoAuNPs) were explored for their use in targeted PDT, where the photosensitiser was localised to the target cell through selective glycan-lectin interactions. Polyacrylamide (PAA)-glycans were chosen to assess glycan binding to the cell lines.

Ring Opening of Glycerol Cyclic Phosphates Leads to a Diverse Array of Potentially Prebiotic Phospholipids.

Phospholipids are the primary constituents of cell membranes across all domains of life, but how and when phospholipids appeared on early Earth remains unknown. Pressingly, most prebiotic syntheses of complex phospholipids rely upon substrates not yet shown to have been available on early Earth. Here, we describe potentially prebiotic syntheses of a diverse array of complex phospholipids and their building blocks.

STrain Analysis and Mapping of the Plantar Surface (STAMPS): A novel technique of plantar load analysis during gait.

Diabetic foot ulceration is driven by peripheral neuropathy, resulting in abnormal foot biomechanics and elevated plantar load. Plantar load comprises normal pressure and tangential shear stress. Currently, there are no in-shoe devices measuring both components of plantar load.

Mechanism of rotenone binding to respiratory complex I depends on ligand flexibility.

Respiratory complex I is a major cellular energy transducer located in the inner mitochondrial membrane. Its inhibition by rotenone, a natural isoflavonoid, has been used for centuries by indigenous peoples to aid in fishing and, more recently, as a broad-spectrum pesticide or even a possible anticancer therapeutic. Unraveling the molecular mechanism of rotenone action will help to design tuned derivatives and to understand the still mysterious catalytic mechanism of complex I.

Guidelines on the classification of foot ulcers in people with diabetes (IWGDF 2023 update).

Background: This publication represents a scheduled update of the 2019 guidelines of the International Working Group of the Diabetic Foot (IWGDF) addressing the use of systems to classify foot ulcers in people with diabetes in routine clinical practice. The guidelines are based on a systematic review of the available literature that identified 28 classifications addressed in 149 articles and, subsequently, expert opinion using the GRADE methodology.

Methods: First, we have developed a list of classification systems considered as being potentially adequate for use in a clinical setting, through the summary of judgements for diagnostic tests, focussing on the usability, accuracy and reliability of each system to predict ulcer-related complications as well as use of resources.

Prebiotic Synthesis of Formylaminonitriles and Derivatives in Formamide.

Amino acids and their derivatives were probably instrumental in the transition of prebiotic chemistry to early biology. Accordingly, amino acid formation under prebiotic conditions has been intensively investigated. Unsurprisingly, most of these studies have taken place with water as the solvent.

Classification of foot ulcers in people with diabetes: A systematic review.

Background: Classification and scoring systems can help both clinical management and audit the outcomes of routine care.

Aim: This study aimed to assess published systems used to characterise ulcers in people with diabetes to determine which should be recommended to (a) aid communication between health professionals, (b) predict clinical outcome of individual ulcers, (c) characterise people with infection and/or peripheral arterial disease, and (d) audit to compare outcomes in different populations. This systematic review is part of the process of developing the 2023 guidelines to classify foot ulcers from the International Working Group on Diabetic Foot.

Multidisciplinary Team Decisions in Management of Abdominal Aortic Aneurysm: A Service and Quality Evaluation.

Objective: To investigate whether decisions made by the multidisciplinary team (MDT) were implemented and review the MDT process to identify areas for improvement.

Methods: This was a retrospective service evaluation project. Consecutive cases of abdominal aortic aneurysm (AAA) from vascular surgery MDT meetings were reviewed.

Prebiotic Photochemical Coproduction of Purine Ribo- and Deoxyribonucleosides.

The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest. The recent finding that two RNA subunits (cytidine, C, and uridine, U) and two DNA subunits (deoxyadenosine, dA, and deoxyinosine, dI) can be coproduced in the same reaction network, compatible with a consistent geological scenario, supports this theory. However, a prebiotically plausible synthesis of the missing units (purine ribonucleosides and pyrimidine deoxyribonucleosides) in a unified reaction network remains elusive.

Plantar shear stress in the diabetic foot: A systematic review and meta-analysis.

Aims: Diabetic foot ulceration (DFU) is a multifactorial process involving undetected, repetitive trauma resulting in inflammation and tissue breakdown. Shear stress forms a major part of plantar load, the aim of this review is to determine whether elevated shear stress results in ulceration.

Methods: A systematic review of the Ovid Medline, EMBASE, CINAHL and Cochrane library databases was performed.

Timescales for Prebiotic Photochemistry Under Realistic Surface Ultraviolet Conditions.

Ultraviolet (UV) light has long been invoked as a source of energy for prebiotic chemical synthesis, but experimental support does not involve sources of UV light that look like the young Sun. Here we experimentally investigate whether the UV flux available on the surface of early Earth, given a favorable atmosphere, can facilitate a variety of prebiotic chemical syntheses. We construct a solar simulator for the UV light of the faint young Sun on the surface of early Earth, called StarLab.

Activation chemistry drives the emergence of functionalised protocells.

The complexity of the simplest conceivable cell suggests that the chemistry of prebiotic mixtures needs to be explored to understand the intricate network of prebiotic reactions that led to the emergence of life. Early cells probably relied upon compatible and interconnected chemistries to link RNA, peptides and membranes. Here we show that several types of vesicles, composed of prebiotically plausible mixtures of amphiphiles, spontaneously form and sustain the methyl isocyanide-mediated activation of amino acids, peptides and nucleotides.

Peptide directed phthalocyanine-gold nanoparticles for selective photodynamic therapy of EGFR overexpressing cancers.

Gold nanoparticles, covalently functionalised with the photosensitiser C11Pc and PEG, were actively targeted towards epidermal growth factor receptor overexpressing cancers using the peptide FITC-βAAEYLRK. Selective phototoxicity was observed at nanomolar concentrations with minimal dark toxicity.

Antithrombotic therapy in diabetes: which, when, and for how long?

Cardiovascular disease remains the main cause of mortality in individuals with diabetes mellitus (DM) and also results in significant morbidity. Premature and more aggressive atherosclerotic disease, coupled with an enhanced thrombotic environment, contributes to the high vascular risk in individuals with DM. This prothrombotic milieu is due to increased platelet activity together with impaired fibrinolysis secondary to quantitative and qualitative changes in coagulation factors.

Harnessing chemical energy for the activation and joining of prebiotic building blocks.

Life is an out-of-equilibrium system sustained by a continuous supply of energy. In extant biology, the generation of the primary energy currency, adenosine 5'-triphosphate and its use in the synthesis of biomolecules require enzymes. Before their emergence, alternative energy sources, perhaps assisted by simple catalysts, must have mediated the activation of carboxylates and phosphates for condensation reactions.

Active targeting of gold nanoparticles as cancer therapeutics.

Gold nanoparticles (AuNPs) are of increasing interest for their unique properties and their biocompatability, minimal toxicity, multivalency and size tunability make them exciting drug carriers. The functionalisaton of AuNPs with targeting moieties allows for their selective delivery to cancers, with antibodies, proteins, peptides, aptamers, carbohydrates and small molecules all exploited. Here, we review the recent advances in targeted-AuNPs for the treatment of cancer, with a particular focus on these classes of targeting ligands.

A Peptide-Duocarmycin Conjugate Targeting the Thomsen-Friedenreich Antigen Has Potent and Selective Antitumor Activity.

Solid-phase synthesis allowed the rapid generation of a peptide-drug conjugate. A peptide targeting the Thomsen-Friedenreich antigen (TFα) was conjugated to the alkylating subunit of the potent cytotoxin duocarmycin SA. The compound, containing a cathepsin B cleavable linker, was shown to be active and selective against TFα expressing tumor cell lines.