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In order to demonstrate various applications of the proposed bending module, reconfigurable robotic fingers are assembled and shown to be capable of generating different motion profiles. In addition, robotic grippers are built for lifting both delicate and heavy objects, demonstrating applications that require both high force and compliant handling.Transition metal dichalcogenides (TMDs) materials are from Two-dimensional (2D) materials family having many benefits, comprising high carrier mobility and conductivity, high optical transparency, outstanding mechanical flexibility, and chemical stability, and also the favorable gas sensing materials because of their high surface-area-to-volume ratio. Nevertheless, their low gas-sensing performance in terms of low response, partial recovery, and poor selectivity obstruct the apprehension as a high-performance 2D TMDs gas sensing materials. At this time, we explain the enhancement in gas-sensing performance of molybdenum disulfide (MoS2) nanoflakes (NF) by decorating with Lanthanum (La) at room temperature (25 ºC). Our experiments show that the dynamic sensing response of the La decorated few-layered MoS2 (La@MoS2) sensor increases by ∼6 times than the pristine few-layered MoS2, which positions it first-ever reported values for NO2 gas detection. The sensitivity of the MoS2 and La@MoS2 found 0.627 and 3.346 ppm-1, respectively, towards NO2 gas. It is noteworthy that La has introduced to MoS2, and its selectivity towards the volatile organic compounds (VOCs) and other toxic gases improved drastically. Our outcomes show that the suggested method represents a successful approach for improving the gas sensing response of 2D TMDs sensors.Objective Advanced Neuroimaging has been proving to be pivotal in acute ischemic stroke management. CT Perfusion (CTP) core and penumbra parameters have not yet been investigated to predict the outcome in Wake-up Stroke (WUS) patients in everyday clinical scenario. The aim of our study is to investigate the predictive power of CTP-parameters on functional and morphological outcomes in rTPA treated WUS patients. Approach We analyzed clinical data and processed CTP images of 80 consecutive WUS rTPA treated patients. The predictive power of whole-brain CTP features and of the clinical stroke related parameters to predict NIHSS at 7th day and Ischemic Lesion Volume outcome was investigated by means of multivariate regression analysis as well as LASSO modeling. Main results Multivariate analysis showed that CTP core volume (β 0.403, p= 0.000), NIHSS at admission (β 0.323, p= 0.005) and ASPECTS (β -0.224, p= 0.012) predict NIHSS at 7-days, while total hypoperfused volume (β 0.542, p= 0.000) and core volume on CTP (β 0.441, p= 0.000) predict infarct lesion volume at follow-up CT. The LASSO modeling approach confirmed the significant predictive power of CTP core volume, CTP total hypoperfused, NIHSS at baseline and ASPECTS producing a sparse model with adequate reliability (RMSE on previously unseen testing dataset was 3.68). https://www.selleckchem.com/products/SB-431542.html Significance Our findings highlight the importance of CT multimodal imaging features in the decision-making and predictivity in the hyperacute phase of WUS. The predictive model supports the hypothesis that irreversible necrotic core rather the extent of penumbra is the main prognostic determinant in rTPA treated WUS patients.Based on a model of coupled processes with differently time-dependent decay kinetics we present a critical review on photoluminescence (PL) and transient absorption (TA) experiments in undoped and Mg or Fe-doped LiNbO3, together with a comprehensive interpretation of visible radiative and parallel non-radiative decay processes on timescales ranging from 50 ns up to minutes. Analogies and peculiarities of the kinetics of mobile self-trapped and pinned excitons are investigated and compared with those of hopping polarons in the same system. Exciton hopping with an activation energy of ≈0.18 eV is shown to govern the lifetime and quenching of the short PL component above 100 K. Strong interaction between excitons and dipolar pinning defects explains the exorbitant lifetimes and large depinning energies characterizing delayed TA components in doped LiNbO3, while restricted hopping of the pinned excitons is proposed to play a role in strongly delayed PL in LiNbO3Mg exhibiting a narrowed emission band due to locall to liquids and biophysical systems.The all-optical magnetization reversal of magnetic layers, by picosecond optical pulses, is of particular interest as it shows the potential for energy-efficient and fast magnetic tunnel junction (MTJ) elements. This approach requires memory elements that are optically and electronically accessible, for optical writing and electronic read-out In this paper, we propose the integration of indium tin oxide (ITO) as a transparent conducting electrode for magnetic tunnel junctions in integrated spintronic - photonic circuits. To provide light with sufficient energy to the MTJ free layer and allow electrical read-out of the MTJ state, we successfully integrated indium tin oxide as a top transparent electrode. The study shows that ITO film deposition by physical vapor deposition with conditions such as high source power and low O2flow achieves smooth and conductive thin films. Increases in grain size was associated with low resistivity. Deposition of 150 nm ITO at 300 W, O2flow of 1 sccm and 8.10-3mbar vacuum pressure results in 4.8×10-4Ω.cm resistivity and up to 80 % transmittance at 800 nm wavelengths. The patterning of ITO using CH4/H2chemistry in a reactive ion etch process was investigated showing almost vertical sidewalls for diameters down to 50 nm. The ITO based process flow was compared to a standard magnetic tunnel junctions fabrication process flow based on Ta hard mask. Electrical measurements validate that the proposed process based on ITO results in properties equivalent to the standard process. We also show electrical results of magnetic tunnel junctions having all-optical switching top electrode fabricated with ITO for optical access. The developed ITO process flow shows very promising initial results and provides a way to fabricate these new devices to integrate all-optical switching magnetic tunnel junctions with electronic and photonic elements.
In order to demonstrate various applications of the proposed bending module, reconfigurable robotic fingers are assembled and shown to be capable of generating different motion profiles. In addition, robotic grippers are built for lifting both delicate and heavy objects, demonstrating applications that require both high force and compliant handling.Transition metal dichalcogenides (TMDs) materials are from Two-dimensional (2D) materials family having many benefits, comprising high carrier mobility and conductivity, high optical transparency, outstanding mechanical flexibility, and chemical stability, and also the favorable gas sensing materials because of their high surface-area-to-volume ratio. Nevertheless, their low gas-sensing performance in terms of low response, partial recovery, and poor selectivity obstruct the apprehension as a high-performance 2D TMDs gas sensing materials. At this time, we explain the enhancement in gas-sensing performance of molybdenum disulfide (MoS2) nanoflakes (NF) by decorating with Lanthanum (La) at room temperature (25 ºC). Our experiments show that the dynamic sensing response of the La decorated few-layered MoS2 (La@MoS2) sensor increases by ∼6 times than the pristine few-layered MoS2, which positions it first-ever reported values for NO2 gas detection. The sensitivity of the MoS2 and La@MoS2 found 0.627 and 3.346 ppm-1, respectively, towards NO2 gas. It is noteworthy that La has introduced to MoS2, and its selectivity towards the volatile organic compounds (VOCs) and other toxic gases improved drastically. Our outcomes show that the suggested method represents a successful approach for improving the gas sensing response of 2D TMDs sensors.Objective Advanced Neuroimaging has been proving to be pivotal in acute ischemic stroke management. CT Perfusion (CTP) core and penumbra parameters have not yet been investigated to predict the outcome in Wake-up Stroke (WUS) patients in everyday clinical scenario. The aim of our study is to investigate the predictive power of CTP-parameters on functional and morphological outcomes in rTPA treated WUS patients. Approach We analyzed clinical data and processed CTP images of 80 consecutive WUS rTPA treated patients. The predictive power of whole-brain CTP features and of the clinical stroke related parameters to predict NIHSS at 7th day and Ischemic Lesion Volume outcome was investigated by means of multivariate regression analysis as well as LASSO modeling. Main results Multivariate analysis showed that CTP core volume (β 0.403, p= 0.000), NIHSS at admission (β 0.323, p= 0.005) and ASPECTS (β -0.224, p= 0.012) predict NIHSS at 7-days, while total hypoperfused volume (β 0.542, p= 0.000) and core volume on CTP (β 0.441, p= 0.000) predict infarct lesion volume at follow-up CT. The LASSO modeling approach confirmed the significant predictive power of CTP core volume, CTP total hypoperfused, NIHSS at baseline and ASPECTS producing a sparse model with adequate reliability (RMSE on previously unseen testing dataset was 3.68). https://www.selleckchem.com/products/SB-431542.html Significance Our findings highlight the importance of CT multimodal imaging features in the decision-making and predictivity in the hyperacute phase of WUS. The predictive model supports the hypothesis that irreversible necrotic core rather the extent of penumbra is the main prognostic determinant in rTPA treated WUS patients.Based on a model of coupled processes with differently time-dependent decay kinetics we present a critical review on photoluminescence (PL) and transient absorption (TA) experiments in undoped and Mg or Fe-doped LiNbO3, together with a comprehensive interpretation of visible radiative and parallel non-radiative decay processes on timescales ranging from 50 ns up to minutes. Analogies and peculiarities of the kinetics of mobile self-trapped and pinned excitons are investigated and compared with those of hopping polarons in the same system. Exciton hopping with an activation energy of ≈0.18 eV is shown to govern the lifetime and quenching of the short PL component above 100 K. Strong interaction between excitons and dipolar pinning defects explains the exorbitant lifetimes and large depinning energies characterizing delayed TA components in doped LiNbO3, while restricted hopping of the pinned excitons is proposed to play a role in strongly delayed PL in LiNbO3Mg exhibiting a narrowed emission band due to locall to liquids and biophysical systems.The all-optical magnetization reversal of magnetic layers, by picosecond optical pulses, is of particular interest as it shows the potential for energy-efficient and fast magnetic tunnel junction (MTJ) elements. This approach requires memory elements that are optically and electronically accessible, for optical writing and electronic read-out In this paper, we propose the integration of indium tin oxide (ITO) as a transparent conducting electrode for magnetic tunnel junctions in integrated spintronic - photonic circuits. To provide light with sufficient energy to the MTJ free layer and allow electrical read-out of the MTJ state, we successfully integrated indium tin oxide as a top transparent electrode. The study shows that ITO film deposition by physical vapor deposition with conditions such as high source power and low O2flow achieves smooth and conductive thin films. Increases in grain size was associated with low resistivity. Deposition of 150 nm ITO at 300 W, O2flow of 1 sccm and 8.10-3mbar vacuum pressure results in 4.8×10-4Ω.cm resistivity and up to 80 % transmittance at 800 nm wavelengths. The patterning of ITO using CH4/H2chemistry in a reactive ion etch process was investigated showing almost vertical sidewalls for diameters down to 50 nm. The ITO based process flow was compared to a standard magnetic tunnel junctions fabrication process flow based on Ta hard mask. Electrical measurements validate that the proposed process based on ITO results in properties equivalent to the standard process. We also show electrical results of magnetic tunnel junctions having all-optical switching top electrode fabricated with ITO for optical access. The developed ITO process flow shows very promising initial results and provides a way to fabricate these new devices to integrate all-optical switching magnetic tunnel junctions with electronic and photonic elements.0 Comments 0 Shares 526 Views 0 ReviewsPlease log in to like, share and comment! -
In 2018 the SINch (Italian Society of Neurosurgery) Neuro-Oncology section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. https://www.selleckchem.com/products/ZLN005.html For operational purposes, the Task Force was divided into 5 Working Groups diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.OBJECTIVE Navigated instrumented spine surgery is burden by a low but significant screw mispositioning risks, respectively, for the 2D imaging system from 15 to 40% and, for the 3D imaging system, ranging from 4.1 to 11.5%. The primary objective of this study was to demonstrate the efficacy of a new "screw-like" tool in order to further decrease pedicle screws mispositioning rate during vertebral navigated spine surgery. MATERIALS AND METHODS Between January and June 2019 an initial case series of 18 patients were enrolled. All patients underwent a pedicle screw fixation, both in thoracic (Th10-Th12) and lumbosacral (L1-S1) spine, using O-arm (Medtronic Navigation, Louisville, Colorado) and StealthStation S7 surgical navigation system (Medtronic Navigation, Louisville, CO). Evaluation of pedicle screws placement accuracy using the new tool in adjunct to the classic reference frame, was performed following the Gertzbein and Robbins classification. RESULTS A total of 94 screws have been placed. Among them, the 98.9% were completely inside cortical bone (Grade A) and only the 1.1% with a breach of less than 2 mm (Grade B). CONCLUSIONS Our new "screw-like" tool coupled to the classic reference frame device could improve accuracy during navigated spine surgery and potentially reducing to zero the risks for screw mispositioning.INTRODUCTION Augmented Reality (AR) is as a useful and reliable tool in cranial surgery. We report the case of a left fronto-temporal meningioma in contact with the left Sylvian bifurcation, managed surgically with the aid of AR. We complete the picture with a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. EVIDENCE ACQUISITION Preoperatively, a careful segmentation of the tumor and the neighboring vessels was performed using our AR navigation software. A left fronto- temporal craniotomy was performed. Using the augmented optics technology, AR images injected into the microscope binocular during the surgery, allowed easy identification of the MCA branches and bifurcation. A systematic review of the literature was performed according to the PRISMA-P guidelines. EVIDENCE SYNTHESIS A Simpson I resection was obtained, with no new neurological deficit and an uneventful recovery after surgery. The literature review identified 8 separate articles published between 1998-2019, totaling 20 meningiomas surgically managed with the use of AR. Different AR systems are described in neurosurgery, with their respective advantages and disadvantages. Augmented optics allow the surgeon to focus on the procedure. No systematic data on postoperative radiological and clinical outcome were reported. CONCLUSIONS The use of AR in meningioma surgery might help surgeons when confronted to lesions surrounded by complex structures. However, little data is available so far to support its routine use.BACKGROUND The purpose of this study was to evaluate the technical efficacy and safety of transvenous Onyx embolization for dural arteriovenous fistulas (DAVFs) with concomitant transvenous balloon protection of the venous sinus when transarterial route failed or was not feasible. METHODS Between September 2010 and December 2016, thirty-six patients presenting with intracranial DAVFs underwent transvenous balloon-assisted Onyx embolization. The technical efficacy, treatment-related complications, and angiographic and clinical outcomes were reviewed from our prospectively maintained DAVF database. RESULTS According to the Cognard classification, 11 patients presented with clinically symptomatic Cognard type I; 11 cases with Cognard type IIa; 10 cases with Cognard type IIb and 4 cases with Cognard type IIa+b. Complete angiographic occlusion of the DAVFs at the latest follow-up (mean 18 months after transvenous embolization) was achieved in 28 patients (77.8%), near-complete angiographic occlusion with minimal residual fistula in 5 patients (13.9%) and significant flow reduction of the DAVF in 2 patients (5.6%) and residual fistula for further treatment in 1 (2.8%) patient. Total clinical cure or remission of the pre-treatment symptoms was achieved in 31 patients (31/36, 86.1%; 26 and 5 cases respectively). Affected venous sinus was preserved in 28 patients, intentionally occluded in 7 patients and gradually occluded in 1 patient. There were no immediate or long term persistent complications after treatment. CONCLUSIONS Transvenous Onyx embolization of dural arteriovenous fistulas with combined transvenous balloon protection of the venous sinus is safe and effective in achieving high occlusion rate, low embolization-related complications and satisfactory clinical outcomes.INTRODUCTION To report an extremely rare case of sellar neuroblastoma, which mimicked invasive pituitary adenoma with supra- and parasellar extensions, treated through endoscopic endonasal approach. A systematic review of the literature on diagnosis and management of patients affected by sellar neuroblastomas has been performed. EVIDENCE ACQUIITION A literature search according to the PRISMA statement was conducted using MEDLINE, Google Scholar, and EBSCO databases, searching for the following MeSH terms (sellar OR parasellar OR suprasellar OR sphenoidal) AND (neuroblastoma OR extranasal esthesioneuroblastoma OR central neuroblastoma). EVIDENCE SYNTHESIS Sixty-eight studies were identified. We included 16 papers in our systematic review, comprising a total of 16 patients, 37.5% males and 62.5% females, with a mean age of 47.2 years. Visual disturbances were found in 56.2% of them, hyperprolactinemia in 43.7%, panhypopituitarism in 12.5%, normal pituitary function in 6.25%, SIADH in 25%, but no data is available in 25% of cases.
In 2018 the SINch (Italian Society of Neurosurgery) Neuro-Oncology section, AINO (Italian Association of Neuro-Oncology) and SIN (Italian Association of Neurology) Neuro-Oncology section formed a collaborative Task Force to look at the diagnosis and treatment of low-grade gliomas (LGGs). The Task Force included neurologists, neurosurgeons, neuro-oncologists, pathologists, radiologists, radiation oncologists, medical oncologists, a neuropsychologist and a methodologist. https://www.selleckchem.com/products/ZLN005.html For operational purposes, the Task Force was divided into 5 Working Groups diagnosis, surgical treatment, adjuvant treatments, supportive therapies, and follow-up. The resulting guidance document is based on the available evidence and provides recommendations on diagnosis and treatment of LGG patients, considering all aspects of patient care along their disease trajectory.OBJECTIVE Navigated instrumented spine surgery is burden by a low but significant screw mispositioning risks, respectively, for the 2D imaging system from 15 to 40% and, for the 3D imaging system, ranging from 4.1 to 11.5%. The primary objective of this study was to demonstrate the efficacy of a new "screw-like" tool in order to further decrease pedicle screws mispositioning rate during vertebral navigated spine surgery. MATERIALS AND METHODS Between January and June 2019 an initial case series of 18 patients were enrolled. All patients underwent a pedicle screw fixation, both in thoracic (Th10-Th12) and lumbosacral (L1-S1) spine, using O-arm (Medtronic Navigation, Louisville, Colorado) and StealthStation S7 surgical navigation system (Medtronic Navigation, Louisville, CO). Evaluation of pedicle screws placement accuracy using the new tool in adjunct to the classic reference frame, was performed following the Gertzbein and Robbins classification. RESULTS A total of 94 screws have been placed. Among them, the 98.9% were completely inside cortical bone (Grade A) and only the 1.1% with a breach of less than 2 mm (Grade B). CONCLUSIONS Our new "screw-like" tool coupled to the classic reference frame device could improve accuracy during navigated spine surgery and potentially reducing to zero the risks for screw mispositioning.INTRODUCTION Augmented Reality (AR) is as a useful and reliable tool in cranial surgery. We report the case of a left fronto-temporal meningioma in contact with the left Sylvian bifurcation, managed surgically with the aid of AR. We complete the picture with a systematic review of the literature according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. EVIDENCE ACQUISITION Preoperatively, a careful segmentation of the tumor and the neighboring vessels was performed using our AR navigation software. A left fronto- temporal craniotomy was performed. Using the augmented optics technology, AR images injected into the microscope binocular during the surgery, allowed easy identification of the MCA branches and bifurcation. A systematic review of the literature was performed according to the PRISMA-P guidelines. EVIDENCE SYNTHESIS A Simpson I resection was obtained, with no new neurological deficit and an uneventful recovery after surgery. The literature review identified 8 separate articles published between 1998-2019, totaling 20 meningiomas surgically managed with the use of AR. Different AR systems are described in neurosurgery, with their respective advantages and disadvantages. Augmented optics allow the surgeon to focus on the procedure. No systematic data on postoperative radiological and clinical outcome were reported. CONCLUSIONS The use of AR in meningioma surgery might help surgeons when confronted to lesions surrounded by complex structures. However, little data is available so far to support its routine use.BACKGROUND The purpose of this study was to evaluate the technical efficacy and safety of transvenous Onyx embolization for dural arteriovenous fistulas (DAVFs) with concomitant transvenous balloon protection of the venous sinus when transarterial route failed or was not feasible. METHODS Between September 2010 and December 2016, thirty-six patients presenting with intracranial DAVFs underwent transvenous balloon-assisted Onyx embolization. The technical efficacy, treatment-related complications, and angiographic and clinical outcomes were reviewed from our prospectively maintained DAVF database. RESULTS According to the Cognard classification, 11 patients presented with clinically symptomatic Cognard type I; 11 cases with Cognard type IIa; 10 cases with Cognard type IIb and 4 cases with Cognard type IIa+b. Complete angiographic occlusion of the DAVFs at the latest follow-up (mean 18 months after transvenous embolization) was achieved in 28 patients (77.8%), near-complete angiographic occlusion with minimal residual fistula in 5 patients (13.9%) and significant flow reduction of the DAVF in 2 patients (5.6%) and residual fistula for further treatment in 1 (2.8%) patient. Total clinical cure or remission of the pre-treatment symptoms was achieved in 31 patients (31/36, 86.1%; 26 and 5 cases respectively). Affected venous sinus was preserved in 28 patients, intentionally occluded in 7 patients and gradually occluded in 1 patient. There were no immediate or long term persistent complications after treatment. CONCLUSIONS Transvenous Onyx embolization of dural arteriovenous fistulas with combined transvenous balloon protection of the venous sinus is safe and effective in achieving high occlusion rate, low embolization-related complications and satisfactory clinical outcomes.INTRODUCTION To report an extremely rare case of sellar neuroblastoma, which mimicked invasive pituitary adenoma with supra- and parasellar extensions, treated through endoscopic endonasal approach. A systematic review of the literature on diagnosis and management of patients affected by sellar neuroblastomas has been performed. EVIDENCE ACQUIITION A literature search according to the PRISMA statement was conducted using MEDLINE, Google Scholar, and EBSCO databases, searching for the following MeSH terms (sellar OR parasellar OR suprasellar OR sphenoidal) AND (neuroblastoma OR extranasal esthesioneuroblastoma OR central neuroblastoma). EVIDENCE SYNTHESIS Sixty-eight studies were identified. We included 16 papers in our systematic review, comprising a total of 16 patients, 37.5% males and 62.5% females, with a mean age of 47.2 years. Visual disturbances were found in 56.2% of them, hyperprolactinemia in 43.7%, panhypopituitarism in 12.5%, normal pituitary function in 6.25%, SIADH in 25%, but no data is available in 25% of cases.0 Comments 0 Shares 148 Views 0 Reviews -
Binary logistic regression revealed first-degree relative having RLS symptom to be significantly associated with RLS in study patients (OR 5.06, p<0.01). Multivariate linear regression showed RLS to be independently associated with school (behavior) (Β=1.18, p=0.05) and life skills (Β=2.36, p=0.05) impairment.
RLS was found to be common in ADHD children and adolescents. RLS-mimic conditions were found in two-thirds of patients who previously met 4 essential RLS criteria. First-degree relative with RLS symptom was associated with RLS, and RLS was associated with functional impairment in the life skills and school (behavior) domains.
RLS was found to be common in ADHD children and adolescents. RLS-mimic conditions were found in two-thirds of patients who previously met 4 essential RLS criteria. First-degree relative with RLS symptom was associated with RLS, and RLS was associated with functional impairment in the life skills and school (behavior) domains.
This study aimed to investigate differences in functional connectivity (FC) among different resting state networks (RSN) in clinically non-progressive mild cognitive impairment (MCI) and Alzheimer's disease (AD).
Using 3T MRI acquired resting-state functional MRI (rs-fMRI), we attempted identification of different RSN using independent component analysis (ICA) in amnestic-MCI, convertors to early AD and age-matched cognitively normal healthy controls. Regions of interest (ROI) that showed significant differences in connectivity on group ICA were selected as seeds for seed-voxel analysis. Group differences in FC for each network-connectivity map were entered into a general linear model with age, gender and total intra-cranial volume (TIV) as covariates.
In this cross-sectional design 31 HC, 30 MCI and 30 MCI-convertors to early AD were evaluated. Seed-based analysis between AD and controls revealed reduced posterior connectivity within the default mode (DMN), dorsal attention (DAN) and antero-posterior centiate between AD and MCI-nonconvertors to dementia. Longitudinal studies are required into utility of these measures.
The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date, single-fiber recordings have not been recorded from the human auditory nerve, and many unknowns remain about the firing properties that underlie the eCAP in patients with CIs. In particular, the temporal properties of auditory nerve fiber firing might contain valuable information that may be used to estimate the condition of the surviving auditory nerve fibers. This study aimed to evaluate the temporal properties of neural firing underlying human eCAPs with a new deconvolution model.
Assuming that each auditory nerve fiber produces the same unitary response (UR), the eCAP can be seen as a convolution of a UR with a compound discharge latency distribution (CDLD). We developed an iterative deconvolution model that derived a two-component Gaussian CDLD and a UR from recorded eCAPs. https://www.selleckchem.com/products/pamapimod-r-1503-ro4402257.html The choices were based on a deconvolution fitting error minimization nction of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs.
This study described an iterative method that deconvolved human eCAPs into CDLDs, under the assumption that auditory nerve fibers had the same electrically evoked UR. Based on human eCAPs, we found a human UR that was different from the guinea pig UR. Furthermore, we found that CDLD characteristics revealed age-related temporal differences between human eCAPs. This temporal information may contain valuable clinical information on the survival and function of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs.While most studies on person recognition examine the face alone, recent studies have shown evidence for the contribution of the body and gait to person recognition beyond the face. Nevertheless, little is known on whether person recognition can be performed based on the body alone. In this study, we examined two sources of information that may enhance body-based person recognition body motion and whole person context. Body motion has been shown to contribute to person recognition especially when facial information is unclear. Additionally, generating whole person context, by attaching faceless heads to bodies, has been shown to activate face processing mechanisms and may therefore enhance body-based person recognition. To assess body-based person recognition, participants performed a sequential matching task in which they studied a video of a person walking followed by a headless image of the same or different identity. The role of body motion was examined by comparing recognition from dynamic vs. static headless bodies. The role of whole person context was examined by comparing bodies with and without faceless heads. Our findings show that person recognition from the body alone was better in dynamic vs. static displays indicating that body motion contributed to body-based person recognition. In addition, whole person context contributed to body-based person recognition when recognition was performed in static displays. Overall these findings show that recognizing people based on their body alone is challenging but can be performed under certain circumstances that enhance the processing of the body when seeing the whole dynamic person.When remembering an object at a given location, participants tend to return their gaze to that location even after the object has disappeared, known as Looking-at-Nothing (LAN). However, it is unclear whether LAN is associated with better memory performance. Previous studies reporting beneficial effects of LAN have often not systematically manipulated or assessed eye movements. We asked 20 participants to remember the location and identity of eight objects arranged in a circle, shown for 5 s. Participants were prompted to judge whether a location statement (e.g., "Star Right") was correct or incorrect, or referred to a previously unseen object. During memory retrieval, participants either fixated in the screen center or were free to move their eyes. Results reveal no difference in memory accuracy and response time between free-viewing and fixation while a LAN effect was found for saccades during free viewing, but not for microsaccades during fixation. Memory performance was better in those free-viewing trials in which participants made a saccade to the critical location, and scaled with saccade accuracy.
Binary logistic regression revealed first-degree relative having RLS symptom to be significantly associated with RLS in study patients (OR 5.06, p<0.01). Multivariate linear regression showed RLS to be independently associated with school (behavior) (Β=1.18, p=0.05) and life skills (Β=2.36, p=0.05) impairment. RLS was found to be common in ADHD children and adolescents. RLS-mimic conditions were found in two-thirds of patients who previously met 4 essential RLS criteria. First-degree relative with RLS symptom was associated with RLS, and RLS was associated with functional impairment in the life skills and school (behavior) domains. RLS was found to be common in ADHD children and adolescents. RLS-mimic conditions were found in two-thirds of patients who previously met 4 essential RLS criteria. First-degree relative with RLS symptom was associated with RLS, and RLS was associated with functional impairment in the life skills and school (behavior) domains. This study aimed to investigate differences in functional connectivity (FC) among different resting state networks (RSN) in clinically non-progressive mild cognitive impairment (MCI) and Alzheimer's disease (AD). Using 3T MRI acquired resting-state functional MRI (rs-fMRI), we attempted identification of different RSN using independent component analysis (ICA) in amnestic-MCI, convertors to early AD and age-matched cognitively normal healthy controls. Regions of interest (ROI) that showed significant differences in connectivity on group ICA were selected as seeds for seed-voxel analysis. Group differences in FC for each network-connectivity map were entered into a general linear model with age, gender and total intra-cranial volume (TIV) as covariates. In this cross-sectional design 31 HC, 30 MCI and 30 MCI-convertors to early AD were evaluated. Seed-based analysis between AD and controls revealed reduced posterior connectivity within the default mode (DMN), dorsal attention (DAN) and antero-posterior centiate between AD and MCI-nonconvertors to dementia. Longitudinal studies are required into utility of these measures. The electrically evoked compound action potential (eCAP) has been widely studied for its clinical value in evaluating cochlear implants (CIs). However, to date, single-fiber recordings have not been recorded from the human auditory nerve, and many unknowns remain about the firing properties that underlie the eCAP in patients with CIs. In particular, the temporal properties of auditory nerve fiber firing might contain valuable information that may be used to estimate the condition of the surviving auditory nerve fibers. This study aimed to evaluate the temporal properties of neural firing underlying human eCAPs with a new deconvolution model. Assuming that each auditory nerve fiber produces the same unitary response (UR), the eCAP can be seen as a convolution of a UR with a compound discharge latency distribution (CDLD). We developed an iterative deconvolution model that derived a two-component Gaussian CDLD and a UR from recorded eCAPs. https://www.selleckchem.com/products/pamapimod-r-1503-ro4402257.html The choices were based on a deconvolution fitting error minimization nction of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs. This study described an iterative method that deconvolved human eCAPs into CDLDs, under the assumption that auditory nerve fibers had the same electrically evoked UR. Based on human eCAPs, we found a human UR that was different from the guinea pig UR. Furthermore, we found that CDLD characteristics revealed age-related temporal differences between human eCAPs. This temporal information may contain valuable clinical information on the survival and function of auditory nerve fibers. In turn, the surviving nerve condition might have prognostic value for speech outcomes in patients with CIs.While most studies on person recognition examine the face alone, recent studies have shown evidence for the contribution of the body and gait to person recognition beyond the face. Nevertheless, little is known on whether person recognition can be performed based on the body alone. In this study, we examined two sources of information that may enhance body-based person recognition body motion and whole person context. Body motion has been shown to contribute to person recognition especially when facial information is unclear. Additionally, generating whole person context, by attaching faceless heads to bodies, has been shown to activate face processing mechanisms and may therefore enhance body-based person recognition. To assess body-based person recognition, participants performed a sequential matching task in which they studied a video of a person walking followed by a headless image of the same or different identity. The role of body motion was examined by comparing recognition from dynamic vs. static headless bodies. The role of whole person context was examined by comparing bodies with and without faceless heads. Our findings show that person recognition from the body alone was better in dynamic vs. static displays indicating that body motion contributed to body-based person recognition. In addition, whole person context contributed to body-based person recognition when recognition was performed in static displays. Overall these findings show that recognizing people based on their body alone is challenging but can be performed under certain circumstances that enhance the processing of the body when seeing the whole dynamic person.When remembering an object at a given location, participants tend to return their gaze to that location even after the object has disappeared, known as Looking-at-Nothing (LAN). However, it is unclear whether LAN is associated with better memory performance. Previous studies reporting beneficial effects of LAN have often not systematically manipulated or assessed eye movements. We asked 20 participants to remember the location and identity of eight objects arranged in a circle, shown for 5 s. Participants were prompted to judge whether a location statement (e.g., "Star Right") was correct or incorrect, or referred to a previously unseen object. During memory retrieval, participants either fixated in the screen center or were free to move their eyes. Results reveal no difference in memory accuracy and response time between free-viewing and fixation while a LAN effect was found for saccades during free viewing, but not for microsaccades during fixation. Memory performance was better in those free-viewing trials in which participants made a saccade to the critical location, and scaled with saccade accuracy.0 Comments 0 Shares 184 Views 0 Reviews -
Using the best threshold cutoff (mutant allele frequency of 7.9%), ddPCR had superior diagnostic sensitivity (100%) and specificity (100%) relative to the two other techniques. Thus, ddPCR is effective for detecting the KRASG12/G13 mutation in colorectal adenocarcinoma tissue samples. By allowing definition of the optimal cutoff, ddPCR represents a potentially useful diagnostic tool that could improve diagnostic sensitivity and specificity.The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and contractile protein degradation.Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined.
This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality.
This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. https://www.selleckchem.com/products/z-vad(oh)-fmk.html One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors.
In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.
In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair.Background and Objectives This study aimed to group diseases classified by the International Classification of Diseases using principal component analysis, and discuss a systematic approach to reducing the preventable death rate from a perspective of public health. Materials and Methods Using a 10-year follow-up analysis of the Korean Longitudinal Study of Aging (KLoSA) data, this study obtained de-identified data including participants' data of community-dwelling individuals aged ≥45 years from 2006 to 2016. Participants were randomly selected using a multistage, stratified probability sampling based on geographical area and housing type. We excluded 37 participants with missing information at baseline and included 10,217 study participants. This study used the principal component analysis to extract comorbidity patterns, and chi-square test and Cox proportional hazards models for analyzing the association between the factors of interest. Results Principal component 1 (diabetes, heart disease, and hypertension) was associated with an increased hazard ratio (HR) of 1.079 (95% confidence interval (CI) 1.031-1.129, p = 0.001). Principal component 3 (psychiatric and cerebrovascular diseases) was related to an increased HR of 1.134 (95% CI 1.094-1.175, p less then 0.0001). Moreover, principal component 4 was associated with a high HR of 1.172 (95% CI 1.130-1.215, p less then 0.0001). However, among participants aged between 45 and 64 years, principal component 4 showed a meaningfully increased HR of 1.262 (95% CI 1.184-1.346, p less then 0.001). In this study, among the four principal components, three were statistically associated with increased mortality. Conclusions The principal component analysis for predicting mortality may become a useful tool, and artificial intelligence (AI) will improve a value-based healthcare strategy, along with developing a clinical decision support model.
Using the best threshold cutoff (mutant allele frequency of 7.9%), ddPCR had superior diagnostic sensitivity (100%) and specificity (100%) relative to the two other techniques. Thus, ddPCR is effective for detecting the KRASG12/G13 mutation in colorectal adenocarcinoma tissue samples. By allowing definition of the optimal cutoff, ddPCR represents a potentially useful diagnostic tool that could improve diagnostic sensitivity and specificity.The molecular mechanism for worsening left ventricular (LV) function after mitral valve (MV) repair for chronic mitral regurgitation remains unknown. We wished to assess the LV transcriptome and identify determinants associated with worsening LV function post-MV repair. A total of 13 patients who underwent MV repair for chronic primary mitral regurgitation were divided into two groups, preserved LV function (N = 8) and worsening LV function (N = 5), for the study. Specimens of LV from the patients taken during surgery were used for the gene microarray study. Cardiomyocyte cell line HL-1 cells were transfected with gene-containing plasmids and further evaluated for mRNA and protein expression, apoptosis, and contractile protein degradation. Of 67,258 expressed sequence tags, microarrays identified 718 genes to be differentially expressed between preserved-LVF and worsening-LVF, including genes related to the protein ubiquitination pathway, bone morphogenetic protein (BMP) receptors, and regulation of eIF4 and contractile protein degradation.Knowledge of the outcomes of critically ill patients is crucial for health and government officials who are planning how to address local outbreaks. The factors associated with outcomes of critically ill patients with coronavirus disease 2019 (Covid-19) who required treatment in an intensive care unit (ICU) are yet to be determined. This was a retrospective registry-based case series of patients with laboratory-confirmed SARS-CoV-2 who were referred for ICU admission and treated in the ICUs of the 13 participating centers in Israel between 5 March and 27 April 2020. Demographic and clinical data including clinical management were collected and subjected to a multivariable analysis; primary outcome was mortality. This study included 156 patients (median age = 72 years (range = 22-97 years)); 69% (108 of 156) were male. Eighty-nine percent (139 of 156) of patients had at least one comorbidity. https://www.selleckchem.com/products/z-vad(oh)-fmk.html One hundred three patients (66%) required invasive mechanical ventilation. As of 8 May 2020, the median length of stay in the ICU was 10 days (range = 0-37 days). The overall mortality rate was 56%; a multivariable regression model revealed that increasing age (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), the presence of sepsis (OR = 1.08 for each year of age, 95%CI = 1.03-1.13), and a shorter ICU stay(OR = 0.90 for each day, 95% CI = 0.84-0.96) were independent prognostic factors. In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection. In our case series, we found lower mortality rates than those in exhausted health systems. The results of our multivariable model suggest that further evaluation is needed of antiviral and antibacterial agents in the treatment of sepsis and secondary infection.Edge-to-edge repair for mitral valve regurgitation is being increasingly performed in high-surgical risk patients using minimally invasive mitral clipping devices. Known procedural complications include chordal rupture and mitral leaflet perforation. Hence, it is important to quantitatively evaluate the effect of edge-to-edge repair on chordal integrity. in this study, we employ a computational mitral valve model to simulate functional mitral regurgitation (FMR) by creating papillary muscle displacement. Edge-to-edge repair is then modeled by simulated coaptation of the mid portion of the mitral leaflets. in the setting of simulated FMR, edge-to-edge repair was shown to sustain low regurgitant orifice area, until a two fold increase in the inter-papillary muscle distance as compared to the normal mitral valve. Strain in the chordae was evaluated near the papillary muscles and the leaflets. Following edge-to-edge repair, strain near the papillary muscles did not significantly change relative to the unrepaired valve, while strain near the leaflets increased significantly relative to the unrepaired valve. These data demonstrate the potential for computational simulations to aid in the pre-procedural evaluation of possible complications such as chordal rupture and leaflet perforation following percutaneous edge-to-edge repair.Background and Objectives This study aimed to group diseases classified by the International Classification of Diseases using principal component analysis, and discuss a systematic approach to reducing the preventable death rate from a perspective of public health. Materials and Methods Using a 10-year follow-up analysis of the Korean Longitudinal Study of Aging (KLoSA) data, this study obtained de-identified data including participants' data of community-dwelling individuals aged ≥45 years from 2006 to 2016. Participants were randomly selected using a multistage, stratified probability sampling based on geographical area and housing type. We excluded 37 participants with missing information at baseline and included 10,217 study participants. This study used the principal component analysis to extract comorbidity patterns, and chi-square test and Cox proportional hazards models for analyzing the association between the factors of interest. Results Principal component 1 (diabetes, heart disease, and hypertension) was associated with an increased hazard ratio (HR) of 1.079 (95% confidence interval (CI) 1.031-1.129, p = 0.001). Principal component 3 (psychiatric and cerebrovascular diseases) was related to an increased HR of 1.134 (95% CI 1.094-1.175, p less then 0.0001). Moreover, principal component 4 was associated with a high HR of 1.172 (95% CI 1.130-1.215, p less then 0.0001). However, among participants aged between 45 and 64 years, principal component 4 showed a meaningfully increased HR of 1.262 (95% CI 1.184-1.346, p less then 0.001). In this study, among the four principal components, three were statistically associated with increased mortality. Conclusions The principal component analysis for predicting mortality may become a useful tool, and artificial intelligence (AI) will improve a value-based healthcare strategy, along with developing a clinical decision support model.0 Comments 0 Shares 134 Views 0 Reviews -
Primary outcomes include number of days abstinent during the challenge, change in patient-reported self-efficacy after the challenge, time to first quit attempt following the challenge, and 7-day point prevalent smoking cessation at six months. CONCLUSION Take a Break is an innovative approach to engage those not prepared for a quit attempt. Take a Break provides motivation phase smokers with tools and a brief experience to prepare them for a quit attempt, filling a gap in tobacco cessation support and current research. Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment. Cannabis is the most used illicit drug worldwide and its medicinal use is under discussion, being regulated in several countries. However, the psychotropic effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive compound of Cannabis sativa, are of concern. Thus, the interest in the isolated constituents without psychotropic activity, such as cannabidiol (CBD) and cannabidivarin (CBDV) is growing. CBD and CBDV are lipophilic molecules with poor oral bioavailability and are mainly metabolized by cytochrome P450 (CYP450) enzymes. The pharmacodynamics of CBD is the best explored, being able to interact with diverse molecular targets, like cannabinoid receptors, G protein-coupled receptor-55, transient receptor potential vanilloid 1 channel and peroxisome proliferator-activated receptor-γ. Considering the therapeutic potential, several clinical trials are underway to study the efficacy of CBD and CBDV in different pathologies, such as neurodegenerative diseases, epilepsy, autism spectrum disorders and pain conditions. The anti-cancer properties of CBD have also been demonstrated by several pre-clinical studies in different types of tumour cells. Although less studied, CBDV, a structural analogue of CBD, is receiving attention in the last years. CBDV exhibits anticonvulsant properties and, currently, clinical trials are underway for the treatment of autism spectrum disorders. Despite the benefits of these phytocannabinoids, it is important to highlight their potential interference with relevant physiologic mechanisms. In fact, CBD interactions with CYP450 enzymes and with drug efflux transporters may have serious consequences when co-administered with other drugs. This review summarizes the therapeutic advances of CBD and CBDV and explores some aspects of their pharmacokinetics, pharmacodynamics and possible interactions. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Moreover, it also highlights the therapeutic potential of CBD and CBDV in several medical conditions and clinical applications. Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing osteomyelitis. The tendency of MRSA to evade standard antibiotic treatment by hiding inside bone cells and biofilms is a major cause of frequent osteomyelitis recurrence. In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA. The optimal LIN-LPN formulation demonstrated both high linezolid payload (12.0% by weight of nanoparticles) and controlled release characteristics (gradually released the entrapped antibiotic in 120 h). Although it achieved lower activities against bacteria including USA300-0114, CDC-587, RP-62A in planktonic form, it was substantially superior against the intracellular MRSA reservoir inside osteoblast cells. The differences of intracellular activities between LIN-LPN and linezolid were 87.0-fold, 12.3-fold, and 12.6-fold in CFU/ml (p less then 0.05 or less then 0.01) at 2 µg/ml, 4 µg/ml, and 8 µg/ml linezolid concentrations, respectively. LIN-LPN also suppressed the MRSA biofilm growth to 35-60% of the values achieved with free linezolid (p less then 0.05). These enhanced intracellular and anti-biofilm activities of LIN-LPN were likely contributed by the extensive accumulation of LIN-LPN inside the MRSA-infected osteoblasts and biofilms as revealed in the confocal microscope images. The study thus validates the feasibility of exploiting the good nanoparticle-host cell and nanoparticle-biofilm interactions for improving the antibiotic drug activities against the poorly accessible bacteria, and supports LIN-LPN as a new alternative therapy for preventing the recurrence of MRSA-mediated bone infections. V.This article reports the results from an ERP study on the processing of anaphoric reference to quantifying expressions in Swedish (e.g. Many students attended the lecture and that they were present was noted). Negative quantifiers (e.g. few) differ from positive quantifiers (e.g. many), in allowing anaphoric expressions to target either the ref(erence) set ('students attending the lecture') or the comp(lement) set ('students not attending the lecture'), while positive quantifiers only allow Refset continuations. Results from the present study show that negative quantifiers give rise to an enhanced frontal negativity at the anaphoric pronoun in the negative condition, relative to positive quantifiers. At the critical word disambiguating between a Refset and Compset reading, we found P600 effects for the anomalous relative to the non-anomalous conditions. We interpret the frontal negativity found with negative quantifiers as an indication of referential ambiguity interfering in the processing of anaphoric reference.
Primary outcomes include number of days abstinent during the challenge, change in patient-reported self-efficacy after the challenge, time to first quit attempt following the challenge, and 7-day point prevalent smoking cessation at six months. CONCLUSION Take a Break is an innovative approach to engage those not prepared for a quit attempt. Take a Break provides motivation phase smokers with tools and a brief experience to prepare them for a quit attempt, filling a gap in tobacco cessation support and current research. Cigarette smoking remains a leading cause of preventable death in the United States, contributing to over 480,000 deaths each year. Although significant strides have been made in the development of effective smoking cessation treatments, most established interventions are associated with high relapse rates. One avenue for increasing the effectiveness of smoking cessation interventions is to design focused, efficient, and rigorous experiments testing engagement of well-defined mechanistic targets. Toward this aim, the current protocol will apply a pharmacologic augmentation strategy informed by basic research in animal models of addiction. Our goal is to evaluate the enhancing effect of isradipine, an FDA-approved calcium channel blocker, on the extinction of craving-a key mechanism of drug relapse after periods of abstinence. To activate craving robustly in human participants, we will use multimodal smoking cues including novel 360° video environments developed for this project and delivered through consumer virtual reality headsets. Adult smokers will take either isradipine or placebo and complete the cue exposure protocol in a double-blind randomized control trial. In order to test the hypothesis that isradipine will enhance retention of craving extinction, participants will repeat cue exposure 24 h later without the administration of isradipine or placebo. The study will be implemented in a primary care setting where adult smokers receive healthcare, and smoking behavior will be tracked throughout the trial with ecological momentary assessment. Cannabis is the most used illicit drug worldwide and its medicinal use is under discussion, being regulated in several countries. However, the psychotropic effects of Δ9-tetrahydrocannabinol (THC), the main psychoactive compound of Cannabis sativa, are of concern. Thus, the interest in the isolated constituents without psychotropic activity, such as cannabidiol (CBD) and cannabidivarin (CBDV) is growing. CBD and CBDV are lipophilic molecules with poor oral bioavailability and are mainly metabolized by cytochrome P450 (CYP450) enzymes. The pharmacodynamics of CBD is the best explored, being able to interact with diverse molecular targets, like cannabinoid receptors, G protein-coupled receptor-55, transient receptor potential vanilloid 1 channel and peroxisome proliferator-activated receptor-γ. Considering the therapeutic potential, several clinical trials are underway to study the efficacy of CBD and CBDV in different pathologies, such as neurodegenerative diseases, epilepsy, autism spectrum disorders and pain conditions. The anti-cancer properties of CBD have also been demonstrated by several pre-clinical studies in different types of tumour cells. Although less studied, CBDV, a structural analogue of CBD, is receiving attention in the last years. CBDV exhibits anticonvulsant properties and, currently, clinical trials are underway for the treatment of autism spectrum disorders. Despite the benefits of these phytocannabinoids, it is important to highlight their potential interference with relevant physiologic mechanisms. In fact, CBD interactions with CYP450 enzymes and with drug efflux transporters may have serious consequences when co-administered with other drugs. This review summarizes the therapeutic advances of CBD and CBDV and explores some aspects of their pharmacokinetics, pharmacodynamics and possible interactions. https://www.selleckchem.com/products/z-vad(oh)-fmk.html Moreover, it also highlights the therapeutic potential of CBD and CBDV in several medical conditions and clinical applications. Methicillin-resistant Staphylococcus aureus (MRSA) is the most prevalent pathogen causing osteomyelitis. The tendency of MRSA to evade standard antibiotic treatment by hiding inside bone cells and biofilms is a major cause of frequent osteomyelitis recurrence. In this study, we developed a lipid-polymer hybrid nanoparticle loading the antibiotic linezolid (LIN-LPN), and focused on evaluating if this new nanoantibiotic can achieve significant in vitro activities against these intracellular and biofilm-embedded MRSA. The optimal LIN-LPN formulation demonstrated both high linezolid payload (12.0% by weight of nanoparticles) and controlled release characteristics (gradually released the entrapped antibiotic in 120 h). Although it achieved lower activities against bacteria including USA300-0114, CDC-587, RP-62A in planktonic form, it was substantially superior against the intracellular MRSA reservoir inside osteoblast cells. The differences of intracellular activities between LIN-LPN and linezolid were 87.0-fold, 12.3-fold, and 12.6-fold in CFU/ml (p less then 0.05 or less then 0.01) at 2 µg/ml, 4 µg/ml, and 8 µg/ml linezolid concentrations, respectively. LIN-LPN also suppressed the MRSA biofilm growth to 35-60% of the values achieved with free linezolid (p less then 0.05). These enhanced intracellular and anti-biofilm activities of LIN-LPN were likely contributed by the extensive accumulation of LIN-LPN inside the MRSA-infected osteoblasts and biofilms as revealed in the confocal microscope images. The study thus validates the feasibility of exploiting the good nanoparticle-host cell and nanoparticle-biofilm interactions for improving the antibiotic drug activities against the poorly accessible bacteria, and supports LIN-LPN as a new alternative therapy for preventing the recurrence of MRSA-mediated bone infections. V.This article reports the results from an ERP study on the processing of anaphoric reference to quantifying expressions in Swedish (e.g. Many students attended the lecture and that they were present was noted). Negative quantifiers (e.g. few) differ from positive quantifiers (e.g. many), in allowing anaphoric expressions to target either the ref(erence) set ('students attending the lecture') or the comp(lement) set ('students not attending the lecture'), while positive quantifiers only allow Refset continuations. Results from the present study show that negative quantifiers give rise to an enhanced frontal negativity at the anaphoric pronoun in the negative condition, relative to positive quantifiers. At the critical word disambiguating between a Refset and Compset reading, we found P600 effects for the anomalous relative to the non-anomalous conditions. We interpret the frontal negativity found with negative quantifiers as an indication of referential ambiguity interfering in the processing of anaphoric reference.0 Comments 0 Shares 174 Views 0 Reviews -
The facile step we have taken to modify Ti and the biological performance of the final surface finish are appealing properties that may attract the attention of implant manufacturers in the future.The T cells are key players of the response to checkpoint blockade immunotherapy (CBI) and monitoring the strength and specificity of antitumor T-cell reactivity remains a crucial but elusive component of precision immunotherapy. The entire assembly of T-cell receptor (TCR) sequences accounts for antigen specificity and strength of the T-cell immune response. The TCR repertoire hence represents a "footprint" of the conditions faced by T cells that dynamically evolves according to the challenges that arise for the immune system, such as tumor neo-antigenic load. Hence, TCR repertoire analysis is becoming increasingly important to comprehensively understand the nature of a successful antitumor T-cell response, and to improve the success and safety of current CBI.Glycerol is the main by-product of biodiesel production. For this reason, its valorization into value-added products, by using green procedures, represents an important goal. Different sulfonic acid silica- or titania-based catalysts were prepared, characterized and tested in the glycerol etherification process, assisted by microwaves, in order to obtain biodiesel additives. The surface and structural properties of the catalysts were investigated by means of N2 adsorption isotherms, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and acid capacity measurements by X-Ray Fluorescence Spectroscopy (XRF). The best performance in terms of activity was achieved in the presence of the sulfonic function directly linked to the amorphous silica. By the correlation of the structure properties of the materials and their activity, the performance of the catalysts was shown to be influenced mainly by the surface area, pore volume and acidity. Recycling experiments performed over the most active systems showed that the sulfonic silica-based materials maintained their performance during several cycles.After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. https://www.selleckchem.com/products/Fluvastatin-Sodium(Lescol).html A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.Among the hundreds of reported Achillea species, A. membranacea (Labill.) DC. is one of the six that grow in Jordan. Many species of this genus are used in folk medicine to treat a variety of ailments and several biological and pharmacological activities have been ascribed to their essential oil (EO). For this study, the EO obtained from a specimen of A. membranacea grown in Jordan was analyzed by GC-MS. Ninety-six compounds were detected, of which oxygenated monoterpenes was the predominant class (47.9%), followed by non-terpene derivatives (27.9%), while sesquiterpenes represented 14.2% of the total composition. The most abundant compound in the EO was 1,8-cineole (21.7%). The cytotoxic activity of the EO was evaluated against three cancer cell lines (MCF7, A2780 and HT29), and one normal fibroblast cell line (****) by MTT assay. Significant growth inhibition was observed in EO-exposed A2780 and HT29 cells (IC50 = 12.99 and 14.02 μg/mL, respectively), while MCF7 and **** were less susceptible. The EO induced apoptosis and increased the preG1 events in A2780 cells. 1,8-Cineole, the major constituent of the EO, exhibited submicromolar cytotoxicity against A2780 cells, and was 42 times more selective against **** cells. Its cytotoxicity against A2780 cells was comparable with that of doxorubicin, but 1,8-cineole was more selective for **** normal cells. Interestingly, 1,8-cineole enhanced apoptosis in A2780, and caused a remarkable dose-dependent increase in preG1 events. Thus, 1,8-cineole has demonstrated promising cytotoxic and proapoptotic properties.Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.
The facile step we have taken to modify Ti and the biological performance of the final surface finish are appealing properties that may attract the attention of implant manufacturers in the future.The T cells are key players of the response to checkpoint blockade immunotherapy (CBI) and monitoring the strength and specificity of antitumor T-cell reactivity remains a crucial but elusive component of precision immunotherapy. The entire assembly of T-cell receptor (TCR) sequences accounts for antigen specificity and strength of the T-cell immune response. The TCR repertoire hence represents a "footprint" of the conditions faced by T cells that dynamically evolves according to the challenges that arise for the immune system, such as tumor neo-antigenic load. Hence, TCR repertoire analysis is becoming increasingly important to comprehensively understand the nature of a successful antitumor T-cell response, and to improve the success and safety of current CBI.Glycerol is the main by-product of biodiesel production. For this reason, its valorization into value-added products, by using green procedures, represents an important goal. Different sulfonic acid silica- or titania-based catalysts were prepared, characterized and tested in the glycerol etherification process, assisted by microwaves, in order to obtain biodiesel additives. The surface and structural properties of the catalysts were investigated by means of N2 adsorption isotherms, thermogravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS) and acid capacity measurements by X-Ray Fluorescence Spectroscopy (XRF). The best performance in terms of activity was achieved in the presence of the sulfonic function directly linked to the amorphous silica. By the correlation of the structure properties of the materials and their activity, the performance of the catalysts was shown to be influenced mainly by the surface area, pore volume and acidity. Recycling experiments performed over the most active systems showed that the sulfonic silica-based materials maintained their performance during several cycles.After myocardial ischemia-reperfusion, fatty acid oxidation shows fast recovery while glucose oxidation rates remain depressed. A metabolic shift aimed at increasing glucose oxidation has shown to be beneficial in models of myocardial ischemia-reperfusion. However, strategies aimed at increasing glucose consumption in the clinic have provided mixed results and have not yet reached routine clinical practice. https://www.selleckchem.com/products/Fluvastatin-Sodium(Lescol).html A better understanding of the mechanisms underlying the protection afforded by increased glucose oxidation may facilitate the transfer to the clinic. The purpose of this study was to evaluate if the modulation of reactive oxygen species (ROS) was involved in the protection afforded by increased glucose oxidation. Firstly, we characterized an H9C2 cellular model in which the use of glucose or galactose as substrates can modulate glycolysis and oxidative phosphorylation pathways. In this model, there were no differences in morphology, cell number, or ATP and PCr levels. However, galactose-grown cells consumed more oxygen and had an increased Krebs cycle turnover, while cells grown in glucose had increased aerobic glycolysis rate as demonstrated by higher lactate and alanine production. Increased aerobic glycolysis was associated with reduced ROS levels and protected the cells against simulated ischemia-reperfusion injury. Furthermore, ROS scavenger N-acetyl cysteine (NAC) was able to reduce the amount of ROS and to prevent cell death. Lastly, cells grown in galactose showed higher activation of mTOR/Akt signaling pathways. In conclusion, our results provide evidence indicating that metabolic shift towards increased glycolysis reduces mitochondrial ROS production and prevents cell death during ischemia-reperfusion injury.Among the hundreds of reported Achillea species, A. membranacea (Labill.) DC. is one of the six that grow in Jordan. Many species of this genus are used in folk medicine to treat a variety of ailments and several biological and pharmacological activities have been ascribed to their essential oil (EO). For this study, the EO obtained from a specimen of A. membranacea grown in Jordan was analyzed by GC-MS. Ninety-six compounds were detected, of which oxygenated monoterpenes was the predominant class (47.9%), followed by non-terpene derivatives (27.9%), while sesquiterpenes represented 14.2% of the total composition. The most abundant compound in the EO was 1,8-cineole (21.7%). The cytotoxic activity of the EO was evaluated against three cancer cell lines (MCF7, A2780 and HT29), and one normal fibroblast cell line (MRC5) by MTT assay. Significant growth inhibition was observed in EO-exposed A2780 and HT29 cells (IC50 = 12.99 and 14.02 μg/mL, respectively), while MCF7 and MRC5 were less susceptible. The EO induced apoptosis and increased the preG1 events in A2780 cells. 1,8-Cineole, the major constituent of the EO, exhibited submicromolar cytotoxicity against A2780 cells, and was 42 times more selective against MRC5 cells. Its cytotoxicity against A2780 cells was comparable with that of doxorubicin, but 1,8-cineole was more selective for MRC5 normal cells. Interestingly, 1,8-cineole enhanced apoptosis in A2780, and caused a remarkable dose-dependent increase in preG1 events. Thus, 1,8-cineole has demonstrated promising cytotoxic and proapoptotic properties.Scaffold hopping is a frequently-used strategy in the development of non-nucleoside reverse transcriptase inhibitors. Herein, CH(CN)-DAPYs were designed by hopping the cyano-methylene linker of our previous published CH(CN)-DABOs onto the etravirine (ETR). Eighteen CH(CN)-DAPYs were synthesized and evaluated for their anti-HIV activity. Most compounds exhibited promising activity against wild-type (WT) HIV-1. Compounds B4 (EC50 = 6 nM) and B6 (EC50 = 8 nM) showed single-digit nanomolar potency against WT HIV-1. Moreover, these two compounds had EC50 values of 0.06 and 0.08 μM toward the K103N mutant, respectively, which were comparable to the reference efavirenz (EFV) (EC50 = 0.08 μM). The preliminary structure-activity relationship (SAR) indicated that introducing substitutions on C2 of the 4-cyanophenyl group could improve antiviral activity. Molecular docking predicted that the cyano-methylene linker was positioned into the hydrophobic cavity formed by Y181/Y188 and V179 residues.0 Comments 0 Shares 180 Views 0 Reviews -
Understanding the environmental justice implications of the mortality impacts of air pollution exposure is a public health priority, as some subpopulations may face a disproportionate health burden. We examined which residential environmental and social factors may affect disparities in the air pollution-mortality relationship in North Carolina, US, using a time-stratified case-crossover design. Results indicate that air pollution poses a higher mortality risk for some persons (e.g., elderly) than others. Our findings have implications for environmental justice regarding protection of those who suffer the most from exposure to air pollution and policies to protect their health.Although racial residential segregation and interpersonal racial discrimination are associated with cardiovascular disease, few studies have examined their link with diabetes risk or management. We used longitudinal data from 2,175 black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine associations of racial residential segregation (Gi* statistic) and experiences of racial discrimination with diabetes incidence and management. Multivariable Cox models estimated associations for incident diabetes and GEE logistic regression estimated associations with diabetes management (meeting targets for HbA1c, systolic blood pressure, and LDL cholesterol). Neither segregation nor discrimination were associated with diabetes incidence or management.Exposure to greenspace in urban environments is associated with a range of improved health and well-being outcomes. There is a need to understand which aspects of greenspace influence which components of health. We investigate the relationship of indicators of greenspace quantity (total and specific types of greenspace), accessibility and quality with poor general health, depression, and severe mental illness, in the city of Sheffield, UK. We find complex relationships with multiple greenspace indicators that are different for each health measure, highlighting a need for future studies to include multiple, nuanced indicators of neighbourhood greenspace in order to produce results that can inform planning and policy guidance.This article addresses embodied and emotional geographies of (not)belonging for disabled people in Aotearoa New Zealand. The concept of 'embodied belonging' is used to show that bodies, things, place and space intersect in complex ways to produce contradictory feeling of (not)belonging in 'disability spaces'. Disability spaces can offer a direct challenge to ableism and create feelings of belonging for disabled people. They can also, however, reinforce normative identities and ideologies within and beyond disability spaces. We draw upon qualitative data collected through individual and focus group interviews, and written responses from 12 disabled people and three family members of disabled people to show that disability spaces are not inherently more inclusive of disabled people but rather bodies, things, place and space combine in various ways to produce shifting exclusionary and/or enabling arrangements. A focus on lived, felt and spatial elements of belonging to and in disability spaces can deepen understandings of what it means for disabled people to feel in and out of place.Health researchers and policy-makers increasingly use volunteered geographic information (VGI) to analyze spatial variation in health and wellbeing and to develop interventions. As socially constructed data, health VGI reflect the people who perceive issues and choose to report them, and the digital systems that structure the reporting process. We propose a conceptual framework that describes the interlocking effects of socioeconomic, behavioral, geographic, and technological processes on VGI accuracy and credibility. GIS and statistical methods are used to analyze social and geographical biases in health-related VGI through a case study of bed bug complaint data from New York City's 311 system. Reports of bed bug infestation from 311 are mapped and modeled to uncover associations with socioeconomic and built environment characteristics. Factors associated with bed bug report credibility are examined by comparing characteristics of confirmed reports with those for reports in which inspectors found no evidence of infestation (negative reports). A multilevel model of credibility incorporating report-, building-, and tract-level variables reveals strong geographical and socioeconomic biases, with negative reports generated more frequently from high-value residential buildings located in high-income neighborhoods with predominately white, non-Hispanic populations. Using 311 data for all bed bug reports, rather than confirmed reports, obscures the burden of these pests in high poverty neighborhoods and diminishes socioeconomic disparities. Mistaken reporting also has economic costs, as each report triggers an inspection by city inspectors that entails time, monetary, and opportunity costs.The interrelationships between nature, health, and wellbeing are increasingly recognized and incorporated into therapeutic interventions. Care farming, the concept of utilizing agricultural places and practices for providing care, therapy, and rehabilitation, is a paradigmatic example of this shift. https://www.selleckchem.com/products/pyridostatin-trifluoroacetate-salt.html This mixed method study empirically evaluates the efficacy of care farming as an intervention for individuals affected by traumatic grief, a complex experiential condition. Both quantitative and qualitative results suggest this care farm intervention was beneficial, yielding significant reductions in subjective distress to grief intensity. The study's findings add to the growing body of evidence on care farming and support green care as a therapeutic potential for individuals affected by traumatic grief.Depression and loneliness act in a synergistic way among older adults. We tested two indicators of the perceived neighborhood built environment (BE) as moderators of the association between these conditions in older European adults. Positive perceptions of neighborhood BE were related to lower levels of loneliness but not to major depressive disorder (MDD). Reporting low BE usability was significantly related to a higher likelihood of feeling lonely except for those suffering from MDD, whereas reporting low BE walkability was significantly related with a high likelihood of loneliness particularly among those with MDD. Therefore, improving neighborhood BE and, specifically, its walkability, might result in a reduction in the prevalence of loneliness.
Understanding the environmental justice implications of the mortality impacts of air pollution exposure is a public health priority, as some subpopulations may face a disproportionate health burden. We examined which residential environmental and social factors may affect disparities in the air pollution-mortality relationship in North Carolina, US, using a time-stratified case-crossover design. Results indicate that air pollution poses a higher mortality risk for some persons (e.g., elderly) than others. Our findings have implications for environmental justice regarding protection of those who suffer the most from exposure to air pollution and policies to protect their health.Although racial residential segregation and interpersonal racial discrimination are associated with cardiovascular disease, few studies have examined their link with diabetes risk or management. We used longitudinal data from 2,175 black participants in the Coronary Artery Risk Development in Young Adults (CARDIA) Study to examine associations of racial residential segregation (Gi* statistic) and experiences of racial discrimination with diabetes incidence and management. Multivariable Cox models estimated associations for incident diabetes and GEE logistic regression estimated associations with diabetes management (meeting targets for HbA1c, systolic blood pressure, and LDL cholesterol). Neither segregation nor discrimination were associated with diabetes incidence or management.Exposure to greenspace in urban environments is associated with a range of improved health and well-being outcomes. There is a need to understand which aspects of greenspace influence which components of health. We investigate the relationship of indicators of greenspace quantity (total and specific types of greenspace), accessibility and quality with poor general health, depression, and severe mental illness, in the city of Sheffield, UK. We find complex relationships with multiple greenspace indicators that are different for each health measure, highlighting a need for future studies to include multiple, nuanced indicators of neighbourhood greenspace in order to produce results that can inform planning and policy guidance.This article addresses embodied and emotional geographies of (not)belonging for disabled people in Aotearoa New Zealand. The concept of 'embodied belonging' is used to show that bodies, things, place and space intersect in complex ways to produce contradictory feeling of (not)belonging in 'disability spaces'. Disability spaces can offer a direct challenge to ableism and create feelings of belonging for disabled people. They can also, however, reinforce normative identities and ideologies within and beyond disability spaces. We draw upon qualitative data collected through individual and focus group interviews, and written responses from 12 disabled people and three family members of disabled people to show that disability spaces are not inherently more inclusive of disabled people but rather bodies, things, place and space combine in various ways to produce shifting exclusionary and/or enabling arrangements. A focus on lived, felt and spatial elements of belonging to and in disability spaces can deepen understandings of what it means for disabled people to feel in and out of place.Health researchers and policy-makers increasingly use volunteered geographic information (VGI) to analyze spatial variation in health and wellbeing and to develop interventions. As socially constructed data, health VGI reflect the people who perceive issues and choose to report them, and the digital systems that structure the reporting process. We propose a conceptual framework that describes the interlocking effects of socioeconomic, behavioral, geographic, and technological processes on VGI accuracy and credibility. GIS and statistical methods are used to analyze social and geographical biases in health-related VGI through a case study of bed bug complaint data from New York City's 311 system. Reports of bed bug infestation from 311 are mapped and modeled to uncover associations with socioeconomic and built environment characteristics. Factors associated with bed bug report credibility are examined by comparing characteristics of confirmed reports with those for reports in which inspectors found no evidence of infestation (negative reports). A multilevel model of credibility incorporating report-, building-, and tract-level variables reveals strong geographical and socioeconomic biases, with negative reports generated more frequently from high-value residential buildings located in high-income neighborhoods with predominately white, non-Hispanic populations. Using 311 data for all bed bug reports, rather than confirmed reports, obscures the burden of these pests in high poverty neighborhoods and diminishes socioeconomic disparities. Mistaken reporting also has economic costs, as each report triggers an inspection by city inspectors that entails time, monetary, and opportunity costs.The interrelationships between nature, health, and wellbeing are increasingly recognized and incorporated into therapeutic interventions. Care farming, the concept of utilizing agricultural places and practices for providing care, therapy, and rehabilitation, is a paradigmatic example of this shift. https://www.selleckchem.com/products/pyridostatin-trifluoroacetate-salt.html This mixed method study empirically evaluates the efficacy of care farming as an intervention for individuals affected by traumatic grief, a complex experiential condition. Both quantitative and qualitative results suggest this care farm intervention was beneficial, yielding significant reductions in subjective distress to grief intensity. The study's findings add to the growing body of evidence on care farming and support green care as a therapeutic potential for individuals affected by traumatic grief.Depression and loneliness act in a synergistic way among older adults. We tested two indicators of the perceived neighborhood built environment (BE) as moderators of the association between these conditions in older European adults. Positive perceptions of neighborhood BE were related to lower levels of loneliness but not to major depressive disorder (MDD). Reporting low BE usability was significantly related to a higher likelihood of feeling lonely except for those suffering from MDD, whereas reporting low BE walkability was significantly related with a high likelihood of loneliness particularly among those with MDD. Therefore, improving neighborhood BE and, specifically, its walkability, might result in a reduction in the prevalence of loneliness.0 Comments 0 Shares 323 Views 0 Reviews -
Inflammasome activation leads to pyroptotic cell death, thereby eliminating the replicative niche of virulent pathogens. Although inflammasome-associated cytokines IL-1β and IL-18 have an established role in T cell function, whether inflammasome activation in dendritic cells (DCs) is critical for T cell priming is not clear. Here, we find that conventional DCs (cDCs) suppress inflammasome activation to prevent pyroptotic cell death, thus preserving their ability to prime both CD4 and CD8 T cells. Transcription factors IRF8 and IRF4, in cDC1s and cDC2s, respectively, mediate suppression of inflammasome activation by limiting the expression of inflammasome-associated genes. Overexpression of IRF4 or IRF8 inhibits inflammasome activation in macrophages, while reduced expression of IRF8 leads to aberrant inflammasome activation in cDC1s and hampers their ability to prime CD8 T cells. Thus, activation of inflammasome in DCs is detrimental to adaptive immunity, and our results reveal that cDCs use IRF4 and IRF8 to suppress this response. An important but still enigmatic function of DNARNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog of the human helicase Senataxin, is recruited at an HO endonuclease-induced DSB and limits the local accumulation of DNARNA hybrids. In the absence of Sen1, hybrid accumulation proximal to the DSB promotes increased binding of the Ku70-80 (KU) complex at the break site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated end joining (MMEJ), and chromosome translocations. We also show that homology-directed recombination (HDR) by gene conversion is mostly proficient in sen1 mutants after single DSB. However, in the absence of Sen1, DNARNA hybrids, Mre11, and Dna2 initiate resection through a non-canonical mechanism. We propose that this resection mechanism through local DNARNA hybrids acts as a backup to prime HDR when canonical pathways are altered, but at the expense of genome integrity. Liver X receptors (LXRs) and their ligands are potent regulators of midbrain dopaminergic (mDA) neurogenesis and differentiation. However, the molecular mechanisms by which LXRs control these functions remain to be elucidated. Here, we perform a combined transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analysis of midbrain cells after LXR activation, followed by bioinformatic analysis to elucidate the transcriptional networks controlling mDA neurogenesis. Our results identify the basic helix-loop-helix transcription factor sterol regulatory element binding protein 1 (SREBP1) as part of a cluster of proneural transcription factors in radial glia and as a regulator of transcription factors controlling mDA neurogenesis, such as Foxa2. Moreover, loss- and gain-of-function experiments in vitro and in vivo demonstrate that Srebf1 is both required and sufficient for mDA neurogenesis. Our data, thus, identify Srebf1 as a central player in mDA neurogenesis. Attempts to generate functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful, mainly due to the lack of understanding of the regulatory network of human hematopoiesis. In this study, we identified leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) as an essential regulator of early hematopoietic differentiation of hPSCs. The deletion of LGR4 severely impairs mesoderm development, thereby limiting hematopoietic differentiation both in vitro and in vivo. In contrast, LGR5 is dispensable for hPSC hematopoiesis. The four R-spondin proteins show differential activities and dependencies on LGR4 in hematopoietic differentiation. The deletion of LGR4 almost entirely abolishes the enhancement induced by R-spondin1 and R-spondin3, but not R-spondin2. In addition, ZNRF3 is required for the response of R-spondin1-R-spondin3. https://www.selleckchem.com/products/ca3.html At the mechanistic level, LGR4 regulates transforming growth factor beta (TGF-beta) signaling to control hematopoietic differentiation. Together, our results reveal vital roles of LGR4 in hematopoietic development and uncover distinct functions and underlying mechanisms for R-spondins. Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon. Here, we show that β adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in **** lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsαKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, β3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type **** enhances both thermogenesis and DNL in sWAT. Mechanistically, T3 action on UCP1 expression in sWAT depends upon cAMP and is blocked in Adipo-GsαKO **** even as elevated DNL persists. Thus, T3 enhances sWAT thermogenesis by amplifying cAMP signaling, while its control of adipocyte DNL can be mediated independently of both cAMP and rapamycin-sensitive mTORC1.
Inflammasome activation leads to pyroptotic cell death, thereby eliminating the replicative niche of virulent pathogens. Although inflammasome-associated cytokines IL-1β and IL-18 have an established role in T cell function, whether inflammasome activation in dendritic cells (DCs) is critical for T cell priming is not clear. Here, we find that conventional DCs (cDCs) suppress inflammasome activation to prevent pyroptotic cell death, thus preserving their ability to prime both CD4 and CD8 T cells. Transcription factors IRF8 and IRF4, in cDC1s and cDC2s, respectively, mediate suppression of inflammasome activation by limiting the expression of inflammasome-associated genes. Overexpression of IRF4 or IRF8 inhibits inflammasome activation in macrophages, while reduced expression of IRF8 leads to aberrant inflammasome activation in cDC1s and hampers their ability to prime CD8 T cells. Thus, activation of inflammasome in DCs is detrimental to adaptive immunity, and our results reveal that cDCs use IRF4 and IRF8 to suppress this response. An important but still enigmatic function of DNARNA hybrids is their role in DNA double-strand break (DSB) repair. Here, we show that Sen1, the budding yeast ortholog of the human helicase Senataxin, is recruited at an HO endonuclease-induced DSB and limits the local accumulation of DNARNA hybrids. In the absence of Sen1, hybrid accumulation proximal to the DSB promotes increased binding of the Ku70-80 (KU) complex at the break site, mutagenic non-homologous end joining (NHEJ), micro-homology-mediated end joining (MMEJ), and chromosome translocations. We also show that homology-directed recombination (HDR) by gene conversion is mostly proficient in sen1 mutants after single DSB. However, in the absence of Sen1, DNARNA hybrids, Mre11, and Dna2 initiate resection through a non-canonical mechanism. We propose that this resection mechanism through local DNARNA hybrids acts as a backup to prime HDR when canonical pathways are altered, but at the expense of genome integrity. Liver X receptors (LXRs) and their ligands are potent regulators of midbrain dopaminergic (mDA) neurogenesis and differentiation. However, the molecular mechanisms by which LXRs control these functions remain to be elucidated. Here, we perform a combined transcriptome and chromatin immunoprecipitation sequencing (ChIP-seq) analysis of midbrain cells after LXR activation, followed by bioinformatic analysis to elucidate the transcriptional networks controlling mDA neurogenesis. Our results identify the basic helix-loop-helix transcription factor sterol regulatory element binding protein 1 (SREBP1) as part of a cluster of proneural transcription factors in radial glia and as a regulator of transcription factors controlling mDA neurogenesis, such as Foxa2. Moreover, loss- and gain-of-function experiments in vitro and in vivo demonstrate that Srebf1 is both required and sufficient for mDA neurogenesis. Our data, thus, identify Srebf1 as a central player in mDA neurogenesis. Attempts to generate functional blood cells from human pluripotent stem cells (hPSCs) remain largely unsuccessful, mainly due to the lack of understanding of the regulatory network of human hematopoiesis. In this study, we identified leucine-rich-repeat-containing G-protein-coupled receptor 4 (LGR4) as an essential regulator of early hematopoietic differentiation of hPSCs. The deletion of LGR4 severely impairs mesoderm development, thereby limiting hematopoietic differentiation both in vitro and in vivo. In contrast, LGR5 is dispensable for hPSC hematopoiesis. The four R-spondin proteins show differential activities and dependencies on LGR4 in hematopoietic differentiation. The deletion of LGR4 almost entirely abolishes the enhancement induced by R-spondin1 and R-spondin3, but not R-spondin2. In addition, ZNRF3 is required for the response of R-spondin1-R-spondin3. https://www.selleckchem.com/products/ca3.html At the mechanistic level, LGR4 regulates transforming growth factor beta (TGF-beta) signaling to control hematopoietic differentiation. Together, our results reveal vital roles of LGR4 in hematopoietic development and uncover distinct functions and underlying mechanisms for R-spondins. Better understanding of the progression of neural stem cells (NSCs) in the developing cerebral cortex is important for modeling neurogenesis and defining the pathogenesis of neuropsychiatric disorders. Here, we use RNA sequencing, cell imaging, and lineage tracing of mouse and human in vitro NSCs and monkey brain sections to model the generation of cortical neuronal fates. We show that conserved signaling mechanisms regulate the acute transition from proliferative NSCs to committed glutamatergic excitatory neurons. As human telencephalic NSCs develop from pluripotency in vitro, they transition through organizer states that spatially pattern the cortex before generating glutamatergic precursor fates. NSCs derived from multiple human pluripotent lines vary in these early patterning states, leading differentially to dorsal or ventral telencephalic fates. This work furthers systematic analyses of the earliest patterning events that generate the major neuronal trajectories of the human telencephalon. Here, we show that β adrenergic signaling coordinately upregulates de novo lipogenesis (DNL) and thermogenesis in subcutaneous white adipose tissue (sWAT), and both effects are blocked in mice lacking the cAMP-generating G protein-coupled receptor Gs (Adipo-GsαKO) in adipocytes. However, UCP1 expression but not DNL activation requires rapamycin-sensitive mTORC1. Furthermore, β3-adrenergic agonist CL316243 readily upregulates thermogenic but not lipogenic genes in cultured adipocytes, indicating that additional regulators must operate on DNL in sWAT in vivo. We identify one such factor as thyroid hormone T3, which is elevated locally by adrenergic signaling. T3 administration to wild-type mice enhances both thermogenesis and DNL in sWAT. Mechanistically, T3 action on UCP1 expression in sWAT depends upon cAMP and is blocked in Adipo-GsαKO mice even as elevated DNL persists. Thus, T3 enhances sWAT thermogenesis by amplifying cAMP signaling, while its control of adipocyte DNL can be mediated independently of both cAMP and rapamycin-sensitive mTORC1.0 Comments 0 Shares 136 Views 0 Reviews -
Sex differences and interpersonal variability were analyzed by multiple linear regressions. Measurements were also correlated with patient height. An optimization analysis was used to estimate the number of femoral implant sizes required. There were significant sex differences in the distal femur, where men had higher values than women in all measurements. Great interpersonal variability was found. The height of the lateral condyle was correlated with patient height, but the correlation was not strong. Twenty-five femoral implant sizes were required to meet the shape variations in our sample. Conclusions The shape of the distal femur in patients with osteoarthritis shows great interpersonal variability, with men showing significantly higher values than women. A total of 25 different implant sizes would be necessary to adequately meet the variations observed in our study population.Purpose We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). https://www.selleckchem.com/products/SB-431542.html Methods We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). Results The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. Conclusion EVL-CT may predict the outcome of the early phase after lung transplantation.This paper describes the role of ambient pressure in self-heating torrefaction of livestock manure. We explored the initiating temperatures required to cause self-heating of wet dairy cattle manure at different ambient pressures (0.1, 0.4, 0.7, and 1.0 MPa). Then, we conducted proximate, elemental, and calorific analyses of biochar torrefied at 210, 250, and 290°C. The results showed that self-heating was induced at 155°C or higher for 0.1 MPa and at 115°C or lower for 0.4 MPa or higher. The decrease of the initiating temperature at elevated pressure was due not only to more oxygen, but also to the retention of moisture that can promote chemical oxidation of manure. Biochar yields decreased with increasing torrefaction temperature and pressure, and the yield difference at 0.1 and 1.0 MPa was more substantial at lower temperatures a 29.8, 16.4, and 9.4% difference at 210, 250, and 290°C, respectively. Proximate and elemental analyses showed that elevated pressure promotes devolatilization, deoxygenation, and coalification compared to atmospheric pressure; its impact, however, was less at higher temperatures as the torrefaction temperature became more dominant. Calorific analysis revealed that elevated pressure can increase the higher heating value (HHV) on a dry and ash-free basis at 210°C because of the increase in carbon content, but its impact is limited at 250 and 290°C. Meanwhile, the HHV on a dry basis exhibited the opposite trend due primarily to an enlargement of ash content. The present study revealed that ambient pressure considerably affects the initiating temperature of self-heating and the chemical properties of biochar at a low torrefaction temperature.Paltering is a form of deception whereby true statements are used to mislead and is widely employed in negotiations, marketing, espionage, and ordinary communications where speakers hold ulterior motives. We argue that paltering is accomplished through strategic violations of communicative norms such as the Gricean cooperative principles of relevance, quantity, quality and manner. We further argue that, just as genuine paltering deceives by deliberately violating communicative norms, inadvertent violations of these norms may be just as misleading. In this work, we demonstrated that educational information presented prominently on the American Diabetes Association website violated the Gricean communicative principles and disrupted readers' performance on a test of diabetes knowledge. To establish the effects of these communicative violations, we revised the ADA's information to preserve the original content while better adhering to pragmatic principles. When these ADA explanations were judiciously revised to minimize pragmatic violations, they were transformed from misleading to educational.Understanding the effects of obesity on the immune profile of renal cell carcinoma (RCC) patients is critical, given the rising use of immunotherapies to treat advanced disease and recent reports of differential cancer immunotherapy outcomes with obesity. Here, we evaluated multiple immune parameters at the genetic, soluble protein, and cellular levels in peripheral blood and renal tumors from treatment-naive clear cell RCC (ccRCC) subjects (n = 69), to better understand the effects of host obesity (Body Mass Index "BMI" ≥ 30 kg/m2) in the absence of immunotherapy. Tumor-free donors (n = 38) with or without obesity were used as controls. In our ccRCC cohort, increasing BMI was associated with decreased percentages of circulating activated PD-1+CD8+ T cells, CD14+CD16neg classical monocytes, and Foxp3+ regulatory T cells (Tregs). Only CD14+CD16neg classical monocytes and Tregs were reduced when obesity was examined as a categorical variable. Obesity did not alter the percentages of circulating IFNγ+ CD8 T cells or IFNγ+, IL-4+, or IL-17A+ CD4 T cells in ccRCC subjects.
Sex differences and interpersonal variability were analyzed by multiple linear regressions. Measurements were also correlated with patient height. An optimization analysis was used to estimate the number of femoral implant sizes required. There were significant sex differences in the distal femur, where men had higher values than women in all measurements. Great interpersonal variability was found. The height of the lateral condyle was correlated with patient height, but the correlation was not strong. Twenty-five femoral implant sizes were required to meet the shape variations in our sample. Conclusions The shape of the distal femur in patients with osteoarthritis shows great interpersonal variability, with men showing significantly higher values than women. A total of 25 different implant sizes would be necessary to adequately meet the variations observed in our study population.Purpose We developed an ex vivo lung CT (EVL-CT) technique that allows us to obtain detailed CT images and morphologically assess the retrieved lung from a donor for transplantation. After we recovered the lung graft from a brain-dead donor, we transported it to our hospital and CT images were obtained ex vivo before lung transplant surgery. The objective of this study was to investigate the correlation between the EVL-CT findings and post-transplant outcome in patients who underwent bilateral lung transplantation (BLT) or single lung transplantation (SLT). https://www.selleckchem.com/products/SB-431542.html Methods We retrospectively reviewed the records of 70 patients with available EVL-CT data who underwent BLT (34 cases) or SLT (36 cases) in our hospital between October 2007 and September 2017. The recipients were divided into 2 groups (control group, infiltration group) according to the findings of EVL-CT of the lung graft in BLT and SLT, respectively. Recipients in the control group were transplanted lung grafts without any infiltrates (BLT control group, SLT control group). Recipients in the infiltration group received lung grafts with infiltrates (BLT infiltration group, SLT infiltration group). Results The recipients in the BLT infiltration group showed significantly slower recovery from primary graft dysfunction and a longer mechanical ventilation period and ICU stay period than those in the BLT control group. The mechanical ventilation period was significantly longer in the recipients in the SLT infiltration group than those in the SLT control group. Conclusion EVL-CT may predict the outcome of the early phase after lung transplantation.This paper describes the role of ambient pressure in self-heating torrefaction of livestock manure. We explored the initiating temperatures required to cause self-heating of wet dairy cattle manure at different ambient pressures (0.1, 0.4, 0.7, and 1.0 MPa). Then, we conducted proximate, elemental, and calorific analyses of biochar torrefied at 210, 250, and 290°C. The results showed that self-heating was induced at 155°C or higher for 0.1 MPa and at 115°C or lower for 0.4 MPa or higher. The decrease of the initiating temperature at elevated pressure was due not only to more oxygen, but also to the retention of moisture that can promote chemical oxidation of manure. Biochar yields decreased with increasing torrefaction temperature and pressure, and the yield difference at 0.1 and 1.0 MPa was more substantial at lower temperatures a 29.8, 16.4, and 9.4% difference at 210, 250, and 290°C, respectively. Proximate and elemental analyses showed that elevated pressure promotes devolatilization, deoxygenation, and coalification compared to atmospheric pressure; its impact, however, was less at higher temperatures as the torrefaction temperature became more dominant. Calorific analysis revealed that elevated pressure can increase the higher heating value (HHV) on a dry and ash-free basis at 210°C because of the increase in carbon content, but its impact is limited at 250 and 290°C. Meanwhile, the HHV on a dry basis exhibited the opposite trend due primarily to an enlargement of ash content. The present study revealed that ambient pressure considerably affects the initiating temperature of self-heating and the chemical properties of biochar at a low torrefaction temperature.Paltering is a form of deception whereby true statements are used to mislead and is widely employed in negotiations, marketing, espionage, and ordinary communications where speakers hold ulterior motives. We argue that paltering is accomplished through strategic violations of communicative norms such as the Gricean cooperative principles of relevance, quantity, quality and manner. We further argue that, just as genuine paltering deceives by deliberately violating communicative norms, inadvertent violations of these norms may be just as misleading. In this work, we demonstrated that educational information presented prominently on the American Diabetes Association website violated the Gricean communicative principles and disrupted readers' performance on a test of diabetes knowledge. To establish the effects of these communicative violations, we revised the ADA's information to preserve the original content while better adhering to pragmatic principles. When these ADA explanations were judiciously revised to minimize pragmatic violations, they were transformed from misleading to educational.Understanding the effects of obesity on the immune profile of renal cell carcinoma (RCC) patients is critical, given the rising use of immunotherapies to treat advanced disease and recent reports of differential cancer immunotherapy outcomes with obesity. Here, we evaluated multiple immune parameters at the genetic, soluble protein, and cellular levels in peripheral blood and renal tumors from treatment-naive clear cell RCC (ccRCC) subjects (n = 69), to better understand the effects of host obesity (Body Mass Index "BMI" ≥ 30 kg/m2) in the absence of immunotherapy. Tumor-free donors (n = 38) with or without obesity were used as controls. In our ccRCC cohort, increasing BMI was associated with decreased percentages of circulating activated PD-1+CD8+ T cells, CD14+CD16neg classical monocytes, and Foxp3+ regulatory T cells (Tregs). Only CD14+CD16neg classical monocytes and Tregs were reduced when obesity was examined as a categorical variable. Obesity did not alter the percentages of circulating IFNγ+ CD8 T cells or IFNγ+, IL-4+, or IL-17A+ CD4 T cells in ccRCC subjects.0 Comments 0 Shares 4 Views 0 Reviews -
BACKGROUND Computerised provider order entry (CPOE) systems are widely used in clinical settings for the electronic ordering of medications, laboratory tests and radiological therapies. However, evidence regarding effects of CPOE-based medication ordering on clinical and safety outcomes is mixed. We conducted an overview of systematic reviews (SRs) to characterise the cumulative effects of CPOE use for medication ordering in clinical settings. METHODS MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched to identify published SRs from inception to 12 February 2018. SRs investigating the effects of the use of CPOE for medication ordering were included. Two reviewers independently extracted data and assessed the methodological quality of included SRs. RESULTS Seven SRs covering 118 primary studies were included for review. Pooled studies from the SRs in inpatient settings showed that CPOE use resulted in statistically significant decreases in medication errors and adverse drug events (ADEs); however, there was considerable variation in the magnitude of their relative risk reduction (54%-92% for errors, 35%-53% for ADEs). There was no significant relative risk reduction on hospital mortality or length of stay. Bibliographic analysis showed limited overlap (24%) among studies included across all SRs. CONCLUSION SRs on CPOEs included predominantly non-randomised controlled trials and observational studies with varying foci. SRs predominantly focused on inpatient settings and often lacked comparison groups; SRs used inconsistent definitions of outcomes, lacked descriptions regarding the effects on patient harm and did not differentiate among the levels of available decision support. With five of the seven SRs having low to moderate quality, findings from the SRs must be interpreted with caution. We discuss potential directions for future primary studies and SRs of CPOE. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA 3D structure prediction. With agreement from crystallographers, the RNA structures are predicted by various groups before the publication of the crystal structures. We now report the prediction of six RNA sequences four structures of nucleolytic ribozymes and two of riboswitches. Systematic protocols for comparing models and crystal structures are described and analyzed. In these six puzzles, we discuss a) the comparison between the automated web server and human experts; b) the prediction of coaxial stacking; c) the prediction of structural details and ligand binding; d) the development of novel prediction methods; and e) the potential improvements to be made. It is illustrated that correct coaxial stacking and tertiary contacts are key for the prediction of RNA architecture, while ligand binding modes can be only predicted with low resolution and accurate ligand binding prediction still remains out of reach. All the predicted models are available for the future development of force field parameters and the improvement of comparison and assessment tools. Published by Cold Spring Harbor Laboratory Press for the RNA Society.Nop9 is an essential factor in the processing of pre-ribosomal RNA. Its absence in yeast is lethal, and defects in the human ortholog are associated with breast cancer, autoimmunity, and learning/language impairment. PUF family RNA-binding proteins are best known for sequence-specific RNA recognition, and most contain eight α-helical repeats that bind to the RNA bases of single-stranded RNA. Nop9 is an unusual member of this family in that it contains eleven repeats and recognizes both RNA structure and sequence. Here we report a crystal structure of Saccharomyces cerevisiae Nop9 in complex with its target RNA within the 20S pre-ribosomal RNA. https://www.selleckchem.com/products/diltiazem.html This structure reveals that Nop9 brings together a C-terminal module recognizing the 5' single-stranded region of the RNA and a bifunctional N-terminal module recognizing the central double-stranded stem region. We further show that the 3' single-stranded region of the 20S target RNA adds sequence-independent binding energy to the RNA-Nop9 interaction. Both the N- and C-terminal modules retain the characteristic sequence-specific recognition of PUF proteins but the N-terminal module has also evolved a distinct interface, which allows Nop9 to recognize either single-stranded RNA sequences or RNAs with a combination of single-stranded and structured elements. Published by Cold Spring Harbor Laboratory Press for the RNA Society.The use of haplotypes may improve the accuracy of genomic prediction over single SNPs because haplotypes can better capture linkage disequilibrium and genomic similarity in different lines and may capture local high-order allelic interactions. Additionally, prediction accuracy could be improved by portraying population structure in the calibration set. A set of 383 advanced lines and cultivars that represent the diversity of the University of Minnesota wheat breeding program was phenotyped for yield, test weight, and protein content and genotyped using the Illumina 90K SNP Assay. Population structure was confirmed using single SNPs. Haplotype blocks of 5, 10, 15, and 20 adjacent markers were constructed for all chromosomes. A multi-allelic haplotype prediction algorithm was implemented and compared with single SNPs using both k-fold cross validation and stratified sampling optimization. After confirming population structure, the stratified sampling improved the predictive ability compared with k-fold cross validation for yield and protein content, but reduced the predictive ability for test weight. In all cases, haplotype predictions outperformed single SNPs. Haplotypes of 15 adjacent markers showed the best improvement in accuracy for all traits; however, this was more pronounced in yield and protein content. The combined use of haplotypes of 15 adjacent markers and training population optimization significantly improved the predictive ability for yield and protein content by 14.3 (four percentage points) and 16.8% (seven percentage points), respectively, compared with using single SNPs and k-fold cross validation. These results emphasize the effectiveness of using haplotypes in genomic selection to increase genetic gain in self-fertilized crops. Copyright © The Author(s) 2020. Published by the Genetics Society of America.
BACKGROUND Computerised provider order entry (CPOE) systems are widely used in clinical settings for the electronic ordering of medications, laboratory tests and radiological therapies. However, evidence regarding effects of CPOE-based medication ordering on clinical and safety outcomes is mixed. We conducted an overview of systematic reviews (SRs) to characterise the cumulative effects of CPOE use for medication ordering in clinical settings. METHODS MEDLINE, EMBASE, CINAHL and the Cochrane Library were searched to identify published SRs from inception to 12 February 2018. SRs investigating the effects of the use of CPOE for medication ordering were included. Two reviewers independently extracted data and assessed the methodological quality of included SRs. RESULTS Seven SRs covering 118 primary studies were included for review. Pooled studies from the SRs in inpatient settings showed that CPOE use resulted in statistically significant decreases in medication errors and adverse drug events (ADEs); however, there was considerable variation in the magnitude of their relative risk reduction (54%-92% for errors, 35%-53% for ADEs). There was no significant relative risk reduction on hospital mortality or length of stay. Bibliographic analysis showed limited overlap (24%) among studies included across all SRs. CONCLUSION SRs on CPOEs included predominantly non-randomised controlled trials and observational studies with varying foci. SRs predominantly focused on inpatient settings and often lacked comparison groups; SRs used inconsistent definitions of outcomes, lacked descriptions regarding the effects on patient harm and did not differentiate among the levels of available decision support. With five of the seven SRs having low to moderate quality, findings from the SRs must be interpreted with caution. We discuss potential directions for future primary studies and SRs of CPOE. © Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.RNA-Puzzles is a collective endeavor dedicated to the advancement and improvement of RNA 3D structure prediction. With agreement from crystallographers, the RNA structures are predicted by various groups before the publication of the crystal structures. We now report the prediction of six RNA sequences four structures of nucleolytic ribozymes and two of riboswitches. Systematic protocols for comparing models and crystal structures are described and analyzed. In these six puzzles, we discuss a) the comparison between the automated web server and human experts; b) the prediction of coaxial stacking; c) the prediction of structural details and ligand binding; d) the development of novel prediction methods; and e) the potential improvements to be made. It is illustrated that correct coaxial stacking and tertiary contacts are key for the prediction of RNA architecture, while ligand binding modes can be only predicted with low resolution and accurate ligand binding prediction still remains out of reach. All the predicted models are available for the future development of force field parameters and the improvement of comparison and assessment tools. Published by Cold Spring Harbor Laboratory Press for the RNA Society.Nop9 is an essential factor in the processing of pre-ribosomal RNA. Its absence in yeast is lethal, and defects in the human ortholog are associated with breast cancer, autoimmunity, and learning/language impairment. PUF family RNA-binding proteins are best known for sequence-specific RNA recognition, and most contain eight α-helical repeats that bind to the RNA bases of single-stranded RNA. Nop9 is an unusual member of this family in that it contains eleven repeats and recognizes both RNA structure and sequence. Here we report a crystal structure of Saccharomyces cerevisiae Nop9 in complex with its target RNA within the 20S pre-ribosomal RNA. https://www.selleckchem.com/products/diltiazem.html This structure reveals that Nop9 brings together a C-terminal module recognizing the 5' single-stranded region of the RNA and a bifunctional N-terminal module recognizing the central double-stranded stem region. We further show that the 3' single-stranded region of the 20S target RNA adds sequence-independent binding energy to the RNA-Nop9 interaction. Both the N- and C-terminal modules retain the characteristic sequence-specific recognition of PUF proteins but the N-terminal module has also evolved a distinct interface, which allows Nop9 to recognize either single-stranded RNA sequences or RNAs with a combination of single-stranded and structured elements. Published by Cold Spring Harbor Laboratory Press for the RNA Society.The use of haplotypes may improve the accuracy of genomic prediction over single SNPs because haplotypes can better capture linkage disequilibrium and genomic similarity in different lines and may capture local high-order allelic interactions. Additionally, prediction accuracy could be improved by portraying population structure in the calibration set. A set of 383 advanced lines and cultivars that represent the diversity of the University of Minnesota wheat breeding program was phenotyped for yield, test weight, and protein content and genotyped using the Illumina 90K SNP Assay. Population structure was confirmed using single SNPs. Haplotype blocks of 5, 10, 15, and 20 adjacent markers were constructed for all chromosomes. A multi-allelic haplotype prediction algorithm was implemented and compared with single SNPs using both k-fold cross validation and stratified sampling optimization. After confirming population structure, the stratified sampling improved the predictive ability compared with k-fold cross validation for yield and protein content, but reduced the predictive ability for test weight. In all cases, haplotype predictions outperformed single SNPs. Haplotypes of 15 adjacent markers showed the best improvement in accuracy for all traits; however, this was more pronounced in yield and protein content. The combined use of haplotypes of 15 adjacent markers and training population optimization significantly improved the predictive ability for yield and protein content by 14.3 (four percentage points) and 16.8% (seven percentage points), respectively, compared with using single SNPs and k-fold cross validation. These results emphasize the effectiveness of using haplotypes in genomic selection to increase genetic gain in self-fertilized crops. Copyright © The Author(s) 2020. Published by the Genetics Society of America.0 Comments 0 Shares 5 Views 0 Reviews -
It provides an overview of detector designs; system configurations; multimodality PET imaging systems; image reconstruction and analysis tools; and an overview of research and commercially available small animal PET systems. It concludes with a look toward developing technologies/methodologies that will further enhance the impact of small animal PET imaging on medical research in the future. © 2020 Institute of Physics and Engineering in Medicine.To date, a handful of topological semimetals (TMs) with multiple types of topological nodal line (TNL) states have been theoretically predicted in novel materials. However, their TNLs are often affected by many factors, such as spin-orbit coupling (SOC) effect, strain, and the extraneous bands near the band crossing points, and therefore, the TNL states cannot be easily verified by experiments. Here, by using first-principles calculations, we report that the Pnma LiBH is a potential TM with twofold and quadruple degenerate topological nodal lines. These TNLs situate very close to the Fermi level, and do not coexist with other extraneous bands. More importantly, the TNLs of this material are very robust to the effect of SOC, uniform strain, and biaxial strain. The nontrivial band structure in LiBH produces drum-head-like surface states in the (001) surface projection. Our result reveals that LiBH material is an excellent candidate to study the multiple kinds of TNLs. © 2020 IOP Publishing Ltd.OBJECTIVE Identification of the motor area during awake craniotomy is crucial for preservation of motor function when resecting gliomas located within or close to the motor area or the pyramidal tract. Nevertheless, sometimes the surgeon cannot identify the motor area during awake craniotomy. However, the factors that influence failure to identify the motor area have not been elucidated. The aim of this study was to assess whether tumor localization was correlated with a negative cortical response in motor mapping during awake craniotomy in patients with gliomas located within or close to the motor area or pyramidal tract. METHODS Between April 2000 and May 2019 at Tokyo Women's Medical University, awake craniotomy was performed to preserve motor function in 137 patients with supratentorial glioma. Ninety-one of these patients underwent intraoperative cortical motor mapping for a primary glioma located within or close to the motor area or pyramidal tract and were enrolled in the study. MRI was used to evaluaten a supratentorial glioma is localized to the precentral gyrus. The authors' findings are important when performing awake craniotomy for glioma located within or close to the motor area or the pyramidal tract. A combination of transcortical motor evoked potential monitoring and awake craniotomy including subcortical motor mapping may be needed for removal of gliomas showing negative responses in the motor area to preserve the motor-related subcortical fibers.OBJECTIVE This prospective case-control study was conducted to examine whether spherical deconvolution (SD) can unveil microstructural abnormalities in the corticospinal tract (CST) caused by IDH-mutant gliomas. To determine the significance of abnormal microstructure, the authors investigated the correlation between diffusion parameters and neurophysiological data collected with navigated transcranial magnetic stimulation (nTMS). METHODS Twenty participants (10 patients and 10 healthy controls) were recruited. Diffusion-weighted images were acquired on a 3-T MRI scanner using a cardiac-gated single-shot spin echo echo-planar imaging multiband sequence (TE 80 msec, TR 4000 msec) along 90 diffusion directions with a b-value of 2500 sec/mm2 (FOV 256 × 256 mm). Diffusion tensor imaging tractography and SD tractography were performed with deterministic tracking. The anterior portion of the ipsilateral superior peduncle and the precentral gyrus were used as regions of interest to delineate the CST. https://www.selleckchem.com/products/sis3.html Diffusion indicphere (p = 0.038). All measurements contralateral to the glioma, except for the mean amplitude of MEPs (p = 0.001), are similar to those of healthy controls. Mean diffusivity and axial diffusivity from SD tractography are positively correlated with rMT in the hemisphere ipsilateral to glioma (p = 0.02 and 0.006, respectively). The interhemispheric difference in HMOA and rMT is correlated in glioma patients (p = 0.007). CONCLUSIONS SD tractography can demonstrate microstructural abnormality within the CST of patients with IDH1-mutant gliomas that correlates to the functional abnormality measured with nTMS.OBJECTIVE The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE). METHODS The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized. RESULTS Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12-74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 e RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006). CONCLUSIONS At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.OBJECTIVE The authors describe a novel "in-out-in" technique as an alternative option for posterior C2 screw fixation in cases that involve narrow C2 isthmus. Here, they report the preliminary radiological and clinical outcomes in 12 patients who had a minimum 12-month follow-up period. METHODS Twelve patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation. All patients had unilateral hypoplasia of the C2 isthmus that prohibited insertion of pedicle screws. A new method, the C2 medial pedicle screw (C2MPS) fixation, was used as an alternative. In this technique, the inner cortex of the narrow C2 isthmus was drilled to obtain space for screw insertion, such that the lateral cortex could be well preserved and the risk of vertebral artery injury could be largely reduced. The C2MPS traveled along the drilled inner cortex into the anterior vertebral body, achieving a 3-column fixation of the axis with multicortical purchase. RESULTS Satisfactory C2MPS placement and reduction were achieved in all 12 patients.
It provides an overview of detector designs; system configurations; multimodality PET imaging systems; image reconstruction and analysis tools; and an overview of research and commercially available small animal PET systems. It concludes with a look toward developing technologies/methodologies that will further enhance the impact of small animal PET imaging on medical research in the future. © 2020 Institute of Physics and Engineering in Medicine.To date, a handful of topological semimetals (TMs) with multiple types of topological nodal line (TNL) states have been theoretically predicted in novel materials. However, their TNLs are often affected by many factors, such as spin-orbit coupling (SOC) effect, strain, and the extraneous bands near the band crossing points, and therefore, the TNL states cannot be easily verified by experiments. Here, by using first-principles calculations, we report that the Pnma LiBH is a potential TM with twofold and quadruple degenerate topological nodal lines. These TNLs situate very close to the Fermi level, and do not coexist with other extraneous bands. More importantly, the TNLs of this material are very robust to the effect of SOC, uniform strain, and biaxial strain. The nontrivial band structure in LiBH produces drum-head-like surface states in the (001) surface projection. Our result reveals that LiBH material is an excellent candidate to study the multiple kinds of TNLs. © 2020 IOP Publishing Ltd.OBJECTIVE Identification of the motor area during awake craniotomy is crucial for preservation of motor function when resecting gliomas located within or close to the motor area or the pyramidal tract. Nevertheless, sometimes the surgeon cannot identify the motor area during awake craniotomy. However, the factors that influence failure to identify the motor area have not been elucidated. The aim of this study was to assess whether tumor localization was correlated with a negative cortical response in motor mapping during awake craniotomy in patients with gliomas located within or close to the motor area or pyramidal tract. METHODS Between April 2000 and May 2019 at Tokyo Women's Medical University, awake craniotomy was performed to preserve motor function in 137 patients with supratentorial glioma. Ninety-one of these patients underwent intraoperative cortical motor mapping for a primary glioma located within or close to the motor area or pyramidal tract and were enrolled in the study. MRI was used to evaluaten a supratentorial glioma is localized to the precentral gyrus. The authors' findings are important when performing awake craniotomy for glioma located within or close to the motor area or the pyramidal tract. A combination of transcortical motor evoked potential monitoring and awake craniotomy including subcortical motor mapping may be needed for removal of gliomas showing negative responses in the motor area to preserve the motor-related subcortical fibers.OBJECTIVE This prospective case-control study was conducted to examine whether spherical deconvolution (SD) can unveil microstructural abnormalities in the corticospinal tract (CST) caused by IDH-mutant gliomas. To determine the significance of abnormal microstructure, the authors investigated the correlation between diffusion parameters and neurophysiological data collected with navigated transcranial magnetic stimulation (nTMS). METHODS Twenty participants (10 patients and 10 healthy controls) were recruited. Diffusion-weighted images were acquired on a 3-T MRI scanner using a cardiac-gated single-shot spin echo echo-planar imaging multiband sequence (TE 80 msec, TR 4000 msec) along 90 diffusion directions with a b-value of 2500 sec/mm2 (FOV 256 × 256 mm). Diffusion tensor imaging tractography and SD tractography were performed with deterministic tracking. The anterior portion of the ipsilateral superior peduncle and the precentral gyrus were used as regions of interest to delineate the CST. https://www.selleckchem.com/products/sis3.html Diffusion indicphere (p = 0.038). All measurements contralateral to the glioma, except for the mean amplitude of MEPs (p = 0.001), are similar to those of healthy controls. Mean diffusivity and axial diffusivity from SD tractography are positively correlated with rMT in the hemisphere ipsilateral to glioma (p = 0.02 and 0.006, respectively). The interhemispheric difference in HMOA and rMT is correlated in glioma patients (p = 0.007). CONCLUSIONS SD tractography can demonstrate microstructural abnormality within the CST of patients with IDH1-mutant gliomas that correlates to the functional abnormality measured with nTMS.OBJECTIVE The authors sought to describe the long-term recurrence patterns, prognostic factors, and effect of adjuvant or salvage radiotherapy (RT) on treatment outcomes for patients with spinal myxopapillary ependymoma (MPE). METHODS The authors reviewed a tertiary institution IRB-approved database and collected data regarding patient, tumor, and treatment characteristics for all patients treated consecutively from 1974 to 2015 for histologically confirmed spinal MPE. Key outcomes included relapse-free survival (RFS), postrecurrence RFS, failure patterns, and influence of timing of RT on recurrence patterns. Cox proportional hazards regression and Kaplan-Meier analyses were utilized. RESULTS Of the 59 patients included in the study, the median age at initial surgery was 34 years (range 12-74 years), 30 patients (51%) were female, and the most common presenting symptom was pain (n = 52, 88%). Extent of resection at diagnosis was gross-total resection (GTR) in 39 patients (66%), subtotal resection (STR) in 15 e RFS (median 9.5 years vs 1.6 years; log-rank, p = 0.006). CONCLUSIONS At initial diagnosis of spinal MPE, GTR is key to long-term RFS, with no benefit to immediate adjuvant RT observed in this series. RT at the time of recurrence, however, is associated with a significantly longer time to second disease recurrence. Surveillance imaging of the entire neuraxis remains crucial, as distant failure is not uncommon in this patient population.OBJECTIVE The authors describe a novel "in-out-in" technique as an alternative option for posterior C2 screw fixation in cases that involve narrow C2 isthmus. Here, they report the preliminary radiological and clinical outcomes in 12 patients who had a minimum 12-month follow-up period. METHODS Twelve patients with basilar invagination and atlantoaxial dislocation underwent atlantoaxial reduction and fixation. All patients had unilateral hypoplasia of the C2 isthmus that prohibited insertion of pedicle screws. A new method, the C2 medial pedicle screw (C2MPS) fixation, was used as an alternative. In this technique, the inner cortex of the narrow C2 isthmus was drilled to obtain space for screw insertion, such that the lateral cortex could be well preserved and the risk of vertebral artery injury could be largely reduced. The C2MPS traveled along the drilled inner cortex into the anterior vertebral body, achieving a 3-column fixation of the axis with multicortical purchase. RESULTS Satisfactory C2MPS placement and reduction were achieved in all 12 patients.0 Comments 0 Shares 4 Views 0 Reviews
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