Decoupling the Functional Pleiotropy of Stem Cell Factor by Tuning c-Kit Signaling.

Most secreted growth factors and cytokines are functionally pleiotropic because their receptors are expressed on diverse cell types. While important for normal mammalian physiology, pleiotropy limits the efficacy of cytokines and growth factors as therapeutics. Stem cell factor (SCF) is a growth factor that acts through the c-Kit receptor tyrosine kinase to elicit hematopoietic progenitor expansion but can be toxic when administered in vivo because it concurrently activates mast cells. We engineered a mechanism-based SCF partial agonist that impaired c-Kit dimerization, truncating downstream signaling amplitude. This SCF variant elicited biased activation of hematopoietic progenitors over mast cells in vitro and in vivo. Mouse models of SCF-mediated anaphylaxis, radioprotection, and hematopoietic expansion revealed that this SCF partial agonist retained therapeutic efficacy while exhibiting virtually no anaphylactic off-target effects. The approach of biasing cell activation by tuning signaling thresholds and outputs has applications to many dimeric receptor-ligand systems.

Ligand-Dependent Modulation of G Protein Conformation Alters Drug Efficacy.

G protein-coupled receptor (GPCR) signaling, mediated by hetero-trimeric G proteins, can be differentially controlled by agonists. At a molecular level, this is thought to occur principally via stabilization of distinct receptor conformations by individual ligands. These distinct conformations control subsequent recruitment of transducer and effector proteins. Here, we report that ligand efficacy at the calcitonin GPCR (CTR) is also correlated with ligand-dependent alterations to G protein conformation. We observe ligand-dependent differences in the sensitivity of the G protein ternary complex to disruption by GTP, due to conformational differences in the receptor-bound G protein hetero-trimer. This results in divergent agonist-dependent receptor-residency times for the hetero-trimeric G protein and different accumulation rates for downstream second messengers. This study demonstrates that factors influencing efficacy extend beyond receptor conformation(s) and expands understanding of the molecular basis for how G proteins control/influence efficacy. This has important implications for the mechanisms that underlie ligand-mediated biased agonism. VIDEO ABSTRACT.

Intravenous Doxycycline, Azithromycin, or Both for Severe Scrub Typhus.

BACKGROUND: The appropriate antibiotic treatment for severe scrub typhus, a neglected but widespread reemerging zoonotic infection, is unclear. METHODS: In this multicenter, double-blind, randomized, controlled trial, we compared the efficacy of intravenous doxycycline, azithromycin, or a combination of both in treating severe scrub typhus. Patients who were 15 years of age or older with severe scrub typhus with at least one organ involvement were enrolled. The patients were assigned to receive a 7-day course of intravenous doxycycline, azithromycin, or both (combination therapy). The primary outcome was a composite of death from any cause at day 28, persistent complications at day 7, and persistent fever at day 5. RESULTS: Among 794 patients (median age, 48 years) who were included in the modified intention-to-treat analysis, complications included those that were respiratory (in 62%), hepatic (in 54%), cardiovascular (in 42%), renal (in 30%), and neurologic (in 20%). The use of combination therapy resulted in a lower incidence of the composite primary outcome than the use of doxycycline (33% and 47%, respectively), for a risk difference of -13.3 percentage points (95% confidence interval [CI], -21.6 to -5.1; P = 0.002). The incidence with combination therapy was also lower than that with azithromycin (48%), for a risk difference of -14.8 percentage points (95% CI, -23.1 to -6.5; P<0.001). No significant difference was seen between the azithromycin and doxycycline groups (risk difference, 1.5 percentage points; 95% CI, -7.0 to 10.0; P = 0.73). The results in the per-protocol analysis were similar to those in the primary analysis. Adverse events and 28-day mortality were similar in the three groups. CONCLUSIONS: Combination therapy with intravenous doxycycline and azithromycin was a better therapeutic option for the treatment of severe scrub typhus than monotherapy with either drug alone. (Funded by the India Alliance and Wellcome Trust; INTREST Clinical Trials Registry-India number, CTRI/2018/08/015159.).

S. aureus biofilm properties correlate with immune B cell subset frequencies and severity of chronic rhinosinusitis.

Staphylococcus aureus mucosal biofilms are associated with recalcitrant chronic rhinosinusitis (CRS). However, S. aureus colonisation of sinus mucosa is frequent in the absence of mucosal inflammation. This questions the relevance of S. aureus biofilms in CRS etiopathogenesis. This study aimed to investigate whether strain-level variation in in vitro-grown S. aureus biofilm properties relates to CRS disease severity, in vitro toxicity, and immune B cell responses in sinonasal tissue from CRS patients and non-CRS controls. S. aureus clinical isolates, tissue samples, and matched clinical datasets were collected from CRS patients with nasal polyps (CRSwNP), CRS without nasal polyps (CRSsNP), and controls. B cell responses in tissue samples were characterised by FACS. S. aureus biofilms were established in vitro, followed by measuring their properties of metabolic activity, biomass, colony-forming units, and exoprotein production. S. aureus virulence was evaluated using whole-genome sequencing, mass spectrometry and application of S. aureus biofilm exoproteins to air-liquid interface cultures of primary human nasal epithelial cells (HNEC-ALI). In vitro S. aureus biofilm properties were correlated with increased CRS severity scores, infiltration of antibody-secreting cells and loss of regulatory B cells in tissue samples. Biofilm exoproteins from S. aureus with high biofilm metabolic activity had enriched virulence genes and proteins, and negatively affected the barrier function of HNEC-ALI cultures. These findings support the notion of strain-level variation in S. aureus biofilms to be critical in the pathophysiology of CRS.

Pharokka: a fast scalable bacteriophage annotation tool.

SUMMARY: In recent years, there has been an increasing interest in bacteriophages, which has led to growing numbers of bacteriophage genomic sequences becoming available. Consequently, there is a need for a rapid and consistent genomic annotation tool dedicated for bacteriophages. Existing tools either are not designed specifically for bacteriophages or are web- and email-based and require significant manual curation, which makes their integration into bioinformatic pipelines challenging. Pharokka was created to provide a tool that annotates bacteriophage genomes easily, rapidly and consistently with standards compliant outputs. Moreover, Pharokka requires only two lines of code to install and use and takes under 5 min to run for an average 50-kb bacteriophage genome. AVAILABILITY AND IMPLEMENTATION: Pharokka is implemented in Python and is available as a bioconda package using 'conda install -c bioconda pharokka'. The source code is available on GitHub (https://github.com/gbouras13/pharokka). Pharokka has been tested on Linux-64 and MacOSX machines and on Windows using a Linux Virtual Machine.

A comparison between full-length 16S rRNA Oxford nanopore sequencing and Illumina V3-V4 16S rRNA sequencing in head and neck cancer tissues.

Describing the microbial community within the tumour has been a key aspect in understanding the pathophysiology of the tumour microenvironment. In head and neck cancer (HNC), most studies on tissue samples have only performed 16S rRNA short-read sequencing (SRS) on V3-V5 region. SRS is mostly limited to genus level identification. In this study, we compared full-length 16S rRNA long-read sequencing (FL-ONT) from Oxford Nanopore Technology (ONT) to V3-V4 Illumina SRS (V3V4-Illumina) in 26 HNC tumour tissues. Further validation was also performed using culture-based methods in 16 bacterial isolates obtained from 4 patients using MALDI-TOF MS. We observed similar alpha diversity indexes between FL-ONT and V3V4-Illumina. However, beta-diversity was significantly different between techniques (PERMANOVA - R2 = 0.131, p < 0.0001). At higher taxonomic levels (Phylum to Family), all metrics were more similar among sequencing techniques, while lower taxonomy displayed more discrepancies. At higher taxonomic levels, correlation in relative abundance from FL-ONT and V3V4-Illumina were higher, while this correlation decreased at lower levels. Finally, FL-ONT was able to identify more isolates at the species level that were identified using MALDI-TOF MS (75% vs. 18.8%). FL-ONT was able to identify lower taxonomic levels at a better resolution as compared to V3V4-Illumina 16S rRNA sequencing.

Challenges and patient outcomes in chronic subdural haematoma at the level of a regional care system A multi-centre, mixed-methods study from the East of England.

BACKGROUND: Chronic subdural haematoma (cSDH) is a common neurosurgical pathology affecting older patients with other health conditions. A significant proportion (up-to 90%) of referrals for surgery in neurosciences units (NSU) come from secondary care. However, the organisation of this care and the experience of patients repatriated to non-specialist centres are currently unclear. OBJECTIVES: This study aimed to clarify patient outcome in non-specialist centres following NSU discharge for cSDH surgery and to understand key system challenges. The study was set within a representative neurosurgical care system in the east of England. DESIGN AND METHODS: We performed a retrospective cohort analysis of patients referred for cSDH surgery. Alongside case record review, patient and staff experience were explored using surveys as well as an interactive c-design workshop. Challenges were identified from thematic analysis of survey responses and triangulated by focussed workshop discussions. RESULTS: Data on 381 patients referred for cSDH surgery from six centres was reviewed. One hundred and fifty-six (41%) patients were repatriated following surgery. Sixty-one (39%) of those repatriated suffered an inpatient complication (new infection, troponin rise or renal injury) following NSU discharge, with 58 requiring institutional discharge or new care. Surveys for staff (n = 42) and patients (n = 209) identified that resourcing, communication, and inter-hospital distance posed care challenges. This was corroborated through workshop discussions with stakeholders from two institutions. CONCLUSIONS: A significant amount of perioperative care for cSDH is delivered outside of specialist centres. Future improvement initiatives must recognise the system-wide nature of delivery and the challenges such an arrangement presents.

A new, adaptive, self-administered, and generalizable method used to measure visual acuity.

SIGNIFICANCE: Angular Indication Measurement (AIM) is an adaptive, self-administered, and generalizable orientation-judgment method designed to interrogate visual functions. We introduce AIM Visual Acuity (VA) and show its features and outcome measures. Angular Indication Measurement VA's ability to detect defocus was comparable with that of an Early Treatment of Diabetic Retinopathy Study (ETDRS) letter chart and showed greater sensitivity to astigmatic blur. PURPOSE: This proof-of-concept study introduces Angular Indication Measurement and applies it to VA. METHODS: First, we compared the ability of AIM-VA and ETDRS to detect defocus and astigmatic blur in 22 normally sighted adults. Spherical and cylindrical lenses in the dominant eye induced blur. Second, we compared repeatability over two tests of AIM-VA and ETDRS. RESULTS: A repeated-measure analysis of variance showed a main effect for defocus blur and test. For the astigmatism experiment, an interaction between blur and orientation was found. Pairwise comparisons showed that AIM was more sensitive to astigmatic-induced VA loss than ETDRS. Bland-Altman plots showed small bias and no systematic learning effect for either test type and improved repeatability with more than two adaptive steps for AIM-VA. CONCLUSIONS: Angular Indication Measurement VA's ability to detect defocus was comparable with that of an ETDRS letter chart and showed greater sensitivity to induced astigmatic blur, and AIM-VA's repeatability is comparable with ETDRS when using two or more adaptive steps. Angular Indication Measurement's self-administered orientation judgment approach is generalizable to interrogate other visual functions, e.g., contrast, color, motion, and stereovision.

Citizens from 13 countries share similar preferences for COVID-19 vaccine allocation priorities.

How does the public want a COVID-19 vaccine to be allocated? We conducted a conjoint experiment asking 15,536 adults in 13 countries to evaluate 248,576 profiles of potential vaccine recipients who varied randomly on five attributes. Our sample includes diverse countries from all continents. The results suggest that in addition to giving priority to health workers and to those at high risk, the public favors giving priority to a broad range of key workers and to those with lower income. These preferences are similar across respondents of different education levels, incomes, and political ideologies, as well as across most surveyed countries. The public favored COVID-19 vaccines being allocated solely via government programs but were highly polarized in some developed countries on whether taking a vaccine should be mandatory. There is a consensus among the public on many aspects of COVID-19 vaccination, which needs to be taken into account when developing and communicating rollout strategies.

Does the implementation of a trauma system affect injury-related morbidity and economic outcomes? A systematic review.

BACKGROUND: Trauma accounts for a huge burden of disease worldwide. Trauma systems have been implemented in multiple countries across the globe, aiming to link and optimise multiple aspects of the trauma care pathway, and while they have been shown to reduce overall mortality, much less is known about their cost-effectiveness and impact on morbidity. METHODS: We performed a systematic review to explore the impact the implementation of a trauma system has on morbidity, quality of life and economic outcomes, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. All comparator study types published since 2000 were included, both retrospective and prospective in nature, and no limits were placed on language. Data were reported as a narrative review. RESULTS: Seven articles were identified that met the inclusion criteria, all of which reported a pre-trauma and post-trauma system implementation comparison in high-income settings. The overall study quality was poor, with all studies demonstrating a severe risk of bias. Five studies reported across multiple types of trauma patients, the majority describing a positive impact across a variety of morbidity and health economic outcomes following trauma system implementation. Two studies focused specifically on traumatic brain injury and did not demonstrate any impact on morbidity outcomes. DISCUSSION: There is currently limited and poor quality evidence that assesses the impact that trauma systems have on morbidity, quality of life and economic outcomes. While trauma systems have a fundamental role to play in high-quality trauma care, morbidity and disability data can have large economic and cultural consequences, even if mortality rates have improved. The sociocultural and political context of the surrounding healthcare infrastructure must be better understood before implementing any trauma system, particularly in resource-poor and fragile settings. PROSPERO REGISTRATION NUMBER: CRD42022348529 LEVEL OF EVIDENCE: Level III.

An In Vitro Study Evaluating the Safety of Mesalazine on Human Nasoepithelial Cells.

Chronic rhinosinusitis (CRS) is a disease characterised by the inflammation of the nasal and paranasal cavities. It is a widespread condition with considerable morbidity for patients. Current treatment for chronic rhinosinusitis consists of appropriate medical therapy followed by surgery in medically resistant patients. Although oral steroids are effective, they are associated with significant morbidity, and disease recurrence is common when discontinued. The development of additional steroid sparing therapies is therefore needed. Mesalazine is a commonly used therapeutic in inflammatory bowel disease, which shares a similar disease profile with chronic rhinosinusitis. This exploratory in vitro study aims to investigate whether mesalazine could be repurposed to a nasal wash, which is safe on human nasoepithelial cells, and retains its anti-inflammatory effects. CRS patients' human nasal epithelial cells (HNECs) were collected. HNECs were grown at an air-liquid interface (ALIs) and in a monolayer and challenged with mesalazine or a non-medicated control. Transepithelial electrical resistance, paracellular permeability, and toxicity were measured to assess epithelial integrity and safety. The anti-inflammatory effects of mesalazine on the release of interleukin (IL)-6 and tumour necrosis factor alpha (TNF-α) were analysed using human leukemia monocytic cell line (THP-1). mesalazine did not impact the barrier function of HNEC-ALIs and was not toxic when applied to HNECs or THP-1 cells at concentrations up to 20 mM. mesalazine at 0.5 and 1 mM concentrations significantly inhibited TNF-α release by THP-1 cells. mesalazine effectively decreases TNF-α secretion from THP-1 cells, indicating the possibility of its anti-inflammatory properties. The safety profile of mesalazine at doses up to 20 mM suggests that it is safe when applied topically on HNECs.

Staphylococcus aureus Biofilm-Secreted Factors Cause Mucosal Damage, Mast Cell Infiltration, and Goblet Cell Hyperplasia in a Rat Rhinosinusitis Model.

Chronic rhinosinusitis (CRS) is an inflammatory condition of the sinonasal mucosa. Despite being a common health issue, the exact cause of CRS is yet to be understood. However, research suggests that Staphylococcus aureus, particularly in its biofilm form, is associated with the disease. This study aimed to investigate the impact of long-term exposure to secreted factors of Staphylococcus aureus biofilm (SABSFs), harvested from clinical isolates of non-CRS carrier and CRS patients, on the nasal mucosa in a rat model. Animals were randomised (n = 5/group) to receive daily intranasal instillations of 40 µL (200 µg/µL) SABSFs for 28 days or vehicle control. The sinonasal samples were analysed through histopathology and transcriptome profiling. The results showed that all three intervention groups displayed significant lymphocytic infiltration (p ≤ 0.05). However, only the SABSFs collected from the CRSwNP patient caused significant mucosal damage, mast cell infiltration, and goblet cell hyperplasia compared to the control. The transcriptomics results indicated that SABSFs significantly enriched multiple inflammatory pathways and showed distinct transcriptional expression differences between the control group and the SABSFs collected from CRS patients (p ≤ 0.05). Additionally, the SABSF challenges induced the expression of IgA and IgG but not IgE. This in vivo study indicates that long-term exposure to SABSFs leads to an inflammatory response in the nasal mucosa with increased severity for S. aureus isolated from a CRSwNP patient. Moreover, exposure to SABSFs does not induce local production of IgE.

A Novel Model of Staphylococcus aureus-Induced Lymphoplasmacytic Rhinosinusitis in Rats.

Chronic rhinosinusitis (CRS) is characterized by sinonasal mucosal inflammation. Staphylococcus aureus (S. aureus) is associated with severe CRS phenotypes. Different animal models have been proposed to study the association of CRS and S. aureus. However, current animal models are expensive due to the use of large animals, have high barriers to ethics approval, or require invasive surgical intervention, necessitating a need for a model that can overcome these limitations. This study aimed at establishing a reliable and efficient rat lymphoplasmacytic inflammatory model for rhinosinusitis. Sprague Dawley rats received a daily intranasal application of 20 µL of saline, S. aureus CI-182 exoprotein (250 µg/mL), or exoprotein CI-182 in combination with S. aureus clinical isolate (CI-908 or CI-913) 108 colony-forming unit (CFU)/mL. The rats' sinuses were harvested at 1 and 2 weeks post-intervention. The CFU and histopathologic examination of inflammation were evaluated. S. aureus clinical isolates CI-908 or CI-913 in combination with the exoprotein (CI-182) had higher CFUs and caused persistently higher inflammation at both the 1 and 2-week post-intervention compared to the exoprotein and saline group. The observed inflammatory cell type was lymphoplasmacytic. This study provided evidence that the combination of a S. aureus exoprotein with S. aureus induces inflammation that persists for a minimum of two weeks post-intervention. This model is the first known animal model to create the lymphoplasmacytic inflammation subtype seen in CRS patients. This offers a cost-effective, accessible, non-invasive, and easy-to-replicate model to study the causes and treatment of such inflammation.

Think Globally, Adapt Locally: The ISCCM Guidelines and Position Statements.

How to cite this article: Myatra SN, Peter JV, Juneja D, Kulkarni AP. Think Globally, Adapt Locally: The ISCCM Guidelines and Position Statements. Indian J Crit Care Med 2024;28(S2):S1-S3.

Incidence and Risk Factors for Deep Venous Thrombosis and Its Impact on Outcome in Patients Admitted to Medical Critical Care.

Objectives: This study evaluated the incidence and risk factors for deep venous thrombosis (DVT) while on thromboprophylaxis, in patients admitted to the medical intensive care unit (MICU), and to assess its impact on outcomes. Methods: Consecutive patients admitted to the MICU underwent compression ultrasound of the jugular, axillary, femoral, and popliteal veins at admission, day 3 and 7 to screen for DVT. All patients were on pharmacological and/or mechanical thromboprophylaxis as per protocol. The primary outcome was the incidence of DVT (defined as occurrence on day 3 or 7). Secondary outcomes were death and duration of hospitalization. Risk factors for DVT were explored using bivariate and multivariable logistic regression analysis and expressed as risk ratio (RR) with 95% confidence intervals (CIs). Results: The incidence of DVT was 17.2% (95% CI 12.0, 22.3) (n = 35/203); two-thirds were catheter associated (23/35). There was no difference in mortality between those with and without incident DVT (9/35 vs 40/168, p = 0.81). The mean (SD) duration of hospitalization was longer in the DVT group (20.1 (17) vs 12.9 (8.5) days, p = 0.007). Although day 3 INR (RR 2.1, 95% CI 0.9-5.3), age >40 years (2.1, 0.8-5.3), vasopressor use (1.0, 0.4-2.9) and SOFA score (0.9, 0.85-1.1) were associated with the development of DVT on bivariate analysis, only central venous catheters (15.97, 1.9-135.8) was independently associated with DVT on multivariable analysis. Conclusions: Despite thromboprophylaxis, 17% of ICU patients develop DVT. The central venous catheter is the main risk factor. DVT is not associated with increased mortality in the setting of prophylaxis. How to cite this article: Krishnamoorthy A, Hansdak SG, Peter JV, Pichamuthu K, Rajan SJ, Sudarsan TI, et al. Incidence and Risk Factors for Deep Venous Thrombosis and Its Impact on Outcome in Patients Admitted to Medical Critical Care. Indian J Crit Care Med 2024;28(6):607-613.

ISCCM Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis.

Tuberculosis (TB) is an important cause of morbidity and mortality globally. About 3-4% of hospitalized TB patients require admission to the intensive care unit (ICU); the mortality in these patients is around 50-60%. There is limited literature on the evaluation and management of patients with TB who required ICU admission. The Indian Society of Critical Care Medicine (ISCCM) constituted a working group to develop a position paper that provides recommendations on the various aspects of TB in the ICU setting based on available evidence. Seven domains were identified including the categorization of TB in the critically ill, diagnostic workup, drug therapy, TB in the immunocompromised host, organ support, infection control, and post-TB sequelae. Forty-one questions pertaining to these domains were identified and evidence-based position statements were generated, where available, keeping in focus the critical care aspects. Where evidence was not available, the recommendations were based on consensus. This position paper guides the approach to and management of critically ill patients with TB. How to cite this article: Chacko B, Chaudhry D, Peter JV, Khilnani G, Saxena P, Sehgal IS, et al. isccm Position Statement on the Approach to and Management of Critically Ill Patients with Tuberculosis. Indian J Crit Care Med 2024;28(S2):S67-S91.

Tuberculosis Molecular Bacterial Load Assay Reveals Early Delayed Bacterial Killing in Patients With Relapse.

Bacterial killing in patients with tuberculosis (TB) relapse was compared to that in patients achieving cure, measured by TB molecular bacterial load assay (TB-MBLA) or mycobacteria growth indicator tube (MGIT) time to positivity (TTP). TB-MBLA in 4 relapsed patients was significantly different compared to 132 cured patients after 2 weeks of treatment; MGIT TTP showed a significant difference from week 8.

Staphylococcus aureus biofilm properties and chronic rhinosinusitis severity scores correlate positively with total CD4+ T-cell frequencies and inversely with its Th1, Th17 and regulatory cell frequencies.

Chronic rhinosinusitis (CRS) represents chronic inflammation of the sinus mucosa characterised by dysfunction of the sinuses' natural defence mechanisms and induction of different inflammatory pathways ranging from a Th1 to a Th2 predominant polarisation. Recalcitrant CRS is associated with Staphylococcus aureus dominant mucosal biofilms; however, S. aureus colonisation of the sinonasal mucosa has also been observed in healthy individuals challenging the significance of S. aureus in CRS pathogenesis. We aimed to investigate the relationship between CRS key inflammatory markers, S. aureus biofilm properties/virulence genes and the severity of the disease. Tissue samples were collected during endoscopic sinus surgery from the ethmoid sinuses of CRS patients with (CRSwNP) and without (CRSsNP) nasal polyps and controls (n = 59). CD3+ T-cell subset frequencies and key inflammatory markers of CD4+ helper T cells were determined using FACS analysis. Sinonasal S. aureus clinical isolates were isolated (n = 26), sequenced and grown into biofilm in vitro, followed by determining their properties, including metabolic activity, biomass, colony-forming units and exoprotein production. Disease severity was assessed using Lund-Mackay radiologic scores, Lund-Kennedy endoscopic scores and SNOT22 quality of life scores. Our results showed that S. aureus biofilm properties and CRS severity scores correlated positively with total CD4+ T-cell frequencies but looking into CD4+ T-cell subsets showed an inverse correlation with Th1 and Th17 cell frequencies. CD4+ T-cell frequencies were higher in patients harbouring lukF.PV-positive S. aureus while its regulatory and Th17 cell subset frequencies were lower in patients carrying sea- and sarT/U-positive S. aureus. Recalcitrant CRS is characterised by increased S. aureus biofilm properties in relation to increased total CD4+ helper T-cell frequencies and reduced frequencies of its Th1, Th17 and regulatory T-cell subsets. These findings offer insights into the pathophysiology of CRS and could lead to the development of more targeted therapies.

CW coherent detection lidar for micro-Doppler sensing and raster-scan imaging of drones.

We demonstrate a continuous-wave (CW) coherent detection lidar (CDL) capable of detecting micro-Doppler (propeller) signatures and acquiring raster-scan images of small unmanned aerial systems/vehicles (UAS/UAV). The system uses a narrow-linewidth 1550 nm CW laser and takes advantage of mature and low-cost fiber-optics components from the telecommunications industry. Using either collimated or focused probe beam geometry, lidar based detection of characteristic periodic motions of drone propellers up to a remote distance of 500 m has been achieved. Furthermore, by raster scanning a focused CDL beam with a galvo-resonant mirror beamscanner, two-dimensional images of flying UAVs up to 70 m range were obtained. Each pixel of the raster-scan images provides both lidar return signal amplitude and target radial speed information. The raster-scan images obtained up to 5 frames per second make it possible to discriminate various UAV types based on their profile and even resolve the presence of payloads. With feasible improvements, the anti-drone lidar is a promising alternative to expensive EO/IR and active SWIR cameras used in counter-UAV systems.

Staphylococcal protein A modulates inflammation by inducing interferon signaling in human nasal epithelial cells.

OBJECTIVE AND DESIGN: Staphylococcus aureus (S. aureus) is one of the leading causes of human respiratory tract infections. The function of Staphylococcal protein A (SpA), expressed on the S. aureus bacterial membrane and released in the environment, on human nasal epithelial cells (HNECs) have not been fully elucidated. In this study, we tested the SpA expression in S. aureus from chronic rhinosinusitis patients and investigated the effects of SpA on HNECs inflammation through Interferon Gamma Receptor 1(IFNGR1)/phosphorylated Janus Kinase 2 (p-JAK2) pathway. METHODS: RNA profiling was performed to investigate inflammatory activation in a S. aureus chronic rhinosinusitis (CRS) mouse model. SpA release by S. aureus clinical isolates was determined using ELISA. The effect of purified SpA and SpA enriched conditioned media from S. aureus clinical isolates on HNECs cytotoxicity, apoptosis and release of inflammatory cytokines was evaluated using lactate dehydrogenase assays, and flow cytometry. SpA dependent IFNGR1 and p-JAK2 expression were assessed by qPCR, immunofluorescence and western blot in HNECs. RESULTS: 49 genes were significantly induced in S. aureus CRS mice indicative of activation of interferon signaling. SpA release was significantly higher in S. aureus clinical isolates from chronic rhinosinusitis with nasal polyps (CRSwNP) patients. Purified SpA significantly increased IFNGR1 mRNA and protein expression in HNECs. SpA induced cytotoxic effects and induced the release of Interleukin-6 (IL-6) and IL-8 in an IFNGR1 dependent way. CONCLUSION: SpA induces interferon signaling through activation of the IFNGR1-JAK-2 pathway, which provides an understanding of how S. aureus SpA affects the inflammatory process in the upper airways.