Search

Experiments were performed to study the physical characteristics of smoke aerosols generated by burning three types of stick incense in a 4 m3 clean room. Sidestream cigarette smoke was also examined under the same conditions to provide a comparison. Among the parameters measured were (a) masses of aerosol, carbon monoxide and nitrogen oxides generated by burning the incense or cigarettes, (b) rates of decay of the particles from the air, and (c) estimates of count median particle size during a 7 h period post-burning. There was variability among the types of incense studied with respect to many of the parameters. Also, as a general trend, the greater the initial particulate mass concentration, the more rapid the rate of decay of the smoke. In relation to the quantity of particulate generated, cigarette smoke was found to produce proportionally larger quantities of carbon monoxide and nitrogen oxides than did incense. Due to the fact that burning incense was found to generate large quantities of particulate (an average of greater than 45 mg/g burned, as opposed to about 10 mg/g burned for the cigarettes), it is likely, in cases in which incense is habitually burned in indoor settings, that such a practice would produce substantial airborne particulate concentrations.

A new pregnane steroid, jasminanthoside ( 1 ), together with three known compounds, telosmoside A7 ( 2 ), syringaresinol ( 3 ), and methyl 6-deoxy-3- O -methyl- β -D-allopyranosyl-(1→4)- β -D-oleandropyranoside ( 4 ) were isolated from the ethyl acetate extract of Jasminanthes tuyetanhiae roots collected in Vietnam. Their chemical structures were elucidated by NMR and MS spectroscopic data analysis along with the comparison of their data with the published ones in the literature. Although 4 was a known compound, its full NMR data were reported for the first time. All isolated compounds, evaluated for their α-glucosidase inhibition, showed activities stronger than the positive control acarbose. Among them, 1 was the best with the IC 50 value of 7.41 ± 0.59 µM.

Platelets are core components of thrombi but their effect on thrombus burden during deep vein thrombosis (DVT) has not been fully characterized. We examined the role of thrombopoietin-altered platelet count on thrombus burden in a murine stasis model of DVT. To modulate platelet count compared to baseline, CD1 mice were pretreated with thrombopoietin antisense oligonucleotide (THPO-ASO, 56% decrease), thrombopoietin mimetic (TPO-mimetic, 36% increase), or saline (within 1%). Thrombi and vein walls were examined on postoperative days (POD) 3 and 7. Thrombus weights on POD 3 were not different between treatment groups ( p  = .84). The mean thrombus weights on POD 7 were significantly increased in the TPO-mimetic cohort compared to the THPO-ASO ( p  = .005) and the saline ( p  = .012) cohorts. Histological grading at POD 3 revealed a significantly increased smooth muscle cell presence in the thrombi and CD31 positive channeling in the vein wall of the TPO-mimetic cohort compared to the saline and THPO-ASO cohorts ( p  < .05). No differences were observed in histology on POD 7. Thrombopoietin-induced increased platelet count increased thrombus weight on POD 7 indicating platelet count may regulate thrombus burden during early resolution of venous thrombi in this murine stasis model of DVT.

Background: Imaging evaluation of acute deep vein thrombosis (DVT) or post-thrombotic syndrome (PTS) in animal or clinical models is limited to anatomical assessment of the location and extent of thrombi. We hypothesize that Fe-MRI, used to evaluate macrophage content in other inflammatory diseases, can be useful to evaluate the thromboinflammatory features after DVT over time., Methods: Nineteen wild-type CD-1 mice underwent surgical IVC ligation to induce DVT. Mice received either saline or 5 mg/kg of 14E11, a Factor XI inhibitor, before the procedure. Fe-MRI was performed on days 6-7 after ligation to evaluate thrombus volume, perfusion, and macrophage content via T 2 -weighted images. Mice were euthanized at days 3-15 after surgery. The thrombi and adjacent vein walls were excised, weighed, formalin-fixed, and paraffin-embedded for immunohistological analysis. Specimens were stained with specific antibodies to evaluate macrophage content, collagen deposition, neovascularization, and recanalization. Significance was determined using the Mann-Whitney U or Student's t-test., Results: After IVC-ligation in control mice, thrombus weights decreased by 59 % from day 3 to 15. Thrombus volumes peaked on day 5 before decreasing by 85 % by day 13. FXI inhibition led to reduced macrophage content in both thrombi (p = .008) and vein walls (p = .01), decreased thrombus volume (p = .03), and decreased thrombus mass (p = .01) compared to control mice. CCR2+ staining corroborated these findings, showing significantly reduced macrophage presence in the thrombi (p = .002) and vein wall (p = .002)., Conclusions: Fe-MRI T 2 relaxation times can be used to characterize and quantify post-thrombotic changes of perfusion, macrophage content, and thrombus volume over time in a surgical mouse model of venous thrombosis. This approach could lead to better quantification of in vivo inflammation correlating monocyte and macrophage content within resolving thrombi and veins and may serve as a useful tool for research and clinically in the evaluation of the post-thrombotic environment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

This study explored, for the first time, the antioxidant (total antioxidant content, reducing power, ferric ion reducing antioxidant power, hydroxyl radical scavenging, ferrous ion-chelating assays), anti-tyrosinase, anti-inflammatory properties, and hepatoprotective effect in HepG2 cell lines of Ochna integerrima (Loureiro) Merrill flowers and seeds. All extracts except n -hexane exhibited significant antioxidant activity, with high levels of tannin and proanthocyanidins. Luteolin ( 1 ), 6- γ , γ -dimethylallylkaempferol7- O - β -d-glucopyranoside ( 2 ), 6- γ , γ -dimethylallylquercetin7- O - β -d-glucopyranoside ( 3 ), and 6- γ , γ -dimethylallyldihydrokaempferol 7- O - β -d-glucopyranoside ( 4 ) were isolated using semi-preparative HPLC. Compounds 1 - 3 demonstrated good anti-tyrosinase activity. The most active hepatoprotective extracts were found to be aqueous extracts. The flower extracts exhibited greater anti-inflammatory properties by the decrease of NO in RAW 264.7 cells and bovine serum albumin protein. Among them, the n -hexane and EtOAc extracts from flowers displayed promising anti-inflammatory activity. This was predicted by in silico analysis of 1 - 4 . In summary, O. integerrima appears to be a promising natural source for antioxidant, anti-tyrosinase, and anti-inflammatory applications.

We evaluated whether universal chlorhexidine bathing (decolonization) with or without COVID-19 intensive training impacted COVID-19 rates in 63 nursing homes (NHs) during the 2020-2021 Fall/Winter surge. Decolonization was associated with a 43% lesser rise in staff case-rates ( P < .001) and a 52% lesser rise in resident case-rates ( P < .001) versus control.

Background: Insurance companies have adopted variable and inconsistent approval criteria for chronic venous disease (CVD) treatment. Although vein ablation (VA) is accepted as the standard of care for venous ulcers, the treatment criteria for patients with milder forms of CVD remain controversial. This study aims to identify factors associated with a lack of clinical improvement (LCI) in patients with less severe CVD without ulceration undergoing VA to improve patient selection for treatment., Methods: We performed a retrospective analysis of patients undergoing VA for CEAP C2 to C4 disease in the Vascular Quality Initiative varicose veins database from 2014 to 2023. Patients who required intervention in multiple veins, had undergone prior interventions, or presented with CEAP C5 to C6 disease were excluded. The difference (Δ) in venous clinical severity score (VCSS; VCSS before minus after the procedure) was used to categorize the patients. Patients with a ΔVCSS of ≤0 were defined as having LCI after VA, and patients with ≥1 point decrease in the VCSS after VA (ΔVCSS ≥1) as having some benefit from the procedure and, therefore, "clinical improvement." The characteristics of both groups were compared, and multivariable regression analysis was performed to identify factors independently associated with LCI. A second analysis was performed based on the VVSymQ instrument, which measures patient-reported outcomes using five specific symptoms (ie, heaviness, achiness, swelling, throbbing pain, and itching). Patients with LCI showed no improvement in any of the five symptoms, and those with clinical improvement had a decrease in severity of at least one symptom., Results: A total of 3544 patients underwent initial treatment of CVD with a single VA. Of the 3544 patients, 2607 had VCSSs available before and after VA, and 420 (16.1%) had LCI based on the ΔVCSS. Patients with LCI were more likely to be significantly older and African American and have CEAP C2 disease compared with patients with clinical improvement. Patients with clinical improvement were more likely to have reported using compression stockings before treatment. The vein diameters were not different between the two groups. The incidence of complications was overall low, with minor differences between the two groups. However, the patients with LCI were significantly more likely to have symptoms after intervention than those with improvement. Patients with LCI were more likely to have technical failure, defined as vein recanalization. On multivariable regression, age (odds ratio [OR], 1.01; 95% confidence interval [CI], 1.00-1.02) and obesity (OR, 1.47; 95% CI, 1.09-2.00) were independently associated with LCI, as was treatment of less severe disease (CEAP C2; OR, 1.82; 95% CI, 1.30-2.56) compared with more advanced disease (C4). The lack of compression therapy before intervention was also associated with LCI (OR, 6.05; 95% CI, 4.30-8.56). The analysis based on the VVSymQ showed similar results., Conclusions: LCI after VA is associated with treating patients with a lower CEAP class (C2 vs C4) and a lack of compression therapy before intervention. Importantly, no significant association between vein size and clinical improvement was observed., Competing Interests: Disclosures None., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Cardiovascular implantable devices, such as vascular stents, are critical for the treatment of cardiovascular diseases. However, their success is dependent on robust and often long-term antithrombotic therapies. Yet, the current standard-of-care therapies often pose significant bleeding risks to patients. Coagulation factor (F)XI and FXII have emerged as potentially safe and efficacious targets to safely reduce pathologic thrombin generation in medical devices., Objectives: To study the efficacy of monoclonal antibody-targeting FXII and FXI of the contact pathway in preventing vascular device-related thrombosis., Methods: The effects of inhibition of FXII and FXI using function-blocking monoclonal antibodies were examined in a nonhuman primate model of nitinol stent-related thrombosis under arterial and venous flow conditions., Results: We found that function-blocking antibodies of FXII and FXI reduced markers of stent-induced thrombosis in vitro and ex vivo. However, FXI inhibition resulted in more effective mitigation of thrombosis markers under varied flow conditions., Conclusion: This work provides further support for the translation of contact pathway of coagulation inhibitors for their adjunctive clinical use with cardiovascular devices., Competing Interests: Declaration of competing interests M.W. and E.I.T. are employees of Aronora Inc, and they as well as Oregon Health & Science University may have a financial interest in the results of this study. This potential conflict of interest has been reviewed and managed by Oregon Health & Science University. The remaining authors declare no competing financial interests., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: This review summarizes recent advances in developing targeted diagnostics for venous thromboembolism (VTE) and unaddressed knowledge gaps in patient management. Without addressing these critical data needs, the morbidity in VTE patients will persist., Recent Findings: Recent studies investigating plasma protein profiles in VTE patients have identified key diagnostic targets to address the currently unmet need for low-cost, confirmatory, point-of-care VTE diagnostics. These studies and a growing body of evidence from animal model studies have revealed the importance of inflammatory and vascular pathology in driving VTE, which are currently unaddressed targets for VTE therapy. To enhance the translation of preclinical animal studies, clinical quantification of thrombus burden and comparative component analyses between modeled VTE and clinical VTE are necessary., Summary: Lead candidates from protein profiling of VTE patients' plasma offer a promising outlook in developing low cost, confirmatory, point-of-care testing for VTE. Additionally, addressing the critical knowledge gap of quantitatively measuring clinical thrombi will allow for an array of benefits in VTE management and informing the translatability of experimental therapeutics., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

A new cucurbitacin, 3 β -( β -D-glucopyranosyloxy)-5 β ,6 β :16 α ,23 α -diepoxycucurbit-24-en-11-one or hygrocucurbin A (1) , along with two known compounds, including 3 β -( β -D-glucopyranosyloxy)-16 α ,23 α -epoxycucurbita-5,24-dien-11-one (2) and (+)-lyoniresinol (3) , were isolated from the bark of Elaeocarpus hygrophilus . Their chemical structures were elucidated by spectroscopic NMR, HR-IDA- TOF-MS analysis, and by comparison with the spectral data of corresponding compounds in the literature. Two cucurbitacins (1) and (2) were evaluated for their α -glucosidase inhibitory activity and cytotoxic against KB, MCF-7, Hep G2, and A549 cancer cell lines. For the α -glucosidase inhibitory activity, compound 1 showed an equivalent effect (IC 50 197.4 ± 4.1 µM) compared to the acarbose, a positive control (IC 50 208.5 ± 4.7 µM). And for the cytotoxicity, 2 was inactive while 1 was slightly sensitive against KB cells (IC 50 233.3 ± 2.5 µM).

Two new triterpenoid saponins, named spermacosides A-B ( 1  -  2 ), together with two known oleanane-type triterpenoid saponins, 3- O - β- D-xylopyranosyl-(1→3)- β- D-glucopyranosylbayogenin ( 3) and 3- O - β -D-glucopyranosylbayogenin ( 4 ), were isolated from the ethyl acetate extract of Spermacoce ocymoides Burm.f. in a phytochemical investigation. Their chemical structures were elucidated by spectroscopic data analysis (1D and 2D NMR, and HR-ESI-MS), as well as comparison with reported data. All these compounds were evaluated for inhibiting nitric oxide production in lipopolysaccharide-stimulated RAW 264.7 cells. Among them, 1 showed a slight effect with an IC 50 value of 108.65 ± 7.91 µM, and compounds 2-4 were inactive.

Despite the prevalence of Parkinson's disease (PD), there are no clinically-accepted neuroimaging biomarkers to predict the trajectory of motor or cognitive decline or differentiate Parkinson's disease from atypical progressive parkinsonian diseases. Since abnormal connectivity in the motor circuit and basal ganglia have been previously shown as early markers of neurodegeneration, we hypothesize that patterns of interregional connectivity could be useful to form patient-specific predictive models of disease state and of PD progression. We use fMRI data from subjects with Multiple System Atrophy (MSA), Progressive Supranuclear Palsy (PSP), idiopathic PD, and healthy controls to construct predictive models for motor and cognitive decline and differentiate between the four subgroups. Further, we identify the specific connections most informative for progression and diagnosis. When predicting the one-year progression in the MDS-UPDRS-III 1* and Montreal Cognitive assessment (MoCA), we achieve new state-of-the-art mean absolute error performance. Additionally, the balanced accuracy we achieve in the diagnosis of PD, MSA, PSP, versus healthy controls surpasses that attained in most clinics, underscoring the relevance of the brain connectivity features. Our models reveal the connectivity between deep nuclei, motor regions, and the thalamus as the most important for prediction. Collectively these results demonstrate the potential of fMRI connectivity as a prognostic biomarker for PD and increase our understanding of this disease., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Standardized observation of bed baths and showers for 100 residents in 8 nursing homes revealed inadequate cleansing of body sites (88%-100% failure) and >90% process failure involving lather, firm massage, changing dirty wipes or cloths, and following clean-to-dirty sequence. Insufficient water warmth affected 86% of bathing opportunities. Bathing training and adequate resources are needed.

Optogenetic stimulation of Adora2a receptor-expressing spiny projection neurons (A2A-SPNs) in the striatum drives locomotor suppression and transient punishment, results attributed to activation of the indirect pathway. The sole long-range projection target of A2A-SPNs is the external globus pallidus (GPe). Unexpectedly, we found that inhibition of the GPe drove transient punishment but not suppression of movement. Within the striatum, A2A-SPNs inhibit other SPNs through a short-range inhibitory collateral network, and we found that optogenetic stimuli that drove motor suppression shared a common mechanism of recruiting this inhibitory collateral network. Our results suggest that the indirect pathway plays a more prominent role in transient punishment than in motor control and challenges the assumption that activity of A2A-SPNs is synonymous with indirect pathway activity., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 Elsevier Inc. All rights reserved.)

We hosted a confidential helpline to address concerns about COVID-19 prevention among staff in 12 nursing homes in Orange County, California. We fielded 301 inquiries from April 2021-April 2022, most commonly involving questions about vaccines (40%), nursing home COVID-19 prevention (28%), SARS-CoV-2 variants (18%), symptom reporting (10%), and home and community COVID-19 prevention (5%). During COVID-19 surges, staff dominantly expressed fear, anger, and exhaustion. During nadirs, sentiment shifted towards optimism and acceptance., (Copyright © 2022 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Objective: Obesity is highly prevalent and a major risk factor for deep vein thrombosis (DVT) and chronic venous disease. It can also technically limit duplex ultrasound evaluations for lower extremity DVT. We compared the rates and results of repeat lower extremity venous duplex ultrasound (LEVDUS) after an initial incomplete and negative (IIN) LEVDUS in overweight (body mass index [BMI] ≤25-30 kg/m 2 ) and obese (BMI ≥30 kg/m 2 ) patients with those of patients with a BMI <25 kg/m 2 to evaluate whether increasing the rate of follow-up examinations in overweight and obese patients might facilitate improved patient care., Methods: We performed a retrospective review of 617 patients with an IIN LEVDUS study from December 31, 2017 to December 31, 2020. Demographic and imaging data of the patients with an IIN LEVDUS and the frequency of repeat studies performed within 2 weeks were abstracted from the electronic medical records. The patients were divided into three BMI-based groups: normal (BMI <25 kg/m 2 ), overweight (BMI 25-30 kg/m 2 ), and obese (BMI ≥30 kg/m 2 )., Results: Of the 617 patients with an IIN LEVDUS, 213 (34.5%) were normal weight, 177 (29%) were overweight, and 227 (37%) were obese. The repeat LEVDUS rates were significantly different across the three weight groups (P < .001). After an IIN LEVDUS, the rate of repeat LEVDUS for the normal weight, overweight, and obese groups was 46% (98 of 213), 28% (50 of 227), and 32% (73 of 227), respectively. The overall rates of thrombosis (both DVT and superficial vein thrombosis) in the repeat LEVDUS examinations were not significantly different among the normal weight (14%), overweight (11%), and obese (18%) patients (P = .431)., Conclusions: Overweight and obese patients (BMI ≥25 kg/m 2 ) received fewer follow-up examinations after an IIN LEVDUS. Follow-up LEVDUS examinations of overweight and obese patients after an IIN LEVDUS study have similar rates of venous thrombosis compared with normal weight patients. Targeting improving usage of follow-up LEVDUS studies for all patients, but especially for those who are overweight and obese, with an IIN LEVDUS through quality improvement efforts could help minimize missed diagnoses of venous thrombosis and improve the quality of patient care., (Copyright © 2023. Published by Elsevier Inc.)

Natural science datasets frequently violate assumptions of independence. Samples may be clustered (e.g., by study site, subject, or experimental batch), leading to spurious associations, poor model fitting, and confounded analyses. While largely unaddressed in deep learning, this problem has been handled in the statistics community through mixed effects models, which separate cluster-invariant fixed effects from cluster-specific random effects. We propose a general-purpose framework for Adversarially-Regularized Mixed Effects Deep learning (ARMED) models through non-intrusive additions to existing neural networks: 1) an adversarial classifier constraining the original model to learn only cluster-invariant features, 2) a random effects subnetwork capturing cluster-specific features, and 3) an approach to apply random effects to clusters unseen during training. We apply ARMED to dense, convolutional, and autoencoder neural networks on 4 datasets including simulated nonlinear data, dementia prognosis and diagnosis, and live-cell image analysis. Compared to prior techniques, ARMED models better distinguish confounded from true associations in simulations and learn more biologically plausible features in clinical applications. They can also quantify inter-cluster variance and visualize cluster effects in data. Finally, ARMED matches or improves performance on data from clusters seen during training (5-28% relative improvement) and generalization to unseen clusters (2-9% relative improvement) versus conventional models.

Fragment antigen-binding domains of antibodies (F ab s) are powerful probes of structure-function relationships of assembly line polyketide synthases (PKSs). We report the discovery and characterization of F ab s interrogating the structure and function of the ketosynthase-acyltransferase (KS-AT) core of Module 2 of the 6-deoxyerythronolide B synthase (DEBS). Two F ab s (AC2 and BB1) were identified to potently inhibit the catalytic activity of Module 2. Both AC2 and BB1 were found to modulate ACP-mediated reactions catalyzed by this module, albeit by distinct mechanisms. AC2 primarily affects the rate ( k cat ), whereas BB1 increases the K M of an ACP-mediated reaction. A third F ab , AA5, binds to the KS-AT fragment of DEBS Module 2 without altering either parameter; it is phenotypically reminiscent of a previously characterized F ab , 1B2, shown to principally recognize the N-terminal helical docking domain of DEBS Module 3. Crystal structures of AA5 and 1B2 bound to the KS-AT fragment of Module 2 were solved to 2.70 and 2.65 Å resolution, respectively, and revealed entirely distinct recognition features of the two antibodies. The new tools and insights reported here pave the way toward advancing our understanding of the structure-function relationships of DEBS Module 2, arguably the most well-studied module of an assembly line PKS.

Two new oleanane saponins, hedyocoronin A (1) and hedyocoronin B ( 2 ), were isolated from the aerial parts of Hedyotis coronaria (Kurz) Craib, Rubiaceae, collected at Da Oai district, Lam Dong province in Vietnam. Their chemical structures were elucidated by HR-MS, 1D and 2D-NMR spectra, along with the comparison with those reported in the literature. Compounds 1 and 2 showed weak cytotoxicity against KB and HeLa-S3 cancer cell lines with IC 50 values of more than 54 µM.

Introduction: Data augmentation improves the accuracy of deep learning models when training data are scarce by synthesizing additional samples. This work addresses the lack of validated augmentation methods specific for synthesizing anatomically realistic four-dimensional (4D) (three-dimensional [3D] + time) images for neuroimaging, such as functional magnetic resonance imaging (fMRI), by proposing a new augmentation method. Methods: The proposed method, Brain Library Enrichment through Nonlinear Deformation Synthesis (BLENDS), generates new nonlinear warp fields by combining intersubject coregistration maps, computed using symmetric normalization, through spatial blending. These new warp fields can be applied to existing 4D fMRI to create new augmented images. BLENDS was tested on two neuroimaging problems using de-identified data sets: (1) the prediction of antidepressant response from task-based fMRI (original data set n  = 163), and (2) the prediction of Parkinson's disease (PD) symptom trajectory from baseline resting-state fMRI regional homogeneity (original data set n  = 43). Results: BLENDS readily generates hundreds of new fMRI from existing images, with unique anatomical variations from the source images, that significantly improve prediction performance. For antidepressant response prediction, augmenting each original image once (2 × the original training data) significantly increased prediction R 2 from 0.055 to 0.098 ( p < 1 e - 6 ), whereas at 10 × augmentation R 2 increased to 0.103. For the prediction of PD trajectory, 10 × augmentation R 2 increased from -0.044 to 0.472 ( p < 1 e - 6 ). Conclusions: Augmentation of fMRI through nonlinear transformations with BLENDS significantly improved the performance of deep learning models on clinically relevant predictive tasks. This method will help neuroimaging researchers overcome data set size limitations and achieve more accurate predictive models.

A new glutinane-triterpenoid, nepetifoliol ( 1 ), together with two known compounds, dymacrin D ( 2 ), and (+)-ar-tumerone ( 3 ) were isolated from the n -hexane extract of the aerial parts of Leonotis nepetifolia . Their chemical structures were elucidated by spectroscopic data analysis as well as the comparison of their NMR data with the ones published in the literatures. A putative biosynthetic pathway for the formation of the new compound ( anti- diaxial-5,6-diol) ( 1 ) from the precursor triterpene glutinol was proposed. Compounds ( 2 ), ( 3 ) and some previously reported ones, isolated from this extract, including 5α-stigmasta-22-ene-3-one ( 4 ), friedelin ( 5 ), chrysophanol ( 6 ), physcion ( 7 ), and 4'- O -methylalpinumisoflavone ( 8 ) were evaluated for their α-glucosidase inhibition. Among tested compounds, 3 and 6 showed good activities with their IC 50 values of 5.3 ± 0.2 and 4.9 ± 0.3 µg/mL, respectively, comparing to the positive control, acarbose (IC 50 127.7 ± 0.2 µg/mL).

In resting-state functional magnetic resonance imaging (rs-fMRI), artefactual signals arising from subject motion can dwarf and obfuscate the neuronal activity signal. Typical motion correction approaches involve the generation of nuisance regressors, which are timeseries of non-brain signals regressed out of the fMRI timeseries to yield putatively artifact-free data. Recent work suggests that concatenating all regressors into a single regression model is more effective than the sequential application of individual regressors, which may reintroduce previously removed artifacts. This work compares 18 motion correction pipelines consisting of head motion, independent components analysis, and non-neuronal physiological signal regressors in sequential or concatenated combinations. The pipelines are evaluated on a dataset of cognitively normal individuals with repeat imaging and on datasets of studies of Autism Spectrum Disorder, Major Depressive Disorder, and Parkinson's Disease. Extensive metrics of motion artifact removal are measured, including resting state network recovery, Quality Control-Functional Connectivity (QC-FC) correlation, distance-dependent artifact, network modularity, and test-retest reliability of multiple rs-fMRI analyses. The results reveal limitations in previously proposed metrics, including the QC-FC correlation and modularity quality, and identify more robust artifact removal metrics. The results also reveal limitations in the concatenated regression approach, which is outperformed by the sequential regression approach in the test-retest reliability metrics. Finally, pipelines are recommended that perform well based on quantitative and qualitative comparisons across multiple datasets and robust metrics. These new insights and recommendations help address the need for effective motion artifact correction to reduce noise and confounds in rs-fMRI., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Deep vein thrombosis (DVT) and post-thrombotic syndrome (PTS) remain highly prevalent despite modern medical therapy. Contact activation is a promising target for safe antithrombotic anticoagulation. The anti-factor XI (FXI) monoclonal antibody 14E11 reduces circulating levels of FXI without compromising hemostasis. The human recombinant analog, AB023, is in clinical development. The role of FXI in mediation of inflammation during DVT resolution is unknown., Objectives: Investigate the effects of pharmacological targeting of FXI with 14E11 in an experimental model of venous thrombosis., Methods: Adult wild-type CD1 mice were treated with subcutaneous anti-FXI antibody (14E11, 5 mg/kg) versus saline prior to undergoing surgical constriction of the inferior vena cava (IVC). Mice were evaluated at various time points to assess thrombus weight and volume, as well as histology analysis, ferumoxytol enhanced magnetic resonance imaging (Fe-MRI), and whole blood flow cytometry., Results: 14E11-treated mice had reduced thrombus weights and volumes after IVC constriction on day 7 compared to saline-treated mice. 14E11 treatment reduced circulating monocytes by flow cytometry and macrophage content within thrombi as evaluated by histologic staining and Fe-MRI. Collagen deposition was increased at day 3 while CD31 and smooth muscle cell actin expression was increased at day 7 in the thrombi of 14E11-treated mice compared to saline-treated mice., Conclusion: Pharmacologic targeting of FXI enhances the early stages of experimental venous thrombus resolution in wild-type CD1 mice, and may be of interest for future clinical evaluation of the antibody in DVT and PTS., (© 2022 International Society on Thrombosis and Haemostasis. This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.)

Introduction: Transtibial below-knee amputation (BKA) is associated with considerable morbidity, particularly in the vasculopathic population. The purpose of this study was to determine the cumulative probability of undergoing transfemoral above-knee amputation (AKA) conversion within 5 years of BKA and associated risk factors while accounting for the competing risk of death., Methods: This is a retrospective, national database study with structured query of the Veterans Affairs (VA) database for patients who underwent BKA from 1999 to 2020, identified by Current Procedural Terminology codes. Above-knee amputation conversion was identified using Current Procedural Terminology codes in combination with natural language processing to match procedure laterality. After internally validating our patient identification method, risk factors were collected. Competing risk analysis estimated the cumulative incidence rate of AKA conversion and associated risk factors with death as a competing risk., Results: Our query yielded 19,875 patients (19,640 men, 98.8%) who underwent BKA with a median age of 66 years (interquartile range, 60 to 73). The median follow-up was 951 days (interquartile range, 275 to 2,026). The crude cumulative probabilities of AKA conversion and death at 5 years were 15.4% (95% confidence interval [CI], 14.9% to 16.0%) and 47.7% (95% CI, 46.9% to 48.4%), respectively. In the Fine and Gray subdistribution hazard model, peripheral vascular disease had the highest AKA conversion risk (hazard ratio [HR] 2.66; 95% CI, 2.22 to 3.20; P < 0.001). Other factors independently associated with AKA conversion included urgent operation (HR 1.32; 95% CI, 1.23 to 1.42), cerebrovascular disease (HR 1.19; 95% CI, 1.11 to 1.28), chronic obstructive pulmonary disease (HR 1.15; 95% CI, 1.07 to 1.24), and previous myocardial infarction (HR 1.10; 95% CI, 1.02 to 1.19) (All P < 0.02)., Discussion: Within this predominantly male, VA population, BKA carries a high risk of conversion to AKA within 5 years, without reaching a steady risk of AKA conversion within 5 years. Peripheral vascular disease, chronic obstructive pulmonary disease, cerebrovascular disease, previous myocardial infarction, and urgent BKA increase the risk of AKA conversion., Level of Evidence: Level III., (Copyright © 2022 by the American Academy of Orthopaedic Surgeons.)

CaiB is a DR cluster actinobacteriophage that was isolated from soil in Florida using Gordonia rubripertincta NRRL B-16540 as the host. The genome is 61,620 bp, has a GC content of 68.6%, and contains 85 predicted protein coding genes. CaiB has several putative operons and has repeated intergenic regions that may be involved in gene regulation.

Chemical investigation of the lichen Parmotrema tinctorum (Nyl.) Hale led to the isolation of two new phenolic compounds, 2-ethylhexyl orsellinate ( 1 ) and tinctorinone ( 2 ). The structures were determined by analysis of their MS and NMR data as well as by comparison with literature data. The 2-ethylhexyl ester group of 2-ethylhexyl orsellinate is uncommon among lichen metabolites. Tinctorinone revealed strong inhibition towards α-glucosidase.

Chemical investigation of the Vietnamese plant Aegiceras floridum Roem. & Schult. (Primulaceae) led to the isolation of the new compound 3-methoxy-5-nonylphenol ( 1 ) along with five known ones 2,8,10-trihydroxy-6 H -benzo[ c ]chromen-6-one ( 2 ), 2-hydroxy-5-methoxy-3-nonylbenzo-1,4-quinone ( 3 ), 5-(3-hydroxypropyl)-7-methoxy-3-(methylbenzofuran-2-yl)-3-methoxyphenol ( 4 ), 2,8-dihydroxy-7-methoxy-3,9-diundecyldibenzofuran-1,4-dione ( 5 ) and 10-hydroxy-4-methoxy-2,11-diundecylgomphilactone ( 6 ). The structures were elucidated by analysis of their HRESIMS and NMR data as well as the comparison of their NMR data with those reported in the literature. The cytotoxic activity of selected isolated compounds against some cancer cell lines such as human epithelial carcinoma (HeLa), human lung cancer (NCI-H460), liver hepatocellular carcinoma (HepG2), human breast cancer (MCF-7), and acute T cell leukemia (Jurkat) was evaluated. Among them, 3 showed moderate activities against MCF-7 with an IC 50 of 17.77 µM and NCI-H460 with an IC 50 of 25.02 µM. The result of DPPH radical scavenging activity assay indicated that compounds 2-4 and 6 revealed weak antioxidant activity.

Chemical investigation of the lichen Usnea ceratina Arch led to the isolation of five depsidones, including one new compound ceratinalone (1) along with four known compounds bailesidone (2), stictic acid (3) , 8'- O -methylstictic acid (4) and 8'- O -ethylstictic acid (5) . The structures were determined by analysis of their MS and NMR data as well as by comparison with literature values. Compounds 1 and 4 were evaluated the cytotoxic activity against HeLa (human epithelial carcinoma), NCI-H460 (human lung cancer), HepG2 (liver hepatocellular carcinoma), and MCF-7 (human breast cancer) cell lines, showing the moderate activity.

Three new phenolic compounds, peruvinides A-C were isolated from the lichen Ramalina peruviana Ach. (Ramalinaceae). Their structures were unambiguously determined by extensive spectroscopic analyses and comparison with literature data. Peruvinides A and B bearing unusual moieties were found for the first time among lichen metabolites.

Neflamapimod, a selective inhibitor of p38 mitogen activated protein kinase alpha (MAPKα), is under clinical investigation for its efficacy in Alzheimer's disease (AD) and dementia with Lewy Bodies (DLB). Here, we investigated if neflamapimod-mediated acute inhibition of p38 MAPKα could induce vasodilation in resistance-size rat mesenteric arteries. Our pressure myography data demonstrated that neflamapimod produced a dose-dependent vasodilation in mesenteric arteries. Our Western blotting data revealed that acute neflamapimod treatment significantly reduced the phosphorylation of p38 MAPKα and its downstream target heat-shock protein 27 (Hsp27) involved in cytoskeletal reorganization and smooth muscle contraction. Likewise, non-selective inhibition of p38 MAPK by SB203580 attenuated p38 MAPKα and Hsp27 phosphorylation, and induced vasodilation. Endothelium denudation or pharmacological inhibition of endothelium-derived vasodilators such as nitric oxide (NO) and prostacyclin (PGI 2 ) had no effect on such vasodilation. Neflamapimod-evoked vasorelaxation remained unaltered by the inhibition of smooth muscle cell K + channels. Altogether, our data for the first time demonstrates that in resistance mesenteric arteries, neflamapimod inhibits p38 MAPKα and phosphorylation of its downstream actin-associated protein Hsp27, leading to vasodilation. This novel finding may be clinically significant and is likely to improve systemic blood pressure and cognitive deficits in AD and DLB patients for which neflamapimod is being investigated., (© 2022. The Author(s).)

Background: The lack of biomarkers to inform antidepressant selection is a key challenge in personalized depression treatment. This work identifies candidate biomarkers by building deep learning predictors of individual treatment outcomes using reward processing measures from functional magnetic resonance imaging, clinical assessments, and demographics., Methods: Participants in the EMBARC (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care) study (n = 222) underwent reward processing task-based functional magnetic resonance imaging at baseline and were randomized to 8 weeks of sertraline (n = 106) or placebo (n = 116). Subsequently, sertraline nonresponders (n = 37) switched to 8 weeks of bupropion. The change in Hamilton Depression Rating Scale was measured after treatment. Reward processing, clinical measurements, and demographics were used to train treatment-specific deep learning models., Results: The predictive model for sertraline achieved R 2 of 48% (95% CI, 33%-61%; p < 10 -3 ) in predicting the change in Hamilton Depression Rating Scale and number-needed-to-treat (NNT) of 4.86 participants in predicting response. The placebo model achieved R 2 of 28% (95% CI, 15%-42%; p < 10 -3 ) and NNT of 2.95 in predicting response. The bupropion model achieved R 2 of 34% (95% CI, 10%-59%, p < 10 -3 ) and NNT of 1.68 in predicting response. Brain regions where reward processing activity was predictive included the prefrontal cortex and cerebellar crus 1 for sertraline and the cingulate cortex, caudate, orbitofrontal cortex, and crus 1 for bupropion., Conclusions: These findings demonstrate the utility of reward processing measurements and deep learning to predict antidepressant outcomes and to form multimodal treatment biomarkers., (Copyright © 2021 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.)

Autism spectrum disorder (ASD) is the fourth most common neurodevelopmental disorder, with a prevalence of 1 in 160 children. Accurate diagnosis relies on experts, but such individuals are scarce. This has led to increasing interest in the development of machine learning (ML) models that can integrate neuroimaging features from functional and structural MRI (fMRI and sMRI) to help reveal central nervous system alterations characteristic of ASD. We optimized and compared the performance of 12 of the most popular and powerful ML models. Each was separately trained using 15 different combinations of fMRI and sMRI features and optimized with an unbiased model search. Deep learning models predicted ASD with the highest diagnostic accuracy and generalized well to other MRI datasets. Our model achieves state-of-the-art 80% area under the ROC curve (AUROC) in diagnosis on test data from the IMPAC dataset; and 86% and 79% AUROC on the external ABIDE I and ABIDE II datasets (with further improvement to 93% and 90% after supervised domain adaptation). The highest performing models identified reproducible putative biomarkers for accurate ASD diagnosis in accord with known ASD markers as well as novel cerebellar biomarkers. Such reproducibility lends credence to their tremendous potential for defining and using a set of truly generalizable ASD biomarkers that will advance scientific understanding of neuronal changes in ASD., (© 2022. The Author(s).)

Our objective was to assess the utility of an assessment battery capturing health literacy (HL) and biopsychosocial determinants of health in predicting 30-day readmission in comparison to a currently well-adopted readmission risk calculator. We also sought to capture the distribution of inpatient HL, with emphasis on inadequate and marginal HL (an intermediate HL level). A prospective observational study was conducted to obtain HL and biopsychosocial data on general medicine inpatients admitted to the UCLA health system. Five hundred thirty-seven subjects were tracked prospectively for 30-day readmission after index hospitalization. HL was significantly better at predicting readmission compared to LACE + (Length, admission acuity, comorbidities, emergency room visits) alone ( P  = .013). A multivariate model including education, insurance, and language comfort was a strong predictor of adequate HL ( P  < .001). In conclusion, HL offered significant improvement in risk stratification in comparison to LACE + alone. Patients with marginal HL were high-risk, albeit difficult to characterize. Incorporating robust HL and biopsychosocial determinant assessments may allow hospital systems to allocate educational resources towards at-risk patients, thereby mitigating readmission risk., Competing Interests: Declaration of Conflicting Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Reflectance confocal microscopy (RCM) enables noninvasive Demodex mite detection in rosacea. Objective scoring of rosacea severity is currently lacking., Objectives: To determine the value of RCM for monitoring Demodex , inflammation and vascular parameters in rosacea during treatment., Methods: In 20 rosacea patients, clinical and RCM examination were performed before, during, and 12 weeks after a 16-week treatment course with topical ivermectin. Using RCM, number of mites and inflammatory cells, epidermal thickness, and vascular density and diameter were measured. RCM features were correlated with clinical assessment., Results: Treatment resulted in clinical reduction of inflammatory lesions. Mites were detected in 80% of patients at baseline, 30% at week 16, and 63% at week 28. The number of mites reduced significantly during treatment, but no changes in inflammatory cells, epidermal thickness or vascular parameters were observed. Correlation between number of inflammatory lesions and mites was low. None of the RCM variables were significant predictors for clinical success., Conclusions: RCM enables anti-inflammatory effect monitoring of topical ivermectin by determining mite presence. Quantifying exact mite number, and inflammatory and vascular characteristics is challenging due to device limitations. In its current form, RCM seems of limited value for noninvasive follow-up of rosacea in clinical practice.

A new glycoside, telosmoside A 21 ( 1 ) and two known compounds, telosmoside A 6 ( 2 ) and telosmoside A 1 ( 3 ), were isolated from the roots of Jasminanthes tuyetanhiae . The structure of compound 1 was identified from its spectroscopic data and by comparison with the literature.

Arterial bypass grafts are a standard preclinical model for evaluating physiology and pathophysiology at graft-material interfaces. Implantations of vascular grafts are commonly done as end-to-end grafts in small animal models. Here we detail bilateral end-to-side aortoiliac graft implantation, which requires open surgery and the creation of vascular anastomoses between the graft material and the infrarenal aorta and iliac artery in a nonhuman primate model. In this model, the aortoiliac graft configuration is created using two 4 mm inner diameter vascular grafts (e.g., ePTFE). After exposure and control of the infrarenal aorta and bilateral common iliac arteries and heparinization, the proximal aortic-graft anastomosis is sewn on the lateral wall of the aorta, and subsequently the distal graft-common iliac anastomosis is sewn on the anterior wall of the common iliac artery with one tube graft. Another tube graft is sewn on the contralateral side in the same manner., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Objective: A lower extremity venous duplex ultrasound (LEVDUS) examination is the standard diagnostic test to evaluate patients for lower extremity deep vein thrombosis (DVT). However, some studies will be incomplete for a variety of reasons, including patient-related factors such as pain, edema, a large leg circumference, or the presence of overlying bandages or orthopedic devices. We previously reported that the frequency of obtaining a follow-up examination after an incomplete and negative (I/N) LEVDUS examination was low but that the rates of DVT found on the follow-up studies of initially I/N LEVDUS studies were similar to the rates of DVT found with initially complete LEVDUS examinations. Therefore, we recommended process improvements to increase follow-up LEVDUS studies after an I/N LEVDUS examination. In the present study, we have described the results of appending a recommendation to obtain a follow-up LEVDUS study to preliminary and final reports of I/N LEVDUS., Methods: Starting in January 2019 through December 2019, a recommendation to obtain a repeat LEVDUS examination after an I/N study was appended to the preliminary and final reports of all I/N LEVDUS examination of patients who did not, otherwise, have an indication for anticoagulation (group 2). The patients were identified on an ongoing basis through the study period and entered into an Excel database (Microsoft Corp, Redmond, Wash). Group 2 was compared with a previously reported historic control cohort of patients identified from January 2017 to December 2017 (group 1). We compared groups 1 and 2 with respect to the frequency of the repeat studies performed within 4 weeks after an I/N LEVDUS examination and the DVT rates found from the follow-up LEVDUS examinations after an I/N LEVDUS study., Results: Of the patients in groups 1 and 2, 187 and 229 had had I/N LEVDUS examinations, with 28% and 40.2% of group 1 and 2 studies having follow-up LEVDUS examinations (P < .01). Previously unidentified lower extremity thrombi were discovered in 21% of the group 2 follow-up examinations. Also, the rate of new thrombi detected was not different between groups 2 and 1 (historic controls; DVT, 14.3% vs 18.5% [P = .25]; SVT, 6.3% vs 3.3% [P = .15]). A definitive finding of either positive or negative for DVT and SVT with a complete examination in 50% of the group 2 patients with follow-up examinations., Conclusions: A recommendation to obtain a follow-up examination appended to the preliminary and final I/N LEVDUS reports was associated with an increased rate of follow-up examinations, which revealed many previously undetected DVTs and SVTs or had allowed for definitive exclusion of DVT., (Published by Elsevier Inc.)

Robust locomotion is critical to many species' survival, yet the mechanisms by which efficient locomotion is learned and maintained are poorly understood. In mice, a common paradigm for assaying locomotor learning is the rotarod task, in which mice learn to maintain balance atop of an accelerating rod. However, the standard metric for learning in this task is improvements in latency to fall, which gives little insight into the rich kinematic adjustments that accompany locomotor learning. In this study, we developed a rotarod-like task called the RotaWheel in which changes in paw kinematics are tracked using high-speed cameras as mice learn to stay atop an accelerating wheel. Using this device, we found that learning was accompanied by stereotyped progressions of paw kinematics that correlated with early, intermediate, and late stages of performance. Within the first day, mice sharpened their interlimb coordination using a timed pause in the forward swing of their forepaws. Over the next several days, mice reduced their stride length and took shorter, quicker steps. By the second week of training, mice began to use a more variable locomotor strategy, where consecutive overshoots or undershoots in strides were selected across paws to drive forward and backward exploration of the wheel. Collectively, our results suggest that mouse locomotor learning occurs through multiple mechanisms evolving over separate time courses and involving distinct corrective actions. These data provide insights into the kinematic strategies that accompany locomotor learning and establish an experimental platform for studying locomotor skill learning in mice., (Copyright © 2021 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A series of usnic acid benzylidene derivatives (groups I-V ) were designed, synthesized and evaluated for their anticancer activity in the search for potentially new anticancer agents. Compounds 1a , 5b , 2b , 2e and 2f exhibited the most potent cytotoxcity against K562 cell line with IC 50 values of 10.0 ± 3.6, 5.6 ± 0.4, 8.8 ± 1.0, 4.5 ± 0.1 and 8.4 ± 0.4 μM, respectively. It is noteworthy that compound 2e displayed potent cytotoxicity against K562 cells without any cytotoxic effect on HEK293 normal cell line.

Introduction: Predictive biomarkers of Parkinson's Disease progression are needed to expedite neuroprotective treatment development and facilitate prognoses for patients. This work uses measures derived from resting-state functional magnetic resonance imaging, including regional homogeneity (ReHo) and fractional amplitude of low frequency fluctuations (fALFF), to predict an individual's current and future severity over up to 4 years and to elucidate the most prognostic brain regions., Methods: ReHo and fALFF are measured for 82 Parkinson's Disease subjects and used to train machine learning predictors of baseline clinical and future severity at 1 year, 2 years, and 4 years follow-up as measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Predictive performance is measured with nested cross-validation, validated on an external dataset, and again validated through leave-one-site-out cross-validation. Important predictive features are identified., Results: The models explain up to 30.4% of the variance in current MDS-UPDRS scores, 55.8% of the variance in year 1 scores, and 47.1% of the variance in year 2 scores (p < 0.0001). For distinguishing high and low-severity individuals at each timepoint (MDS-UPDRS score above or below the median, respectively), the models achieve positive predictive values up to 79% and negative predictive values up to 80%. Higher ReHo and fALFF in several regions, including components of the default motor network, predicted lower severity across current and future timepoints., Conclusion: These results identify an accurate prognostic neuroimaging biomarker which may be used to better inform enrollment in trials of neuroprotective treatments and enable physicians to counsel their patients., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Feeding is critical for survival, and disruption in the mechanisms that govern food intake underlies disorders such as obesity and anorexia nervosa. It is important to understand both food intake and food motivation to reveal mechanisms underlying feeding disorders. Operant behavioral testing can be used to measure the motivational component to feeding, but most food intake monitoring systems do not measure operant behavior. Here, we present a new solution for monitoring both food intake and motivation in rodent home-cages: the Feeding Experimentation Device version 3 (FED3). FED3 measures food intake and operant behavior in rodent home-cages, enabling longitudinal studies of feeding behavior with minimal experimenter intervention. It has a programmable output for synchronizing behavior with optogenetic stimulation or neural recordings. Finally, FED3 design files are open-source and freely available, allowing researchers to modify FED3 to suit their needs., Competing Interests: BM, TE, MA, EC, JW, AS, AL, KB, LM, MN, YC, KN, EL, AR, RC, RS, SC, RA, JM, MC, VC, MB, MK, ZA, AK No competing interests declared, FC Director of Open Ephys Production Site