Porokeratosis: Two Faces, One Family

Porokeratosis is a disorder of keratinisation whose pathogenesis is yet unclear. It has been postulated that it results from the proliferation of an abnormal clone of keratinocytes, triggered by several factors, such as immunosuppression or prolonged ultraviolet exposure. Various clinical forms are recognized whose common denominator is a keratotic ring surrounding a central zone of atrophy. The histological hallmark is the cornoid lamella, a thin column of hyperproliferative abnormal keratinocytes. We describe two cases of porokeratosis. A 67-year-old woman with an erythematous purplish round plaque surrounded by a keratotic border that had appeared 6 years previously on the left sural region was diagnosed as ‘giant’ porokeratosis. A 49-year-old man presented with small papules coalescent in an erythematous oval plaque on the lateral side of the left foot consistent with linear porokeratosis

Synthetic guidelines for the precision engineering of gold nanoparticles

Gold nanoparticles (AuNPs) are one of the most studied nanomaterials with applications spanning from catalysis to biomedicine. While numerous chemical protocols exist that allow bespoke tailoring of chemical, physical and biological properties, their translation towards industrial-scale production remains a challenge. Batch synthesis often suffers from poor reproducibility and scalability, while emerging approaches, such as continuous flow synthesis, are not widely implemented in research labs. Herein, we provide a critical review of recent developments in the field of AuNP synthesis and identify synthetic guidelines for precision engineering of nanoparticle properties

Biomechanical analysis of the upper body during overhead industrial tasks using electromyography and motion capture integrated with digital human models

In this paper, we present a biomechanical analysis of the upper body, which includes upper-limb, neck and trunk, during the execution of overhead industrial tasks. The analysis is based on multiple performance metrics obtained from a biomechanical analysis of the worker during the execution of a specific task, i.e. an overhead drilling task, performed at different working heights. The analysis enables a full description of human movement and internal load state during the execution of the task, thought the evaluation of joint angles, joint torques and muscle activations. A digital human model is used to simulate and replicate the worker’s task in a virtual environment. The experiments were conduced in laboratory setting, where four subjects, with different anthropometric characteristics, have performed 48 drilling tasks in two different working heights defined as low configuration and middle configuration. The results of analysis have impact on providing the best configuration of the worker within the industrial workplace and/or providing guidelines for developing assistance devices which can reduce the physical overloading acting on the worker’s body

Single-Cell RNA Sequencing Analysis: A Step-by-Step Overview

Thanks to innovative sample-preparation and sequencing technologies, gene expression in individual cells can now be measured for thousands of cells in a single experiment. Since its introduction, single-cell RNA sequencing (scRNA-seq) approaches have revolutionized the genomics field as they created unprecedented opportunities for resolving cell heterogeneity by exploring gene expression profiles at a single-cell resolution. However, the rapidly evolving field of scRNA-seq invoked the emergence of various analytics approaches aimed to maximize the full potential of this novel strategy. Unlike population-based RNA sequencing approaches, scRNA seq necessitates comprehensive computational tools to address high data complexity and keep up with the emerging single-cell associated challenges. Despite the vast number of analytical methods, a universal standardization is lacking. While this reflects the fields’ immaturity, it may also encumber a newcomer to blend in. In this review, we aim to bridge over the abovementioned hurdle and propose four ready-to-use pipelines for scRNA-seq analysis easily accessible by a newcomer, that could fit various biological data types. Here we provide an overview of the currently available single-cell technologies for cell isolation and library preparation and a step by step guide that covers the entire canonical analytic workflow to analyse scRNA-seq data including read mapping, quality controls, gene expression quantification, normalization, feature selection, dimensionality reduction, and cell clustering useful for trajectory inference and differential expression. Such workflow guidelines will escort novices as well as expert users in the analysis of complex scRNA-seq datasets, thus further expanding the research potential of single-cell approaches in basic science, and envisaging its future implementation as best practice in the field

Compulsory treatments in eating disorders: a systematic review and meta-analysis

Introduction: The aims of this systematic review and meta-analysis are to provide a summary of the current literature concerning compulsory treatments in patients with eating disorders (ED) and to understand whether compulsorily and involuntarily treated patients differ in terms of baseline characteristics and treatment outcomes. Methods: Relevant articles were identified following the PRISMA guidelines by searching the following terms: “treatment refusal”, “forced feeding”, “compulsory/coercive/involuntary/forced treatment/admission”, “eating disorders”, “feeding and eating disorders”, “anorexia nervosa”, “bulimia nervosa”. Research was restricted to articles concerning humans and published between 1975 and 2020 in English. Results: Out of 905 articles retrieved, nine were included for the analyses allowing the comparisons between 242 compulsorily and 738 voluntarily treated patients. Mean body mass index (BMI) was slightly lower in patients compelled to treatments. Mean illness duration, BMI at discharge and BMI variation showed no significant differences between the two groups. Average length of hospitalization was 3 weeks longer among compulsory-treated patients, but this did not result in a higher increase in BMI. No significant risk difference on mortality was estimated (three studies). Conclusions: Compulsory treatments are usually intended for patients having worse baseline conditions than voluntary ones. Those patients are unlikely to engage in treatments without being compelled but, after the treatments, albeit with longer hospitalisations, they do achieve similar outcomes. Therefore, we can conclude that forcing patients to treatment is a conceivable option. Level of evidence: Level I, systematic review and meta-analysis

Highly reproducible, high-yield flow synthesis of gold nanoparticles based on a rational reactor design exploiting the reduction of passivated Au(III)

Reproducibility in the synthesis of nanomaterials is a crucial aspect for their real-life applications. It is particularly pertinent in the context of gold nanoparticles, where a plethora of seeded-growth methods are being developed to control particle morphology and size. The translation of such methods to manufacturing can be hindered by poor reproducibility of the seed production step. This study focuses on the development of a highly reproducible platform for the synthesis of gold nanoparticles, as potential substrates for glucose sensing. A flow reactor was designed, starting from a detailed study of the synthesis in batch. The well-established Turkevich synthesis was investigated via in situ time-resolved UV-vis spectroscopy. In order to enhance the reproducibility of the synthesis the effect of passivating the gold precursor stock before its use in the synthesis was investigated. It is shown that starting from a pre-passivated precursor provided improved control over the initial reaction stage, at the expense of a small increase in the reaction time. At the optimal reaction conditions, the proposed modified Turkevich method allowed for the synthesis in batch of ∼12 nm monodisperse (RSD ∼10%) particles, with a variability from batch to batch of only ∼5%. The information gathered from the batch study, in particular the reaction time, was used to translate the synthesis from batch to flow. The system utilized for the flow synthesis consisted of a segmented flow reactor, where an organic stream was employed to segment the reactive aqueous stream to avoid reactor fouling and improve monodispersity. The use of segmented flow enables treating each droplet as a “travelling batch”, hence allowing the direct use of the kinetic data obtained in batch to design the flow reactor, leading to the rapid identification of the minimum residence time to allow for reaction completion. The flow reactor enabled the synthesis of ∼11 nm monodisperse (RSD ∼10%) particles, with full precursor conversion and reproducibility between reactor runs higher than that obtained in batch (variability of ∼2%). The flow-produced gold nanoparticles were tested for glucose sensing, exploiting their glucose oxidase-mimicking behaviour and demonstrated satisfactory glucose detection in the range of 1–10 mM

Kinetics-based design of a flow platform for highly reproducible on demand synthesis of gold nanoparticles with controlled size between 50 and 150 nm and their application in SERS and PIERS sensing

Seeded-growth synthetic protocols enable precise control of particle size and shape, crucial for many sensing applications. However, scaling-up these syntheses in a reproducible way is challenging, as minimal variation in process parameters such as seed size, concentration or reaction temperature can significantly alter the final product. Flow reactors enable tight control in the process parameters and high reproducibility of the synthesis, representing a potential technology to perform seeded-growth syntheses in large scale. This work reports the design of a flow platform for the controlled synthesis of spherical gold nanoparticles with size up to 150nm through a seeded-growth approach, and their use in Surface Enhanced Raman Scattering (SERS) and Photoinduced Enhanced Raman Spectroscopy (PIERS). The particle growth kinetics were studied via in situ time-resolved UV–Vis spectroscopy. The spectroscopic data were fitted with a kinetic model, which was subsequently used for the design of the reactor. The kinetics-based design approach enabled fast translation of the growth synthesis in flow, eventually allowing the on demand flow synthesis of particles with controllable size, ranging from 50 to 150nm, with high reproducibility and full precursor conversion. The particles were tested for SERS and PIERS for different substrates, including warfare agents and biomolecules, with enhancement factors between 103 and 108 depending on the analyte, demonstrating their potential for detection of various analytes

Microwave-assisted flow synthesis of multicore iron oxide nanoparticles

Coprecipitation is by far the most common synthesis method for iron oxide nanoparticles (IONPs). However, reproducibility and scalability represent a major challenge. Therefore, innovative processes for scalable production of IONPs are highly sought after. Here, we explored the combination of microwave heating with a flow reactor producing IONPs through coprecipitation. The synthesis was initially studied in a well-characterised microwave-heated flow system, enabling the synthesis of multicore IONPs, with control over both the single core size and the multicore hydrodynamic diameter. The effect of residence time and microwave power was investigated, enabling the synthesis of multicore nanostructures with hydrodynamic diameter between ∼35 and 70 nm, with single core size of 3–5 nm. Compared to particles produced under conventional heating, similar single core sizes were observed, though with smaller hydrodynamic diameters. The process comprised of the initial IONP coprecipitation followed by the addition of the stabiliser (citric acid and dextran). The ability of precisely controlling the stabiliser addition time (distinctive of flow reactors), contributed to the synthesis reproducibility. Finally, scale-up by increasing the reactor length and using a different microwave cavity was demonstrated, producing particles of similar structure as those from the small scale system, with a throughput of 3.3 g/h

Development of site-specific biomechanical indices for estimating injury risk in cycling

In this paper we present novel biomechanical indices for site-specific assessment of injury risk in cycling. The indices are built from a multifactorial analysis based on the kinematics and kinetics of the cyclist from the biomechanical side, and muscle excitations and muscle synergies from the neurophysiological side. The indices are specifics for three body regions (back, knee, ankle) which are strongly affected by overuse injuries in cycling. We use these indices for injury risks analysis of a recreational cyclist, who offered to participate in the experiments. The preliminary results are promising towards the use of such indices for planning and/or evaluating training schedule with the final goal of reducing non-traumatic injuries in cycling

Small iron oxide nanoparticles as MRI T1 contrast agent: scalable inexpensive water-based synthesis using a flow reactor

Small iron oxide nanoparticles (IONPs) were synthesised in water via co-precipitation by quenching particle growth after the desired magnetic iron oxide phase formed. This was achieved in a millifluidic multistage flow reactor by precisely timed addition of an acidic solution. IONPs (≤5 nm), a suitable size for positive T1 magnetic resonance imaging (MRI) contrast agents, were obtained and stabilised continuously. This novel flow chemistry approach facilitates a reproducible and scalable production, which is a crucial paradigm shift to utilise IONPs as contrast agents and replace currently used Gd complexes. Acid addition had to be timed carefully, as the inverse spinel structure formed within seconds after initiating the co-precipitation. Late quenching allowed IONPs to grow larger than 5 nm, whereas premature acid addition yielded undesired oxide phases. Use of a flow reactor was not only essential for scalability, but also to synthesise monodisperse and non-agglomerated small IONPs as (i) co-precipitation and acid addition occurred at homogenous environment due to accurate temperature control and rapid mixing and (ii) quenching of particle growth was possible at the optimum time, i.e., a few seconds after initiating co-precipitation. In addition to the timing of growth quenching, the effect of temperature and dextran present during co-precipitation on the final particle size was investigated. This approach differs from small IONP syntheses in batch utilising either growth inhibitors (which likely leads to impurities) or high temperature methods in organic solvents. Furthermore, this continuous synthesis enables the low-cost (<£10 per g) and large-scale production of highly stable small IONPs without the use of toxic reagents. The flow-synthesised small IONPs showed high T1 contrast enhancement, with transversal relaxivity (r2) reduced to 20.5 mM−1 s−1 and longitudinal relaxivity (r1) higher than 10 mM−1 s−1, which is among the highest values reported for water-based IONP synthesis