In-shoe plantar pressure measurement technologies for the diabetic foot: A systematic review.

Introduction: Loss of cutaneous protective sensation and high plantar pressures increase the risk for diabetic foot patients. Trauma and ulceration are imminent threats, making assessment and monitoring essential. This systematic review aims to identify systems and technologies for measuring in-shoe plantar pressures, focusing on the at-risk diabetic foot population. Methods: A systematic search was conducted across four electronic databases (Scopus, Web of Science, PubMed, Oxford Journals) using PRISMA methodology, covering articles published in English from 1979 to 2024. Only studies addressing systems or sensors exclusively measuring plantar pressures inside the shoe were included. Results: A total of 87 studies using commercially available devices and 45 articles proposing new systems or sensors were reviewed. The prevailing market offerings consist mainly of instrumented insoles. Emerging technologies under development often feature configurations with four, six or eight resistive sensors strategically placed within removable insoles. Despite some variability due to the inherent heterogeneity of human gait, these devices assess plantar pressure, although they present significant differences between them in measurement results. Individuals with diabetic foot conditions appears exhibit elevated plantar pressures, with reported peak pressures reaching approximately 1000 kPa. The results also showed significant differences between the diabetic and non-diabetic groups. Conclusion: Instrumented insoles, particularly those incorporating resistive sensor technology, dominate the field. Systems employing eight sensors at critical locations represent a pragmatic approach, although market options extend to systems with up to 960 sensors. Differences between devices can be a critical factor in measurement and highlights the importance of individualized patient assessment using consistent measurement devices.

A global survey of prokaryotic genomes reveals the eco-evolutionary pressures driving horizontal gene transfer.

Horizontal gene transfer, the exchange of genetic material through means other than reproduction, is a fundamental force in prokaryotic genome evolution. Genomic persistence of horizontally transferred genes has been shown to be influenced by both ecological and evolutionary factors. However, there is limited availability of ecological information about species other than the habitats from which they were isolated, which has prevented a deeper exploration of ecological contributions to horizontal gene transfer. Here we focus on transfers detected through comparison of individual gene trees to the species tree, assessing the distribution of gene-exchanging prokaryotes across over a million environmental sequencing samples. By analysing detected horizontal gene transfer events, we show distinct functional profiles for recent versus old events. Although most genes transferred are part of the accessory genome, genes transferred earlier in evolution tend to be more ubiquitous within present-day species. We find that co-occurring, interacting and high-abundance species tend to exchange more genes. Finally, we show that host-associated specialist species are most likely to exchange genes with other host-associated specialist species, whereas species found across different habitats have similar gene exchange rates irrespective of their preferred habitat. Our study covers an unprecedented scale of integrated horizontal gene transfer and environmental information, highlighting broad eco-evolutionary trends.

Challenges in computational discovery of bioactive peptides in 'omics data.

Peptides have a plethora of activities in biological systems that can potentially be exploited biotechnologically. Several peptides are used clinically, as well as in industry and agriculture. The increase in available 'omics data has recently provided a large opportunity for mining novel enzymes, biosynthetic gene clusters, and molecules. While these data primarily consist of DNA sequences, other types of data provide important complementary information. Due to their size, the approaches proven successful at discovering novel proteins of canonical size cannot be naïvely applied to the discovery of peptides. Peptides can be encoded directly in the genome as short open reading frames (smORFs), or they can be derived from larger proteins by proteolysis. Both of these peptide classes pose challenges as simple methods for their prediction result in large numbers of false positives. Similarly, functional annotation of larger proteins, traditionally based on sequence similarity to infer orthology and then transferring functions between characterized proteins and uncharacterized ones, cannot be applied for short sequences. The use of these techniques is much more limited and alternative approaches based on machine learning are used instead. Here, we review the limitations of traditional methods as well as the alternative methods that have recently been developed for discovering novel bioactive peptides with a focus on prokaryotic genomes and metagenomes.

Optical pH Sensor Based on a Long-Period Fiber Grating Coated with a Polymeric Layer-by-Layer Electrostatic Self-Assembled Nanofilm.

An optical fiber pH sensor based on a long-period fiber grating (LPFG) is reported. Two oppositely charged polymers, polyethylenimine (PEI) and polyacrylic acid (PAA), were alternately deposited on the sensing structure through a layer-by-layer (LbL) electrostatic self-assembly technique. Since the polymers are pH sensitive, their refractive index (RI) varies when the pH of the solution changes due to swelling/deswelling phenomena. The fabricated multilayer coating retained a similar property, enabling its use in pH-sensing applications. The pH of the PAA dipping solution was tuned so that a coated LPFG achieved a pH sensitivity of (6.3 ± 0.2) nm/pH in the 5.92-9.23 pH range. Only two bilayers of PEI/PAA were used as an overlay, which reduces the fabrication time and increases the reproducibility of the sensor, and its reversibility and repeatability were demonstrated by tracking the resonance band position throughout multiple cycles between different pH solutions. With simulation work and experimental results from a low-finesse Fabry-Perot (FP) cavity on a fiber tip, the coating properties were estimated. When saturated at low pH, it has a thickness of 200 nm and 1.53 ± 0.01 RI, expanding up to 310 nm with a 1.35 ± 0.01 RI at higher pH values, mostly due to the structural changes in the PAA.

Plantar pressure thresholds as a strategy to prevent diabetic foot ulcers: A systematic review.

Background: The development of ulcers in the plantar region of the diabetic foot originates mainly from sites subjected to high pressure. The monitoring of these events using maximum allowable pressure thresholds is a fundamental procedure in the prevention of ulceration and its recurrence. Objective: The aim of this review was to identify data in the literature that reveal an objective threshold of plantar pressure in the diabetic foot, where pressure is classified as promoting ulceration. The aim is not to determine the best and only pressure threshold for ulceration, but rather to clarify the threshold values most used in clinical practice and research, also considering the devices used and possible applications for offloading plantar pressure. Design: A systematic review. Methods: The search was performed in three electronic databases, by the PRISMA methodology, for studies that used a pressure threshold to minimize the risk of ulceration in the diabetic foot. The selected studies were subjected to eligibility criteria. Results: Twenty-six studies were included in this review. Seven thresholds were identified, five of which are intended for the inside of the shoe: a threshold of average peak pressure of 200 kPa; 25 % and 40-80 % reduction from initial baseline pressure; 32-35 mm Hg for a capillary perfusion pressure; and a matrix of thresholds based on patient risk, shoe size and foot region. Two other thresholds are intended for the barefoot, 450 and 750 kPa. The threshold of 200 kPa of pressure inside the shoe is the most agreed upon among the studies. Regarding the prevention of ulceration and its recurrence, the efficacy of the proposed threshold matrix and the threshold of reducing baseline pressure by 40-80 % has not yet been evaluated, and the evidence for the remaining thresholds still needs further studies. Conclusions: Some heterogeneity was found in the studies, especially regarding the measurement systems used, the number of regions of interest and the number of steps to be considered for the threshold. Even so, this review reveals the way forward to obtain a threshold indicative of an effective steppingstone in the prevention of diabetic foot ulcer.

SPIRE: a Searchable, Planetary-scale mIcrobiome REsource.

Meta'omic data on microbial diversity and function accrue exponentially in public repositories, but derived information is often siloed according to data type, study or sampled microbial environment. Here we present SPIRE, a Searchable Planetary-scale mIcrobiome REsource that integrates various consistently processed metagenome-derived microbial data modalities across habitats, geography and phylogeny. SPIRE encompasses 99 146 metagenomic samples from 739 studies covering a wide array of microbial environments and augmented with manually-curated contextual data. Across a total metagenomic assembly of 16 Tbp, SPIRE comprises 35 billion predicted protein sequences and 1.16 million newly constructed metagenome-assembled genomes (MAGs) of medium or high quality. Beyond mapping to the high-quality genome reference provided by proGenomes3 (http://progenomes.embl.de), these novel MAGs form 92 134 novel species-level clusters, the majority of which are unclassified at species level using current tools. SPIRE enables taxonomic profiling of these species clusters via an updated, custom mOTUs database (https://motu-tool.org/) and includes several layers of functional annotation, as well as crosslinks to several (micro-)biological databases. The resource is accessible, searchable and browsable via http://spire.embl.de.

Platelet transfusions in adult thrombocytopenic ICU patients: Protocol for a sub-study of the PLOT-ICU cohort.

INTRODUCTION: Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. METHODS: This is a protocol and statistical analysis plan for a post hoc sub-study of 504 thrombocytopenic patients from the 'Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU)'. The primary outcome will be the number of patients receiving platelet transfusion in the ICU reported according to the type of product received (apheresis-derived versus pooled whole-blood-derived transfusions). Secondary platelet transfusion outcomes will include platelet transfusion volumes; timing of platelet transfusion; approach to platelet transfusion dosing (fixed dosing versus weight-based dosing) and platelet count increments for prophylactic transfusions. Secondary clinical outcomes will include the number of patients receiving red blood cell- and plasma transfusions during ICU stay; the number of patients who bled in the ICU, the number of patients who had a new thrombosis in the ICU, and the number of patients who died. The duration of follow-up was 90 days. Baseline characteristics and secondary clinical outcomes will be stratified according to platelet transfusion status in the ICU and severity of thrombocytopenia. Data will be presented descriptively. CONCLUSIONS: The outlined study will provide detailed epidemiological data on the use of platelet transfusions in adult ICU patients with thrombocytopenia using data from the large international PLOT-ICU cohort study. The findings will inform the design of future randomised trials evaluating platelet transfusions in ICU patients.

Functional and evolutionary significance of unknown genes from uncultivated taxa.

Many of the Earth's microbes remain uncultured and understudied, limiting our understanding of the functional and evolutionary aspects of their genetic material, which remain largely overlooked in most metagenomic studies1. Here we analysed 149,842 environmental genomes from multiple habitats2-6 and compiled a curated catalogue of 404,085 functionally and evolutionarily significant novel (FESNov) gene families exclusive to uncultivated prokaryotic taxa. All FESNov families span multiple species, exhibit strong signals of purifying selection and qualify as new orthologous groups, thus nearly tripling the number of bacterial and archaeal gene families described to date. The FESNov catalogue is enriched in clade-specific traits, including 1,034 novel families that can distinguish entire uncultivated phyla, classes and orders, probably representing synapomorphies that facilitated their evolutionary divergence. Using genomic context analysis and structural alignments we predicted functional associations for 32.4% of FESNov families, including 4,349 high-confidence associations with important biological processes. These predictions provide a valuable hypothesis-driven framework that we used for experimental validatation of a new gene family involved in cell motility and a novel set of antimicrobial peptides. We also demonstrate that the relative abundance profiles of novel families can discriminate between environments and clinical conditions, leading to the discovery of potentially new biomarkers associated with colorectal cancer. We expect this work to enhance future metagenomics studies and expand our knowledge of the genetic repertory of uncultivated organisms.

How Artificial Intelligence Is Shaping Medical Imaging Technology: A Survey of Innovations and Applications.

The integration of artificial intelligence (AI) into medical imaging has guided in an era of transformation in healthcare. This literature review explores the latest innovations and applications of AI in the field, highlighting its profound impact on medical diagnosis and patient care. The innovation segment explores cutting-edge developments in AI, such as deep learning algorithms, convolutional neural networks, and generative adversarial networks, which have significantly improved the accuracy and efficiency of medical image analysis. These innovations have enabled rapid and accurate detection of abnormalities, from identifying tumors during radiological examinations to detecting early signs of eye disease in retinal images. The article also highlights various applications of AI in medical imaging, including radiology, pathology, cardiology, and more. AI-based diagnostic tools not only speed up the interpretation of complex images but also improve early detection of disease, ultimately delivering better outcomes for patients. Additionally, AI-based image processing facilitates personalized treatment plans, thereby optimizing healthcare delivery. This literature review highlights the paradigm shift that AI has brought to medical imaging, highlighting its role in revolutionizing diagnosis and patient care. By combining cutting-edge AI techniques and their practical applications, it is clear that AI will continue shaping the future of healthcare in profound and positive ways.

Kinetics of C-Reactive Protein and Procalcitonin in the Early Identification of ICU-Acquired Infections in Critically Ill COVID-19 Patients.

The SARS-CoV-2 infection is a cause of hypoxemic acute respiratory failure, leading to frequent intensive care unit (ICU) admission. Due to invasive organ support and immunosuppressive therapies, these patients are prone to nosocomial infections. Our aim was to assess the value of daily measurements of C-reactive protein (CRP) and Procalcitonin (PCT) in the early identification of ICU-acquired infections in COVID-19 patients. METHODS: We undertook a prospective observational cohort study (12 months). All adult mechanically ventilated patients admitted for ≥72 h to ICU with COVID-19 pneumonia were divided into an infected group (n = 35) and a non-infected group (n = 83). Day 0 was considered as the day of the diagnosis of infection (infected group) and Day 10 was that of ICU stay (non-infected group). The kinetics of CRP and PCT were assessed from Day -10 to Day 10 and evaluated using a general linear model, univariate, repeated-measures analysis. RESULTS: 118 patients (mean age 63 years, 74% males) were eligible for the analysis. The groups did not differ in patient age, gender, CRP and PCT serum levels at ICU admission. However, the infected group encompassed patients with a higher severity (SOFA score at ICU admission, p = 0.009) and a higher 28-day mortality (p < 0.001). Before D0, CRP kinetics showed a significant increase in infected patients, whereas in noninfected it remained almost unchanged (p < 0.001), while PCT kinetics did not appear to retain diagnostic value to predict superinfection in COVID-19 patients (p = 0.593). CONCLUSION: COVID-19 patients who developed ICU-acquired infections exhibited different biomarker kinetics before the diagnosis of those infections. Daily CRP monitoring and the recognition of the CRP kinetics could be useful in the prediction of ICU-acquired infections.

Thrombocytopenia and platelet transfusions in ICU patients: an international inception cohort study (PLOT-ICU).

PURPOSE: Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. METHODS: We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequencies of thrombocytopenia, use of platelet transfusions and clinical outcomes including mortality. We evaluated pre-selected potential risk factors for the development of thrombocytopenia during ICU stay and associations between thrombocytopenia at ICU admission and 90-day mortality using pre-specified logistic regression analyses. RESULTS: We analysed 1166 ICU patients; the median age was 63 years and 39.5% were female. Overall, 43.2% (95% confidence interval (CI) 40.4-46.1) had thrombocytopenia; 23.4% (20-26) had thrombocytopenia at ICU admission, and 19.8% (17.6-22.2) developed thrombocytopenia during their ICU stay. Absence of acquired immune deficiency syndrome (AIDS), non-cancer-related immune deficiency, liver failure, male sex, septic shock, and bleeding at ICU admission were associated with the development of thrombocytopenia during ICU stay. Among patients with thrombocytopenia, 22.6% received platelet transfusion(s), and 64.3% of in-ICU transfusions were prophylactic. Patients with thrombocytopenia had higher occurrences of bleeding and death, fewer days alive without the use of life-support, and fewer days alive and out of hospital. Thrombocytopenia at ICU admission was associated with 90-day mortality (adjusted odds ratio 1.7; 95% CI 1.19-2.42). CONCLUSION: Thrombocytopenia occurred in 43% of critically ill patients and was associated with worse outcomes including increased mortality. Platelet transfusions were given to 23% of patients with thrombocytopenia and most were prophylactic.

European Network for ICU-Related Respiratory Infections (ENIRRIs): a multinational, prospective, cohort study of nosocomial LRTI.

PURPOSE: Lower respiratory tract infections (LRTI) are the most frequent infectious complication in patients admitted to the intensive care unit (ICU). We aim to report the clinical characteristics of ICU-admitted patients due to nosocomial LRTI and to describe their microbiology and clinical outcomes. METHODS: A prospective observational study was conducted in 13 countries over two continents from 9th May 2016 until 16th August 2019. Characteristics and outcomes of ventilator-associated pneumonia (VAP), ventilator-associated tracheobronchitis (VAT), ICU hospital-acquired pneumonia (ICU-HAP), HAP that required invasive ventilation (VHAP), and HAP in patients transferred to the ICU without invasive mechanical ventilation were collected. The clinical diagnosis and treatments were per clinical practice and not per protocol. Descriptive statistics were used to compare the study groups. RESULTS: 1060 patients with LRTI (72.5% male sex, median age 64 [50-74] years) were included in the study; 160 (15.1%) developed VAT, 556 (52.5%) VAP, 98 (9.2%) ICU-HAP, 152 (14.3%) HAP, and 94 (8.9%) VHAP. Patients with VHAP had higher serum procalcitonin (PCT) and Sequential Organ Failure Assessment (SOFA) scores. Patients with VAP or VHAP developed acute kidney injury, acute respiratory distress syndrome, multiple organ failure, or septic shock more often. One thousand eight patients had microbiological samples, and 711 (70.5%) had etiological microbiology identified. The most common microorganisms were Pseudomonas aeruginosa (18.4%) and Klebsiella spp (14.4%). In 382 patients (36%), the causative pathogen shows some antimicrobial resistance pattern. ICU, hospital and 28-day mortality were 30.8%, 37.5% and 27.5%, respectively. Patients with VHAP had the highest ICU, in-hospital and 28-day mortality rates. CONCLUSION: VHAP patients presented the highest mortality among those admitted to the ICU. Multidrug-resistant pathogens frequently cause nosocomial LRTI in this multinational cohort study.

Computational exploration of the global microbiome for antibiotic discovery.

Novel antibiotics are urgently needed to combat the antibiotic-resistance crisis. We present a machine learning-based approach to predict prokaryotic antimicrobial peptides (AMPs) by leveraging a vast dataset of 63,410 metagenomes and 87,920 microbial genomes. This led to the creation of AMPSphere, a comprehensive catalog comprising 863,498 non-redundant peptides, the majority of which were previously unknown. We observed that AMP production varies by habitat, with animal-associated samples displaying the highest proportion of AMPs compared to other habitats. Furthermore, within different human-associated microbiota, strain-level differences were evident. To validate our predictions, we synthesized and experimentally tested 50 AMPs, demonstrating their efficacy against clinically relevant drug-resistant pathogens both in vitro and in vivo. These AMPs exhibited antibacterial activity by targeting the bacterial membrane. Additionally, AMPSphere provides valuable insights into the evolutionary origins of peptides. In conclusion, our approach identified AMP sequences within prokaryotic microbiomes, opening up new avenues for the discovery of antibiotics.

Evidence of a causal and modifiable relationship between kidney function and circulating trimethylamine N-oxide.

The host-microbiota co-metabolite trimethylamine N-oxide (TMAO) is linked to increased cardiovascular risk but how its circulating levels are regulated remains unclear. We applied "explainable" machine learning, univariate, multivariate and mediation analyses of fasting plasma TMAO concentration and a multitude of phenotypes in 1,741 adult Europeans of the MetaCardis study. Here we show that next to age, kidney function is the primary variable predicting circulating TMAO, with microbiota composition and diet playing minor, albeit significant, roles. Mediation analysis suggests a causal relationship between TMAO and kidney function that we corroborate in preclinical models where TMAO exposure increases kidney scarring. Consistent with our findings, patients receiving glucose-lowering drugs with reno-protective properties have significantly lower circulating TMAO when compared to propensity-score matched control individuals. Our analyses uncover a bidirectional relationship between kidney function and TMAO that can potentially be modified by reno-protective anti-diabetic drugs and suggest a clinically actionable intervention for decreasing TMAO-associated excess cardiovascular risk.

Inclusion and adaptation beyond disability: Using virtual reality to foster empathy.

BACKGROUND: Virtual reality (VR) has the potential to be a powerful tool in promoting empathy towards inclusion, particularly for individuals with impairments such as mobility difficulties, vision deficits, or autism but also about pregnancy, which can create temporary difficulties. By immersing users in simulated environments that replicate the experiences of those with different abilities, VR can create a sense of understanding and empathy for those who face challenges in their daily lives. For example, VR experiences can simulate the experience of navigating space as someone with a mobility impairment, providing a new perspective and appreciation for the difficulties that others face. Similarly, VR experiences can simulate the experience of vision impairment, pregnancy, or autism, providing a window into the challenges faced by those with these conditions and fostering empathy and understanding. MATERIAL AND METHODS: During the development of this study, field experts were consulted to ensure the robustness of the methods employed. Then, questionnaires were specifically developed to explore disabilities and challenges related to inclusion and were administered to a large population. Additionally, guided interviews were conducted with individuals who possess specific impairments to gather first-hand insights. RESULTS: The results obtained from the questionnaires and interviews provide a comprehensive overview of the inclusion challenges that necessitate attention and resolution. By drawing on the expertise of both experts and individuals with lived experiences, a holistic landscape of inclusion challenges has been established. CONCLUSIONS: The VR emerges as a powerful tool for promoting inclusion and fostering understanding among individuals. Its capacity to create immersive experiences that facilitate empathy has the potential to reshape society into a more compassionate and empathetic one. By leveraging the unique capabilities of VR, we can bridge the gap between different perspectives, fostering greater understanding, acceptance, and inclusivity. Med Pr. 2023;74(3):171-85.

Enhancing empathy through virtual reality: Developing a universal design training application for students.

The lack of empathy towards disability is a significant societal issue that hampers inclusivity and understanding. Many struggle to comprehend the daily challenges and experiences faced by people with disabilities, leading to ignorance, prejudice, and exclusion. However, empathy plays a pivotal role in addressing this problem and serves as the foundation for developing and creating better products, services, and environments. This article explores the potential of developing virtual reality (VR) applications to enhance students' empathy towards individuals with disabilities. By increasing empathy levels, students are expected to gain significant qualifications in universal design (UD). The full application development process covers the most suitable head-mounted display (HMD) set. The implementation methodology using the Unity programming platform, the approach adopted for conducting classes using the developed VR application, and the deployment stage. Testing was successfully conducted on a student population, receiving positive user feedback. Through the integration of VR technology, the authors thoroughly describe how to address the empathy gap and equip students with essential skills for inclusive and accessible design. The findings presented in this study provide valuable guidance for educators and developers interested in harnessing VR's potential to foster empathy and advance universal design practices. With the presented methodology and proposed application, the authors demonstrate the effectiveness of VR applications in elevating students' empathy levels, consequently enhancing their qualifications in universal design. Med Pr. 2023;74(3):199-210.

Universal design and empathic design for engineers.

This article explores the relevance of universal design and empathic design in education. The universal design focuses on creating accessible and usable products, environments, and systems for individuals with diverse abilities. Empathy, on the other hand, involves understanding and sharing the feelings of others, encompassing cognitive, emotional, and compassionate empathy. The article investigates the application of empathy in design, particularly its importance for engineers. Teaching empathy to engineers is emphasized as a crucial aspect. By developing empathic skills, engineers gain a deeper understanding of user needs and perspectives, leading to more inclusive and user-centered design solutions. Effective communication techniques such as asking open-ended questions, active listening, observation, and perspective-taking are explored to enhance empathy in communication. The article also explores methods for measuring empathy, thus enabling engineers to assess the effectiveness of their empathic design approaches. The challenges facing students, teachers, and university authorities in implementing such courses are also bulleted. Med Pr. 2023;74(3):211-25.

Viral genetic clustering and transmission dynamics of the 2022 mpox outbreak in Portugal.

Pathogen genome sequencing during epidemics enhances our ability to identify and understand suspected clusters and investigate their relationships. Here, we combine genomic and epidemiological data of the 2022 mpox outbreak to better understand early viral spread, diversification and transmission dynamics. By sequencing 52% of the confirmed cases in Portugal, we identified the mpox virus sublineages with the highest impact on case numbers and fitted them into a global context, finding evidence that several international sublineages probably emerged or spread early in Portugal. We estimated a 62% infection reporting rate and that 1.3% of the population of men who have sex with men in Portugal were infected. We infer the critical role played by sexual networks and superspreader gatherings, such as sauna attendance, in the dissemination of mpox virus. Overall, our findings highlight genomic epidemiology as a tool for the real-time monitoring and control of mpox epidemics, and can guide future vaccine policy in a highly susceptible population.