The genomic and cellular basis of biosynthetic innovation in rove beetles.

How evolution at the cellular level potentiates macroevolutionary change is central to understanding biological diversification. The >66,000 rove beetle species (Staphylinidae) form the largest metazoan family. Combining genomic and cell type transcriptomic insights spanning the largest clade, Aleocharinae, we retrace evolution of two cell types comprising a defensive gland-a putative catalyst behind staphylinid megadiversity. We identify molecular evolutionary steps leading to benzoquinone production by one cell type via a mechanism convergent with plant toxin release systems, and synthesis by the second cell type of a solvent that weaponizes the total secretion. This cooperative system has been conserved since the Early Cretaceous as Aleocharinae radiated into tens of thousands of lineages. Reprogramming each cell type yielded biochemical novelties enabling ecological specialization-most dramatically in symbionts that infiltrate social insect colonies via host-manipulating secretions. Our findings uncover cell type evolutionary processes underlying the origin and evolvability of a beetle chemical innovation.

Cortical perfusion measurements with laser speckle contrast imaging during adenosine induced cardiac arrest for aneurysm clipping: a case report.

Adenosine induced cardiac arrest (AiCA) is one of the methods used to facilitate microsurgical aneurysm clipping by providing more visibility and less pressure in the aneurysmal sac and neighboring vessels. We report the use of laser speckle contrast imaging (LSCI) during AiCA to monitor the changes in pulsation and perfusion on the cortical surface during adenosine induced cardiac arrest for aneurysm clipping surgery. Application of this technology for perfusion monitoring may improve workflow and surgical guidance and provide valuable feedback continuously throughout the procedure. ClinicalTrials.gov identifier: NCT0502840.

Evaluation of the critical warzone experiences scale among Gulf War I-era veterans: Associations with PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors.

Prior research has established the psychometric properties of the Critical Warzone Experiences (CWE) scale among post-9/11 Iraq/Afghanistan-era veterans; however, the psychometric properties of the CWE among Gulf War I-era veterans have not yet been established. The first objective of the present study was to examine the psychometric properties of the CWE among Gulf War I-era veterans. The second objective was to test the hypothesis that the CWE would have a significant indirect effect on suicidal thoughts and behaviors via posttraumatic stress disorder (PTSD) and depressive symptoms. To test these hypotheses, a survey packet that included the CWE and measures of PTSD symptoms, depressive symptoms, and suicidal thoughts and behaviors was administered to 1,153 Gulf War I-era veterans. Consistent with prior research in post-9/11 Iraq/Afghanistan-era veterans, the CWE exhibited good internal consistency (α = .85), a unidimensional factor structure (RMSEA = .056, CFI = .959, SRMR = .033; average factor loading = .69), and good concurrent validity with PTSD (r = .47, p < .001) and depressive (r = .31, p < .001) symptoms among Gulf War I-era veterans. Additionally, as hypothesized, a significant indirect effect from the CWE to suicidal thoughts and behaviors via PTSD and depressive symptoms (ß = .35, p < .001) was also observed. Taken together, our findings provide strong support for using the CWE with Gulf War I-era veterans.

Laser speckle contrast imaging versus microvascular Doppler sonography in aneurysm surgery: A prospective study.

Objective: This study aimed to compare microvascular Doppler sonography (MDS) and laser speckle contrast imaging (LSCI) for assessing vessel patency and aneurysm occlusion during microsurgical clipping of intracranial aneurysms. Methods: MDS and LSCI were used after clip placement during six neurovascular procedures including six patients, and agreement between the two techniques was assessed. LSCI was performed in parallel or right after MDS evaluation. The Doppler response was assessed through listening while flow in the LSCI videos was evaluated by three blinded neurovascular surgeons after the surgery. Statistical analysis determined the agreement between the techniques in assessing flow in 18 regions of interest (ROIs). Results: Agreement between MDS and LSCI in assessing vessel patency was observed in 87 % of the ROIs. LSCI accurately identified flow in 93.3 % of assessable ROIs, with no false positive or negative measurements. Three ROIs were not assessable with LSCI due to motion artifacts or poor image quality. No complications were observed. Conclusions: LSCI demonstrated high agreement with MDS in assessing vessel patency during microsurgical clipping of intracranial aneurysms. It provided continuous, real-time, full-field imaging with high spatial resolution and temporal resolution. While MDS allowed evaluation of deep vascular regions, LSCI complemented it by offering unlimited assessment of surrounding vessels.

Cardiac sarcoid or arrhythmogenic right ventricular cardiomyopathy: a role for positron emission tomography (PET)?

We present a case of cardiac sarcoidosis of insidious onset mimicking arrhythmogenic right ventricular cardiomyopathy. Our patient initially presented with systemic sarcoidosis but later developed palpitations. The similarity in clinical presentation and cardiac magnetic resonance findings in both conditions posed a challenge in differentiating between the two in the absence of histological diagnosis. We highlighted the role of positron emission tomography in aiding a diagnosis.

Continuous hemodynamics monitoring during arteriovenous malformation microsurgical resection with laser speckle contrast imaging: case report.

AVM surgery is challenging due to progressive and often unforeseeable flow changes during its resection which involve both the AVM and the surrounding brain tissue. Hence, accurate monitoring of blood flow is crucial to minimize complications and improve outcomes. The following case report illustrates the usefulness of complimentary non-invasive tools that can provide real time blood flow assessment. We present a case demonstrating the application of laser speckle contrast imaging (LSCI) in evaluating vessel flow dynamics during AVM surgery. A 30-year-old female presented with sudden headaches, nausea, vomiting, and vertigo. Emergency imaging revealed a ruptured cerebellar AVM necessitating surgical intervention. LSCI was integrated into the surgical workflow, providing continuous visualization of relative cerebral blood flow (rCBF) of vessels surrounding the AVM. Before AVM resection, LSCI measurements revealed the arterialized vasculature supplying the AVM nidus; measurements after AVM resection showed significant hemodynamic changes including normal flow in the initially arterialized AVM draining veins and adjacent arterial branches. LSCI also detected blood flow alterations during temporary occlusion, enabling assessment of downstream vascular regions. In conclusion, we provide an example supporting the utility of LSCI for real-time hemodynamic monitoring during AVM resection surgery. LSCI offers non-invasive, continuous, and immediate blood flow information, complementing conventional imaging methods like indocyanine green angiography. Additionally, our findings suggest that LSCI has the potential to provide a non-invasive means of identifying the specific superficial vessel branches or cortical areas that receive blood supply from a particular vessel.

Sedation with dexmedetomidine decreases skin perfusion in cats.

OBJECTIVE: To evaluate skin perfusion in cats receiving dexmedetomidine compared to a placebo. ANIMALS: 9 healthy adult research cats. METHODS: A randomized, blinded, placebo-controlled study design was used. Two sites, the dorsal metatarsus (site: limb) and lateral flank (site: flank), were evaluated with laser speckle contrast imaging (LSCI) at baseline and following administration of dexmedetomidine (1, 3, or 5 mcg/kg, IV) or a placebo (0.9% saline, IV). Mean speckle contrast (MSC), a surrogate for perfusion, was obtained from LSCI and compared between treatments. Heart rate, sedation score, and body temperature were recorded. Skin perfusion to the flank and limb, reported as MSC, was assessed via LSCI at baseline and at 5, 10, and 15 minutes posttreatment. RESULTS: There was a significant decrease in heart rate (P < .001) in cats receiving 1, 3, and 5 mcg/kg dexmedetomidine compared to placebo. There was a significant increase in median sedation score at all time points postsedation compared to baseline (P < .018). Changes in MSC for the metatarsus were not significantly different between treatments at any time point (P = .12). For the flank, MSC was significantly higher for cats treated with dexmedetomidine compared to baseline (P ≤ .01). Skin perfusion to the flank decreased as early as 5 minutes posttreatment with dexmedetomidine and persisted for at least 15 minutes, regardless of dexmedetomidine dose. CLINICAL RELEVANCE: Dexmedetomidine decreased skin perfusion in cats, even at low doses. Veterinarians may elect for an alternative sedative medication when decreased skin perfusion is a concern.

Intraoperative Laser Speckle Contrast Imaging to Assess Vessel Flow in Neurosurgery: A Pilot Study.

BACKGROUND AND OBJECTIVES: Laser speckle contrast imaging (LSCI) has emerged as a promising tool for assessment of vessel flow during neurosurgery. We aimed to investigate the feasibility of visualizing vessel flow in the macrocirculation with a new fully microscope-integrated LSCI system and assess the validity and objectivity of findings compared with fluorescence angiography (FA). METHODS: This is a single-center prospective observational study enrolling adult patients requiring microsurgical treatment for brain vascular pathologies or brain tumors. Three independent raters, blinded toward findings of FA, reviewed regions of interest (ROIs) placed in exposed vessels and target structures. The primary end point was the validity of LSCI for assessment of vessel flow as measured by the agreement with FA. The secondary end point was objectivity, measured as the inter-rater agreement of LSCI findings. RESULTS: During 18 surgical procedures, 23 observations using FA and LSCI were captured simultaneously. Using LSCI, vessel flow was assessable in 62 (86.1%) and not assessable in 10 (13.9%) ROIs. The agreement between LSCI and FA was 86.1%, with an agreement coefficient of 0.85 (95% CI: 0.75-0.94). Disagreement between LSCI and FA was observed in the 10 ROIs that were not assessable. The agreement between ROIs that were assessable using LSCI and FA was 100%. The inter-rater agreement of LSCI findings was 87.9%, with an agreement coefficient of 0.86 (95% CI: 0.79-0.94). CONCLUSION: Fully microscope-integrated LSCI is feasible and has a high potential for clinical utility. Because of its characteristics, LSCI can be viewed as a full-field visual micro-Doppler that can be used as a complementary method to FA for assessing vessel flow during neurosurgery. Despite technical limitations related to the early development phase of the fully microscope-integrated system, we demonstrated reasonable validity and objectivity of findings compared with FA. Further research and refinement of the system may enhance its value in neurosurgical applications.

The genomic and cellular basis of biosynthetic innovation in rove beetles.

How evolution at the cellular level potentiates change at the macroevolutionary level is a major question in evolutionary biology. With >66,000 described species, rove beetles (Staphylinidae) comprise the largest metazoan family. Their exceptional radiation has been coupled to pervasive biosynthetic innovation whereby numerous lineages bear defensive glands with diverse chemistries. Here, we combine comparative genomic and single-cell transcriptomic data from across the largest rove beetle clade, Aleocharinae. We retrace the functional evolution of two novel secretory cell types that together comprise the tergal gland-a putative catalyst behind Aleocharinae's megadiversity. We identify key genomic contingencies that were critical to the assembly of each cell type and their organ-level partnership in manufacturing the beetle's defensive secretion. This process hinged on evolving a mechanism for regulated production of noxious benzoquinones that appears convergent with plant toxin release systems, and synthesis of an effective benzoquinone solvent that weaponized the total secretion. We show that this cooperative biosynthetic system arose at the Jurassic-Cretaceous boundary, and that following its establishment, both cell types underwent ∼150 million years of stasis, their chemistry and core molecular architecture maintained almost clade-wide as Aleocharinae radiated globally into tens of thousands of lineages. Despite this deep conservation, we show that the two cell types have acted as substrates for the emergence of adaptive, biochemical novelties-most dramatically in symbiotic lineages that have infiltrated social insect colonies and produce host behavior-manipulating secretions. Our findings uncover genomic and cell type evolutionary processes underlying the origin, functional conservation and evolvability of a chemical innovation in beetles.

Continuous blood flow visualization with laser speckle contrast imaging during neurovascular surgery.

Significance: Laser speckle contrast imaging (LSCI) has emerged as a promising tool for intraoperative cerebral blood flow (CBF) monitoring because it produces real-time full-field blood flow maps noninvasively and label free. Aim: We aim to demonstrate the ability of LSCI to continuously visualize blood flow during neurovascular procedures. Approach: LSCI hardware was attached to the surgical microscope and did not interfere with the normal operation of the microscope. To more easily visualize CBF in real time, LSCI images were registered with the built-in microscope white light camera such that LSCI images were overlaid on the white light images and displayed to the neurosurgeon continuously in real time. Results: LSCI was performed throughout each surgery when the microscope was positioned over the patient, providing the surgeon with real-time visualization of blood flow changes before, during, and after aneurysm clipping or arteriovenous malformation (AVM) resection in humans. LSCI was also compared with indocyanine green angiography (ICGA) to assess CBF during aneurysm clipping and AVM surgery; integration of the LSCI hardware with the microscope enabled simultaneous acquisition of LSCI and ICGA. Conclusions: The results suggest that LSCI can provide continuous and real-time CBF visualization without affecting the surgeon workflow or requiring a contrast agent. The results also demonstrate that LSCI and ICGA provide different, yet complementary information about vessel perfusion.

The Value of Family History in Colorectal Screening Decisions for Oldest Old Geriatric Populations.

INTRODUCTION: Colorectal cancer (CRC) is the second most common form of cancer affecting both men and women. Extensive screening guidelines have been developed to help reduce the incidence of disease. Currently, United States Preventative Service Task Force guidelines recommend against routine screening in those 85 years and older. However, octogenarians and nonagenarians continue to be screened for CRC with no consensus on indications. The aim of this study is to examine family history of CRC as a risk factor and clinical indication for providing screening colonoscopies to the "oldest old" geriatric population, defined as aged 80 years and above. METHODS: We conducted a retrospective review of a Veterans' Health Administration database to identify male veterans aged 80 years and older who underwent screening colonoscopy. Subsequently, we examined those who tested positive for CRC with a family history of CRC. RESULTS: Of the 458,224 patients who are 80 years and older in the Veterans Affairs (VA) database, 17.8% underwent a screening colonoscopy; 11.42% of these individuals were further diagnosed with CRC; and 8.89% of those with diagnosed CRC had a documented family history of CRC. CONCLUSION: Family history should not be used as an inclusionary criterion for CRC screening in the 80 years and above age group as the rate of CRC in these patients with a family history of CRC is significantly lower than that in the younger age groups with a family history of CRC.

Patient-derived glial enriched progenitors repair functional deficits due to white matter stroke and vascular dementia in rodents.

Subcortical white matter stroke (WMS) accounts for up to 30% of all stroke events. WMS damages primarily astrocytes, axons, oligodendrocytes, and myelin. We hypothesized that a therapeutic intervention targeting astrocytes would be ideally suited for brain repair after WMS. We characterize the cellular properties and in vivo tissue repair activity of glial enriched progenitor (GEP) cells differentiated from human-induced pluripotent stem cells, termed hiPSC-derived GEPs (hiPSC-GEPs). hiPSC-GEPs are derived from hiPSC-neural progenitor cells via an experimental manipulation of hypoxia inducible factor activity by brief treatment with a prolyl hydroxylase inhibitor, deferoxamine. This treatment permanently biases these cells to further differentiate toward an astrocyte fate. hiPSC-GEPs transplanted into the brain in the subacute period after WMS in mice migrated widely, matured into astrocytes with a prorepair phenotype, induced endogenous oligodendrocyte precursor proliferation and remyelination, and promoted axonal sprouting. hiPSC-GEPs enhanced motor and cognitive recovery compared to other hiPSC-differentiated cell types. This approach establishes an hiPSC-derived product with easy scale-up capabilities that might be effective for treating WMS.

Infected nonunions of diaphyseal fractures of the forearm.

BACKGROUND: There are no reported series that specifically deal with repair of infected nonunions of the diaphysis of the forearm bones. We sought to determine whether a standardized treatment protocol we have utilized for 15 patients from 1989 to 2005 results in a high union rate, resolution of infection, and a good functional outcome. METHODS: The study cohort included nine male and six female patients who presented to a University hospital setting with an infected nonunion of the diaphysis of the radius or ulna. Every patient had a minimum of 2-year follow-up. The average patient age was 45 years (range 17-79). Eight of the patients had fractures involving their dominant arm. Thirteen patients had initially fractured both the radius and ulna, but two of these patients had subsequently healed one of the bones. One patient had an isolated radius fractures, and one patient fractured the ulna alone. All patients underwent a protocol that combines aggressive surgical debridements as necessary, definitive fixation after 7-14 days, tricortical iliac crest bone grafting for segmental defects, leaving wounds open to heal by secondary intention, 6 weeks of culture-specific intravenous antibiotics, and early active range of motion (ROM) exercises. We sought to report our success rate of nonunion repair, number of re-interventions, complication rate, final ROM, and the ability to eradicate the infection using this treatment regimen. RESULTS: At most recent follow-up (average 5 years, range 2-15 years), all patients had united and resolved their infections. One case was considered a failure, although he did go on to unite a one-bone forearm and was free of infection at most recent follow-up. All but three patients, including the one failure, had at least 50 degrees of supination/pronation and 30-130 degrees of flexion/extension arc. Excluding the one failure that united his one-bone forearm at 46 months, the average time to union was 13.2 weeks (range 10-15 weeks). CONCLUSIONS: The results of this study indicate that our standard protocol for treatment of infected nonunion of the shafts of the radius and ulna is reliable at obtaining fracture union with a good functional result, while also resolving the infection.

The Two Challenges in Management of Gastric Glomus Tumors.

Gastric glomus tumors (GGTs) are rare gastrointestinal lesions originating from the neuromuscular arterial canal or vascular lumen which share many overlapping features with other stromal lesions. Despite most cases of GGTs being benign, there is a lack of reliable histological features predictive of tumor behavior. We present a case of a 42-year-old male who was determined to have a GGT via histological diagnosis and underwent surgical wedge resection. This case highlights the importance of establishing an accurate diagnosis and the various factors that must be taken into consideration to best determine malignant potential and management options.

Effect of vascular structure on laser speckle contrast imaging.

Laser speckle contrast imaging (LSCI) is a powerful tool for non-invasive, real-time imaging of blood flow in tissue. However, the effect of tissue geometry on the form of the electric field autocorrelation function and speckle contrast values is yet to be investigated. In this paper, we present an ultrafast forward model for simulating a speckle contrast image with the ability to rapidly update the image for a desired illumination pattern and flow perturbation. We demonstrate the first simulated speckle contrast image and compare it against experimental results. We simulate three mouse-specific cerebral cortex decorrelation time images and implement three different schemes for analyzing the effects of homogenization of vascular structure on correlation decay times. Our results indicate that dissolving structure and assuming homogeneous geometry creates up to ∼ 10x shift in the correlation function decay times and alters its form compared with the case for which the exact geometry is simulated. These effects are more pronounced for point illumination and detection imaging schemes, highlighting the significance of accurate modeling of the three-dimensional vascular geometry for accurate blood flow estimates.

Cluster and solute velocity distributions in free-jet expansions of supercritical CO(2).

The free-jet expansions of high-pressure CO(2) supercritical solutions are probed by direct sampling mass spectrometry. Both cluster intensity measurements and velocity distribution measurements are reported for expansions which result in cluster formation by condensation and fragmentation of supersaturated vapors and superheated liquids. The resulting velocity distributions for these highly nonequilibrated expansions are characterized by up to three different peaks, depending on the source conditions: two primary peaks associated with very large clusters, the slower of which is associated with liquid fragmentation, and a smaller faster peak associated with monomers and small CO(2) clusters. We have associated the slow peak, observed only for fragmentation of superheated liquid expansions, with a liquid or condensed phase fragment by measuring the velocity distribution of low vapor pressure solutes in the expansion of supercritical CO(2) mixtures.

A comparison of Lagrangian model estimates to light detection and ranging (LIDAR) measurements of dust plumes from field tilling.

A Lagrangian particle model has been adapted to examine human exposures to particulate matter < or = 10 microm (PM10) in agricultural settings. This paper reports the performance of the model in comparison to extensive measurements by elastic LIDAR (light detection and ranging). For the first time, the LIDAR measurements allowed spatially distributed and time dynamic measurements to be used to test the predictions of a field-scale model. The model outputs, which are three-dimensional concentration distribution maps from an agricultural disking operation, were compared with the LIDAR-scanned images. The peak cross-correlation coefficient and the offset distance of the measured and simulated plumes were used to quantify both the intensity and location accuracy. The appropriate time averaging and changes in accuracy with height of the plume were examined. Inputs of friction velocity, Monin-Obukhov length, and wind direction (1 sec) were measured with a three-axis sonic anemometer at a single point in the field (at 1.5-m height). The Lagrangian model of Wang et al. predicted the near-field concentrations of dust plumes emitted from a field disking operation with an overall accuracy of approximately 0.67 at 3-m height. Its average offset distance when compared with LIDAR measurements was approximately 38 m, which was 6% of the average plume moving distance during the simulation periods. The model is driven by weather measurements, and its near-field accuracy is highest when input time averages approach the turbulent flow time scale (3-70 sec). The model accuracy decreases with height because of smoothing and errors in the input wind field, which is modeled rather than measured at heights greater than the measurement anemometer. The wind steadiness parameter (S) can be used to quantify the combined effects of wind speed and direction on model accuracy.

Polymer dots enable deep in vivo multiphoton fluorescence imaging of microvasculature.

Deep in vivo imaging of vasculature requires small, bright, and photostable fluorophores suitable for multiphoton microscopy (MPM). Although semiconducting polymer dots (pdots) are an emerging class of highly fluorescent contrast agents with favorable advantages for the next generation of in vivo imaging, their use for deep MPM has never before been demonstrated. Herein, we characterize the multiphoton properties of three pdot variants and perform deep in vivo MPM imaging of cortical rodent microvasculature. We find pdot brightness exceeds conventional fluorophores, including quantum dots, and their broad multiphoton absorption spectrum permits imaging at wavelengths better-suited for biological imaging and confers compatibility with a range of longer excitation wavelengths. This results in substantial improvements in signal-to-background ratio (>3.5-fold) and greater cortical imaging depths (z = 1,300 µm). Ultimately, pdots are a versatile tool for MPM due to their extraordinary brightness and broad absorption, enabling interrogation of deep structures in vivo.

Near-field dust exposure from cotton field tilling and harvesting.

The frequency and intensities of dust exposures in and near farm fields, which potentially contribute to high intensity human exposure events, are undocumented due to the transient nature of local dust plumes and the difficulties of making accurate concentration measurements. The objective of this study is to measure near-field spatial concentrations of the dust plumes emitted during tilling and harvesting of an irrigated cotton field outside of Las Cruces, NM (soil class: fine-loamy, mixed, superactive, thermic Typic Calciargid). A comparison of remote lidar measurements of plumes emitted from cotton field operations with in situ samplers shows a strong agreement between the two techniques: r2 = 0.79 for total suspended particulates (TSP) and r2 = 0.61 for particulate matter with diameter less than or equal to 10 microm (PM10). Plume movement was dependent on the short-term wind field and atmospheric stability. Horizontal spread rate of the plumes, determined from lidar measured Gaussian dispersion parameters, was less than expected by a factor of 7. Thus, in-plume downwind concentrations were higher than expected. Vertical dispersion was dependent on the rise of "cells" of warm air convecting off the soil surface. On a windy day, discing the field showed TSP and PM10 concentrations at the source itself of up to 176 microg m(-3) and 120 microg m(-3), respectively. These resulted in in-plume peak TSP concentrations of about 1.22 microg m(-3) at 10 m downwind and 0.33 microg m(-3) at 100 m downwind. The measured concentrations highlight a potential exposure risk to people in and around farming operations.