Molecular Evaluation of the Impact of Polymorphic Variants in Apoptotic (Bcl-2/Bax) and Proinflammatory Cytokine (TNF-α/IL-8) Genes on the Susceptibility and Progression of Myeloproliferative Neoplasms: A Case-Control Biomarker Study.

The regulation of apoptosis (the programmed cell death) is dependent on the crucial involvement of BCL2 and BAX. The Bax-248G>A and Bcl-2-938 C>A polymorphic variations in the promoter sequences of the Bax and Bcl-2 gene have been recently associated with low Bax expression, progression to advanced stages, treatment resistance, and shortened overall survival rate in some hematological malignancies, including chronic myeloid leukemia (CML) and other myeloproliferative neoplasms. Chronic inflammation has been linked to various stages of carcinogenesis wherein pro-inflammatory cytokines play diverse roles in influencing cancer microenvironment leading to cell invasion and cancer progression. Cytokines such as TNF-α and IL-8 have been implicated in cancer growth in both solid and hematological malignancies with studies showing their elevated levels in patients. Genomic approaches have in recent years provided significant knowledge with the regard to the association of certain SNPs (single nucleotide polymerphisms) either in a gene or its promoter that can influence its expression, with the risk and susceptibility to human diseases including cancer. This study has investigated the consequences of promoter SNPs in apoptosis genes Bax-248G>A (rs4645878)/Bcl-2-938C>A (rs2279115) and pro-inflammatory cytokines TNF-α rs1800629 G>A/IL-8 rs4073 T>A on the risk and susceptibility towards hematological cancers. The study design has 235 individuals both male and female enrolled as subjects that had 113 cases of MPDs (myeloproliferative disorders) and 122 healthy individuals as controls. The genotyping studies were conducted through ARMS PCR (amplification-refractory mutation system PCR). The Bcl-2-938 C>A polymorphism showed up in 22% of patients in the study, while it was observed in only 10% of normal controls. This difference in genotype and allele frequency between the two groups was significant (p = 0.025). Similarly, the Bax-248G>A polymorphism was detected in 6.48% of the patients and 4.54% of the normal controls, with a significant difference in genotype and allele frequency between the groups (p = 0.048). The results suggest that the Bcl-2-938 C>A variant is linked to an elevated risk of MPDs in the codominant, dominant, and recessive inheritance models. Moreover, the study indicated allele A as risk allele which can significantly increase the risk of MPDs unlike the C allele. In case of Bax gene covariants, these were associated with an increased risk of MPDs in the codominant inheritance model and dominant inheritance model. It was found that the allele A significantly enhanced the risk of MPDs unlike the G allele. The frequencies of IL-8 rs4073 T>A in patients was found to be TT (16.39%), AT (36.88%) and AA (46.72%), compared to controls who were more likely to have frequencies of TT (39.34%), AT (37.70%) and AA (22.95%) as such, respectively. There was a notable overrepresentation of the AA genotype and GG homozygotes among patients compared to controls in TNF-α polymorphic variants, with 6.55% of patients having the AA genotype and 84% of patients being GG homozygotes, compared to 1.63% and 69%, respectively in controls. The data from the current study provide partial but important evidence that polymorphisms in apoptotic genes Bcl-2-938C>A and Bax-248G>A and pro-inflammatory cytokines IL-8 rs4073 T>A and TNF-α G>A may help predict the clinical outcomes of patients and determine the significance of such polymorphic variations in the risk of myeloproliferative diseases and their role as prognostic markers in disease management using a case-control study approach.

Molecular Property Diagnostic Suite Compound Library (MPDS-CL): a structure-based classification of the chemical space.

Molecular Property Diagnostic Suite Compound Library (MPDS-CL) is an open-source Galaxy-based cheminformatics web portal which presents a structure-based classification of the molecules. A structure-based classification of nearly 150 million unique compounds, obtained from 42 publicly available databases and curated for redundancy removal through 97 hierarchically well-defined atom composition-based portions, has been done. These are further subjected to 56-bit fingerprint-based classification algorithm which led to the formation of 56 structurally well-defined classes. The classes thus obtained were further divided into clusters based on their molecular weight. Thus, the entire set of molecules was put into 56 different classes and 625 clusters. This led to the assignment of a unique ID, named as MPDS-AadharID, for each of these 149,169,443 molecules. MPDS-AadharID is akin to the unique number given to citizens in India (similar to SSN in the US and NINO in the UK). The unique features of MPDS-CL are (a) several search options, such as exact structure search, substructure search, property-based search, fingerprint-based search, using SMILES, InChIKey and key-in; (b) automatic generation of information for the processing for MPDS and other galaxy tools; (c) providing the class and cluster of a molecule which makes it easier and fast to search for similar molecules and (d) information related to the presence of the molecules in multiple databases. The MPDS-CL can be accessed at https://mpds.neist.res.in:8086/ .

Towards systematic exploration of chemical space: building the fragment library module in molecular property diagnostic suite.

A fragment-based drug discovery (FBDD) approach has traditionally been of utmost significance in drug design studies. It allows the exploration of large chemical space to find novel scaffolds and chemotypes which can be improved into selective inhibitors with good affinity. In the current work, several public domain chemical libraries (ChEMBL, DrugCentral, PDB ligands, COCONUT, and SAVI) comprising bioactive and virtual molecules were retrieved to develop a fragment library. A systematic fragmentation method that breaks a given molecule into rings, linkers, and substituents was used to cleave the molecules and the fragments were analyzed. Further, only the ring framework was taken into the consideration to develop a fragment library that consists of a total number of 107,614 unique fragments. This set represents a rich diverse structure framework that covers a wide variety of yet-to-be-explored fragments for a wide range of small molecule-based applications. This fragment library is an integral part of the molecular property diagnostic suite (MPDS) suite that can be used with other modeling and informatics methods for FBDD approaches. The fragment library module of MPDS can be accessed at http://mpds.neist.res.in:8085 .

Molecular property diagnostic suite for diabetes mellitus (MPDSDM): An integrated web portal for drug discovery and drug repurposing.

Molecular Property Diagnostic Suite - Diabetes Mellitus (MPDSDM) is a Galaxy-based, open source disease-specific web portal for diabetes. It consists of three modules namely (i) data library (ii) data processing and (iii) data analysis tools. The data library (target library and literature) module provide extensive and curated information about the genes involved in type 1 and type 2 diabetes onset and progression stage (available at http://www.mpds-diabetes.in). The database also contains information on drug targets, biomarkers, therapeutics and associated genes specific to type 1, and type 2 diabetes. A unique MPDS identification number has been assigned for each gene involved in diabetes mellitus and the corresponding card contains chromosomal data, gene information, protein UniProt ID, functional domains, druggability and related pathway information. One of the objectives of the web portal is to have an open source data repository that contains all information on diabetes and use this information for developing therapeutics to cure diabetes. We also make an attempt for computational drug repurposing for the validated diabetes targets. We performed virtual screening of 1455 FDA approved drugs on selected 20 type 1 and type 2 diabetes proteins using docking protocol and their biological activity was predicted using "PASS Online" server (http://www.way2drug.com/passonline) towards anti-diabetic activity, resulted in the identification of 41 drug molecules. Five drug molecules (which are earlier known for anti-malarial/microbial, anti-viral, anti-cancer, anti-pulmonary activities) were proposed to have a better repurposing potential for type 2 anti-diabetic activity and good binding affinity towards type 2 diabetes target proteins.

Chloroquine as a possible disinfection adjunct of disinfection solutions against Acanthamoeba.

Acanthamoeba keratitis is commonly encountered by contact lens wearers. Contact lens solution plays an important role in the safe use of contact lenses. The most popular products for disinfecting lenses are multipurpose disinfecting solutions (MPDS). However, almost all MPDS retailed in Korea are ineffective in killing Acanthamoeba. The objective of this study was to determine the possibility of using autophagy inhibitor chloroquine as a disinfecting agent to improve the amoebicidal activity of MPDS against Acanthamoeba, especially the cyst. Amoebicidal effects of eight different MPDSs combined with chloroquine (CQ), an autophagy inhibitor, and their cytotoxicities to human corneal epithelium cells were determined. Almost all MPDS showed strong amoebicidal effect on trophozoites after 8 h of exposure. However, they showed inadequate amoebicidal effect on cysts even after 24 h of exposure. MPDSs combined with 100 µM CQ increased their amoebicidal effects on immature cyst by inhibiting formation of mature cysts. Incubation with 100 µM CQ for 30 min did not have cytotoxicity to human corneal epithelial cells.

Effect of 2, 6-Dichlorobenzonitrile on Amoebicidal Activity of Multipurpose Contact Lens Disinfecting Solutions.

Multipurpose contact lens disinfecting solutions (MPDS) are widely used to cleanse and disinfect microorganisms. However, disinfection efficacy of these MPDS against Acanthamoeba cyst remain insufficient. 2, 6-dichlorobenzonitrile (DCB), a cellulose synthesis inhibitor, is capable of increasing the amoebical effect against Acanthamoeba by inhibiting its encystation. In this study, we investigated the possibility of DCB as a disinfecting agent to improve the amoebicidal activity of MPDS against Acanthamoeba cyst. Eight commercial MPDS (from a to h) were assessed, all of which displayed insufficient amoebicidal activity against the mature cysts. Solution e, f, and h showed strong amoebicidal effect on the immature cysts. Amoebicidal efficacy against mature cysts remained inadequate even when the 8 MPDS were combined with 100 µM DCB. However, 4 kinds of MPDS (solution d, e, f, and h) including 100 µM DCB demonstrated strong amoebicidal activity against the immature cysts. The amoebicidal activity of solution d was increased by addition of DCB. Cytotoxicity was absent in human corneal epithelial cells treated with either DCB or mixture of DCB with MPDS. These results suggested that DCB can enhance the amoebicical activity of MPDS against Acanthamoeba immature cyst in vitro.

Efficacy of Korean Multipurpose Contact Lens Disinfecting Solutions against Acanthamoeba castellanii.

Acanthamoeba keratitis has been increasing in recent years. Main risk factors are contact lens wear and their cleaning solutions. Most contact lens wearers use multipurpose disinfecting solutions (MPDS) for cleansing and disinfecting microorganisms because of its convenience. We determined amoebicidal effects of MPDS made in Korea and their cytotoxicity on human corneal epithelium cells. Fifteen commercial MPDS (A to O) were tested for their amoebicidal effects on Acanthamoeba castellanii trophozoites and cysts by using a most probable number (MPN) technique. Among them, 7 kinds of MPDS showed little or no amoebicidal effects for 24 hr exposure. Solutions A, B, G, H, L, and O showed positive amoebicidal effects, and solutions M and N killed almost all trophozoites and cysts after 24 hr exposure. However, 50%-N solution showed 56% cytotoxicity on human corneal epithelial cells within 4 hr exposure, and 50%-O solution also showed 62% cytotoxicity on human cells within 4 hr exposure. Solution A did not show any cytotoxicity on human cells. These results revealed that most MPDS made in Korea were ineffective to kill Acanthamoeba. The solutions having amoebicidal activity also showed high levels of cytotoxicity on human corneal epithelial cells. New formulations for improved MPDS that are amoebicidal but safe for host cells are needed to prevent Acanthamoeba keratitis.

The effect of reduced disclusion time in the treatment of myofascial pain dysfunction syndrome using immediate complete anterior guidance development protocol monitored by digital analysis of occlusion.

STATEMENT OF PROBLEM: Chronic myofascial pain dysfunction syndrome (MPDS) has been a nightmare for patients suffering from it, who have been treated with various treatment options with varied outcomes. This population of patients has been neglected, due to nagging revisits to a clinician and decreased percentage of success. OBJECTIVE: T-Scan-based immediate complete anterior guidance development (ICAGD) has been shown by a researcher to reduce the muscle hyperactivity consistent with MPDS. The purpose of this study is to evaluate the effect of reduced disclusion time in lateral excursions in treating the MPDS symptoms. MATERIALS AND METHODS: Fifty-one myofascial pain patients with symptoms in the area of the head and neck region were treated with ICAGD. The quantified force and time data from T-Scan records were used to correct the prolonged disclusion time, and the subjects were assessed for the symptom relief. The Wilcoxon Signed Ranks Test was used for statistical analysis (P<0·05 denotes significant changes). RESULTS: The changes in disclusion time and intensity of various symptoms were found to be statistically significant (P<0·05) from Day 1 onwards, and patients were relieved of their symptoms after reduction of disclusion time of less than 0·5 seconds. CONCLUSION: The results clearly indicated that ICAGD protocol reduces musculoskeletal-based symptoms of MPDS patients, and this protocol can prove beneficial for the clinical treatment success.

Translocation t(3;12)(q26;q21) in JAK2(V617F) Point Mutation Negative Chronic Idiopathic Myelofibrosis: A Case Report.

The myeloproliferative diseases (MPDs) or myelo-proliferative neoplasms (MPNs) are a group of diseases of the bone marrow in which excess cells are produced. Chronic idiopathic myelofibrosis (CIMF) is a stem cell defect characterized by splenomegaly with multiorgan extramedullary hematopoiesis, immature peripheral blood granulocytes and erythrocytes and progressive bone marrow fibrosis. The most common chromosomal abnormalities seen in CIMF patients include numerical changes of chromosomes 7, 8 and 9, and structural changes of 1q, 5q, 13q and 20q. At least 75.0% of patients with bone marrow abnormalities have one or more of these chromosomal anomalies. Detection of the Janus kinase 2 (JAK2) mutation may be a potential major breakthrough for understanding the pathobiology of MPNs, and is an essential part of the diagnostic algorithm. In this study, we describe a JAK2(V617F) mutation negative CIMF patient who has the chromosomal translocation t(3;12)(q26;q21) in her karyotype.

Comparison of susceptibility of Pseudomonas aeruginosa isolated from keratitis to antibiotics and multipurpose disinfecting solutions.

PURPOSE: This study aimed to assess the susceptibility of ocular isolates of Pseudomonas aeruginosa to two multi-purpose disinfectant solutions (MPDS) and to determine if there was a relationship with resistance to antibiotics. METHODS: Twenty-three strains of P. aeruginosa isolated from microbial keratitis cases in Australia were utilized in this study. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of two commercially available MPDSs, Biotrue and cleadew MPS were determined. Additionally, the MIC of the strains to five antibiotics, ciprofloxacin, levofloxacin, gentamicin, ceftazidime, and imipenem, were analyzed. RESULTS: All strains were susceptible to 100 % of each of the MPDS. However, when MPDSs were diluted, cleadew MPS had significantly lower median MIC (median = 12.5 vs 25; p = 0.00008) and MBC (median = 25 vs 50; p = 0.0027) compared to Biotrue. All tested strains were susceptible to levofloxacin and gentamicin. Susceptibility rates to ciprofloxacin, imipenem, and ceftazidime were 52.2 %, 30.4 %, and 91.3 %, respectively. There were no significant relations between MIC or MBC to either MPDS and resistance to the antibiotics (p≧0.23). CONCLUSION: Both MPDSs were active against P. aeruginosa isolated from microbial keratitis in Australia. However, after dilution, cleadew MPS remained active against P. aeruginosa at lower concentrations. Certain strains of P. aeruginosa were resistant to imipenem, ceftazidime or ciprofloxacin. The lack of association of susceptibility to MPDS and antibiotics suggest that resistance to one did not predispose to resistance to the other.

Galaxy for open-source computational drug discovery solutions.

INTRODUCTION: Drug discovery in academia and industry poses contrasting challenges. While academia focuses on producing new knowledge, industry is keen on product development and success in clinical trials. Galaxy is a web-based open-source computational workbench which is used to analyze large datasets and is customized to integrate analysis and visualization tools in a single framework. Depending on the methodology, one can generate customized and suitable workflows in the Galaxy platform. AREAS COVERED: Herein, the authors appraise the suitability of the Galaxy platform for developing a disease specific web portal called the Molecular Property Diagnostic Suite (MPDS). The authors include their future perspectives in the expert opinion section. EXPERT OPINION: Galaxy is ideally suited for community-based software development as the scripts, tools, and codes developed in the different programming languages can be integrated in an extremely efficient fashion. MPDS puts forth a new approach known as a disease-specific web portal which aims to implement a range of computational methods and algorithms that can be developed and shared freely across the community of computer aided drug design (CADD) scientists.

Assessment of telecommunicator cardiopulmonary resuscitation performance during out-of-hospital cardiac arrest using a standardized tool for audio review.

OBJECTIVE: Telecommunicator cardiopulmonary resuscitation (T-CPR) is a critical component of optimized out-of-hospital cardiac arrest (OHCA) care. We assessed a pilot tool to capture American Heart Association (AHA) T-CPR measures and T-CPR coaching by telecommunicators using audio review. METHODS: Using a pilot tool, we conducted a retrospective review of 911 call audio from 65 emergency medical services-treated out-of-hospital cardiac arrest (OHCA) patients. Data collection included events (e.g., OHCA recognition), time intervals, and coaching quality measures. We calculated summary statistics for all performance and quality measures. RESULTS: Among 65 cases, the patients' mean age was 64.7 years (SD: 14.6) and 17 (26.2%) were women. Telecommunicator recognition occurred in 72% of cases (47/65). Among 18 non-recognized cases, reviewers determined 12 (66%) were not recognizable based on characteristics of the call. Median time-to-recognition was 76 seconds (n = 40; IQR:39-138), while median time-to-first-instructed-compression was 198 seconds (n = 26; IQR:149-233). In 36 cases where coaching was needed, coaching on compression-depth occurred in 27 (75%); -rate in 28 (78%); and chest recoil in 10 (28%) instances. In 30 cases where repositioning was needed, instruction to position the patient's body flat occurred in 18 (60%) instances, on-back in 22 (73%) instances, and on-ground in 22 (73%) instances. CONCLUSIONS: Successful collection of data to calculate AHA T-CPR measures using a pilot tool for audio review revealed performance near AHA benchmarks, although coaching instructions did not occur in many instances. Application of this standardized tool may aid in T-CPR quality review.

Susceptibility of Ocular Staphylococcus aureus to Antibiotics and Multipurpose Disinfecting Solutions.

Staphylococcus aureus is a frequent cause of ocular surface infections worldwide. Of these surface infections, those involving the cornea (microbial keratitis) are most sight-threatening. S. aureus can also cause conjunctivitis and contact lens-related non-infectious corneal infiltrative events (niCIE). The aim of this study was to determine the rates of resistance of S. aureus isolates to antibiotics and disinfecting solutions from these different ocular surface conditions. In total, 63 S. aureus strains from the USA and Australia were evaluated; 14 were from niCIE, 26 from conjunctivitis, and 23 from microbial keratitis (MK). The minimum inhibitory (MIC) and minimum bactericidal concentrations (MBC) of all the strains to ciprofloxacin, ceftazidime, oxacillin, gentamicin, vancomycin, chloramphenicol, azithromycin, and polymyxin B were determined. The MIC and MBC of the niCIE strains to contact lens multipurpose disinfectant solutions (MPDSs) was determined. All isolates were susceptible to vancomycin (100%). The susceptibility to other antibiotics decreased in the following order: gentamicin (98%), chloramphenicol (76%), oxacillin (74%), ciprofloxacin (46%), ceftazidime (11%), azithromycin (8%), and polymyxin B (8%). In total, 87% of all the isolates were multidrug resistant and 17% of the isolates from microbial keratitis were extensively drug resistant. The microbial keratitis strains from Australia were usually susceptible to ciprofloxacin (57% vs. 11%; p = 0.04) and oxacillin (93% vs. 11%; p = 0.02) compared to microbial keratitis isolates from the USA. Microbial keratitis isolates from the USA were less susceptible (55%) to chloramphenicol compared to conjunctivitis strains (95%; p = 0.01). Similarly, 75% of conjunctivitis strains from Australia were susceptible to chloramphenicol compared to 14% of microbial keratitis strains (p = 0.04). Most (93%) strains isolated from contact lens wearers were killed in 100% MPDS, except S. aureus 27. OPTI-FREE PureMoist was the most active MPDS against all strains with 35% of strains having an MIC ≤ 11.36%. There was a significant difference in susceptibility between OPTI-FREE PureMoist and Biotrue (p = 0.02). S. aureus non-infectious CIE strains were more susceptible to antibiotics than conjunctivitis strains and conjunctivitis strains were more susceptible than microbial keratitis strains. Microbial keratitis strains from Australia (isolated between 2006 and 2018) were more susceptible to antibiotics in comparison with microbial keratitis strains from the USA (isolated in 2004). Most of the strains were multidrug-resistant. There was variability in the susceptibility of contact lens isolates to MPDSs with one S. aureus strain, S. aureus 27, isolated from niCIE, in Australia in 1997 being highly resistant to all four MPDSs and three different types of antibiotics. Knowledge of the rates of resistance to antibiotics in different conditions and regions could help guide treatment of these diseases.

Bio Electro Magnetic Energy Regulation (BEMER) therapy in myofascial pain dysfunction syndrome: A preliminary study.

BACKGROUND: Myofacial pain dysfunction syndrome (MPDS) is of the commonest form of orofacial pain encountered in the clinics. Though, many therapies have been suggested in the recent past, still the management of this condition remains a therapeutic problem. The search for newer, relatively safe and effective long term approach lead to the use of magnetic stimulation in pain modulation. Bio Electro Magnetic Energy Regulation is one such modality that has been studied in the musculoskeletal disorders. However, no studies in this regard have been explored in orofacial region. OBJECTIVES: The objective of the present study was to evaluate the efficacy of BEMER therapy as an adjuvant to relieve pain in myofascial pain dysfunction syndrome. MATERIALS AND METHODS: The present randomized comparative study was on 40 patients who were diagnosed with Myofacial pain dysfunction syndrome(MPDS). They were grouped into two groups of 20 each. Group 1 patients were administered analgesic + muscle relaxants & Group 2 was receiving both analgesic + muscle relaxants with BEMER therapy. All the patients were evaluated for pain relief on visual analog scale (VAS) and the mouth opening (MO)was measured using digital vernier callipers. RESULTS: The group 2 showed a significant improvement in the symptoms even after 2 months follow up. In group 2 the mean mouth opening was 45.60 ± 3.648(P < 0.05) and 45.50 ± 3.663(P < 0.05); the Mean VAS Score was 3.10 ± 0.912 and 2.90 ± 0.968(P < 0.05) after one month and after two months respectively. The independent t-test, was used for inferential statistics. CONCLUSION: It can be concluded from this study that Combined therapy proved to be more effective in providing long term symptomatic relief compared to conventional pharmacological therapy. BEMER as an adjuvant therapeutic modality proved to be beneficial in the management of MPDS.

Can a Software-Based Metronome Tool Enhance Compression Rate in a Realistic 911 Call Scenario Without Adversely Impacting Compression Depth for Dispatcher-Assisted CPR?

IntroductionImplementation of high-quality, dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) is critical to improving survival from out-of-hospital cardiac arrest (OHCA). However, despite some studies demonstrating the use of a metronome in a stand-alone setting, no research has yet demonstrated the effectiveness of a metronome tool in improving DA-CPR in the context of a realistic 911 call or using instructions that have been tested in real-world emergency calls.HypothesisUse of the metronome tool will increase the proportion of callers able to perform CPR within the target rate without affecting depth. METHODS: The prospective, randomized, controlled study involved simulated 911 cardiac arrest calls made by layperson-callers and handled by certified emergency medical dispatchers (EMDs) at four locations in Salt Lake City, Utah USA. Participants were randomized into two groups. In the experimental group, layperson-callers received CPR pre-arrival instructions with metronome assistance. In the control group, layperson-callers received only pre-arrival instructions. The primary outcome measures were correct compression rate (counts per minute [cpm]) and depth (mm). RESULTS: A total of 148 layperson-callers (57.4% assigned to experimental group) participated in the study. There was a statistically significant association between the number of participants who achieved the target compression rate and experimental study group (P=.003), and the experimental group had a significantly higher median compression rate than the control group (100 cpm and 89 cpm, respectively; P=.013). Overall, there was no significant correlation between compression rate and depth. CONCLUSION: An automated software metronome tool is effective in getting layperson-callers to achieve the target compression rate and compression depth in a realistic DA-CPR scenario.Scott G, Barron T, Gardett I, Broadbent M, Downs H, Devey L, Hinterman EJ, Clawson J, Olola C. Can a software-based metronome tool enhance compression rate in a realistic 911 call scenario without adversely impacting compression depth for dispatcher-assisted CPR? Prehosp Disaster Med. 2018;33(4):399-405.

Hospital-Confirmed Acute Myocardial Infarction: Prehospital Identification Using the Medical Priority Dispatch System.

Introduction Early recognition of an acute myocardial infarction (AMI) can increase the patient's likelihood of survival. As the first point of contact for patients accessing medical care through emergency services, emergency medical dispatchers (EMDs) represent the earliest potential identification point for AMIs. The objective of the study was to determine how AMI cases were coded and prioritized at the dispatch point, and also to describe the distribution of these cases by patient age and gender. Hypothesis/Problem No studies currently exist that describe the EMD's ability to correctly triage AMIs into Advanced Life Support (ALS) response tiers. METHODS: The retrospective descriptive study utilized data from three sources: emergency medical dispatch, Emergency Medical Services (EMS), and emergency departments (EDs)/hospitals. The primary outcome measure was the distributions of AMI cases, as categorized by Chief Complaint Protocol, dispatch priority code and level, and patient age and gender. The EMS and ED/hospital data came from the Utah Department of Health (UDoH), Salt Lake City, Utah. Dispatch data came from two emergency communication centers covering the entirety of Salt Lake City and Salt Lake County, Utah. RESULTS: Overall, 89.9% of all the AMIs (n=606) were coded in one of the three highest dispatch priority levels, all of which call for ALS response (called CHARLIE, DELTA, and ECHO in the studied system). The percentage of AMIs significantly increased for patients aged 35 years and older, and varied significantly by gender, dispatch level, and chief complaint. A total of 85.7% of all deaths occurred among patients aged 55 years and older, and 88.9% of the deaths were handled in the ALS-recommended priority levels. CONCLUSION: Acute myocardial infarctions may present as a variety of clinical symptoms, and the study findings demonstrated that more than one-half were identified as having chief complaints of Chest Pain or Breathing Problems at the dispatch point, followed by Sick Person and Unconscious/Fainting. The 35-year age cutoff for assignment to higher priority levels is strongly supported. The Falls and Sick Person Protocols offer opportunities to capture atypical AMI presentations. Clawson JJ , Gardett I , Scott G , Fivaz C , Barron T , Broadbent M , Olola C . Hospital-confirmed acute myocardial infarction: prehospital identification using the Medical Priority Dispatch System. Prehosp Disaster Med. 2018;33(1):29-35.

911 Patient Redirection.

Sporer KA . 911 patient redirection. Prehosp Disaster Med. 2017;32(6):589-592.

Toxin yet not toxic: Botulinum toxin in dentistry.

Paracelsus contrasted poisons from nonpoisons, stating that "All things are poisons, and there is nothing that is harmless; the dose alone decides that something is a poison". Living organisms, such as plants, animals, and microorganisms, constitute a huge source of pharmaceutically useful medicines and toxins. Depending on their source, toxins can be categorized as phytotoxins, mycotoxins, or zootoxins, which include venoms and bacterial toxins. Any toxin can be harmful or beneficial. Within the last 100 years, the perception of botulinum neurotoxin (BTX) has evolved from that of a poison to a versatile clinical agent with various uses. BTX plays a key role in the management of many orofacial and dental disorders. Its indications are rapidly expanding, with ongoing trials for further applications. However, despite its clinical use, what BTX specifically does in each condition is still not clear. The main aim of this review is to describe some of the unclear aspects of this potentially useful agent, with a focus on the current research in dentistry.

Using On-scene EMS Responders' Assessment and Electronic Patient Care Records to Evaluate the Suitability of EMD-triaged, Low-acuity Calls for Secondary Nurse Triage in 911 Centers.

INTRODUCTION: Using the Medical Priority Dispatch System (MPDS) - a systematic 911 triage process - to identify a large subset of low-acuity patients for secondary nurse triage in the 911 center is a largely unstudied practice in North America. This study examines the ALPHA-level subset of low-acuity patients in the MPDS to determine the suitability of these patients for secondary triage by evaluating vital signs and necessity of lights-and-siren transport, as determined by attending Emergency Medical Services (EMS) ambulance crews. OBJECTIVES: The primary objective of this study was to determine the clinical status of MPDS ALPHA-level (low-acuity) patients, as determined by on-scene EMS crews' patient care records, in two US agencies. A secondary objective was to determine which ALPHA-level codes are suitable candidates for secondary triage by a trained Emergency Communication Nurse (ECN). METHODS: In this retrospective study, one full year (2013) of both dispatch data and EMS patient records data, associated with all calls coded at the ALPHA-level (low-acuity) in the dispatch protocol, were collected. The primary outcome measure was the number and percentage of ALPHA-level codes categorized as low-acuity, moderate-acuity, high-acuity, and critical using four common vital signs to assign these categories: systolic blood pressure (SBP), pulse rate (PR), oxygen saturation (SpO2), and Glasgow Coma Score (GCS). Vital sign data were obtained from ambulance crew electronic patient care records (ePCRs). The secondary endpoint was the number and percentage of ALPHA-level codes that received a "hot" (lights-and-siren) transport. RESULTS: Out of 19,300 cases, 16,763 (86.9%) were included in the final analysis, after excluding cases from health care providers and those with missing data. Of those, 89% of all cases did not have even one vital sign indicator of unstable patient status (high or critical vital sign). Of all cases, only 1.1% were transported lights-and-siren. CONCLUSION: With the exception of the low-acuity, ALPHA-level seizure cases, the ALPHA-level patients are suitable to transfer for secondary triage in a best-practices, accredited, emergency medical dispatch center that utilizes the MPDS at very high compliance rates. The secondary nurse triage process should identify the few at-risk patients that exist in the low-acuity calls.

Multi-site clinical assessment of Complete Revitalens MPDS in 2981 contact lens wearers across Europe and USA.

PURPOSE: To evaluate ocular response and subject acceptance of a new multipurpose disinfecting solution (MPDS), Complete Revitalens (RevitaLens OcuTec in the US Market), for soft contact lens care in a large "real practice" setting. METHOD: This is an international multi-center, open-label assessment carried out in 10 countries across Europe and in the USA. Up to 10 subjects who were currently wearing soft contact lenses for at least 1 year and using a MPS as a lens care system were included at each investigational site. RESULTS: Data were collected from 996 European and 1985 American wearers, 75% of those patients wore silicone hydrogel contact lenses. Approximately 94% found the new MPDS "somewhat more effective" to "much more effective" in keeping contact lenses feeling clean and 88% found the new MPDS to be somewhat more effective to much more effective in keeping their lenses feeling comfortable in the evening. Over 93% reported an improvement in vision clearness in the evening after approximately 1 month while using the new MPDS. Wearers with grade 2, 3 or 4 of severity decreased by 11.3, 6.4 and 9.8% over 1 month period for redness, burning and irritation, respectively. After approximately 1 month 83% of wearers declared that they would prefer to use the new MPDS. CONCLUSIONS: Over 88% felt their lenses were somewhat to much more comfortable at the end-of-day and 94% found the new MPDS to be somewhat to much more effective in keeping their lenses feeling clean compared to their previous care system.