Edema India: Executive Summary of Screening, Diagnosis, and Management of Edema.

The management of edema requires a systematic approach to screening, diagnosis, and treatment, with an essential initial assessment to differentiate between generalized and localized edema. The Association of Physicians of India (API) aimed to develop the first Indian Edema Consensus (Edema India), offering tailored recommendations for screening, diagnosing, and managing edema based on the insights from the expert panel. The panel suggested when evaluating edema symptoms, important factors to consider include the patient's current illness, medical history, risk factors, family history, and medications. Key diagnostic investigations for edema include complete blood count, cardiovascular imaging and markers, deep vein thrombosis (DVT) assessment, along with renal, hepatic, and thyroid function tests. Edema management involves a combination of pharmacologic and nonpharmacologic interventions, including limb elevation, physiotherapy, compression therapy, fluid removal, diuretics (loop diuretics: first-line therapy), and a sodium-restricted diet. The panel believed that educating patients could foster a preventive mindset, helping to prevent the worsening of edema.

Heavy-Metal-Free Colloidal Quantum Dots: Progress and Opportunities in Solar Technologies.

Colloidal quantum dots (QDs) hold great promise as building blocks in solar technologies owing to their remarkable photostability and adjustable properties through the rationale involving size, atomic composition of core and shell, shapes, and surface states. However, most high-performing QDs in solar conversion contain hazardous metal elements, including Cd and Pb, posing significant environmental risks. Here, a comprehensive review of heavy-metal-free colloidal QDs for solar technologies, including photovoltaic (PV) devices, solar-to-chemical fuel conversion, and luminescent solar concentrators (LSCs), is presented. Emerging synthetic strategies to optimize the optical properties by tuning the energy band structure and manipulating charge dynamics within the QDs and at the QDs/charge acceptors interfaces, are analyzed. A comparative analysis of different synthetic methods is provided, structure-property relationships in these materials are discussed, and they are correlated with the performance of solar devices. This work is concluded with an outlook on challenges and opportunities for future work, including machine learning-based design, sustainable synthesis, and new surface/interface engineering.

Titanium Carbide (Ti3C2Tx) MXene for Sequestration of Aquatic Pollutants.

The rapid expansion of industrialization has resulted in the release of multiple ecological contaminants in gaseous, liquid, and solid forms, which pose significant environmental risks to many different ecosystems. The efficient and cost-effective removal of these environmental pollutants has attracted global attention. This growing concern has prompted the synthesis and optimization of nanomaterials and their application as potential pollutant removal. In this context, MXene is considered an outstanding photocatalytic candidate due to its unique physicochemical and mechanical properties, which include high specific surface area, physiological compatibility, and robust electrodynamics. This review highlights recent advances in shaping titanium carbide (Ti3C2Tx) MXenes, emphasizing the importance of termination groups to boost photoactivity and product selectivity, with a primary focus on engineering aspects. First, a broad overview of Ti3C2Tx MXene is provided, delving into its catalytic properties and the formation of surface termination groups to establish a comprehensive understanding of its fundamental catalytic structure. Subsequently, the effects of engineering the morphology of Ti3C2Tx MXene into different structures, such as two-dimensional (2D) accordion-like forms, monolayers, hierarchies, quantum dots, and nanotubes. Finally, a concise overview of the removal of different environmental pollutants is presented, and the forthcoming challenges, along with their prospective outlooks, are delineated.

Osteoimmunology of Fracture Healing.

PURPOSE OF REVIEW: The purpose of this review is to summarize what is known in the literature about the role inflammation plays during bone fracture healing. Bone fracture healing progresses through four distinct yet overlapping phases: formation of the hematoma, development of the cartilaginous callus, development of the bony callus, and finally remodeling of the fracture callus. Throughout this process, inflammation plays a critical role in robust bone fracture healing. RECENT FINDINGS: At the onset of injury, vessel and matrix disruption lead to the generation of an inflammatory response: inflammatory cells are recruited to the injury site where they differentiate, activate, and/or polarize to secrete cytokines for the purposes of cell signaling and cell recruitment. This process is altered by age and by sex. Bone fracture healing is heavily influenced by the presence of inflammatory cells and cytokines within the healing tissue.

The impact of age and sex on the inflammatory response during bone fracture healing.

Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and cytokine profiles in circulation and in bone tissue to identify age- and sex-dependent differences during homeostasis and repair. During homeostatic aging, male mice demonstrated accumulation of CD4+ helper T cells and CD8+ cytotoxic T cells within bone while both pro-inflammatory "M1" and anti-inflammatory "M2" macrophage numbers decreased. Female mice saw no age-associated changes in immune-cell population in homeostatic bone. Concentrations of IL-1ß, IL-9, IFNγ, and CCL3/MIP-1α increased with age in both male and female mice, whereas concentrations of IL-2, TNFα, TNFR1, IL-4, and IL-10 increased only in female mice - thus we termed these "age-accumulated" cytokines. There were no notable changes in immune cell populations nor cytokines within circulation during aging. Sex-dependent analysis demonstrated slight changes in immune cell and cytokine levels within bone and circulation, which were lost upon fracture injury. Fracture in young male mice caused a sharp decrease in number of M1 macrophages; however, this was not seen in aged male mice nor in female mice of any age. Injury itself induced a decrease in the number of CD8+ T cells within the local tissue of aged male and of female mice but not of young mice. Cytokine analysis of fractured mice revealed that age-accumulated cytokines quickly dissipated after fracture injury, and did not re-accumulate in newly regenerated tissue. Conversely, CXCL1/KC-GRO, CXCL2/MIP-2, IL-6, and CCL2/MCP-1 acted as "fracture response" cytokines: increasing sharply after fracture, eventually returning to baseline. Collectively, we classify measured cytokines into three groups: (1) age-accumulated cytokines, (2) female-specific age-accumulated cytokines, and (3) fracture response cytokines. These inflammatory molecules represent potential points of intervention to improve fracture healing outcome.

Lipid Association of India 2023 update on cardiovascular risk assessment and lipid management in Indian patients: Consensus statement IV.

OBJECTIVE: In 2016, the Lipid Association of India (LAI) developed a cardiovascular risk assessment algorithm and defined low-density lipoprotein cholesterol (LDL-C) goals for prevention of atherosclerotic cardiovascular disease (ASCVD) in Indians. The recent refinements in the role of various risk factors and subclinical atherosclerosis in prediction of ASCVD risk necessitated updating the risk algorithm and treatment goals. METHODS: The LAI core committee held twenty-one meetings and webinars from June 2022 to July 2023 with experts across India and critically reviewed the latest evidence regarding the strategies for ASCVD risk prediction and the benefits and modalities for intensive lipid lowering. Based on the expert consensus and extensive review of published data, consensus statement IV was commissioned. RESULTS: The young age of onset and a more aggressive nature of ASCVD in Indians necessitates emphasis on lifetime ASCVD risk instead of the conventional 10-year risk. It also demands early institution of aggressive preventive measures to protect the young population prior to development of ASCVD events. Wide availability and low cost of statins in India enable implementation of effective LDL-C-lowering therapy in individuals at high risk of ASCVD. Subjects with any evidence of subclinical atherosclerosis are likely to benefit the most from early aggressive interventions. CONCLUSIONS: This document presents the updated risk stratification and treatment algorithm and describes the rationale for each modification. The intent of these updated recommendations is to modernize management of dyslipidemia in Indian patients with the goal of reducing the epidemic of ASCVD among Indians in Asia and worldwide.

Harnessing the Synergetic Effects of Ag, Mn Dopants in Eco-Friendly Ultraviolet Selective Quantum Dots for Luminescent Solar Concentrators.

Quantum dots (QDs) are promising building blocks for luminescent solar concentrators (LSCs), yet most QD-based LSCs suffer from toxic metal composition and color tinting. UV-selective harvesting QDs can enable visible transparency, but their development is restricted by large reabsorption losses and low photoluminescence quantum yield (PLQY). The developed here Ag, Mn: ZnInS2/ZnS QDs show a high PLQY of 53% due to the passivating effect of ZnS shell. These QDs selectively absorb UV light and emit orange-red light with a large Stokes shift of 180 nm. A LSC of 5 × 5 × 0.2 cm3, fabricated using a poly(lauryl methacrylate) (PLMA) as a matrix, maintains 87% of integrated PL after 7 h of UV exposure. The QD-PLMA achieved 90.7% average visible transparency (AVT) and a color rendering index (CRI) of 95.8, which is close to plain PLMA (AVT = 90.8%; CRI = 99.5), yielding excellent visible light transparency. Incorporating Si-PVs at LSC edges, the Ag, Mn: ZIS/ZnS QD-LSC achieved an optical efficiency of 1.42%, ranking competitively among high-performing UV-harvesting LSCs.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

ABSTRACT: Postoperative pain is a major clinical problem imposing a significant burden on patients and society. In a survey 2 years after orthopedic surgery, 57% of patients reported persisting postoperative pain. However, only limited progress has been made in the development of safe and effective therapies to prevent the onset and chronification of pain after orthopedic surgery. We established a tibial fracture mouse model that recapitulates clinically relevant orthopedic trauma surgery, which causes changes in neuropeptide levels in dorsal root ganglia and sustained neuroinflammation in the spinal cord. Here, we monitored extended pain behavior in this model, observing chronic bilateral hindpaw mechanical allodynia in both male and female C57BL/6J mice that persisted for >3 months after surgery. We also tested the analgesic effects of a novel, minimally invasive, bioelectronic approach to percutaneously stimulate the vagus nerve (termed percutaneous vagus nerve stimulation [pVNS]). Weekly pVNS treatment for 30 minutes at 10 Hz for 3 weeks after the surgery strongly reduced pain behaviors compared with untreated controls. Percutaneous vagus nerve stimulation also improved locomotor coordination and accelerated bone healing. In the dorsal root ganglia, vagal stimulation inhibited the activation of glial fibrillary acidic protein-positive satellite cells but without affecting microglial activation. Overall, these data provide novel evidence supportive of the use of pVNS to prevent postoperative pain and inform translational studies to test antinociceptive effects of bioelectronic medicine in the clinic.

Highly bright solid-state carbon dots for efficient anticounterfeiting.

Carbon dots (C-dots) as promising fluorescent materials have attracted much attention because of their low toxicity and excellent optoelectronic properties. However, the aggregation-caused quenching (ACQ) of the solid-state C-dots has limited their potential applications in anti-counterfeiting and optoelectronic devices. In this work, C-dot powder was prepared by directly dispersing the as-prepared C-dots in a polymer matrix or in situ formation of the C-dot/Ca-complex by vacuum heating in the presence of boric acid. The as-prepared C-dots have high quantum yields (QYs) in the range of 40-67% with temperature-dependent photoluminescent (PL) properties. As a proof of concept, the as-synthesized C-dots were used to produce a flexible anti-counterfeiting code and showed high-level security. This highlights the potential of C-dots in solid-state information, anti-information encryption and anti-counterfeiting.

Rational Control of Near-Infrared Colloidal Thick-Shell Eco-Friendly Quantum Dots for Solar Energy Conversion.

Thick-shell colloidal quantum dots (QDs) are promising building blocks for solar technologies due to their size/composition/shape-tunable properties. However, most well-performed thick-shell QDs suffer from frequent use of toxic metal elements including Pb and Cd, and inadequate light absorption in the visible and near-infrared (NIR) region due to the wide bandgap of the shell. In this work, eco-friendly AgInSe2 /AgInS2 core/shell QDs, which are optically active in the NIR region and are suitable candidates to fabricate devices for solar energy conversion, are developed. Direct synthesis suffers from simultaneously controlling the reactivity of multiple precursors, instead, a template-assisted cation exchange method is used. By modulating the monolayer growth of template QDs, gradient AgInSeS shell layers are incorporated into AgInSe2 /AgInS2 QDs. The resulting AgInSe2 /AgInSeS/AgInS2 exhibits better charge transfer than AgInSe2 /AgInS2 due to their favorable electronic band alignment, as predicted by first-principle calculations and confirmed by transient fluorescence spectroscopy. The photoelectrochemical cells fabricated with AgInSe2 /AgInSeS/AgInS2 QDs present ≈1.5-fold higher current density and better stability compared to AgInSe2 /AgInS2 . The findings define a promising approach toward multinary QDs and pave the way for engineering the QDs' electronic band structures for solar-energy conversion.

Are Metastatic Central Lymph Nodes (D3 volume) in right-sided Colon Cancer a Sign of Systemic Disease? A sub-group Analysis of an Ongoing Multicenter Trial.

OBJECTIVE: Assess outcomes of patients with right-sided colon cancer with metastases in the D3 volume after personalized surgery. BACKGROUND: Patients with central lymph node metastasis (D3-PNG) are considered to have a systemic disease with a poor prognosis. A 3-dimensional definition of the dissection volume allows the removal of all central nodes. MATERIALS AND METHODS: D3-PNG includes consecutive patients from an ongoing clinical trial. Patients were stratified into residual disease negative (D3-RDN) and residual disease positive (D3-RDP) groups. D3-RDN was further stratified into 4 periods to identify a learning curve. A personalized D3 volume (defined through arterial origins and venous confluences) was removed " en bloc" through medial-to-lateral dissection, and the D3 volume of the specimen was analyzed separately. RESULTS: D3-PNG contained 42 (26 females, 63.1 SD 9.9 y) patients, D3-RDN:29 (17 females, 63.4 SD 10.1 y), and D3-RDP:13 (9 females, 62.2 SD 9.7 y). The mean overall survival (OS) days were D3-PNG:1230, D3-RDN:1610, and D3-RDP:460. The mean disease-free survival (DFS) was D3-PNG:1023, D3-RDN:1461, and D3-RDP:74 days. The probability of OS/DFS were D3-PNG:52.1%/50.2%, D3-RDN:72.9%/73.1%, D3-RDP: 7.7%/0%. There is a significant change in OS/DFS in the D3-RDN from 2011-2013 to 2020-2022 (both P =0.046) and from 2014-2016 to 2020-2022 ( P =0.028 and P =0.005, respectively). CONCLUSION: Our results indicate that surgery can achieve survival in most patients with central lymph node metastases by removing a personalized and anatomically defined D3 volume. The extent of mesenterectomy and the quality of surgery are paramount since a learning curve has demonstrated significantly improved survival over time despite the low number of patients. These results imply a place for the centralization of this patient group where feasible.

Cardiovascular implications of inflammatory bowel disease: An updated review.

Emerging data highlights the heightened risk of atherosclerotic cardiovascular diseases (ASCVD) in patients with chronic inflammatory disorders, particularly those afflicted with inflammatory bowel disease (IBD). This review delves into the epidemiological connections between IBD and ASCVD, elucidating potential underlying mechanisms. Furthermore, it discusses the impact of current IBD treatments on cardiovascular risk. Additionally, the cardiovascular adverse effects of novel small molecule drugs used in moderate-to-severe IBD are investigated, drawing parallels with observations in patients with rheumatoid arthritis. This article aims to comprehensively evaluate the existing evidence supporting these associations. To achieve this, we conducted a meticulous search of PubMed, spanning from inception to August 2023, using a carefully selected set of keywords. The search encompassed topics related to IBD, such as Crohn's disease and ulcerative colitis, as well as ASCVD, including coronary artery disease, cardiovascular disease, atrial fibrillation, heart failure, conduction abnormalities, heart blocks, and premature coronary artery disease. This review encompasses various types of literature, including retrospective and prospective cohort studies, clinical trials, meta-analyses, and relevant guidelines, with the objective of providing a comprehensive overview of this critical intersection of inflammatory bowel disease and cardiovascular health.

Surface engineering of two-dimensional hexagonal boron-nitride for optoelectronic devices.

Two-dimensional hexagonal boron nitride (2D h-BN) is being extensively studied in optoelectronic devices due to its electronic and photonic properties. However, the controlled optimization of h-BN's insulating properties is necessary to fully explore its potential in energy conversion and storage devices. In this work, we engineered the surface of h-BN nanoflakes via one-step in situ chemical functionalization using a liquid-phase exfoliation approach. The functionalized h-BN (F-h-BN) nanoflakes were subsequently dispersed on the surface of TiO2 to tune the TiO2/QDs interface of the optoelectronic device. The photoelectrochemical (PEC) devices based on TiO2/F-h-BN/QDs with optimized addition of carbon nanotubes (CNTs) and scattering layers showed 46% improvement compared to the control device (TiO2/QDs). This significant improvement is attributed to the reduced trap/carrier recombination and enhanced carrier injection rate of the TiO2-CNTs/F-h-BN/QDs photoanode. Furthermore, by employing an optimized TiO2-CNTs/F-h-BN/QDs photoanode, QDs-sensitized solar cells (QDSCs) yield an 18% improvement in photoconversion efficiency. This represents a potential and adaptability of our approach, and pathway to explore surface-engineered 2D materials to optimize the interface of solar energy conversion and other emerging optoelectronic devices.

Clinical profile and outcome of cardiac manifestations in patients presenting with multisystem inflammatory syndrome in children associated with SARS-CoV-2 infection.

Multisystem inflammatory syndrome in children (MIS-C) can cause significant morbidity and mortality in children. This study was conducted to assess the pattern and outcome of cardiac abnormalities in MIS-C. This retrospective study was conducted in children with MIS-C between 1 month and 18 years. We enrolled 53 children with a mean age of 7.78 ± 4.62 years. Overall, 35.8% of children with MIS-C had cardiac manifestations in the form of coronary artery abnormalities (CAAs) or left ventricular (LV) dysfunction. Younger age (P 0.009) and high C-reactive protein at admission (P = 0.001) were significant predictors of cardiac involvement. CAAs were seen in 11.3% of children. On follow-up, 67% and 83% of children showed regression of CAA at 1 and 6 months, respectively. 24.5% of patients had presented with LV dysfunction. LV ejection fraction improved significantly at 1 month (P = 0.002) and 6 months (P = 0.001). Cardiac outcomes in MIS-C were favorable with timely identification and treatment.

Experimenting with ASL-based arterialized cerebral blood volume as a novel imaging biomarker in grading glial neoplasms.

BACKGROUND: Perfusion imaging is one of the methods used to grade glial neoplasms, and in this study we evaluated the role of ASL perfusion in grading brain glioma. PURPOSE: The aim is to evaluate the role of arterialized cerebral blood volume (aCBV) of multi-delay ASL perfusion for grading glial neoplasm. MATERIALS AND METHODS: This study is a prospective observational study of 56 patients with glial neoplasms of the brain who underwent surgery, and only cases with positive diagnosis of glioma are included to evaluate the novel diagnostic parameter. RESULTS: In the study, ASL-derived normalized aCBV (naCBV) and T2*DSC-derived normalized CBV (nCBV) are showing very high correlation (Pearson's correlation coefficient value of 0.94) in grading glial neoplasms. naCBV and nCBF are also showing very high correlation (Pearson's correlation coefficient value of 0.876). The study also provides cutoff values for differentiating LGG from HGG for normalized aCBV(naCBV) of ASL, normalized CBV (nCBV), and normalized nCBF derived from T2* DCS as 1.12, 1.254, and 1.31, respectively. ASL-derived aCBV also shows better diagnostic accuracy than ASL-derived CBF. CONCLUSION: This study is one of its kind to the best of our knowledge where multi-delay ASL perfusion-derived aCBV is used as a novel imaging biomarker for grading glial neoplasms, and it has shown high statistical correlation with T2* DSC-derived perfusion parameters.

Association Between Diabetes, Chronic Kidney Disease, and Outcomes in People With Heart Failure From Asia.

Background: Diabetes mellitus (DM), chronic kidney disease (CKD), and heart failure (HF) are pathophysiologically linked and increasing in prevalence in Asian populations, but little is known about the interplay of DM and CKD on outcomes in HF. Objectives: This study sought to investigate outcomes in patients with heart failure with preserved ejection fraction (HFpEF) vs heart failure with reduced ejection fraction (HFrEF) in relation to the presence of DM and CKD. Methods: Using the multinational ASIAN-HF registry, we investigated associations between DM only, CKD only, and DM+CKD with: 1) composite of 1-year mortality or HF hospitalization; and 2) Kansas City Cardiomyopathy Questionnaire scores, according to HF subtype. Results: In 5,239 patients with HF (74.6% HFrEF, 25.4% HFpEF; mean age 63 years; 29.1% female), 1,107 (21.1%) had DM only, 1,087 (20.7%) had CKD only, and 1,400 (26.7%) had DM+CKD. Compared with patients without DM nor CKD, DM+CKD was associated with 1-year all-cause mortality or HF hospitalization in HFrEF (adjusted HR: 2.07; 95% CI: 1.68-2.55) and HFpEF (HR: 2.37; 95% CI: 1.40-4.02). In HFrEF, DM only and CKD only were associated with 1-year all-cause mortality or HF hospitalization (both HRs: 1.43; 95% CI: 1.14-1.80), while in HFpEF, CKD only (HR: 2.54; 95% CI: 1.46-4.41) but not DM only (HR: 1.01; 95% CI: 0.52-1.95) was associated with increased risk (interaction P < 0.01). Adjusted Kansas City Cardiomyopathy Questionnaire scores were lower in patients with DM+CKD (HFrEF: mean 60.50, SEM 0.77, HFpEF: mean 70.10, SEM 1.06; P < 0.001) than with no DM or CKD (HFrEF: mean 66.00, SEM 0.65; and HFpEF: mean 75.80, SEM 0.99). Conclusions: Combined DM and CKD adversely effected outcomes independently of HF subtype, with CKD a consistent predictor of worse outcomes. Strategies to prevent and treat DM and CKD in HF are urgently required.

Efficient Photoelectrochemical Hydrogen Generation Using Eco-Friendly "Giant" InP/ZnSe Core/Shell Quantum Dots.

InP quantum dots (QDs) are promising building blocks for use in solar technologies because of their low intrinsic toxicity, narrow bandgap, large absorption coefficient, and low-cost solution synthesis. However, the high surface trap density of InP QDs reduces their energy conversion efficiency and degrades their long-term stability. Encapsulating InP QDs into a wider bandgap shell is desirable to eliminate surface traps and improve optoelectronic properties. Here, we report the synthesis of "giant" InP/ZnSe core/shell QDs with tunable ZnSe shell thickness to investigate the effect of the shell thickness on the optoelectronic properties and the photoelectrochemical (PEC) performance for hydrogen generation. The optical results demonstrate that ZnSe shell growth (0.9-2.8 nm) facilitates the delocalization of electrons and holes into the shell region. The ZnSe shell simultaneously acts as a passivation layer to protect the surface of InP QDs and as a spatial tunneling barrier to extract photoexcited electrons and holes. Thus, engineering the ZnSe shell thickness is crucial for the photoexcited electrons and hole transfer dynamics to tune the optoelectronic properties of "giant" InP/ZnSe core/shell QDs. We obtained an outstanding photocurrent density of 6.2 mA cm-1 for an optimal ZnSe shell thickness of 1.6 nm, which is 288% higher than the values achieved from bare InP QD-based PEC cells. Understanding the effect of shell thickness on surface passivation and carrier dynamics offers fundamental insights into the suitable design and realization of eco-friendly InP-based "giant" core/shell QDs toward improving device performance.

Similar Events but Contrasting Impact: Appraising the Global Digital Reach of World Heart Day and Atrial Fibrillation Awareness Month.

Background: With over 18.6 million deaths annually, cardiovascular diseases (CVDs) are the leading cause of mortality worldwide. One such complication of CVDs that can result in stroke is atrial fibrillation (Afib). As part of global outreach and awareness, World Heart Day and Atrial Fibrillation Awareness Month are celebrated annually on 29 September and the month of September, respectively. Both of these events are important cardiovascular awareness initiatives to assist public education and develop awareness strategies, and they have received considerable support from leading international organizations. Objective: We studied the global digital impact of these campaigns via Google Trends and Twitter. Methods: We evaluated the overall number of tweets, impressions, popularity and top keywords/hashtags, and interest by region to determine the digital impact using various analytical tools. Hashtag network analysis was done using ForceAtlas2 model. Beyond social media, Google Trends web search analysis was carried out for both awareness campaigns to examine 'interest by region' over the past five years by analyzing relative search volume. Results: #WorldHeartDay and #UseHeart (dedicated social media hashtags for World Heart Day by the World Heart Federation) alone amassed over 1.005 billion and 41.89 million impressions as compared with the 1.62 million and 4.42 million impressions of #AfibMonth and #AfibAwarenessMonth, respectively. On Google Trends web search analysis, the impact of Afib awareness month was limited to the USA, but World Heart Day had a comparatively global reach with limited digital involvement in the African continent. Conclusions: World Heart Day and Afib awareness month present a compelling case study of vast digital impact and the effectiveness of targeted campaigning using specific themes and keywords. Though the efforts of the backing organizations are commended, planning and collaboration are needed to further widen the reach of Afib awareness month.

Vagus nerve stimulation rescues persistent pain following orthopedic surgery in adult mice.

Postoperative pain is a major clinical problem imposing a significant burden on our patients and society. Up to 57% of patients experience persistent postoperative pain 2 years after orthopedic surgery [49]. Although many studies have contributed to the neurobiological foundation of surgery-induced pain sensitization, we still lack safe and effective therapies to prevent the onset of persistent postoperative pain. We have established a clinically relevant orthopedic trauma model in mice that recapitulates common insults associated with surgery and ensuing complications. Using this model, we have started to characterize how induction of pain signaling contributes to neuropeptides changes in dorsal root ganglia (DRG) and sustained neuroinflammation in the spinal cord [62]. Here we have extended the characterization of pain behaviors for >3 months after surgery, describing a persistent deficit in mechanical allodynia in both male and female C57BL/6J mice after surgery. Notably, we have applied a novel minimally invasive bioelectronic approach to percutaneously stimulate the vagus nerve (termed pVNS) [24] and tested its anti-nociceptive effects in this model. Our results show that surgery induced a strong bilateral hind-paw allodynia with a slight decrease in motor coordination. However, treatment with pVNS for 30-minutes at10 Hz weekly for 3 weeks prevented pain behavior compared to naïve controls. pVNS also improved locomotor coordination and bone healing compared to surgery without treatment. In the DRGs, we observed that vagal stimulation fully rescued activation of GFAP positive satellite cells but did not affect microglial activation. Overall, these data provide novel evidence for the use of pVNS to prevent postoperative pain and may inform translational studies to test anti-nociceptive effects in the clinic.