Enigmatic missense mutations can cause disease via creation of de novo nuclear export signals.

Disease-causing missense mutations that occur within structurally and functionally unannotated protein regions can guide researchers to new mechanisms of protein regulation and dysfunction. Here, we report that the thrombocytopenia-, myelodysplastic syndromes-, and leukemia-associated P214L mutation in the transcriptional regulator ETV6 creates an XPO1-dependent nuclear export signal to cause protein mislocalization. Strategies to disrupt XPO1 activity fully restore ETV6 P214L protein nuclear localization and transcription regulation activity. Mechanistic insight inspired the design of a 'humanized' ETV6 mice, which we employ to demonstrate that the germline P214L mutation is sufficient to elicit severe defects in thrombopoiesis and hematopoietic stem cell maintenance. Beyond ETV6, we employed computational methods to uncover rare disease-associated missense mutations in unrelated proteins that create a nuclear export signal to disrupt protein function. Thus, missense mutations that operate through this mechanism should be predictable and may suggest rational therapeutic strategies for associated diseases.

Assessment of Various Post Systems' Fracture Resistance after Endodontic Treatment.

Objectives: The study's objective is to evaluate the fracture resistance of a tooth that has had endodontic treatment and has been rebuilt using various post and core systems. Materials and Methods: Thirty-six extracted premolar teeth of similar sizes were picked, and at random, they were separated into three groups: group A received stainless-steel posts, group B received zirconia fiber posts, and group C received glass fiber posts. Dual-cured resin cement was used to cement each post. The acrylic resin blocks have samples imbedded in them. Additionally, fracture loads were measured while a compressive force was given to the tooth at a crosshead speed of 1 mm/minute. The one-way analysis of variance F-test and post hoc Tukey's test were then used to analyze the results. Results: When the mean values and standard deviation were compared, it was found that glass fiber posts had the highest fracture resistance, followed by posts made of zirconia fiber, while stainless-steel posts had the lowest fracture resistance. Conclusion: When compared to zirconia posts and stainless-steel posts, glass fiber posts had the highest level of fracture resistance.

Epidermal growth factor receptor-dependent maintenance of cardiac contractility.

AIMS: Epidermal growth factor receptor (EGFR) is essential to the development of multiple tissues and organs and is a target of cancer therapeutics. Due to the embryonic lethality of global EGFR deletion and conflicting reports of cardiac-overexpressed EGFR mutants, its specific impact on the adult heart, normally or in response to chronic stress, has not been established. Using complimentary genetic strategies to modulate cardiomyocyte-specific EGFR expression, we aim to define its role in the regulation of cardiac function and remodelling. METHODS AND RESULTS: A floxed EGFR mouse model with α-myosin heavy chain-Cre-mediated cardiomyocyte-specific EGFR downregulation (CM-EGFR-KD mice) developed contractile dysfunction by 9 weeks of age, marked by impaired diastolic relaxation, as monitored via echocardiographic, haemodynamic, and isolated cardiomyocyte contractility analyses. This contractile defect was maintained over time without overt cardiac remodelling until 10 months of age, after which the mice ultimately developed severe heart failure and reduced lifespan. Acute downregulation of EGFR in adult floxed EGFR mice with adeno-associated virus 9 (AAV9)-encoded Cre with a cardiac troponin T promoter (AAV9-cTnT-Cre) recapitulated the CM-EGFR-KD phenotype, while AAV9-cTnT-EGFR treatment of adult CM-EGFR-KD mice rescued the phenotype. Notably, chronic administration of the ß-adrenergic receptor agonist isoproterenol effectively and reversibly compensated for the contractile dysfunction in the absence of cardiomyocyte hypertrophy in CM-EGFR-KD mice. Mechanistically, EGFR downregulation reduced the expression of protein phosphatase 2A regulatory subunit Ppp2r3a/PR72, which was associated with decreased phosphorylation of phospholamban and Ca2+ clearance, and whose re-expression via AAV9-cTnT-PR72 rescued the CM-EGFR-KD phenotype. CONCLUSIONS: Altogether, our study highlights a previously unrecognized role for EGFR in maintaining contractile homeostasis under physiologic conditions in the adult heart via regulation of PR72 expression.

Adherence to self-administered biologic disease-modifying antirheumatic drugs across health-system specialty pharmacies.

PURPOSE: Adherence to self-administered biologic disease-modifying antirheumatic drugs (bDMARDs) is necessary for therapeutic benefit. Health-system specialty pharmacies (HSSPs) have reported high adherence rates across several disease states; however, adherence outcomes in rheumatoid arthritis (RA) populations have not yet been established. METHODS: We performed a multisite retrospective cohort study including patients with RA and 3 or more documented dispenses of bDMARDs from January through December 2018. Pharmacy claims were used to calculate proportion of days covered (PDC). Electronic health records of patients with a PDC of <0.8 were reviewed to identify reasons for gaps in pharmacy claims (true nonadherence or appropriate treatment holds). Outcomes included median PDC across sites, reasons for treatment gaps in patients with a PDC of <0.8, and the impact of adjusting PDC when accounting for appropriate therapy gaps. RESULTS: There were 29,994 prescriptions for 3,530 patients across 20 sites. The patient cohort was mostly female (75%), with a median age of 55 years (interquartile range [IQR], 42-63 years). The median PDC prior to chart review was 0.94 (IQR, 0.83-0.99). Upon review, 327 patients had no appropriate treatment gaps identified, 6 patients were excluded due to multiple unquantifiable appropriate gaps, and 420 patients had an adjustment in the PDC denominator due to appropriate treatment gaps (43 instances of days' supply adjusted based on discordant days' supply information between prescriptions and physician administration instructions, 11 instances of missing fills added, and 421 instances of clinically appropriate treatment gaps). The final median PDC after accounting for appropriate gaps in therapy was 0.95 (IQR, 0.87-0.99). CONCLUSION: This large, multisite retrospective cohort study was the first to demonstrate adherence rates across several HSSPs and provided novel insights into rates and reasons for appropriate gaps in therapy.

Comprehensive Knowledge and Preparedness among Dental Community to Confront COVID-19-A Multicentric Cross-Sectional Study.

The healthcare policy changes need to be updated for better management of the COVID-19 outbreak; hence, there is an urgent need to understand the knowledge and preparedness of healthcare workers regarding the infection control COVID-19. Therefore, the present study aims to assess the knowledge and preparedness towards COVID-19 among dentists, undergraduate, and postgraduates in dental universities one year after the COVID-19 outbreak. The multi-centric cross-sectional study was conducted by evaluating 395 structured, pre-coded, and validated questionnaires obtained from sample units comprising full-time dental students (undergraduates, interns, and postgraduates) and dentists who were currently in practice and who were able to comprehend the languages English or Arabic. The first part of the questionnaire included questions related to demographic characteristics. The second part of the survey consisted of questions that address knowledge concerning COVID-19. The third part of the survey addressed questions based on the preparedness to fight against COVID-19 including sharp injuries during this period. Comparing the knowledge scores of dentists, dental undergraduates, and postgraduates using the ANOVA test, dentists have higher knowledge and preparedness scores than postgraduates and undergraduates (p-value < 0.05). Univariate logistic regression analysis demonstrated that undergraduates and postgraduates were 2.567 and 1.352 times less aware of the personal protective measures against COVID-19 than dentists, respectively. Dentists had the comparatively better perception in knowledge and awareness of COVID-19 than undergraduates and postgraduates.

ß2-Adrenergic Receptors Increase Cardiac Fibroblast Proliferation Through the Gαs/ERK1/2-Dependent Secretion of Interleukin-6.

Fibroblasts are an important resident cell population in the heart involved in maintaining homeostasis and structure during normal conditions. They are also crucial in disease states for sensing signals and initiating the appropriate repair responses to maintain the structural integrity of the heart. This sentinel role of cardiac fibroblasts occurs, in part, through their ability to secrete cytokines. ß-adrenergic receptors (ßAR) are also critical regulators of cardiac function in the normal and diseased state and a major therapeutic target clinically. ßAR are known to influence cytokine secretion in various cell types and they have been shown to be involved in cytokine production in the heart, but their role in regulating cytokine production in cardiac fibroblasts is not well understood. Thus, we hypothesized that ßAR activation on cardiac fibroblasts modulates cytokine production to influence fibroblast function. Using primary fibroblast cultures from neonatal rats and adult mice, increased interleukin (IL)-6 expression and secretion occurred following ß2AR activation. The use of pharmacological inhibitors and genetic manipulations showed that IL-6 elevations occurred through the Gαs-mediated activation of ERK1/2 and resulted in increased fibroblast proliferation. In vivo, a lack of ß2AR resulted in increased infarct size following myocardial infarction and impaired wound closure in a murine dermal wound healing assay. These findings identify an important role for ß2AR in regulating fibroblast proliferation through Gαs/ERK1/2-dependent alterations in IL-6 and may lead to the development of improved heart failure therapies through targeting fibrotic function of ß2AR.

The Dynamic Interplay Between Cardiac Inflammation and Fibrosis.

Heart failure is a leading cause of death worldwide. While there are multiple etiologies contributing to the development of heart failure, all cause result in impairments in cardiac function that is characterized by changes in cardiac remodeling and compliance. Fibrosis is associated with nearly all forms of heart failure and is an important contributor to disease pathogenesis. Inflammation also plays a critical role in the heart and there is a large degree of interconnectedness between the inflammatory and fibrotic response. This review discusses the cellular and molecular mechanisms contributing to inflammation and fibrosis and the interplay between the two.

Two-dimensional Periapical, Panoramic Radiography Versus Three-dimensional Cone-beam Computed Tomography in the Detection of Periapical Lesion After Endodontic Treatment: A Systematic Review.

Radiographic imaging is a common resource for endodontic diagnosis, treatment, and prognosis. Two-dimensional (2D) periapical and digital panoramic radiographs often showed image distortion; this issue was resolved with the emergence of three-dimensional (3D) cone-beam computed tomography (CBCT). This review examines the accuracy of various radiographic techniques in the assessment of periapical lesion after endodontic treatment. Our goal was to determine whether a 2D radiograph (periapical and panoramic) is as accurate as a 3D radiograph (i.e., CBCT) in the assessment of periapical lesion after endodontic treatment. We searched the electronic databases Medline and Cochrane and trial registries for ongoing trials. We included both retrospective and prospective studies comparing the efficacy of periapical healing with various radiographic techniques after endodontic treatment. The outcome of interest was the percentage detection of periapical lesions and periapical healing assessment after endodontic treatment. All data were collected using a specially designed extraction form. We assessed the risk of bias in the studies using the Cochrane tool for diagnostic tests (QUADAS). We judged two studies to be at low risk and two to be at moderate risk of bias. Although there was a difference in the percentage detection of periapical healing efficacy by various radiographic techniques, all studies reported that CBCT had higher accuracy in the detection of periapical lesions compared to periapical and panoramic radiography. The next best choice is periapical radiographs, followed by panoramic radiographs as they provide better visualization and accuracy.

Prevalence and Characteristics of Three-rooted Mandibular Molars in Saudi Population: A Retrospective Radiographic Analysis.

AIMS: To study the prevalence of three-rooted mandibular permanent first molars (PFM) among Saudi population in Al Zulfi. MATERIALS AND METHODS: Subjects were selected from the patients' records, College of Dentistry, Majmaah University, Al Zulfi, Kingdom of Saudi Arabia. Healthy patients with the presence of both mandibular PFM, orthopantomogram (OPG) and/or intraoral periapical (IOPA) radiographs were included in the study. All patients included were evaluated by a single examiner using OPG and IOPA radiographs. The occurrence of three roots, status of the tooth and associated anomalies were considered for analysis. Descriptive statistics performed using IBM SPSS (Version 21.0) at a 95% confidence interval (p < 0.05) while the Chi-square test and Fisher test were used for the incidence, and comparison of occurrence of the third root in PFM in the mandibular arch. RESULTS: A sample of 433 subjects was selected randomly based on our inclusion criteria. Only 24 (5.5%) subjects had evidence of three-rooted mandibular PFM with the mean age of 27.67 years. The frequency of bilateral and unilateral three-rooted mandibular PFM was 2.3% (10) and 3.2% (14), respectively. Overall 41.6% of subjects were witnessed with the bilateral occurrence and unilateral occurrence was 58.4% [(57% (8) were on the right and 42% (6) were left side] (p < 0.05). However, no significant relationship was observed between the left and right occurrence of three-rooted mandibular PFM (p < 0.05). Thirty-four (7.8%) PFM were presented with three roots and among them, 70% (24) received treatment. Dilacerations (12.5%), taurodontism (37%) and hypodontia (4%) were associated with three-rooted PFM in the mandibular arch. Kappa statistics showed excellent intra-examiner reliability (κ = 0.9). CONCLUSION: The prevalence of three-rooted PFM was 5.5% in the present study and unilateral occurrence is very common. Over 70% of these PFM received dental treatment in Saudi Arabia population. Always, IOPA radiographs are required to confirm the evidence of three-rooted mandibular PFM where three-dimensional imaging is not available. CLINICAL SIGNIFICANCE: An Eagle's eye of an endodontist on three-rooted PFM is of utmost importance in the treatment protocol when the tooth is planned for root canal therapy.

Prevalence of Periodontal Disease among Obese Young Adult Population in Saudi Arabia-A Cross-Sectional Study.

Background and objectives: We aimed to assess the prevalence of periodontal disease among obese young adults in Saudi Arabia and to analyze the association between different body mass indexes and the severity of periodontal disease. Materials and methods: This descriptive cross-sectional study consisted of 307 obese patients aged 18-39 years, with body mass index (BMI) ≥30. Demographic variables for periodontal disease, anthropometric parameters such as BMI along with clinical parameters such as oral hygiene index-simplified, community periodontal index (CPI) score and loss of attachment (LOA), were assessed. Multivariate binary logistic regression analysis was used to identify the predictors for chronic periodontitis in obese young adults between 18-40 years of age. Results: The majority of the participants (71.3%) had periodontal disease. Obese and extremely obese patients together showed a statistically significant difference in the age group of 21-30 years in terms of CPI score for inflammation (p < 0.05) and LOA (p < 0.001). Logistic regression analysis showed age (OR: 3.180; 95%CL: 1.337-7.561; p <.001), occasional dental visit (OR: 5.965; 95%CL: 3.130-11.368; p < 0.001), smoking >10 cigarettes (OR: 11.868; 95%CL: 3.588-39.254; p < 0.001) and poor oral hygiene status (OR: 17.250; 95%CL: 6.958-42.764; p < 0.001) were associated with a significantly higher risk of having periodontal disease. Conclusions: This study showed a high prevalence of periodontal disease in obese patients among the Saudi Arabian population.

Death receptor 5 contributes to cardiomyocyte hypertrophy through epidermal growth factor receptor transactivation.

Cardiomyocyte survival and death contributes to many cardiac diseases. A common mechanism of cardiomyocyte death is through apoptosis however, numerous death receptors (DR) have been virtually unstudied in the context of cardiovascular disease. Previous studies have identified TNF-related apoptosis inducing ligand (TRAIL) and its receptor, DR5, as being altered in a chronic catecholamine administration model of heart failure, and suggest a role of non-canonical signaling in cardiomyocytes. Furthermore, multiple clinical studies have identified TRAIL or DR5 as biomarkers in the prediction of severity and mortality following myocardial infarction and in heart failure development risk suggesting a role of DR5 signaling in the heart. While TRAIL/DR5 have been extensively studied as a potential cancer therapeutic due to their ability to selectively activate apoptosis in cancer cells, TRAIL and DR5 are highly expressed in the heart where their function is uncharacterized. However, many non-transformed cell types are resistant to TRAIL-induced apoptosis suggesting non-canonical functions in non-cancerous cell types. Our goal was to determine the role of DR5 in the heart with the hypothesis that DR5 does not induce cardiomyocyte apoptosis but initiates non-canonical signaling to promote cardiomyocyte growth and survival. Histological analysis of hearts from mice treated with a DR5 agonists showed increased hypertrophy with no differences in cardiomyocyte death, fibrosis or function. Mechanistic studies in the heart and isolated cardiomyocytes identified ERK1/2 activation with DR5 agonist treatment which contributed to hypertrophy. Furthermore, epidermal growth factor receptor (EGFR) was activated following DR5 agonist treatment through activation of MMP and HB-EGFR cleavage and specific inhibitors of MMP and EGFR prevented DR5-mediated ERK1/2 signaling and hypertrophy. Taken together, these studies identify a previously unidentified role for DR5 in the heart, which does not promote apoptosis but acts through non-canonical MMP-EGFR-ERK1/2 signaling mechanisms to contribute to cardiomyocyte hypertrophy.

Prior ß-blocker treatment decreases leukocyte responsiveness to injury.

Following injury, leukocytes are released from hematopoietic organs and migrate to the site of damage to regulate tissue inflammation and repair, however leukocytes lacking ß2-adrenergic receptor (ß2AR) expression have marked impairments in these processes. ß-blockade is a common strategy for the treatment of many cardiovascular etiologies, therefore the objective of our study was to assess the impact of prior ß-blocker treatment on baseline leukocyte parameters and their responsiveness to acute injury. In a temporal and ßAR isoform-dependent manner, chronic ß-blocker infusion increased splenic vascular cell adhesion molecule-1 (VCAM-1) expression and leukocyte accumulation (monocytes/macrophages, mast cells and neutrophils) and decreased chemokine receptor 2 (CCR2) expression, migration of bone marrow cells (BMC) and peripheral blood leukocytes (PBL), as well as infiltration into the heart following acute cardiac injury. Further, CCR2 expression and migratory responsiveness was significantly reduced in the PBL of patients receiving ß-blocker therapy compared to ß-blocker-naïve patients. These results highlight the ability of chronic ß-blocker treatment to alter baseline leukocyte characteristics that decrease their responsiveness to acute injury and suggest that prior ß-blockade may act to reduce the severity of innate immune responses.

Clinical performance of resin-modified glass ionomer cement, flowable composite, and polyacid-modified resin composite in noncarious cervical lesions: One-year follow-up.

BACKGROUND: The restoration of noncarious cervical lesions (NCCLs) often poses a challenge to the clinician. Various restorative materials are available in the market for the restoration of the same. Each material has various advantages and shortcomings. AIM: The aim of this study was to compare and to evaluate the clinical performance of capsulated resin-modified glass ionomer cement (RMGIC), flowable composite, and polyacid-modified composite resin (PMCR) in NCCLs. MATERIALS AND METHODS: A total of 101 restorations were placed among healthy controls in this clinical trial. A total of 101 restorations were divided into three groups with n = minimum 32 per group (Group 1: 33 restorations, Group 2: 34 restorations, and Group 3: 34 restorations). The restorative materials used were capsulated RMGIC, flowable composite and PMCR. After the placement, the restorations were evaluated for the United States Public Health Services criteria for six parameters, namely retention, marginal adaptation, marginal discoloration, color stability, surface roughness, and sensitivity. The restorations were evaluated at baseline, 6 and 12 months. STATISTICAL ANALYSIS: Statistics was performed using SPSS 21.0 version. Chi-square test was done to compare the proportions between groups. Fisher's exact test was used to compare proportion change between time points. RESULTS: There was no statistically significant difference seen among the three groups for retention, color stability, surface roughness, and hypersensitivity. RMGIC had shown superior characteristics in marginal adaptation and marginal discoloration compared to flowable composite and PMCR, and the difference was statistically significant. CONCLUSION: Within the limitations of this study, all the three restorative materials are clinically acceptable for the restoration of NCCLs. RMGIC is superior regarding marginal adaptation and esthetics for restoring NCCLs.

Pepducin-mediated cardioprotection via ß-arrestin-biased ß2-adrenergic receptor-specific signaling.

Reperfusion as a therapeutic intervention for acute myocardial infarction-induced cardiac injury itself induces further cardiomyocyte death. ß-arrestin (ßarr)-biased ß-adrenergic receptor (ßAR) activation promotes survival signaling responses in vitro; thus, we hypothesize that this pathway can mitigate cardiomyocyte death at the time of reperfusion to better preserve function. However, a lack of efficacious ßarr-biased orthosteric small molecules has prevented investigation into whether this pathway relays protection against ischemic injury in vivo. We recently demonstrated that the pepducin ICL1-9, a small lipidated peptide fragment designed from the first intracellular loop of ß2AR, allosterically engaged pro-survival signaling cascades in a ßarr-dependent manner in vitro. Thus, in this study we tested whether ICL1-9 relays cardioprotection against ischemia/reperfusion (I/R)-induced injury in vivo. Methods: Wild-type (WT) C57BL/6, ß2AR knockout (KO), ßarr1KO and ßarr2KO mice received intracardiac injections of either ICL1-9 or a scrambled control pepducin (Scr) at the time of ischemia (30 min) followed by reperfusion for either 24 h, to assess infarct size and cardiomyocyte death, or 4 weeks, to monitor the impact of ICL1-9 on long-term cardiac structure and function. Neonatal rat ventricular myocytes (NRVM) were used to assess the impact of ICL1-9 versus Scr pepducin on cardiomyocyte survival and mitochondrial superoxide formation in response to either serum deprivation or hypoxia/reoxygenation (H/R) in vitro and to investigate the associated mechanism(s). Results: Intramyocardial injection of ICL1-9 at the time of I/R reduced infarct size, cardiomyocyte death and improved cardiac function in a ß2AR- and ßarr-dependent manner, which led to improved contractile function early and less fibrotic remodeling over time. Mechanistically, ICL1-9 attenuated mitochondrial superoxide production and promoted cardiomyocyte survival in a RhoA/ROCK-dependent manner. RhoA activation could be detected in cardiomyocytes and whole heart up to 24 h post-treatment, demonstrating the stability of ICL1-9 effects on ßarr-dependent ß2AR signaling. Conclusion: Pepducin-based allosteric modulation of ßarr-dependent ß2AR signaling represents a novel therapeutic approach to reduce reperfusion-induced cardiac injury and relay long-term cardiac remodeling benefits.

MCUR1 Is a Scaffold Factor for the MCU Complex Function and Promotes Mitochondrial Bioenergetics.

Mitochondrial Ca(2+) Uniporter (MCU)-dependent mitochondrial Ca(2+) uptake is the primary mechanism for increasing matrix Ca(2+) in most cell types. However, a limited understanding of the MCU complex assembly impedes the comprehension of the precise mechanisms underlying MCU activity. Here, we report that mouse cardiomyocytes and endothelial cells lacking MCU regulator 1 (MCUR1) have severely impaired [Ca(2+)]m uptake and IMCU current. MCUR1 binds to MCU and EMRE and function as a scaffold factor. Our protein binding analyses identified the minimal, highly conserved regions of coiled-coil domain of both MCU and MCUR1 that are necessary for heterooligomeric complex formation. Loss of MCUR1 perturbed MCU heterooligomeric complex and functions as a scaffold factor for the assembly of MCU complex. Vascular endothelial deletion of MCU and MCUR1 impaired mitochondrial bioenergetics, cell proliferation, and migration but elicited autophagy. These studies establish the existence of a MCU complex that assembles at the mitochondrial integral membrane and regulates Ca(2+)-dependent mitochondrial metabolism.

Measuring and monitoring quality in satellite echo services within critical care: an exploration of best practice.

The subspecialty of critical care echocardiography is a rapidly developing area of cardiac imaging. The United Kingdom Committee for Critical Care Echocardiography was set up in 2009 to examine the remit of echocardiography in critical care, and a successful collaboration between the British Society of Echocardiography (BSE) and the Intensive Care Society has resulted in the establishment of two new critical care accreditation processes: Focused Intensive Care Echocardiography and Advanced Critical Care Echocardiography. These accreditation processes are currently driving the development of satellite echo services within critical care departments throughout the UK. Individual practitioner - and more recently, departmental - accreditation have become well-established processes advocated by the BSE. Practitioner accreditation promotes accountability, and departmental accreditation standardises the environment in which practitioners operate. The accreditation of individual echocardiographers has been embraced by the critical care fraternity; we propose that departmental accreditation for critical care echo services be viewed in the same way. Identifying quality indicators for satellite echocardiography services within critical care areas is therefore the focus of the present quality exploration: our aim is to propose a set of parameters against which satellite critical care echo services can be benchmarked. In publishing our suggestions, we hope to stimulate debate in light of the rapid evolution of critical care echocardiography as a subspecialty practice. We suggest that our proposed parameters could be used to maintain satellite critical care service standards and to help identify departments capable of delivering high-quality services and training in critical care echocardiography.

A retrospective evaluation of fondaparinux for confirmed or suspected heparin-induced thrombocytopenia in left-ventricular-assist device patients.

BACKGROUND: Thrombotic events are a common complication of left ventricular assist device placement and warrant prophylactic anticoagulation. Heparin is the most common anticoagulant used for prophylaxis of thrombotic events in left ventricular assist device patients as a transition to oral anticoagulants but carries the risk of heparin-induced thrombocytopenia. Limited data is available for the treatment of heparin-induced thrombocytopenia in this patient population. We report an evaluation of 8 left ventricular assist device patients with suspected or confirmed HIT started on fondaparinux at the time of heparin-induced platelet-factor-4 antibody positivity. METHODS: Adult patients were reported if they were heparin-induced platelet antibody positive, tested via enzyme-linked immunusorbent assay, post-operative after left-ventricular assist device, and were initiated on fondaparinux at the time of heparin-induced platelet antibody positivity. Waiver of informed consent was granted from the institutional review board. Baseline demographics, clinical course of HIT, safety and efficacy variables were collected. RESULTS: Eight patients receiving fondaparinux were identified and included in this report. The patient group was on average 49 years old, weighing 95 kg, with calculated BMI 28.8 and consisted primarily of Caucasian males. Three patients developed new thromboses after initiation of fondaparinux for heparin-induced thrombocytopenia. Only one patient had a major bleeding event of an overt bleed after initiation of fondaparinux therapy. CONCLUSIONS: Given the lack of major bleeding in this evaluation, fondaparinux could be a potentially safe treatment option for left ventricular assist device patients that are heparin-induced platelet antibody positive pending confirmatory testing results. Given the development of new thromboses in 3 of 8 patients, concern exists about the efficacy of fondaparinux in this patient population. Significant limitations exist regarding these conclusions in this evaluation. Controlled, systematic evaluations are necessary to delineate safety and efficacy of fondaparinux for heparin-induced thrombocytopenia in this population.

Comparison of coconut water, propolis, HBSS, and milk on PDL cell survival.

Coconut water is biologically pure and sterile, with a rich presence of amino acids, proteins, vitamins, and minerals. The purpose of this study was to use a collagenase-dispase assay to investigate the potential of a new storage medium, coconut water, in comparison with propolis, Hank's balanced salt solution (HBSS), and milk in maintaining viable periodontal ligament (PDL) cells on simulated avulsed teeth. Seventy freshly extracted human teeth were divided into 4 experimental groups and 2 control groups. The positive and negative controls corresponded to 0-minute and 8-hour dry times, respectively. The experimental teeth were stored dry for 30 minutes and then immersed in 1 of the 4 media (coconut water, propolis, HBSS, and milk). The teeth were then treated with dispase grade II and collagenase for 30 minutes. The number of viable PDL cells was counted with a hemocytometer and analyzed. Statistical analysis showed that coconut water kept significantly more PDL cells viable compared with propolis, HBSS, or milk. Coconut water can be used as a superior transport medium for avulsed teeth.

A quantitative analysis of coconut water: a new storage media for avulsed teeth.

OBJECTIVE: The purpose of this study was to use a Collagenase-Dispase assay to investigate the potential of a new storage media, coconut water, in maintaining viable periodontal ligament (PDL) cells on simulated avulsed teeth. STUDY DESIGN: Fifty freshly extracted human teeth were divided into 3 experimental groups and 2 control groups. The positive and negative controls corresponded to 0 minutes and an 8-hour dry time, respectively. The experimental teeth were stored dry for 30 minutes and then immersed in 1 of the 3 media: coconut water (CW), Hank's balanced salt solution (HBSS), and milk. The teeth were then treated with Dispase grade II and Collagenase for 30 minutes. The number of viable PDL cells were counted with a hemocytometer and analyzed. RESULTS: Statistical analysis demonstrated that CW kept significantly more PDL cells viable compared to either HBSS or milk. CONCLUSION: Within the parameters of this study, it appears that CW may be better alternative to HBSS or milk in terms of maintaining PDL cell viability after avulsion and storage.