State of Sweat: Emerging Wearable Systems for Real-Time, Noninvasive Sweat Sensing and Analytics.

Skin-interfaced wearable systems with integrated colorimetric assays, microfluidic channels, and electrochemical sensors offer powerful capabilities for noninvasive, real-time sweat analysis. This Perspective details recent progress in the development and translation of novel wearable sensors for personalized assessment of sweat dynamics and biomarkers, with precise sampling and real-time analysis. Sensor accuracy, system ruggedness, and large-scale deployment in remote environments represent key opportunity areas, enabling broad deployment in the context of field studies, clinical trials, and recent commercialization.

Flagellin Activates NAIP/NLRC4 and Canonical NLRP3 Inflammasomes in Human Macrophages.

Infection of human macrophages with serovar Typhimurium ( Typhimurium) leads to inflammasome activation. Inflammasomes are multiprotein complexes facilitating caspase-1 activation and subsequent gasdermin D-mediated cell death and IL-1β and IL-18 cytokine release. The NAIP/NLRC4 inflammasome is activated by multiple bacterial protein ligands, including flagellin from the flagellum and the needle protein PrgI from the Typhimurium type III secretion system.

Modifying bacterial flagellin to evade Nod-like Receptor CARD 4 recognition enhances protective immunity against Salmonella.

Pattern recognition receptors (PRRs) expressed in antigen-presenting cells are thought to shape pathogen-specific immunity by inducing secretion of costimulatory cytokines during T-cell activation, yet data to support this notion in vivo are scarce. Here, we show that the cytosolic PRR Nod-like Receptor CARD 4 (NLRC4) suppresses, rather than facilitates, effector and memory CD4 T-cell responses against Salmonella in mice. NLRC4 negatively regulates immunological memory by preventing delayed activation of the cytosolic PRR NLR pyrin domain 3 (NLRP3) that would otherwise amplify the production of cytokines important for the generation of Th1 immunity such as intereukin-18.

A Pivotal Study to Validate the Performance of a Novel Wearable Sensor and System for Biometric Monitoring in Clinical and Remote Environments.

Background: Increasingly, drug and device clinical trials are tracking activity levels and other quality of life indices as endpoints for therapeutic efficacy. Trials have traditionally required intermittent subject visits to the clinic that are artificial, activity-intensive, and infrequent, making trend and event detection between visits difficult. Thus, there is an unmet need for wearable sensors that produce clinical quality and medical grade physiological data from subjects in the home.

Clinical feasibility of a wearable, conformable sensor patch to monitor motor symptoms in Parkinson's disease.

Introduction: Clinical assessment of motor symptoms in Parkinson's disease (PD) is subjective and may not reflect patient real-world experience. This two-part pilot study evaluated the accuracy of the NIMBLE wearable biosensor patch (containing an accelerometer and electromyography sensor) to record body movements in clinic and home environments versus clinical measurement of motor symptoms.

Methods: Patients (Hoehn & Yahr 2-3) had motor symptom fluctuations and were on a stable levodopa dose.

A novel adhesive biosensor system for detecting respiration, cardiac, and limb movement signals during sleep: validation with polysomnography.

Background: Although in-lab polysomnography (PSG) remains the gold standard for objective sleep monitoring, the use of at-home sensor systems has gained popularity in recent years. Two categories of monitoring, autonomic and limb movement physiology, are increasingly recognized as critical for sleep disorder phenotyping, yet at-home options remain limited outside of research protocols. The purpose of this study was to validate the BiostampRC sensor system for respiration, electrocardiography (ECG), and leg electromyography (EMG) against gold standard PSG recordings.

Toll-like receptor 3 activation impairs excitability and synaptic activity via TRIF signalling in immature rat and human neurons.

Toll like receptor 3 (TLR3) belongs to a family of pattern recognition receptors that recognise molecules found on pathogens referred to as pathogen associated molecular patterns (PAMPs). Its involvement in innate immunity is well known but despite its presence in the central nervous system (CNS), our knowledge of its function is limited. Here, we have investigated whether TLR3 activation modulates synaptic activity in primary hippocampal cultures and induced pluripotent stem cell (iPSC)-derived neurons.

Highly flexible, wearable, and disposable cardiac biosensors for remote and ambulatory monitoring.

Contemporary cardiac and heart rate monitoring devices capture physiological signals using optical and electrode-based sensors. However, these devices generally lack the form factor and mechanical flexibility necessary for use in ambulatory and home environments. Here, we report an ultrathin (~1 mm average thickness) and highly flexible wearable cardiac sensor (WiSP) designed to be minimal in cost (disposable), light weight (1.

Assessment of Postural Sway in Individuals with Multiple Sclerosis Using a Novel Wearable Inertial Sensor.

Balance impairment is common in individuals with multiple sclerosis (MS). However, objective assessment of balance usually requires clinical expertise and/or the use of expensive and obtrusive measuring equipment. These barriers to the objective assessment of balance may be overcome with the development of a lightweight inertial sensor system.

Influence of Type I Fimbriae and Fluid Shear Stress on Bacterial Behavior and Multicellular Architecture of Early Escherichia coli Biofilms at Single-Cell Resolution.

Biofilm formation on abiotic surfaces in the food and medical industry can cause severe contamination and infection, yet how biological and physical factors determine the cellular architecture of early biofilms and the bacterial behavior of the constituent cells remains largely unknown. In this study, we examined the specific role of type I fimbriae in nascent stages of biofilm formation and the response of microcolonies to environmental flow shear at the single-cell resolution. The results show that type I fimbriae are not required for reversible adhesion from plankton, but they are critical for the irreversible adhesion of strain MG1655 cells that form biofilms on polyethylene terephthalate (PET) surfaces.

Soft, stretchable, epidermal sensor with integrated electronics and photochemistry for measuring personal UV exposures.

Excessive ultraviolet (UV) radiation induces acute and chronic effects on the skin, eye and immune system. Personalized monitoring of UV radiation is thus paramount to measure the extent of personal sun exposure, which could vary with environment, lifestyle, and sunscreen use. Here, we demonstrate an ultralow modulus, stretchable, skin-mounted UV patch that measures personal UV doses.

Bicarbonate induces high-level resistance to the human antimicrobial peptide LL-37 in Staphylococcus aureus small colony variants.

Objectives: Staphylococcus aureus small colony variants (SCVs) cause persistent infections and are resistant to cationic antibiotics. Antimicrobial peptides (AMPs) have been suggested as promising alternatives for treating antibiotic-resistant bacteria. We investigated the capacity of the human cationic AMP LL-37 to kill SCVs in the presence of physiological concentrations of bicarbonate, which are reported to alter bacterial membrane permeability and change resistance of bacteria to AMPs.

An Ochre Mutation Results in a Small Colony Variant That Can Undergo Phenotypic Switching via Two Alternative Mechanisms.

can undergo phenotypic switching between a normal colony phenotype (NCP) and a small colony variant (SCV). The SCV phenotype confers increased antibiotic resistance and the capacity to persist within human tissues and cells, and because these cells can revert back to the NCP they cause chronic and/or recurrent infections that are very difficult to treat. A complete picture of the genetic events that can lead to phenotypic switching in is currently lacking.

A machine learning approach for gait speed estimation using skin-mounted wearable sensors: From healthy controls to individuals with multiple sclerosis.

Gait speed is a powerful clinical marker for mobility impairment in patients suffering from neurological disorders. However, assessment of gait speed in coordination with delivery of comprehensive care is usually constrained to clinical environments and is often limited due to mounting demands on the availability of trained clinical staff. These limitations in assessment design could give rise to poor ecological validity and limited ability to tailor interventions to individual patients.

Lipopolysaccharide-induced NF-κB nuclear translocation is primarily dependent on MyD88, but TNFα expression requires TRIF and MyD88.

TLR4 signalling through the MyD88 and TRIF-dependent pathways initiates translocation of the transcription factor NF-κB into the nucleus. In cell population studies using mathematical modeling and functional analyses, Cheng et al. suggested that LPS-driven activation of MyD88, in the absence of TRIF, impairs NF-κB translocation.

Monitoring gait in multiple sclerosis with novel wearable motion sensors.

Background: Mobility impairment is common in people with multiple sclerosis (PwMS) and there is a need to assess mobility in remote settings. Here, we apply a novel wireless, skin-mounted, and conformal inertial sensor (BioStampRC, MC10 Inc.) to examine gait characteristics of PwMS under controlled conditions.

The frequency and duration of Salmonella-macrophage adhesion events determines infection efficiency.

Salmonella enterica causes a range of important diseases in humans and a in a variety of animal species. The ability of bacteria to adhere to, invade and survive within host cells plays an important role in the pathogenesis of Salmonella infections. In systemic salmonellosis, macrophages constitute a niche for the proliferation of bacteria within the host organism.

Actin polymerization as a key innate immune effector mechanism to control Salmonella infection.

Salmonellosis is one of the leading causes of food poisoning worldwide. Controlling bacterial burden is essential to surviving infection. Nucleotide-binding oligomerization domain-like receptors (NLRs), such as NLRC4, induce inflammasome effector functions and play a crucial role in controlling Salmonella infection.

Inflammasome activation causes dual recruitment of NLRC4 and NLRP3 to the same macromolecular complex.

Pathogen recognition by nucleotide-binding oligomerization domain-like receptor (NLR) results in the formation of a macromolecular protein complex (inflammasome) that drives protective inflammatory responses in the host. It is thought that the number of inflammasome complexes forming in a cell is determined by the number of NLRs being activated, with each NLR initiating its own inflammasome assembly independent of one another; however, we show here that the important foodborne pathogen Salmonella enterica serovar Typhimurium (S. Typhimurium) simultaneously activates at least two NLRs, whereas only a single inflammasome complex is formed in a macrophage.

Staphylococcus aureus small colony variants are susceptible to light activated antimicrobial agents.

Background: Antibiotic therapy can select for small colony variants of Staphylococcus aureus that are more resistant to antibiotics and can result in persistent infections, necessitating the development of more effective antimicrobial strategies to combat small colony variant infections. Photodynamic therapy is an alternative treatment approach which utilises light in combination with a light-activated antimicrobial agent to kill bacteria via a non-specific mechanism of action. In this study, we investigated whether the combination of 665 nm laser light and the light-activated antimicrobial agent methylene blue was able to successfully kill S.

The lipoprotein components of the Isd and Hts transport systems are dispensable for acquisition of heme by Staphylococcus aureus.

Heme is a key molecule for Staphylococcus aureus and is involved in many aspects of oxidative metabolism. Crucially, heme is required for the activity of cytochromes of the electron transport chain. Staphylococcus aureus is able to obtain heme either through biosynthesis or through acquisition from the host.

Interaction of staphylococci with bone.

Staphylococci, in particular Staphylococcus aureus, are the predominant cause of bone infections worldwide. These infections are painful, debilitating and with the rise in antibiotic-resistant forms, increasingly difficult to treat. The growth in the number of prosthetic joint replacement procedures also provides new opportunities for these infections to take hold.

Multiple redundant stress resistance mechanisms are induced in Salmonella enterica serovar Typhimurium in response to alteration of the intracellular environment via TLR4 signalling.

Toll-like receptor 4 (TLR4) senses bacterial LPS and is required for the control of systemic Salmonella enterica serovar Typhimurium infection in mice. The mechanisms of TLR4 activation and its downstream signalling cascades are well described, yet the direct effects on the pathogen of signalling via this receptor remain unknown. To investigate this we used microarray-based transcriptome profiling of intracellular S.