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To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2010.08.021 Byline: Santanu Chakraborty, Elaine E. Wirrig, Robert B. Hinton, Walter H. Merrill, Douglas B. Spicer, Katherine E. Yutzey Keywords: Heart valve development; Aortic valve disease; Twist1; bHLH transcription factor; Extracellular matrix; Cell proliferation Abstract: During embryogenesis the heart valves develop from undifferentiated mesenchymal endocardial cushions (EC), and activated interstitial cells of adult diseased valves share characteristics of embryonic valve progenitors. Twist1, a class II basic-helix-loop-helix (bHLH) transcription factor, is expressed during early EC development and is down-regulated later during valve remodeling. The requirements for Twist1 down-regulation in the remodeling valves and the consequences of prolonged Twist1 activity were examined in transgenic mice with persistent expression of Twist1 in developing and mature valves. Persistent Twist1 expression in the remodeling valves leads to increased valve cell proliferation, increased expression of Tbx20, and increased extracellular matrix (ECM) gene expression, characteristic of early valve progenitors. Among the ECM genes predominant in the EC, Col2a1 was identified as a direct transcriptional target of Twist1. Increased Twist1 expression also leads to dysregulation of fibrillar collagen and periostin expression, as well as enlarged hypercellular valve leaflets prior to birth. In human diseased aortic valves, increased Twist1 expression and cell proliferation are observed adjacent to nodules of calcification. Overall, these data implicate Twist1 as a critical regulator of valve development and suggest that Twist1 influences ECM production and cell proliferation during disease. Article History: Received 23 June 2010; Revised 12 August 2010; Accepted 19 August 2010

To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.ydbio.2009.11.030 Byline: Christina M. Alfieri, Jonathan Cheek, Santanu Chakraborty, Katherine E. Yutzey Keywords: Heart; Valve; Embryo; Wnt signaling; Osteogenesis Abstract: Wnt signaling mediated by [beta]-catenin has been implicated in early endocardial cushion development, but its roles in later stages of heart valve maturation and homeostasis have not been identified. Multiple Wnt ligands and pathway genes are differentially expressed during heart valve development. At E12.5, Wnt2 is expressed in cushion mesenchyme, whereas Wnt4 and Wnt9b are predominant in overlying endothelial cells. At E17.5, both Wnt3a and Wnt7b are expressed in the remodeling atrioventricular (AV) and semilunar valves. In addition, the TOPGAL Wnt reporter transgene is active throughout the developing AV and semilunar valves at E16.5, with more localized expression in the stratified valve leaflets after birth. In chicken embryo aortic valves, genes characteristic of osteogenic cell lineages including periostin, osteonectin, and Id2 are expressed specifically in the collagen-rich fibrosa layer at E14. Treatment of E14 aortic valve interstitial cells (VICs) in culture with osteogenic media results in increased expression of multiple genes associated with bone formation. Treatment of VIC with Wnt3a leads to nuclear localization of [beta]-catenin and induction of periostin and matrix gla protein but does not induce genes associated with later stages of osteogenesis. Together, these studies provide evidence for Wnt signaling as a regulator of endocardial cushion maturation as well as valve leaflet stratification, homeostasis, and pathogenesis. Author Affiliation: Division of Molecular Cardiovascular Biology, Cincinnati Children's Medical Center, ML 7020, 240 Albert Sabin Way, Cincinnati, OH 45229, USA Article History: Received 29 June 2009; Revised 23 October 2009; Accepted 13 November 2009

Cerebrovascular disease is a broad topic. This document focuses on the imaging recommendations for the varied clinical scenarios involving intracranial aneurysms, vascular malformations, and vasculitis, which all carry high risk of morbidity and mortality. Additional imaging recommendations regarding complications of these conditions, including subarachnoid hemorrhage and vasospasm, are also covered. While each variant presentation has unique imaging recommendations, the major focus of this document is neurovascular imaging techniques. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Head trauma (ie, head injury) is a significant public health concern and is a leading cause of morbidity and mortality in children and young adults. Neuroimaging plays an important role in the management of head and brain injury, which can be separated into acute (0-7 days), subacute (<3 months), then chronic (>3 months) phases. Over 75% of acute head trauma is classified as mild, of which over 75% have a normal Glasgow Coma Scale score of 15, therefore clinical practice guidelines universally recommend selective CT scanning in this patient population, which is often based on clinical decision rules. While CT is considered the first-line imaging modality for suspected intracranial injury, MRI is useful when there are persistent neurologic deficits that remain unexplained after CT, especially in the subacute or chronic phase. Regardless of time frame, head trauma with suspected vascular injury or suspected cerebrospinal fluid leak should also be evaluated with CT angiography or thin-section CT imaging of the skull base, respectively. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Degenerative disease of the central nervous system is a growing public health concern. The primary role of neuroimaging in the workup of patients with probable or possible Alzheimer disease has typically been to exclude other significant intracranial abnormalities. In general, the imaging findings in structural studies, such as MRI, are nonspecific and have limited potential in differentiating different types of dementia. Advanced imaging methods are not routinely used in community or general practices for the diagnosis or differentiation of forms of dementia. Nonetheless, in patients who have been evaluated by a dementia expert, FDG-PET helps to distinguish Alzheimer disease from frontotemporal dementia. In patients with suspected dementia with Lewy bodies, functional imaging of the dopamine transporter (ioflupane) using SPECT may be helpful. In patients with suspected normal-pressure hydrocephalus, DTPA cisternography and HMPAO SPECT/CT brain may provide assessment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Seizures and epilepsy are a set of conditions that can be challenging to diagnose, treat, and manage. This document summarizes recommendations for imaging in different clinical scenarios for a patient presenting with seizures and epilepsy. MRI of the brain is usually appropriate for each clinical scenario described with the exception of known seizures and unchanged semiology (Variant 3). In this scenario, it is unclear if any imaging would provide a benefit to patients. In the emergent situation, a noncontrast CT of the head is also usually appropriate as it can diagnose or exclude emergent findings quickly and is an alternative to MRI of the brain in these clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Seizures and epilepsy are a set of conditions that can be challenging to diagnose, treat, and manage. This document summarizes recommendations for imaging in different clinical scenarios for a patient presenting with seizures and epilepsy. MRI of the brain is usually appropriate for each clinical scenario described with the exception of known seizures and unchanged semiology (Variant 3). In this scenario, it is unclear if any imaging would provide a benefit to patients. In the emergent situation, a noncontrast CT of the head is also usually appropriate as it can diagnose or exclude emergent findings quickly and is an alternative to MRI of the brain in these clinical scenarios. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Movement disorders and neurodegenerative diseases are a variety of conditions that involve progressive neuronal degeneration, injury, or death. Establishing the correct diagnosis of a movement disorder or neurodegenerative process can be difficult due to the variable features of these conditions, unusual clinical presentations, and overlapping symptoms and characteristics. MRI has an important role in the initial assessment of these patients, although a combination of imaging and laboratory and genetic tests is often needed for complete evaluation and management. This document summarizes the imaging appropriateness data for rapidly progressive dementia, chorea, Parkinsonian syndromes, suspected neurodegeneration with brain iron accumulation, and suspected motor neuron disease. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Degenerative disease of the central nervous system is a growing public health concern. The primary role of neuroimaging in the workup of patients with probable or possible Alzheimer disease has typically been to exclude other significant intracranial abnormalities. In general, the imaging findings in structural studies, such as MRI, are nonspecific and have limited potential in differentiating different types of dementia. Advanced imaging methods are not routinely used in community or general practices for the diagnosis or differentiation of forms of dementia. Nonetheless, in patients who have been evaluated by a dementia expert, FDG-PET helps to distinguish Alzheimer disease from frontotemporal dementia. In patients with suspected dementia with Lewy bodies, functional imaging of the dopamine transporter (ioflupane) using SPECT may be helpful. In patients with suspected normal-pressure hydrocephalus, DTPA cisternography and HMPAO SPECT/CT brain may provide assessment. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Headache is one of the most common human afflictions. In most cases, headaches are benign and idiopathic, and resolve spontaneously or with minor therapeutic measures. Imaging is not required for many types of headaches. However, patients presenting with headaches in the setting of "red flags" such as head trauma, cancer, immunocompromised state, pregnancy, patients 50 years or older, related to activity or position, or with a corresponding neurological deficit, may benefit from CT, MRI, or noninvasive vascular imaging to identify a treatable cause. This publication addresses the initial imaging strategies for headaches associated with the following features: severe and sudden onset, optic disc edema, "red flags," migraine or tension-type, trigeminal autonomic origin, and chronic headaches with and without new or progressive features. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Nontraumatic neck pain is a leading cause of disability, with nearly 50% of individuals experiencing ongoing or recurrent symptoms. Radiographs are appropriate as initial imaging for cervical or neck pain in the absence of "red flag" symptoms or if there are unchanging chronic symptoms; however, spondylotic changes are commonly identified and may result in both false-positive and false-negative findings. Noncontrast CT can be complementary to radiographs for evaluation of new or changing symptoms in the setting of prior cervical spine surgery or in the assessment of extent of ossification in the posterior longitudinal ligament. Noncontrast MRI is usually appropriate for assessment of new or increasing radiculopathy due to improved nerve root definition. MRI without and with contrast is usually appropriate in patients with new or increasing cervical or neck pain or radiculopathy in the setting of suspected infection or known malignancy. Imaging may be appropriate; however, it is not always indicated for evaluation of cervicogenic headache without neurologic deficit. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Acute changes in mental status represent a broad collection of symptoms used to describe disorders in mentation and level of arousal, including the more narrowly defined diagnoses of delirium and psychosis. A wide range of precipitating factors may be responsible for symptom onset including infection, intoxication, and metabolic disorders. Neurologic causes that may be detected on neuroimaging include stroke, traumatic brain injury, nonconvulsive seizure, central nervous system infection, tumors, hydrocephalus, and inflammatory disorders. Not infrequently, two or more precipitating factors may be found. Neuroimaging with CT or MRI is usually appropriate if the clinical suspicion for an acute neurological cause is high, where the cause of symptoms is not found on initial assessment, and for patients whose symptoms do not respond appropriately to management. There was disagreement regarding the appropriateness of neuroimaging in cases where a suspected, nonneurologic cause is found on initial assessment. Neuroimaging with CT is usually appropriate for patients presenting with delirium, although the yield may be low in the absence of trauma or a focal neurological deficit. Neuroimaging with CT or MRI may be appropriate in the evaluation of new onset psychosis, although the yield may be low in the absence of a neurologic deficit. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

A palpable neck mass may be the result of neoplastic, congenital, or inflammatory disease. Older age suggests neoplasia, and a congenital etiology is more prevalent in the pediatric population. The imaging approach is based on the patient age, mass location, and clinical pulsatility. Underlying human papillomavirus-related malignancy should be considered in all age groups. Although the imaging appearance of some processes in the head and neck overlap, choosing the appropriate imaging examination may allow a specific diagnosis, or a limited differential diagnosis. Tissue sampling is indicated to confirm suspected malignancy. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

This article presents guidelines for imaging utilization in patients presenting with hearing loss or vertigo, symptoms that sometimes occur concurrently due to proximity of receptors and neural pathways responsible for hearing and balance. These guidelines take into account the superiority of CT in providing bony details and better soft-tissue resolution offered by MRI. It should be noted that a dedicated temporal bone CT rather than a head CT best achieves delineation of disease in many of these patients. Similarly, optimal assessment often requires a dedicated high-resolution protocol designed to assess temporal bone and internal auditory canals even though such a study will be requested and billed as a brain MRI. Angiographic techniques are helpful in some patients, especially in the setting of vertigo. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment. [ABSTRACT FROM AUTHOR]

Background The effectiveness of intravenous tissue plasminogen activator in the management of acute ischemic strokes diminishes significantly with time. Advanced computed tomography (CT) imaging can be helpful to identify candidates for neurointerventional procedures. We have successfully used a 320-slice Toshiba volume CT scanner since mid-2008. Other centers have forgone advanced imaging because of concerns of time delay. This study is to assess the time delay while using this scanner compared with our 64-slice scanner. Methods Treatment times of patients scanned with advanced imaging (CT head, dynamic CT angiography, and whole brain perfusion–group A) and patients scanned in a 64-slice scanner (CT head and traditional CT angiogram–group B) were compared. Two groups of stroke patients from November-March 2009-2010 (group 1) and 2012-2013 (group 2) were audited to assess temporal improvement. Multiple timing variables were analyzed. Results One hundred fifty-three cases from 2009/10 and 192 cases from 2012/13 were analyzed. The median door-to-needle time (DNT) for group 1A and group 2A was 57 minutes and 47 minutes, respectively. The median DNT for group 1B and group 2B was 54 minutes and 49 minutes, respectively. Decrease in the overall DNT with group A can be attributed to the “streamlining” of the stroke code process. There was no difference in the DNT for patients who presented during working hours versus those who presented during nonworking hours. Conclusions With adequate experience and training, advanced stroke imaging with whole brain perfusion/dynamic CT angiography can be performed with treatment times that are comparable with traditional CT scanning. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Medical Imaging & Radiation Sciences is the property of Elsevier B.V. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Abstract: This paper develops a sequential scheduling algorithm for consultation periods not divided into slots. Patients call a scheduler and request appointments with a specified provider. The scheduler provides the patient with an appointment time before the call terminates. In making the appointment, the scheduler cannot alter the appointments of previously scheduled patients. Service times are random and each scheduled patient has a probability of “no-showing” for the appointment. Each arriving patient generates a given amount of revenue, and costs are incurred from patient waiting and provider overtime. The scheduling method selects the calling patient's appointment time by minimizing the total expected cost. We prove that total expected cost is a convex function of appointment times and that the expected profit of the schedule is unimodal, which provides a unique stopping criterion for the scheduling algorithm. Computational studies compare this approach with no-show based sequential scheduling methods for out-patient clinics where a predefined slot structure is assumed. The new method yields higher expected profit and less overtime than when service periods are pre-divided into slots. Because slot scheduling is ingrained in healthcare, we use the model to design slot structures that account for no-show and service time variation. [Copyright &y& Elsevier]

Considering the importance of developing selective COX-2 inhibitors, the present paper explores selectivity requirements for COX-2 versus COX-1 binding of 3,4-diaryloxazolones using electrotopological state (E-state) index. The study also shows the utility of E-state index in developing statistically acceptable model having direct physicochemical significance: electron density distribution of different atoms of the oxazolone ring and attached two phenyl rings are important for the selective binding with COX-2 over COX-1. Moreover, the use of indicator variable shows that presence of ortho R1 substituent (except fluoro) on the N3-phenyl ring decreases COX-2 selectivity. Further, an amino substituent at R2 position (i.e., sulfonamide compound) is favorable for increasing COX-2 selectivity when the R3 position is unsubstituted. [Copyright &y& Elsevier]

The countrywide COVID-19 pandemic lockdown accomplished what aggressive plans could not do throughout the long-term cleaning of the Ganga River. Here, we illustrated Hooghly River surface water quality [physico-chemical parameters, biological parameters, dissolved heavy metals] improvement by analyzing eight sampling station before and during the lockdown. Because of shutdown of industrial units and individuals staying at home, a complete decrease in industrial wastes, contaminants, and self-purging of the stream improved significantly water quality by about 40% to 50%. Among dissolved heavy metals, the concentrations of Cd (50%), Pb (53%), demonstrated noteworthy variations during the lockdown. Diminishing trends were also observed for TDS (62%), and BOD (52%), with significant reduction in the total coliform (63%), faecal coliform (61%), notably. Principal component analysis and paired t -test signify the alteration of water quality. The study concludes that the aquatic ecosystem can be revived if wastewater, and anthropogenic activities are properly managed by environmental surveillance. [Display omitted] • Engravings of revival were seen in the surface water following pandemic lockdown. • Dissolve heavy metals have demonstrated noteworthy variation throughout lockdown. • A noticeable enhancement of DO and diminishing value of TDS, BOD, phosphate notably • Due to low wastes release and limited activities NO3, coliform reduced noticeably. • Factor analyses unravelled improvement of water quality contrast to before lockdown. [ABSTRACT FROM AUTHOR]

In the mammalian heart, fetal cardiomyocytes proliferate prior to birth; however, they exit the cell cycle shortly after birth. Recent studies show that adult cardiomyocytes re-enters the cell cycle postinjury to promote cardiac regeneration. The endoplasmic reticulum (ER) orchestrates the production and assembly of different types of proteins, and a disruption in this machinery leads to the generation of ER stress, which activates the unfolded protein response. There is a very fine balance between ER stress-mediated protective and proapoptotic responses. T-box transcription factor 20 (Tbx20) promotes embryonic and adult cardiomyocyte proliferation postinjury to restore cardiac homeostasis. However, the function and regulatory interactions of Tbx20 in ER stress-induced cardiomyopathy have not yet been reported. We show here that ER stress upregulates Tbx20, which activates downstream bone morphogenetic protein 2 (Bmp2)-pSmad1/5/8 signaling to induce cardiomyocyte proliferation and limit apoptosis. However, augmenting ER stress reverses this protective response. We also show that increased expression of tbx20 during ER stress is mediated by the activating transcription factor 6 arm of the unfolded protein response. Cardiomyocyte-specific loss of Tbx20 results in decreased cardiomyocyte proliferation and increased apoptosis. Administration of recombinant Bmp2 protein during ER stress upregulates Tbx20 leading to augmented proliferation, indicating a feed-forward loop mechanism. In in vivo ER stress, as well as in diabetic cardiomyopathy, the activity of Tbx20 is increased with concomitant increased cardiomyocyte proliferation and decreased apoptosis. These data support a critical role of Tbx20-Bmp2 signaling in promoting cardiomyocyte survival during ER stress-induced cardiomyopathies. [ABSTRACT FROM AUTHOR]

Studies evaluating the use of activated prothrombin complex concentrates (aPCCs) for DOAC-associated bleeding are sparse. We conducted a retrospective study of patients receiving aPCC for DOAC-associated bleeding or for pre-operative optimization of hemostasis prior to urgent surgery. The primary efficacy outcome was hemostatic efficacy, the primary safety outcome was the 30-day thromboembolic complication rate. Eighty-two patients were included in the analysis; 14 patients on dabigatran, 39 patients on rivaroxaban and 29 patients on apixaban. Fifty-four patients received aPCC for major bleeding and 28 patients prior to urgent surgery. Mean aPCC dosing was 2974 IU (SD ± 857 IU). Hemostasis was deemed effective by ISTH criteria in 50% of cases and "Good" or "Moderate" by Sarode criteria in 45.2% and 14.3% of cases, respectively. Surgical hemostasis was rated as "Normal" in 84% of cases pre-operative administration. Median pre-aPCC INR was 1.6 (IQR 0.5) and median post-aPCC INR was 1.2 (IQR 0.2) (p < 0.00001). Median pre-aPCC aPTT was 36 s (IQR 12.8), median post-aPCC aPTT was 29 s (IQR 9.8) (p = 0.0001). The 30-day thromboembolic event rate was 6.1%. Further study is needed to characterize the hemostatic effects and thromboembolic risk of aPCC among patients with DOAC-associated bleeding or for attempted normalization of hemostasis prior to urgent surgery. • In vitro and animal studies have shown that aPCC corrects kinetic and quantitative thrombin generation parameters. • This is a retrospective study of aPCC for the management of DOAC-associated bleeding or prior to urgent surgery. • aPCC might contribute to hemostasis among patients with DOAC-associated bleeding or needing urgent surgery. • aPCC produced significant in vivo corrections in INR and aPTT values in DOAC-treated patients. [ABSTRACT FROM AUTHOR]

Bifenthrin (BF), a synthetic pyrethroid is used worldwide for both agricultural and non-agricultural purposes due to its high insecticidal activity and low toxicity in mammals. However, its improper usage implies a possible risk to aquatic life. The study was aimed to correlate the association of BF toxicity with mitochondrial DNA copy number variation in edible fish Punitus sophore. The 96-h LC 50 of BF in P. sophore was 3.4 μg/L, fish was treated with sub-lethal doses ((⅒ and ⅕ of LC 50 ;0.34 μg/L, 0.68 μg/L) of BF for 15 days. The activity and expression level of cytochrome c oxidase (Mt-COI) were measured to assess mitochondrial dysfunction caused by BF. Results showed BF reduced the level of Mt-COI mRNA in treated groups, hindered complex IV activity and increased ROS generation leading to oxidative damage. mtDNAcn was decreased in the muscle, brain and liver after BF treatment. Furthermore, BF induced neurotoxicity in brain and muscle cells through the inhibition of AchE activity. The treated groups showed elevated level of malondialdehyde (MDA) and an imbalance of antioxidant enzymes activity. Molecular docking and simulation analysis also predicted that BF binds to the active sites of the enzyme and restricts the fluctuation of its residues. Hence, outcome of the study suggests reduction of mtDNAcn could be a potential biomarker to assess Bifenthrin induced toxicity in aquatic ecosystem. [Display omitted] • 96-h LC50 for P. sophore was 3.4 μg/L Biflex (commercial formulation of Bifenthrin). • mtDNA copy number variation was observed in different tissues of fish at sub lethal concentration of BF. • BF induced oxidative stress responses and neurotoxicity (AChE activity) evaluation in brain and muscle tissue. • Inhibition of mitochondrial complex IV activity and expression were detected at 0.34 μg/L and 0.68 μg/L of BF. • Molecular docking analysis confirmed that BF binds to the active site of complex IV. [ABSTRACT FROM AUTHOR]

Flexible electronic materials of polyaniline (PANI) chemically interacted with Na 2 S have been developed with the objective of improving and tuning its electrical transport properties and optical properties. The chemical interaction of Na 2 S with PANI was realized by the synthesis process of physical vapor polymerization of aniline over cellulose substrate. The prepared samples of PANI interacted with Na 2 S at different concentrations (3%, 5%, 7%, and 10%) have been studied through X-ray diffraction (XRD) measurement, scanning electron microscope (SEM) measurement, analysis of FTIR spectra, I-V measurement, and analysis of UV–vis–NIR absorption spectra. From XRD measurement it was observed that the peaks corresponding to the emeraldine form of PANI were obtained during polymerization, which is electrically conductive. Being partially polymerized, this form of PANI provides the scope for further functionalization through chemical interaction with Na 2 S. As a consequence of chemical interaction with Na 2 S, its resistivity was found to increase systematically with the increase of concentration of Na 2 S. A twelve times change in resistivity was recorded with Na 2 S interaction. The temperature dependence of electrical conductivity shows an excellent positive temperature coefficient of resistance, which is of profound technological significance for self-controlled overheating protection of electronic devices. [Display omitted] • Electronic materials on cellulose substrate. • Electrical charge transport modulation through Na 2 S interaction. • Control on formation of charged defect states. • Positive temperature coefficient of resistance. • Economic and scalable strategy for flexible electronics. [ABSTRACT FROM AUTHOR]

Functional nanosized two-dimensional clay mineral particles are considered as ideal host materials to manipulate the properties of incorporated organic molecules due to their high cation exchange capacity, layer structure and intercalation properties. The interlayer height of clay layers can be manipulated by simultaneous wetting and drying steps. Here, we have studied the chromatic behaviour of an organic dye generated in-situ from 1,4-di-bis-indolylmethane-benzene in the interlayer space of synthetic saponite (SSA). Initially transparent, self-standing organo-clay hybrid films become red upon heating due to aerobic oxidation suggesting in-situ generation of organic dye and increases the planarity of the intercalated organic molecules. Upon swelling the same hybrid film becomes yellow, due to the partial disturbance in the planarity of generated dye via C-C bond rotation. Simultaneous heating and swelling resulted in a reversible colour transition (clearly visible through the naked eye) between red and yellow for at least 30 cycles. This kind of system may have potential applications as a colorimetric sensor and in the field of optics (optical switching and optical memory etc). Image 1 • Synthesis of tetraindolyl derivative. • Preparation of clay mineral-tetraindolyl hybrid self-standing film. • Colour switching of hybrid film due to the change in gallery height of clay. • Colour switching was reversible with a very good stability. • Such colour switching is suitable for colorimetric sensor, optical switching, optical memory etc. [ABSTRACT FROM AUTHOR]