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Individuals searching for symptomatic relief or a potential cure are increasingly seeking and using nontraditional therapies for their various diseases. Little is known about the potential adverse effects that patients may encounter while undergoing these alternative treatments. Cesium chloride is an unregulated agent that has been reported to have antineoplastic properties. Cesium chloride is advertised as an alternative agent for many different types of cancers and can be purchased easily on the Internet. Recently, QT prolongation and polymorphic ventricular tachycardia were reported in several patients taking cesium chloride as alternative treatment for cancer. We report acquired QT prolongation and sustained monomorphic ventricular tachycardia in a patient who self-initiated and completed a course of cesium chloride as adjunctive treatment for brain cancer. [ABSTRACT FROM AUTHOR]

Objectives: World Health Organization issued Joint Statement on Data Protection and Privacy in the COVID-19 Response stating that collection of vast amounts of personal data may potentially lead to the infringement of fundamental human rights and freedoms. The Organization for Economic Cooperation and Development called on national governments to adhere to the international principles for data security and confidentiality. This paper describes the methods used to assist the Ministry of Health in bringing awareness of the data ownership, confidentiality and security principles to COVID-19 responders., Methods: The Sierra Leone Epidemiological Data (SLED) Team data managers conducted training for groups of COVID-19 responders. Training included presentations on data confidentiality, information disclosure, physical and electronic data security, and cyber-security; and interactive discussion of real-life scenarios. A game of Jeopardy was created to test the participant's knowledge., Results: This paper describes the methods used by the SLED Team to bring awareness of the DOCS principles to more than 2,500 COVID-19 responders., Conclusion: Similar efforts may benefit other countries where the knowledge, resources, and governing rules for protection of personal data are limited., Competing Interests: The authors declare that they do not have any conflicts of interest., (Copyright © 2024 Kanu, Vandi, Bangura, Draper, Gorina, Foster, Harding, Ikoona, Jambai, Kamara, Kaitibi, Moffett, Singh and Redd.)

Background: Autonomic denervation is an ancillary phenomenon during thermal ablation of atrial fibrillation (AF), that may have synergistic effects on symptomatic improvement and long-term freedom from AF. Pulsed field ablation (PFA), a nonthermal ablation modality, was noninferior to thermal ablation in treating AF; however, PFA's relative myocardial selectivity may minimize autonomic effects., Objectives: This study sought to compare heart rate (HR) and heart rate variability (HRV) metrics as markers of autonomic function after ablation using PFA vs thermal ablation., Methods: ADVENT (FARAPULSE ADVENT PIVOTAL Trial PFA System vs SOC Ablation for Paroxysmal Atrial Fibrillation) was a randomized pivotal study comparing PFA (pentaspline catheter) with thermal ablation (radiofrequency [RF] or cryoballoon [CB]) for treating paroxysmal AF. Baseline HR was acquired from a pre-ablation 12-lead electrocardiogram, whereas follow-up HRs, as well as HRV (standard deviation of all normal to normal RR intervals, standard deviation of 5-minute average RR intervals) metrics, were derived from 72-hour Holter monitors at 6 and 12 months., Results: This study included 379 paroxysmal AF patients undergoing PFA (n = 194) or thermal ablation (n = 185; n = 102 RF, n = 83 CB) completing 6- and 12-month Holter monitoring. Compared with PFA, thermal patients had significantly greater increases in HR from baseline to 6 months (ΔHR; 10.1 vs 5.9 beats/min; P = 0.02) and 12 months (ΔHR; 8.8 vs 5.2 beats/min; P = 0.03). This increase in HR at 6 and 12 months was similar between CB and RF (P = 0.94 and 0.83, respectively). HRV, both standard deviation of all normal to normal RR intervals and standard deviation of 5-minute average RR intervals, were significantly lower at both 6 and 12 months after thermal ablation compared with PFA (P < 0.01)., Conclusions: PFA's effect on the autonomic nervous system was attenuated compared with thermal ablation. Whether this affects long-term freedom from AF or symptomatic bradycardia/pauses after AF ablation requires further study., Competing Interests: Funding Support and Author Disclosures The ADVENT study was funded by Boston Scientific, Inc. Dr Gerstenfeld has served on an advisory board (unpaid) for Boston Scientific; serves as a consultant for Abbott, Adagio Medical and Biosense Webster, unrelated to this work; has received lecture honoraria from Medtronic, Abbott, Boston Scientific, and Biosense Webster; and has received research funding from Abbott, Biosense Webster, and Adagio Medical. Dr Mansour has been a consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens Novartis, Janssen, Boehringer Ingelheim, Pfizer, and SentreHEART/AtriCure; and has equity in EPD-Philips (divested), and NewPace Ltd. Dr Ellis has received research grants (to VUMC), from Boston Scientific, AtriCure, and Medtronic; and has served on advisory boards or received consulting fees from Abbott Medical, Boston Scientific, AtriCure, and Medtronic. Dr Osorio has been a consultant for Boston Scientific, Biosense Webster, Medtronic, Volta, and Abbott Medical; and has served on advisory boards for Boston Scientific, Biosense Webster, and Volta. Dr DeLurgio has been a consultant and speaker for Boston Scientific. Dr McElderry has served as a consultant for Boston Scientific (formerly Farapulse), Abbott, Medtronic, Heamonetics, and Biosense Webster. Ms Richards, Dr Albrecht, Mr Schneider, and Dr Sutton are salaried employees of Boston Scientific. Dr Reddy has equity in Farapulse Inc (now divested), Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, AquaHeart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioFocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, and Valcare, and unrelated to this work, in Atraverse, DRS Vascular, Manual Surgical Sciences, Newpace, Nyra Medical, Soundcath, Surecor, and Vizaramed; has served as a consultant for Boston Scientific Inc and Farapulse Inc, and unrelated to this work, Abbott, Adagio Medical, Append Medical, AtriAN, Biosense-Webster, BioTel Heart, Biotronik, Cairdac, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Novo Nordisk, Philips, Ablacon, Acutus Medical, Affera-Medtronic, Anumana, Apama Medical-Boston Scientific, APN Health, AquaHeart, Atacor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioFocus, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, Laminar Medical, LuxMed, Medlumics, Middlepeak, Neutrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare, and Pulse Biosciences. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: When it occurs, pulmonary vein (PV) stenosis after atrial fibrillation (AF) ablation is associated with significant morbidity. Even mild-to-moderate PV narrowing may have long-term implications. Unlike thermal ablation energies, such as radiofrequency (RF) or cryothermy, pulsed field ablation (PFA) is a non-thermal modality associated with less fibrotic proliferation. Herein, we compared the effects of PFA vs. thermal ablation on PV narrowing after AF ablation., Methods and Results: ADVENT was a multi-centre, randomized, single-blind study comparing PFA (pentaspline catheter) with thermal ablation-force-sensing RF or cryoballoon (CB)-to treat drug-refractory paroxysmal AF. Pulmonary vein diameter and aggregate cross-sectional area were obtained by baseline and 3-month imaging. The pre-specified, formally tested, secondary safety endpoint compared a measure of PV narrowing between PFA vs. thermal groups, with superiority defined by posterior probability > 0.975. Among subjects randomized to PFA (n = 305) or thermal ablation (n = 302), 259 PFA and 255 thermal ablation (137 RF and 118 CB) subjects had complete baseline and 3-month PV imaging. No subject had significant (≥70%) PV stenosis. Change in aggregate PV cross-sectional area was less with PFA (-0.9%) than thermal ablation (-12%, posterior probability > 0.999)-primarily driven by the RF sub-cohort (-19.5%) vs. CB sub-cohort (-3.3%). Almost half of all PFA PV diameters did not decrease, but the majority (80%) of RF PVs decreased, regardless of PV anatomic location., Conclusion: In this first randomized comparison of PFA vs. thermal ablation, PFA resulted in less PV narrowing-thereby underscoring the qualitatively differential and favourable impact of PFA on PV tissue., Competing Interests: Conflict of interest: M.M. is a consultant for Boston Scientific, Biosense Webster, Abbott, Medtronic, Siemens Novartis, Janssen, Boehringer Ingelheim, Pfizer, and SentreHEART/AtriCure and has equity in EPD-Philips (divested), and NewPace Ltd. E.P.G. is a consultant to Farapulse Inc and serves as an unpaid consultant to Boston Scientific Inc and scientific advisory board to Biosense Webster and Adagio Medical, has research support from Biosense-Webster, Adagio Medical, and Abbott, has lecture honoraria from Medtronic, Boston Scientific Inc and Abbott. C.P. is a consultant for Boston Scientific. A.N. is a consultant for Abbott, Baylis, Biotronik, Biosense Webster, Boston Scientific, and Medtronic. W.W. has no relevant disclosures. F.A.C. is a consultant to Boston Scientific and Biosense Webster. S.E.M. is a consultant to Medtronic and Boston Scientific Inc, has research support from Medtronic, Biotronik, Abbott, and CVRx, and has lecture honoraria from Biosense Webster, Medtronic, Boston Scientific Inc, Zoll, and Abbott. D.N.G. is a consultant to Abbott, Baylis, Biotronik, Biosense Webster, Boston Scientific, and Medtronic. J.D.H. has no relevant disclosures. S.K.H. is an employee of Medpace Core Laboratories. C.W.S., A.B.A., E.M.A., and K.M.S. are employees of Boston Scientific. A.S.M. is a consultant to Farapulse Inc and serves as a consultant to Boston Scientific Inc; unrelated to this manuscript, he has also provided statistical consulting and/or Data Safety Monitoring Board services for AtriCure, Abbott, Biosense Webster, and Medtronic. J.W.L. is a consultant to and received equity from Farapulse Inc (now divested) and serves as a consultant to Boston Scientific Inc. V.Y.R. is a Farapulse-Boston Scientific Inc: grant support, consultant, equity (now divested); and unrelated to this manuscript, V.Y.R. also serves as a consultant for and has equity in Ablacon, Acutus Medical, Affera-Medtronic, Apama Medical-Boston Scientific, Anumana, APN Health, AquaHeart, AtaCor, Autonomix, Axon Therapies, Backbeat, BioSig, CardiaCare, CardioNXT/AFTx, Circa Scientific, CoRISMA, Corvia Medical, Dinova-Hangzhou DiNovA EP Technology, East End Medical, EPD-Philips, EP Frontiers, Epix Therapeutics-Medtronic, EpiEP, Eximo, Field Medical, Focused Therapeutics, HRT, Intershunt, Javelin, Kardium, Keystone Heart, LuxMed, MedLumics, Middlepeak, NeuTrace, Nuvera-Biosense Webster, Oracle Health, Restore Medical, Sirona Medical, SoundCath, Valcare; unrelated to this work, V.Y.R. has served as a consultant for Abbott, AtriAN, Biosense Webster, BioTel Heart, Biotronik, Cairdac, CardioFocus, Cardionomic, CoreMap, Fire1, Gore & Associates, Impulse Dynamics, Medtronic, Novartis, Philips, and Pulse Biosciences and has equity in DRS Vascular, Manual Surgical Sciences, NewPace, Nyra Medical, SureCor, and VizaraMed., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Catheter-based pulmonary vein isolation is an effective treatment for paroxysmal atrial fibrillation. Pulsed field ablation, which delivers microsecond high-voltage electrical fields, may limit damage to tissues outside the myocardium. The efficacy and safety of pulsed field ablation as compared with conventional thermal ablation are not known., Methods: In this randomized, single-blind, noninferiority trial, we assigned patients with drug-refractory paroxysmal atrial fibrillation in a 1:1 ratio to undergo pulsed field ablation or conventional radiofrequency or cryoballoon ablation. The primary efficacy end point was freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation. The primary safety end point included acute and chronic device- and procedure-related serious adverse events., Results: A total of 305 patients were assigned to undergo pulsed field ablation, and 302 were assigned to undergo thermal ablation. At 1 year, the primary efficacy end point was met (i.e., no events occurred) in 204 patients (estimated probability, 73.3%) who underwent pulsed field ablation and 194 patients (estimated probability, 71.3%) who underwent thermal ablation (between-group difference, 2.0 percentage points; 95% Bayesian credible interval, -5.2 to 9.2; posterior probability of noninferiority, >0.999). Primary safety end-point events occurred in 6 patients (estimated incidence, 2.1%) who underwent pulsed field ablation and 4 patients (estimated incidence, 1.5%) who underwent thermal ablation (between-group difference, 0.6 percentage points; 95% Bayesian credible interval, -1.5 to 2.8; posterior probability of noninferiority, >0.999)., Conclusions: Among patients with paroxysmal atrial fibrillation receiving a catheter-based therapy, pulsed field ablation was noninferior to conventional thermal ablation with respect to freedom from a composite of initial procedural failure, documented atrial tachyarrhythmia after a 3-month blanking period, antiarrhythmic drug use, cardioversion, or repeat ablation and with respect to device- and procedure-related serious adverse events at 1 year. (Funded by Farapulse-Boston Scientific; ADVENT ClinicalTrials.gov number, NCT04612244.)., (Copyright © 2023 Massachusetts Medical Society.)

Purpose: In 2015, the Sierra Leone Ministry of Health and Sanitation (MoHS) and the Centers for Disease Control and Prevention (CDC) agreed to consolidate data recorded by MoHS and international partners during the Ebola epidemic and create the Sierra Leone Ebola Database (SLED). The primary objectives were helping families to identify the location of graves of their loved ones who died from any cause at the time of the Ebola epidemic and creating a data source for epidemiological research. The Family Reunification Program fulfills the first SLED objective. The purpose of this paper is to describe the Family Reunification Program (Program) development, functioning, and results., Methods: The MoHS, CDC, SLED Team, and Concern Worldwide developed, tested, and implemented methodology and tools to conduct the Program. Family liaisons were trained in protection of the personally identifiable information., Results: The SLED Family Reunification Program allows families in Sierra Leone, who did not know the final resting place of their loved ones, to be reunited with their graves and to bring them relief and closure., Conclusion: Continuing family requests in search of the burial place of loved ones 5 years after the end of the epidemic shows that the emotional burden of losing a family member and not knowing the place of burial does not diminish with time. As of February 2021, the Program continues and is described to allow its replication for other emergency events including COVID-19 and new Ebola outbreaks., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose: During the 2014-2016 Ebola outbreak in West Africa, the Sierra Leone Ministry of Health and Sanitation (MoHS), the US Centers for Disease Control and Prevention, and responding partners under the coordination of the National Ebola Response Center (NERC) and the MoHS's Emergency Operation Center (EOC) systematically recorded information from the 117 Call Center system and district alert phone lines, case investigations, laboratory sample testing, clinical management, and safe and dignified burial records. Since 2017, CDC assisted MoHS in building and managing the Sierra Leone Ebola Database (SLED) to consolidate these major data sources. The primary objectives of the project were helping families to identify the location of graves of their loved ones who died at the time of the Ebola epidemic through the SLED Family Reunification Program and creating a data source for epidemiological research. The objective of this paper is to describe the process of consolidating epidemic records into a useful and accessible data collection and to summarize data characteristics, strength, and limitations of this unique information source for public health research., Methods: Because of the unprecedented conditions during the epidemic, most of the records collected from responding organizations required extensive processing before they could be used as a data source for research or the humanitarian purpose of locating burial sites. This process required understanding how the data were collected and used during the outbreak. To manage the complexity of processing the data obtained from various sources, the Sierra Leone Ebola Database (SLED) Team used an organizational strategy that allowed tracking of the data provenance and lifecycle., Results: The SLED project brought raw data into one consolidated data collection. It provides researchers with secure and ethical access to the SLED data and serves as a basis for the research capacity building in Sierra Leone. The SLED Family Reunification Program allowed Sierra Leonean families to identify location of the graves of loved ones who died during the Ebola epidemic., Conclusions: The SLED project consolidated and utilized epidemic data recorded during the Sierra Leone Ebola Virus Disease outbreak that were collected and contributed to SLED by national and international organizations. This project has provided a foundation for developing a method of ethical and secure SLED data access while preserving the host nation's data ownership. SLED serves as a data source for the SLED Family Reunification Program and for epidemiological research. It presents an opportunity for building research capacity in Sierra Leone and provides a foundation for developing a relational database. Large outbreak data systems such as SLED provide a unique opportunity for researchers to improve responses to epidemics and indicate the need to include data management preparedness in the plans for emergency response., (Published by Elsevier Inc.)

Purpose: Organizations responding to the 2014-2016 Ebola epidemic in Sierra Leone collected information from multiple sources and kept it in separate databases, including distinct data systems for Ebola hot line calls, patient information collected by field surveillance officers, laboratory testing results, clinical information from Ebola treatment and isolation facilities, and burial team records., Methods: After the conclusion of the epidemic, the Sierra Leone Ministry of Health and Sanitation and the U.S. Centers for Disease Control and Prevention partnered to collect these disparate records and consolidate them in the Sierra Leone Ebola Database., Results: The Sierra Leone Ebola Database data are providing a lasting resource for postepidemic data analysis and epidemiologic research, including identifying best strategies in outbreak response, and are used to help families locate the graves of family members who died during the epidemic., Conclusion: This report describes the Ministry of Health and Sanitation and Centers for Disease Control and Prevention processes to safeguard Ebola records while making the data available for public health research., (Published by Elsevier Inc.)

Nonhuman primates (NHPs) are the closest animal models to humans regarding genetics, physiology and behavior. Therefore, NHPs are usually a critical component in translational research projects aimed at developing therapeutics, vaccines, devices or other interventions aimed at preventing, curing or ameliorating human disease. NHPs are often used in conjunction with other animal models, such as rodents, and results obtained using NHPs must often be used as the final criterion for establishing the potential efficacy of a pharmaceutical or vaccine before transition to human clinical trails. In some cases, NHPs may be the only relevant animal models for a particlular translational study. This issue of the ILAR journal brings together, in one place, articles that discuss the use of NHP models for studying human diseases that are highly prevalent and that cause extraordinary human suffering and financial and social burdens. Topics covered in detail include: tuberculosis; viral hepatitis; HIV/AIDS; neurodegenerative disorders; Substance abuse disorders; vision and prevention of blindness; disorder associated with psychosocial processes, such as anxiety, depression and loneliness; cardiovascular disease; metabolic disease, such as obesity and metabolic syndrome; respiratory disease; and female reproduction, prenatal development and women's health. Proper husbandry of NHPs that reduces stress and maintains animal health is critical for the development of NHP models. This issue of the journal includes a review of procedures for environmental enrichment, which helps assure animal health and wellbeing. Taken together, these articles provide detailed reviews of the use of NHP models for translational investigations and discuss successes, limitations, challenges and opportunities associated with this research., (© The Author(s) 2017. Published by Oxford University Press on behalf of the National Academy of Sciences. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Nonhuman primates (NHPs) are important preclinical models for understanding the etiology of human diseases and for developing therapies and vaccines to cure or eliminate disease. Most human diseases have genetic components. Therefore, to be of maximal utility, the NHP species used for translational science should be as well characterized in regard to their genome and transcriptome as possible. This article reviews the current status of genomic information for the five NHP species used most often in translational research: rhesus macaque, cynomolgus macaque, vervet (African green) monkey, baboon, and marmoset NHP. These species have published whole genome sequences (with the exception of the baboon) and relatively well-characterized transcriptomes. Some have also been characterized in regard to specific genetic loci that are particularly related to translational concerns, such as the major histocompatability complex and the cytochrome P40 genes. Genomic resources to aid in stratifying captive populations in regard to genetic and phenotypic characteristics have been developed as an aid to enhancing reproducibility and facilitating more efficient use of animals. Taken together, the current genomic resources and numerous studies currently underway to improve them should enhance the value of NHPs as preclinical models of human disease., (© The Author 2017. Published by Oxford University Press on behalf of the Institute for Laboratory Animal Research. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Opioid misuse may be ignored by providers who are unwilling or not confident in engaging the complex nature of substance use disorders among their patient populations. Addiction is a complex disease, and although providers often are comfortable in identifying, assessing, and treating the complex diseases of their patients, basic knowledge and skills of identification, assessment, and treatment expertise involving opioids for pain, addressing opioid misuse, and treatment of opioid use disorder are lacking. Initiatives to improve knowledge of opioid use, misuse, and opioid use disorder among health care providers are emerging. In this issue of the Substance Abuse journal, we examine the science and evidence base of educational interventions and public initiatives addressing opioid use and addiction. These initiatives include naloxone rescue awareness and programs, community-based training initiatives, and system or public health approaches to improve student, trainee, and clinician education/training revolving around opioid misuse and opioid use disorder. We call on stakeholders to fund more research to investigate and implement the proven means to educate undergraduate students, graduate trainees, and clinicians regarding pain and addiction. We also recognize the 2016 peer reviewers of our journal who have performed meritorious, volunteer service to advance the science of addiction.

Background: A standard approach to recent onset atrial fibrillation (AF) in the emergency department (ED) in the United States has not been established., Purpose: The purpose of this prospective clinical trial was to determine how an ED protocol emphasizing rhythm control for recent onset AF compared similar patients receiving standard therapy in the same facility., Methods: We enrolled consecutive patients presenting to our community hospital with recent onset AF into a protocol, which called for rhythm control with procainamide and if unsuccessful electrical cardioversion and discharge home. We compared this prospective cohort with matched historical controls. Primary outcome was admission rate. We also compared ED conversion rates and lengths of stay (LOS). We reported 30-day data on the study group including ED recidivism, recurrent AF, outpatient follow-up, and any important adverse events., Results: Fifty-four patients were enrolled in the study group with 4 being admitted compared with 30 of 50 in the historical control group. Ninety-four percent of the study group converted compared with 28% in the historical control. Both hospital and ED LOS were significantly shorter for the study group. Six patients had recurrent AF, and 4 of those returned to the ED., Conclusion: An ED protocol that uses rhythm control decreased hospital admission and LOS, and there were no adverse events at 30 days., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Protein A chromatography, employing the recombinant Protein A ligand, is widely used as a capture step for antibody and Fc-fusion proteins manufacture. Protein A ligands in these matrices are susceptible to degradation/loss when exposed to cleaning agents such as sodium hydroxide, resulting in loss of capacity on reuse. In this study, MabSelect Protein A ligand and MabSelect SuRe Protein A ligand were chosen to evaluate the impact of alkaline cleaning solutions on the ligands and the packed columns. The Protein A ligands alone and the Protein A columns were incubated or cycled in different concentrations of sodium hydroxide solutions with and without additives, respectively. Ligand integrity (degradation) and ligand function (binding affinity) were studied using SDS-PAGE and customized Biacore technology, surface plasma resonance (SPR) and were successfully correlated with column performance measurement in terms of static binding capacity (SBC), dynamic binding capacity (DBC) and recovery as a function of exposure to cleaning agents with and without additives. The findings and the methodology presented in this study are not only able to determine appropriate cleaning conditions for Protein A chromatography, but also provided tools to enable systematic and rapid study of the cleaning solutions and conditions., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Developing a workforce of multidisciplinary healthcare professionals equipped with the knowledge and skills to collaboratively address the public health crisis of alcohol and other drug (AOD) use is critical for effectively identifying, preventing, and managing AOD conditions and their sequelae. Despite general enthusiasm for interdisciplinary education and training, little is known overall about the nature and outcomes of interdisciplinary collaboration in addictions education and training. We conducted a five-stage scoping review of the literature to provide an eight domain overview of the state of interdisciplinary collaboration in addictions education (ICAE). In our final review of 30 articles, we identified a lack of conceptual and terminological clarity around ICAE but a wide range of learners and professional collaborators in ICAE initiatives, which focused on a variety of AOD topics and used a constellation of didactic, interactive, and service-learning teaching strategies and formats. Although we found limited substantive educational or practice-oriented outcomes available for ICAE initiatives, learner and faculty feedback reflected high enthusiasm for ICAE and widespread perceptions of benefit for improved clinical care. Facilitators and barriers to the implementation of ICAE initiatives occurred at the level of the individual and the institution and ranged from pragmatic to conceptual. Emerging trends in ICAE initiatives included increased application of learning and implementation theory and extension of ICAE into research training. We conclude with recommendations to support ICAE as a new paradigm for addictions education for all health professionals.

Objectives: This study sought to identify the origin within the pulmonary vein (PV) of reproducible atrial fibrillation (AF) triggers., Background: Triggers for AF frequently originate from PVs. However, a systematic evaluation of the location of origin within the PV orifice and associated techniques for eliciting triggers has not been performed., Methods: Spontaneous triggers and those provoked with isoproterenol (up to 20 microg/min) and/or cardioversion in 45 patients with AF were identified using multipolar catheter recordings. In identifying origin, PVs were divided into 17 equal segments from ipsilateral PVs with "carina zone" (CZ) (7 segments between the PVs) and 10 "noncarina zone" (NCZ) segments., Results: Sixty-three reproducible triggers were noted in 37 of the 45 (82%) patients with 57 from PV and 6 (10%) from non-PV sites. Although triggers were identified from 26 of 34 distinct PV segments, most PV triggers (36, 63%) originated from CZ segments (p < 0.05) from both right (17 triggers) and left (19 triggers) PVs. The CZ triggers were more often spontaneous (11 of 36 in CZ vs. 2 of 21 in NCZ; p < 0.05) or elicited with CV (17 of 36 in CZ vs. 6 of 21 in NCZ; p < 0.05). In contrast, NCZ triggers were more likely to require isoproterenol to be provoked (13 of 21 [62%] vs. 8 of 36 [22%], p < 0.05)., Conclusions: Reproducible spontaneous and provoked PV triggers initiating AF can be observed in most patients undergoing AF ablation. These triggers most commonly originate from the carina region of both right and left PVs. Noncarina PV triggers more commonly require provocation with isoproterenol infusion.

Like the introduction of digitalis more than 200 years ago, novel medical therapies today have the potential to significantly alter the course of heart failure (HF) and save thousands of lives. This review outlines new directions in HF medical management beyond the foundation of neurohormonal blockade. Furthermore, the role of novel risk factors in HF such as chronic renal insufficiency, anemia, and sleep apnea present tantalizing therapeutic targets to extend the morbidity and mortality benefits of current therapies. The course of time will tell which of these risk factors and therapies can hold promise, given the recent litany of negative trials in the HF arena. Advancements in molecular and genetic techniques have allowed us to begin to consider patient specific therapies and lay the groundwork for even further improvements in treatment of symptomatic HF. Finally, advances in telemedicine and device technology will allow the clinician to remotely monitor useful clinical parameters such as heart rate variability and pulmonary filling pressures to make more informed clinical decision-making and improve outcomes.

Objective: High-resolution MRI methods have been used to evaluate carotid artery atherosclerotic plaque content. The purpose of this study was to assess the performance of high-resolution MRI in evaluation of the quantity and pattern of mineral deposition in carotid endarterectomy (CEA) specimens, with quantitative micro-CT as the gold standard., Methods and Results: High-resolution MRI and CT were compared in 20 CEA specimens. Linear regression comparing mineral volumes generated from CT (VCT) and MRI (VMRI) data demonstrated good correlation using simple thresholding (VMRI=-0.01+0.98VCT; R2=0.90; threshold=4xnoise) and k-means clustering methods (VMRI=-0.005+1.38VCT; R2=0.93). Bone mineral density (BMD) and bone mineral content (BMC [mineral mass]) were calculated for CT data and BMC verified with ash weight. Patterns of mineralization like particles, granules, and sheets were more clearly depicted on CT., Conclusions: Mineral volumes generated from MRI or CT data were highly correlated. CT provided a more detailed depiction of mineralization patterns and provided BMD and BMC in addition to mineral volume. The extent of mineralization as well as the morphology may ultimately be useful in assessing plaque stability.

Background: Recent observations indicate that the QTc interval often increases in the early postoperative period (<1 week) after mechanical unloading of severely failing hearts with a left ventricular assist device (LVAD). The present study examined whether early changes in ventricular repolarization after LVAD placement are associated with ventricular arrhythmias., Methods and Results: An electrocardiogram was obtained within 4 days before LVAD placement, <12 hours after LVAD placement, and weekly thereafter. Patient records were reviewed for documented ventricular tachycardia (VT) or ventricular fibrillation (VF) for 1 week preoperatively and the first 2 weeks postoperatively. Differences in QTc interval between patients with and without VT were evaluated. Ten of 17 patients enrolled (59%) had VT or VF after LVAD placement. Of these, 4 required therapeutic intervention because of clinical instability or symptoms. The change in the QTc (DeltaQTc) between the preoperative and immediate postoperative period was significantly different among patients with VT/VF compared with patients without VT/VF (+23 ms vs. -68 ms, P < .001)., Conclusion: The early period after initiation of LVAD support of the failing human heart is associated with a relatively high incidence of significant ventricular arrhythmias after LVAD placement. Beyond the impact of myocardial inflammation and wound healing occurring after all LVAD implants, early postoperative increases in the QTc interval after cardiac unloading appear to predispose to ventricular arrhythmias.

Background: Recognizing that mechanical circulatory support with a left ventricular assist device (LVAD) induces changes in myocardial structure and contractile function, we examined whether there are changes in ventricular conduction and/or repolarization among failing human hearts after LVAD implantation., Methods and Results: We examined 12-lead electrocardiograms before surgery, immediately after LVAD placement, and at a delayed (>1 week) postoperative time point in 23 patients who were receiving LVAD support for refractory heart failure. The immediate effects of hemodynamic unloading via LVAD placement included a decrease in QRS duration from 117+/-6 to 103+/-6 ms (P<0.01), an increase in absolute QT duration from 359+/-6 to 378+/-8 ms (P<0.05), and an increase in the heart rate-corrected QT interval (QTc) from 379+/-10 to 504+/-11 ms (P<0.01). None of these immediate changes were observed among 22 patients undergoing routine coronary artery bypass grafting. With sustained cardiac unloading via LVAD support, there was a marked decrease in the QTc from 504+/-11 to 445+/-9 ms (P<0.001). Studies in isolated cardiac myocytes, obtained at the time of transplantation, confirmed that delayed decreases in heart rate-adjusted QTc were the result of decreases in action potential duration after LVAD support., Conclusions: Acute electrocardiogram responses to LVAD placement demonstrate the dependence of QRS and QT duration on load in the failing human heart. Delayed decreases in QTc and action potential duration reflect reversal of electrophysiologic remodeling in the failing heart. Shortening of the action potential duration likely contributes to the improved cellular contractile performance observed after sustained LVAD support.

Current sequencing technologies are insufficient to cope with large-scale projects such as sequencing the human genome and genomes of model organisms. In addition, as genetic lesions associated with specific human diseases are identified, DNA sequencing will be used increasingly for clinical applications. Thus, new approaches are needed to combine high-throughput with accuracy for both research and diagnostic purposes. A novel technology based on detection of individual fluorescent nucleotides in a flowing sample stream is under development.

The Escherichia coli RNA polymerase core molecule, after denaturation in 6 M guanidine hydrochloride, can be completely reactivated in the absence of sigma subunit. Reactivation is temperature dependent. At 4 degrees a renatured-inactive preparation is formed that has most of the secondary structure of the original native molecule but has a reduced sedimentation coefficient and a smaller Stokes radius and is, therefore, of lower molecular weight. Upon warming to 37 degrees the renatured-inactive preparation is converted in a time-dependent process to the renatured-active preparation, which has the same amount of secondary structure and same molecular weight as native RNA polymerase. Since the renatured-inactive material is probably composed of subunit assemblies and can be readily reactivated, it should be useful for studying the subunit interactions and control of assembly of RNA polymerase.

From a recombinant lambda phage, we have determined a 317-bp sequence containing a mouse tRNAiMet gene. The coding region is precisely homologous to mammalian tRNAiMet if post-transcriptional modifications (including addition of the 3'-terminal CCA) are not considered. The gene does not contain introns and has a typical RNA polymerase III termination site in the 3'-flanking region. It is transcribed by RNA polymerase III in the HeLa cell S-100 system in vitro. Notably, the 5'-flanking region of the mouse tRNAiMet gene shares a "patchwork" pattern of homology with one of the human tRNAiMet genes of Santos and Zasloff [Cell 23 (1981) 699-710]. The 5'-flanking regions of the two genes contain strings of nucleotides, 6 to 32 bp in length, the homology of which is 76-100%. These are separated by short strings of unrelated nucleotides. This is one of the first examples of tRNA genes containing homologous 5'-flanking regions isolated from distantly related mammals. We also report a novel method for constructing deletion mutants of sequences cloned in M13 vectors.

The substituted nucleotide aminohexyl-ATP (AH-ATP) was used for synthesis of RNA probes from a plasmid template using the T7 phage promoter. Following synthesis, RNA probes were modified by reaction with N-hydroxysuccinimide (NHS) esters of biotin or fluorescein. Nearest-neighbor analysis was used to quantitate both the incorporation of the substituted nucleotide into RNA and the subsequent modification of the incorporated nucleotide by the NHS esters. The results indicate that AH-ATP is efficiently incorporated into RNA and that modification of the amine group is also efficient. The T7 polymerase shows a bias for ATP over AH-ATP and truncated transcripts are produced if 100% AH-ATP is used for synthesis. However, the use of 50% AH-ATP in the synthesis reaction yields full-length RNA probes that contain on average one amine-labeled nucleotide every 12 bases. This RNA is readily modified by the respective NHS esters to obtain one biotin group per 15-18 total RNA bases or one fluorescein group per 25-35 bases. Probes modified with biotin or fluorescein were used to detect picogram levels of target DNA in a dot blot hybridization format.

We have sequenced mouse tRNA genes from two recombinant lambda phage. An 1800 bp sequence from one phage contains 3 tRNA genes, potentially encoding tRNAAsp, tRNAGly, and tRNAGlu, separated by spacer sequences of 587 bp and 436 bp, respectively. The mouse tRNA gene cluster is homologous to a rat sequence (Sekiya et al., 1981, Nucleic Acids Res. 9, 2239-2250). The mouse and rat tRNAAsp and tRNAGly coding regions are identical. The tRNAGlu coding regions differ at two positions. The flanking sequences contain 3 non-homologous areas: a c. 100 bp insertion in the first mouse spacer, short tandemly repeated sequences in the second spacers and unrelated sequences at the 3' ends of the clusters. In contrast, most of the flanking regions are homologous, consisting of strings of consecutive, identical residues (5-17 bp) separated by single base differences and short insertions/deletions. The latter are often associated with short repeats. The homology of the flanking regions is c. 75%, similar to other murine genes. The second lambda clone contains a solitary mouse tRNAAsp gene. The coding region is identical to that of the clustered tRNAAsp gene. The 5' flanking regions of the two genes contain homologous areas (10-25 bp) separated by unrelated sequences. Overall, the flanking regions of the two mouse tRNAAsp genes are less homologous than those of the mouse and rat clusters.

We have synthesized and analyzed the functional properties of a novel DNA capture reagent containing a methidium moiety attached to a sepharose bead by a spermine linker. DNA present in a biological fluid or other complex sample binds to the reagent. The DNA-capture reagent complex is then separated from the sample by centrifugation and the DNA is released from the reagent by brief incubation in 0.1 to 0.5 N NaOH or KOH. Capture of DNA from complex samples is independent of the salt concentration of the sample, and occurs in the presence of high concentrations of EDTA, proteinase K and detergents. Many samples can be processed simultaneously. The following specific applications, in which denatured DNA is quantitated or characterized, are demonstrated: 1). Isolation of hepatitis B virus DNA from serum and quantitation by dot-blot hybridization, 2). Isolation and quantitation of DNA from urine, 3). Isolation of human genomic DNA from one microliter of blood or 100 HeLa cells followed by amplification of a specific gene sequence using the Polymerase Chain Reaction, 4). Isolation of single stranded phage M13 sequencing templates from bacterial cultures. These investigations suggest that a capture reagent containing an intercalating moiety bound to a solid support may be useful for many applications in molecular biology and molecular diagnostics.

We have sequenced a 1307 base pair mouse genomic DNA fragment which contains a histidine tRNA gene. The sequence of the putative mouse histidine tRNA differs from the published sequence of sheep liver histidine tRNA by a single base change in the D-loop. It does not contain an unpaired 5' terminal G residue, as reported for Drosophila and sheep histidine tRNAs. The gene does not contain introns. The 3' flanking region contains a typical RNA polymerase III termination site of 6 consecutive T residues. 523 residues after the 3' end of the his tRNA coding region, the mouse DNA contains a sequence 72% homologous to part of the consensus sequence of the B1 (alu) family.

The transcriptional properties of two cloned mouse tRNAAsp genes were examined in vitro. The tRNA(2Asp) gene displays a five fold greater transcriptional activity than the tRNA(1Asp) gene and a greater ability to form stable complexes with transcription factors. Transcription of a hybrid gene with swapped 5' flanking sequences and of 5' flanking region deletion mutants demonstrates that the differential transcription of the genes results from stimulatory sequences in the 5' flanking region of the tRNA(2Asp) gene. Distal sequences including those between positions -53 and -31 stimulate transcription but do not affect factor binding. Proximal sequences between positions -9 and -1 enhance factor binding. Thus, binding of transcription factors and later steps required for transcription can be modulated by separate and distinct 5' flanking sequence motifs in eukaryotic tRNA genes.

We determined the nucleotide sequences of three mouse tRNAHis genes and a tRNAGly gene present in two different lambda clones. One lambda clone contained two tRNAHis genes 600 base pairs (bp) apart in opposite orientations. The other clone contained a tRNAHis and a tRNAGly gene 569 bp apart in the same orientation. The coding regions of the three tRNAHis genes were identical to sequenced mammalian tRNAHis if posttranscriptional modifications are not considered. Notably, the three tRNAHis genes and a fourth gene previously sequenced by us contained within the flanking regions, various amounts of short, conserved 5' leader sequences and 3' trailer sequences directly abutting the coding regions. Otherwise the flanking regions were not homologous. Deletion mutants of one of the tRNAHis genes were constructed which contained 228, 99, 9, and 3 bp of the wild-type 5'-flanking region, respectively. Deletion of 5'-flanking sequences from positions -9 to -4 reduced transcriptional activity substantially (ca. fivefold) in a HeLa cell S-100 lysate. This effect was independent of the vector sequences in the deletion clone, implying that the region from -4 to -9 of the intact gene contains a positive modulatory element for transcription in vitro. The deletion mutant containing 3 bp of wild-type 5'-flanking sequence also had a greatly reduced ability to inhibit the transcription of a second tRNA gene in a competition assay. Thus, the normal 5'-flanking region influences the ability of the gene to form stable complexes with transcription factors. These data further indicate that a mammalian transcription extract is sensitive to 5'-flanking-region effects if a suitable tRNA gene is assayed.

We describe a method for detecting specific DNA sequences cloned in M13 phage vectors, based on the procedure of Woo (in Wu, R., Methods in Enzymology, Vol. 68, Academic Press, New York, 1979, pp. 389-395). M13 plaques are adsorbed to a nitrocellulose filter that has been pre-saturated with bacteria. The filter is incubated on an agar plate to amplify the phage; the DNA is alkali-denatured and then hybridized with a radioactive RNA probe. Unlike standard procedures, this method detects and distinguishes M13 plaques containing phage particles which harbor either the coding or non-coding (RNA-like) DNA strand, when single-stranded RNA is used as probe. We have optimized this procedure with M13 clones containing mouse histidine tRNA gene sequences and have used it to determine the sequence of both strands of a mouse glycine tRNA gene.

From a recombinant lambda phage, we have determined a 387 bp sequence containing a mouse lysine tRNA gene. The putative lys tRNA (anticodon UUU) differs from rabbit liver lys tRNA at five positions. The flanking regions of the mouse gene are not generally homologous to published human and Drosophila lys tRNA genes. However, the mouse gene contains a 14 bp region comprising 13 A-T base pairs, 30-44 bp from the 5' end of the coding region. Cognate A-T rich regions are present in human and Drosophila genes. The coding region is flanked by two 11 bp direct repeats, similar to those associated with alu family sequences. The sequence was determined by a "walking" protocol that employs, as a novel feature, iodinated single-stranded M13 probes to identify M13 subclones which contain sequences partially overlapping and contiguous to an initially determined sequence. The probes can also be used to screen lambda phage and in Southern and dot blot experiments.

Transcription of the 26-kilobase (kb) dihydrofolate reductase (dhfr) gene in CHO cells is initiated at two sites: a major site (approximately 85% of the dhfr mRNA) at -63 relative to the translation start and a minor site (approximately 15%) at -107. Transcription also occurs from the opposite DNA strand in the dhfr 5' region, with a probable initiation site at approximately -195 relative to the dhfr translation start. A 4-kb polyadenylated RNA that is derived from the opposite-strand transcription increases threefold in abundance after serum starvation of CHO cells for 24 h. dhfr mRNA levels do not change during this time. The first dhfr exon lies within a 1-kb genomic region marked by exceptionally high G + C content and lack of DNA methylation. This region also includes a 214-base-pair (bp) exon for the opposite-strand transcript and five of the six DNase I-hypersensitive sites identified at the dhfr locus. Analysis of the DNA sequences of hamster, human (M. Chen, T. Shimada, A. D. Moulton, A. Cline, R. K. Humphries, J. Maizel, and A. W. Nienhuis, J. Biol. Chem. 259:3933-3943, 1984), and mouse (M. McGrogan, C. C. Simonsen, D. T. Smouse, P. J. Farnham, and R. T. Schimke, J. Biol. Chem. 260:2307-2314, 1985) dhfr genes reveals the presence of a 29-bp unit that is conserved 45 to 49 bp upstream of major and minor dhfr transcription start sites. This unit follows the consensus: GRGGCGGTGGCCTNNNNTGTCRCAARTRGGTR. The 5' part of the 29-bp unit contains a GC box that agrees with the GGGCGG consensus-binding site for the RNA polymerase II transcription factor Sp1 (D. Gidoni, W. A. Dynan, and R. Tjian, Nature (London) 312:409-413, 1984). Each of the three mammalian dhfr genes has several G-rich GC boxes proximal to the major dhfr transcription start site and several GC boxes of the opposite orientation (C rich) in a distal region about 500 bp upstream.

The enlargement of the small intestine of mice during lactation is due, at least in part, to hyperplasia in the mucosal crypts and villi. The number of cells per crypt increases by 130% and the cell production rate by 63% after 15 days of lactation. These parameters were measured from crypt squashes and sections using both double-label and PLM techniques. Neither the numbers of crypts and villi in the small intestine nor the turnover time of post-mitotic cells on the villi changed. A number of factors appear to act in concert during lactation to trigger this increase in epithelial cell number in the small intestine. The experiments reported suggest a role for the increased quantity of food consumed by the lactating animal, for changing hormonal levels, and for the increased demands placed on the body by milk production.

We have analyzed the pathways and kinetics of processing of mouse tRNA gene transcripts in vitro. Different transcripts are processed along two alternative pathways. The 3' trailer sequence of the tRNA His primary transcript is excised before the 5' leader sequence. In contrast, for the tRNA Gly primary transcript, the 5' leader sequence is excised before the 3' trailer sequence, as has been found for other monomeric eukaryotic tRNA gene transcripts. Computerized analysis of the kinetics of processing indicates that tRNA Asp, tRNA Gly, tRNA Glu and tRNA His transcripts are processed in a substrate concentration-dependent manner and also reveals the existence of a common rate-limiting step, the rate constant of which is equivalent for three of the four transcripts tested. The processing of one pre-tRNA transcript can be competitively inhibited by addition of another pre-tRNA transcript to the processing reaction. The common rate-limiting step is associated with the conversion of the primary transcript to an intermediate and is independent of sequence and the particular processing pathway of the transcript.