Kidney resident macrophages have distinct subsets and multifunctional roles.

BACKGROUND: The kidney contains distinct glomerular and tubulointerstitial compartments with diverse cell types and extracellular matrix components. The role of immune cells in glomerular environment is crucial for dampening inflammation and maintaining homeostasis. Macrophages are innate immune cells that are influenced by their tissue microenvironment. However, the multifunctional role of kidney macrophages remains unclear. METHODS: Flow and imaging cytometry were used to determine the relative expression of CD81 and CX3CR1 (C-X3-C motif chemokine receptor 1) in kidney macrophages. Monocyte replenishment was assessed in Cx3cr1CreER X R26-yfp-reporter and shielded chimeric mice. Bulk RNA-sequencing and mass spectrometry-based proteomics were performed on isolated kidney macrophages from wild type and Col4a5-/- (Alport) mice. RNAscope was used to visualize transcripts and macrophage purity in bulk RNA assessed by CIBERSORTx analyses. RESULTS: In wild type mice we identified three distinct kidney macrophage subsets using CD81 and CX3CR1 and these subsets showed dependence on monocyte replenishment. In addition to their immune function, bulk RNA-sequencing of macrophages showed enrichment of biological processes associated with extracellular matrix. Proteomics identified collagen IV and laminins in kidney macrophages from wild type mice whilst other extracellular matrix proteins including cathepsins, ANXA2 and LAMP2 were enriched in Col4a5-/- (Alport) mice. A subset of kidney macrophages co-expressed matrix and macrophage transcripts. CONCLUSIONS: We identified CD81 and CX3CR1 positive kidney macrophage subsets with distinct dependence for monocyte replenishment. Multiomic analysis demonstrated that these cells have diverse functions that underscore the importance of macrophages in kidney health and disease.

Long-Range Conductivity in Proteins Mediated by Aromatic Residues.

Single-molecule measurements show that many proteins, lacking any redox cofactors, nonetheless exhibit electrical conductance on the order of a nanosiemen over 10 nm distances, implying that electrons can transit an entire protein in less than a nanosecond when subject to a potential difference of less than 1 V. This is puzzling because, for fast transport (i.e., a free energy barrier of zero), the hopping rate is determined by the reorganization energy of approximately 0.8 eV, and this sets the time scale of a single hop to at least 1 µs. Furthermore, the Fermi energies of typical metal electrodes are far removed from the energies required for sequential oxidation and reduction of the aromatic residues of the protein, which should further reduce the hopping current. Here, we combine all-atom molecular dynamics (MD) simulations of non-redox-active proteins (consensus tetratricopeptide repeats) with an electron transfer theory to demonstrate a molecular mechanism that can account for the unexpectedly fast electron transport. According to our MD simulations, the reorganization energy produced by the energy shift on charging (the Stokes shift) is close to the conventional value of 0.8 eV. However, the non-ergodic sampling of molecular configurations by the protein results in reaction-reorganization energies, extracted directly from the distribution of the electrostatic energy fluctuations, that are only ∼0.2 eV, which is small enough to enable long-range conductivity, without invoking quantum coherent transport. Using the MD values of the reorganization energies, we calculate a current decay with distance that is in agreement with experiment.

A wireless, battery-free device enables oxygen generation and immune protection of therapeutic xenotransplants in vivo.

The immune isolation of cells within devices has the potential to enable long-term protein replacement and functional cures for a range of diseases, without requiring immune suppressive therapy. However, a lack of vasculature and the formation of fibrotic capsules around cell immune-isolating devices limits oxygen availability, leading to hypoxia and cell death in vivo. This is particularly problematic for pancreatic islet cells that have high O2 requirements. Here, we combine bioelectronics with encapsulated cell therapies to develop the first wireless, battery-free oxygen-generating immune-isolating device (O2-Macrodevice) for the oxygenation and immune isolation of cells in vivo. The system relies on electrochemical water splitting based on a water-vapor reactant feed, sustained by wireless power harvesting based on a flexible resonant inductive coupling circuit. As such, the device does not require pumping, refilling, or ports for recharging and does not generate potentially toxic side products. Through systematic in vitro studies with primary cell lines and cell lines engineered to secrete protein, we demonstrate device performance in preventing hypoxia in ambient oxygen concentrations as low as 0.5%. Importantly, this device has shown the potential to enable subcutaneous (SC) survival of encapsulated islet cells, in vivo in awake, freely moving, immune-competent animals. Islet transplantation in Type I Diabetes represents an important application space, and 1-mo studies in immune-competent animals with SC implants show that the O2-Macrodevice allows for survival and function of islets at high densities (~1,000 islets/cm2) in vivo without immune suppression and induces normoglycemia in diabetic animals.

muxGNN: Multiplex Graph Neural Network for Heterogeneous Graphs.

Graph neural networks (GNNs) have become effective learning techniques for many downstream network mining tasks including node and graph classification, link prediction, and network reconstruction. However, most GNN methods have been developed for homogeneous networks with only a single type of node and edge. In this work we present muxGNN, a multiplex graph neural network for heterogeneous graphs. To model heterogeneity, we represent graphs as multiplex networks consisting of a set of relation layer graphs and a coupling graph that links node instantiations across multiple relations. We parameterize relation-specific representations of nodes and design a novel coupling attention mechanism that models the importance of multi-relational contexts for different types of nodes and edges in heterogeneous graphs. We further develop two complementary coupling structures: node invariant coupling suitable for node- and graph-level tasks, and node equivariant coupling suitable for link-level tasks. Extensive experiments conducted on six real-world datasets for link prediction in both transductive and inductive contexts and graph classification demonstrate the superior performance of muxGNN over state-of-the-art heterogeneous GNNs. In addition, we show that muxGNN's coupling attention discovers interpretable connections between different relations in heterogeneous networks.

Wireless, Battery-Free Implants for Electrochemical Catecholamine Sensing and Optogenetic Stimulation.

Neurotransmitters and neuromodulators mediate communication between neurons and other cell types; knowledge of release dynamics is critical to understanding their physiological role in normal and pathological brain function. Investigation into transient neurotransmitter dynamics has largely been hindered due to electrical and material requirements for electrochemical stimulation and recording. Current systems require complex electronics for biasing and amplification and rely on materials that offer limited sensor selectivity and sensitivity. These restrictions result in bulky, tethered, or battery-powered systems impacting behavior and that require constant care of subjects. To overcome these challenges, we demonstrate a fully implantable, wireless, and battery-free platform that enables optogenetic stimulation and electrochemical recording of catecholamine dynamics in real time. The device is nearly 1/10th the size of previously reported examples and includes a probe that relies on a multilayer electrode architecture featuring a microscale light emitting diode (µ-LED) and a carbon nanotube (CNT)-based sensor with sensitivities among the highest recorded in the literature (1264.1 nA µM-1 cm-2). High sensitivity of the probe combined with a center tapped antenna design enables the realization of miniaturized, low power circuits suitable for subdermal implantation even in small animal models such as mice. A series of in vitro and in vivo experiments highlight the sensitivity and selectivity of the platform and demonstrate its capabilities in freely moving, untethered subjects. Specifically, a demonstration of changes in dopamine concentration after optogenetic stimulation of the nucleus accumbens and real-time readout of dopamine levels after opioid and naloxone exposure in freely behaving subjects highlight the experimental paradigms enabled by the platform.

Age-Related Alterations in Macrophage Distribution and Function Are Associated With Delayed Cutaneous Wound Healing.

Ageing-related delays and dysregulated inflammation in wound healing are well-documented in both human and animal models. However, cellular and molecular changes underlying this impairment in healing progression are not fully understood. In this study, we characterised ageing-associated changes to macrophages in wounds of young and aged mice and investigated transcriptomic differences that may impact the progression of wound healing. Full-thickness wounds created on the dorsum of C57BL/6J young and aged mice were excised on Days 3 and 7 post-wounding for analysis by immunohistochemistry, flow cytometry, and RNA sequencing. Our data revealed that macrophages were significantly reduced in aged wounds in comparison to young. Functional transcriptomic analyses showed that macrophages from aged wounds exhibited significantly reduced expression of cell cycle, DNA replication, and repair pathway genes. Furthermore, we uncovered an elevated pro-inflammatory gene expression program in the aged macrophages correlated with poor inflammation resolution and excessive tissue damage observed in aged wounds. Altogether, our work provides insights into how poorly healing aged wounds are phenotypically defined by the presence of macrophages with reduced proliferative capacity and an exacerbated inflammatory response, both of which are pathways that can be targeted to improve healing in the elderly.

Soft, bioresorbable coolers for reversible conduction block of peripheral nerves.

Implantable devices capable of targeted and reversible blocking of peripheral nerve activity may provide alternatives to opioids for treating pain. Local cooling represents an attractive means for on-demand elimination of pain signals, but traditional technologies are limited by rigid, bulky form factors; imprecise cooling; and requirements for extraction surgeries. Here, we introduce soft, bioresorbable, microfluidic devices that enable delivery of focused, minimally invasive cooling power at arbitrary depths in living tissues with real-time temperature feedback control. Construction with water-soluble, biocompatible materials leads to dissolution and bioresorption as a mechanism to eliminate unnecessary device load and risk to the patient without additional surgeries. Multiweek in vivo trials demonstrate the ability to rapidly and precisely cool peripheral nerves to provide local, on-demand analgesia in rat models for neuropathic pain.

[Contrasting Misinformation and Real-Information Dissemination Network Structures on Social Media During a Health Emergency]. / Comparación de las estructuras de difusión de información errónea y verídica en las redes sociales durante una emergencia de salud pública.

OBJECTIVES: To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic. METHODS: We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of "misinformation," identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups. RESULTS: There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too. CONCLUSIONS: Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

Comparación de las estructuras de difusión de información errónea y verídica en las redes sociales durante una emergencia de salud pública

[RESUMEN]. Objetivos. Elaborar un esquema operativo integral para detectar la información errónea principal sobre el zika distribuida en Twitter® en el 2016; reconstruir las redes por las que se difunde información mediante retuiteo; contrastar la información verídica frente a la errónea con diversos parámetros; e investigar cómo se difundió en las redes sociales la información errónea sobre el zika durante la epidemia. Métodos. Revisamos sistemáticamente los 5 000 tuits más retuiteados con información sobre el zika en inglés, definimos “información errónea” a partir de la evidencia, buscamos tuits que tuvieran información errónea y conformamos un grupo equiparable de tuits con información verídica. Elaboramos un algoritmo para reconstruir las redes de retuiteo de 266 tuits con información errónea y 458 tuits equiparables con información verídica. Calculamos y comparamos nueve parámetros para caracterizar la estructura de las redes a varios niveles, entre los dos grupos. Resultados. En los nueve parámetros se aprecian diferencias estadísticamente significativas entre el grupo de información verídica y el de información errónea. La información errónea en general se difunde mediante estructuras más sofisticadas que la información verídica. También hay una considerable variabilidad intragrupal. Conclusiones. Las redes de difusión de la información errónea sobre el zika en Twitter fueron sustancialmente diferentes que las de información verídica, lo cual indica que la información errónea se sirve de mecanismos de difusión distintos. Nuestro estudio permitirá formar una comprensión más holística de los desafíos que plantea la información errónea sobre salud en las redes sociales.

[ABSTRACT]. Objectives. To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic. Methods. We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of “misinformation,” identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups. Results. There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too. Conclusions. Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

Hematopoietic stem and progenitor cells are present in healthy gingiva tissue.

Hematopoietic stem cells reside in the bone marrow, where they generate the effector cells that drive immune responses. However, in response to inflammation, some hematopoietic stem and progenitor cells (HSPCs) are recruited to tissue sites and undergo extramedullary hematopoiesis. Contrasting with this paradigm, here we show residence and differentiation of HSPCs in healthy gingiva, a key oral barrier in the absence of overt inflammation. We initially defined a population of gingiva monocytes that could be locally maintained; we subsequently identified not only monocyte progenitors but also diverse HSPCs within the gingiva that could give rise to multiple myeloid lineages. Gingiva HSPCs possessed similar differentiation potentials, reconstitution capabilities, and heterogeneity to bone marrow HSPCs. However, gingival HSPCs responded differently to inflammatory insults, responding to oral but not systemic inflammation. Combined, we highlight a novel pathway of myeloid cell development at a healthy barrier, defining a gingiva-specific HSPC network that supports generation of a proportion of the innate immune cells that police this barrier.

Comparación de las estructuras de difusión de información errónea y verídica en las redes sociales durante una emergencia de salud pública / Contrasting Misinformation and Real-Information Dissemination Network Structures on Social Media During a Health Emergency

RESUMEN Objetivos. Elaborar un esquema operativo integral para detectar la información errónea principal sobre el zika distribuida en Twitter® en el 2016; reconstruir las redes por las que se difunde información mediante retuiteo; contrastar la información verídica frente a la errónea con diversos parámetros; e investigar cómo se difundió en las redes sociales la información errónea sobre el zika durante la epidemia. Métodos. Revisamos sistemáticamente los 5 000 tuits más retuiteados con información sobre el zika en inglés, definimos "información errónea" a partir de la evidencia, buscamos tuits que tuvieran información errónea y conformamos un grupo equiparable de tuits con información verídica. Elaboramos un algoritmo para reconstruir las redes de retuiteo de 266 tuits con información errónea y 458 tuits equiparables con información verídica. Calculamos y comparamos nueve parámetros para caracterizar la estructura de las redes a varios niveles, entre los dos grupos. Resultados. En los nueve parámetros se aprecian diferencias estadísticamente significativas entre el grupo de información verídica y el de información errónea. La información errónea en general se difunde mediante estructuras más sofisticadas que la información verídica. También hay una considerable variabilidad intragrupal. Conclusiones. Las redes de difusión de la información errónea sobre el zika en Twitter fueron sustancialmente diferentes que las de información verídica, lo cual indica que la información errónea se sirve de mecanismos de difusión distintos. Nuestro estudio permitirá formar una comprensión más holística de los desafíos que plantea la información errónea sobre salud en las redes sociales.

ABSTRACT Objectives. To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic. Methods. We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of "misinformation," identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups. Results. There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too. Conclusions. Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

Contrasting Misinformation and Real-Information Dissemination Network Structures on Social Media During a Health Emergency.

Objectives. To provide a comprehensive workflow to identify top influential health misinformation about Zika on Twitter in 2016, reconstruct information dissemination networks of retweeting, contrast mis- from real information on various metrics, and investigate how Zika misinformation proliferated on social media during the Zika epidemic.Methods. We systematically reviewed the top 5000 English-language Zika tweets, established an evidence-based definition of "misinformation," identified misinformation tweets, and matched a comparable group of real-information tweets. We developed an algorithm to reconstruct retweeting networks for 266 misinformation and 458 comparable real-information tweets. We computed and compared 9 network metrics characterizing network structure across various levels between the 2 groups.Results. There were statistically significant differences in all 9 network metrics between real and misinformation groups. Misinformation network structures were generally more sophisticated than those in the real-information group. There was substantial within-group variability, too.Conclusions. Dissemination networks of Zika misinformation differed substantially from real information on Twitter, indicating that misinformation utilized distinct dissemination mechanisms from real information. Our study will lead to a more holistic understanding of health misinformation challenges on social media.

Longitudinal immune profiling reveals key myeloid signatures associated with COVID-19.

COVID-19 pathogenesis is associated with an exaggerated immune response. However, the specific cellular mediators and inflammatory components driving diverse clinical disease outcomes remain poorly understood. We undertook longitudinal immune profiling on both whole blood and peripheral blood mononuclear cells (PBMCs) of hospitalized patients during the peak of the COVID-19 pandemic in the UK. Here, we report key immune signatures present shortly after hospital admission that were associated with the severity of COVID-19. Immune signatures were related to shifts in neutrophil to T cell ratio, elevated serum IL-6, MCP-1 and IP-10, and most strikingly, modulation of CD14+ monocyte phenotype and function. Modified features of CD14+ monocytes included poor induction of the prostaglandin-producing enzyme, COX-2, as well as enhanced expression of the cell cycle marker Ki-67. Longitudinal analysis revealed reversion of some immune features back to the healthy median level in patients with a good eventual outcome. These findings identify previously unappreciated alterations in the innate immune compartment of COVID-19 patients and lend support to the idea that therapeutic strategies targeting release of myeloid cells from bone marrow should be considered in this disease. Moreover, they demonstrate that features of an exaggerated immune response are present early after hospital admission suggesting immune-modulating therapies would be most beneficial at early timepoints.

Identifying Influential Factors in the Discussion Dynamics of Emerging Health Issues on Social Media: Computational Study.

BACKGROUND: Social media has become a major resource for observing and understanding public opinions using infodemiology and infoveillance methods, especially during emergencies such as disease outbreaks. For public health agencies, understanding the driving forces of web-based discussions will help deliver more effective and efficient information to general users on social media and the web. OBJECTIVE: The study aimed to identify the major contributors that drove overall Zika-related tweeting dynamics during the 2016 epidemic. In total, 3 hypothetical drivers were proposed: (1) the underlying Zika epidemic quantified as a time series of case counts; (2) sporadic but critical real-world events such as the 2016 Rio Olympics and World Health Organization's Public Health Emergency of International Concern (PHEIC) announcement, and (3) a few influential users' tweeting activities. METHODS: All tweets and retweets (RTs) containing the keyword Zika posted in 2016 were collected via the Gnip application programming interface (API). We developed an analytical pipeline, EventPeriscope, to identify co-occurring trending events with Zika and quantify the strength of these events. We also retrieved Zika case data and identified the top influencers of the Zika discussion on Twitter. The influence of 3 potential drivers was examined via a multivariate time series analysis, signal processing, a content analysis, and text mining techniques. RESULTS: Zika-related tweeting dynamics were not significantly correlated with the underlying Zika epidemic in the United States in any of the four quarters in 2016 nor in the entire year. Instead, peaks of Zika-related tweeting activity were strongly associated with a few critical real-world events, both planned, such as the Rio Olympics, and unplanned, such as the PHEIC announcement. The Rio Olympics was mentioned in >15% of all Zika-related tweets and PHEIC occurred in 27% of Zika-related tweets around their respective peaks. In addition, the overall tweeting dynamics of the top 100 most actively tweeting users on the Zika topic, the top 100 users receiving most RTs, and the top 100 users mentioned were the most highly correlated to and preceded the overall tweeting dynamics, making these groups of users the potential drivers of tweeting dynamics. The top 100 users who retweeted the most were not critical in driving the overall tweeting dynamics. There were very few overlaps among these different groups of potentially influential users. CONCLUSIONS: Using our proposed analytical workflow, EventPeriscope, we identified that Zika discussion dynamics on Twitter were decoupled from the actual disease epidemic in the United States but were closely related to and highly influenced by certain sporadic real-world events as well as by a few influential users. This study provided a methodology framework and insights to better understand the driving forces of web-based public discourse during health emergencies. Therefore, health agencies could deliver more effective and efficient web-based communications in emerging crises.

Continuous, noninvasive wireless monitoring of flow of cerebrospinal fluid through shunts in patients with hydrocephalus.

Hydrocephalus is a common disorder caused by the buildup of cerebrospinal fluid (CSF) in the brain. Treatment typically involves the surgical implantation of a pressure-regulated silicone tube assembly, known as a shunt. Unfortunately, shunts have extremely high failure rates and diagnosing shunt malfunction is challenging due to a combination of vague symptoms and a lack of a convenient means to monitor flow. Here, we introduce a wireless, wearable device that enables precise measurements of CSF flow, continuously or intermittently, in hospitals, laboratories or even in home settings. The technology exploits measurements of thermal transport through near-surface layers of skin to assess flow, with a soft, flexible, and skin-conformal device that can be constructed using commercially available components. Systematic benchtop studies and numerical simulations highlight all of the key considerations. Measurements on 7 patients establish high levels of functionality, with data that reveal time dependent changes in flow associated with positional and inertial effects on the body. Taken together, the results suggest a significant advance in monitoring capabilities for patients with shunted hydrocephalus, with potential for practical use across a range of settings and circumstances, and additional utility for research purposes in studies of CSF hydrodynamics.

Resettable skin interfaced microfluidic sweat collection devices with chemesthetic hydration feedback.

Recently introduced classes of thin, soft, skin-mounted microfluidic systems offer powerful capabilities for continuous, real-time monitoring of total sweat loss, sweat rate and sweat biomarkers. Although these technologies operate without the cost, complexity, size, and weight associated with active components or power sources, rehydration events can render previous measurements irrelevant and detection of anomalous physiological events, such as high sweat loss, requires user engagement to observe colorimetric responses. Here we address these limitations through monolithic systems of pinch valves and suction pumps for purging of sweat as a reset mechanism to coincide with hydration events, microstructural optics for reversible readout of sweat loss, and effervescent pumps and chemesthetic agents for automated delivery of sensory warnings of excessive sweat loss. Human subject trials demonstrate the ability of these systems to alert users to the potential for dehydration via skin sensations initiated by sweat-triggered ejection of menthol and capsaicin.

Old Dog New Tricks; Revisiting How Stroke Modulates the Systemic Immune Landscape.

Infections in the post-acute phase of cerebral ischaemia impede optimal recovery by exacerbating morbidity and mortality. Our review aims to reconcile the increased infection susceptibility of patients post-stroke by consolidating our understanding of compartmentalised alterations to systemic immunity. Mounting evidence has catalogued alterations to numerous immune cell populations but an understanding of the mechanisms of long-range communication between the immune system, nervous system and other organs beyond the involvement of autonomic signalling is lacking. By taking our cues from established and emerging concepts of neuro-immune interactions, immune-mediated inter-organ cross-talk, innate immune training and the role of microbiota-derived signals in central nervous system (CNS) function we will explore mechanisms of how cerebral ischaemia could shape systemic immune function. In this context, we will also discuss a key question: how are immune requirements critical for mediating repair of the ischaemic insult balanced by the need for anti-microbial immunity post-stroke, given that they are mediated by mutually exclusive immune networks? Our reformed understanding of the immune landscape post-stroke and novel mechanisms at play could guide targeted therapeutic interventions and initiate a step-change in the clinical management of these infectious complications post-stroke.

Distal Consequences of Oral Inflammation.

Periodontitis is an incredibly prevalent chronic inflammatory disease, which results in the destruction of tooth supporting structures. However, in addition to causing tooth and alveolar bone loss, this oral inflammatory disease has been shown to contribute to disease states and inflammatory pathology at sites distant from the oral cavity. Epidemiological and experimental studies have linked periodontitis to the development and/or exacerbation of a plethora of other chronic diseases ranging from rheumatoid arthritis to Alzheimer's disease. Such studies highlight how the inflammatory status of the oral cavity can have a profound impact on systemic health. In this review we discuss the disease states impacted by periodontitis and explore potential mechanisms whereby oral inflammation could promote loss of homeostasis at distant sites.

Battery-free, fully implantable optofluidic cuff system for wireless optogenetic and pharmacological neuromodulation of peripheral nerves.

Studies of the peripheral nervous system rely on controlled manipulation of neuronal function with pharmacologic and/or optogenetic techniques. Traditional hardware for these purposes can cause notable damage to fragile nerve tissues, create irritation at the biotic/abiotic interface, and alter the natural behaviors of animals. Here, we present a wireless, battery-free device that integrates a microscale inorganic light-emitting diode and an ultralow-power microfluidic system with an electrochemical pumping mechanism in a soft platform that can be mounted onto target peripheral nerves for programmed delivery of light and/or pharmacological agents in freely moving animals. Biocompliant designs lead to minimal effects on overall nerve health and function, even with chronic use in vivo. The small size and light weight construction allow for deployment as fully implantable devices in mice. These features create opportunities for studies of the peripheral nervous system outside of the scope of those possible with existing technologies.