bluuebunny/crossref_metadata_2025 huggingface dataset:
Development of a Coma Scale for Emergency Care
Authors: Marsden Andrew K. , Staniland John R. , Price David J.E.
Published: July 2016

Monitoring of the level of neurological response is an essential component of the diagnostic and therapeutic process in the management of craniocervical injury and neurological catastrophes. When Hippocrates reminded us that “No Head Injury is so mild that it can be neglected,” he cannot have been aware of the significance of the lethal factors of cerebral swelling and intracranial hematoma contributing to poor survival. Neither can he have known how these factors could be detected. Coma scales have evolved to indicate when deterioration is likely and intervention indicated.

Many hospitals use simple grades of responsiveness for their unconscious patients, but the widespread habit of recording the level of response in an abstract manner is as meaningless as measuring temperature in units of feverishness. There is a requirement for a device which can be expressed in numerical terms and, when necessary, related to an analogue or graphical mode.
Psychometric Testing and Carbon Monoxide Poisoning
Authors: Myers Roy A. M. , Mitchell Jeffrey T. , Cowley R. Adams
Published: July 2016

The Maryland Institute for Emergency Medical Services Systems (MIEMSS) is the smoke and carbon monoxide (CO) inhalation referral center for Maryland, particularly Baltimore City and the five surrounding counties. The majority of our patients are from the Baltimore/Washington corridor.

The use of a short screening battery of psychometric tests is an important method for improving the clinical approach to the diagnosis of CO poisoning. Our own experience and a literature survey have shown how poorly the CO level correlates with clinical signs and symptoms. We have reported on six patients who were unconscious from CO poisoning but had a carboxyhemoglobin (HbCO) level of under 1%, and we have seen apparently well oriented patients with HbCO levels of 45%. From these experiences, we have concluded that the HbCO level is only an indicator of exposure to CO, not necessarily of the severity of poisoning. These large discrepancies have necessitated the development of a supplemental test, such as the psychometric battery, to determine generalized cerebral dysfunction.
The Importance of Ketamine and Gamma-Hydroxy-Butyric-Acid as Anesthetics under Disaster Conditions
Authors: Madjidi A.
Published: July 2016

Extensive experiments in animals and humans, as well as clinical experience in disaster areas, have shown that expensive devices and complicated inhalation narcotics are not suited for anesthesia under disaster conditions. Today, the most important drugs are intravenous and, in emergencies, also intramuscular preparations which do not cause any significant central respiratory depression:

1. Ketamine, suited for routine anesthesia under disaster conditions; and

2. Gamma-Hydroxy-Butyric-Acid (Somsanit), suited for poor risk patients with hypoxic injuries and/or shock.
The Red Cross Role in Disaster Preparedness
Authors: Weyand Jürgen
Published: July 2016

We recognize that priorities in disasters are most often the supply of shelter, water and food, but to streamline this paper we have limited ourselves to aspects of Disaster Preparedness pertaining to medical intervention.

It is essential to understand that the overall responsibility in disaster preparedness and for coordination in case of disaster remains under all circumstances with public authorities. National Red Cross Societies, being auxiliary to their governments, are usually given a clearly defined role in disaster. In many cases the tasks assigned to the Red Cross include medical, paramedical and welfare assistance in varying degrees.

The activities described hereafter are therefore not necessarily to be seen as a standard applied to all National Red Cross Societies.
Emergency Preparedness and Disaster Relief Coordination Program of the World Health Organization (Pan American Health Organization, PAHO)
Authors: de Goyet Claude De Ville
Published: July 2016

The Pan American Health Organization (PAHO) has two components: (1) The Pan American Sanitary Bureau (PASB), founded in 1902, serves as the health agency affiliated with the Organization of the American States (OAS); in 1947, the PASB became the Regional office of the World Health Organization for the Americas. (2) The Emergency Preparedness and Disaster Relief Coordination office.

In October 1976, the Directing Council of PAHO, “anxious that the international assistance given to countries affected by natural disasters should be better coordinated, rational, and more effective”, requested that the Director set up a “disaster unit with instructions to define the policy of the Organization, to formulate a plan of action for the various types of disasters, to make an inventory of the human and other resources available, to train the necessary personnel, to prepare and disseminate the appropriate guidelines and manuals, and to promote operational research.” In March 1977, a permanent office for Emergency Preparedness and Disaster Relief Coordination was established at PAHO Headquarters in Washington, D.C.
The Medic-Alert Foundation, International Extension Program
Authors: Hodder Alfred A. , Thompson Douglas S.
Published: July 2016

From the Medic Alert Foundation International, PO Box 1009, Turlock, CA 95381 USA.

Medic Alert Foundation International is dedicated to the thesis that one universally recognized symbol of emergency medical identification will best serve all people. This is why Medic Alert conducts an active program to expand its services internationally.

Volunteer groups in 17 countries presently provide Medic Alert services to over 1.7 million people worldwide. The Foundation's purpose is to give a lifetime of fast reliable protection for a modest, one-time fee. Medic Alert is a non-profit, tax-exempt and charitable organization.

The volunteer organizations in these 17 countries are affiliated with the international headquarters in the United States, but each is autonomous in providing protection to the people of its nation. National boards and staffs actually deliver the total services to their members within their country.
Risk Analysis
Authors: Nehnevajsa Jiri , Swisher Ralph B.
Published: July 2016

Major risks to human health and life are, indeed, as old as life itself. Whether we think of epidemics, hunger and malnutrition, famines, wars, violations of human rights, crime, natural disasters and swarms of other dangers, we cannot but be struck by their pantemporality and ubiquitousness. Acute or chronic, periodic or sporadic, frequent or infrequent, these and other hazards are endemic to the very condition of human existence —unwanted but nonetheless real consequences of being alive and of being social.

It is indeed quite plausible to view some of the central strands and trajectories of human history as efforts to cope with the hazardous conditions of existence: to prevent risks from actualizing, or to mitigate the consequences of hazards which do actualize—those which we have not yet as developed the capability to prevent, and those which we cannot hope to prevent.
Industrial Civil Defense
Authors: Nygaard Herluf
Published: July 2016

Sudden illnesses, accidents, fire catastrophes, explosions, gas leakages and war damage constitute serious threats to industry and other production enterprises all over the world.

To counteract the hazards resulting from such emergencies the Federation of Norwegian Industries in 1948 decided to establish an industrial civil defense organization. The Federation also decided that the industry itself should cover the cost both for operation of a central staff and for organizing and running an industrial civil defense at each individual plant or facility.

In 1953, the organization was legalized through the Norwegian Civil Defense Act and a Royal Decree of 1965 decided that the Industrial Civil Defense central staff should organize and supervise self protection in all enterprises employing 40 or more persons engaged in industrial activity, manufacturing and skilled trades, etc. This applies irrespective of where the facility is situated or where the operation takes place.
Coordination of Responsibilities of Organizations in Disasters
Authors: Tiedeman C. , Oyen O.
Published: July 2016

There are two principal aspects of disaster preparedness. First the daily around the clock routine already existing in ambulance services, hospitals, police forces, firebrigade, voluntary humanitarian organizations, etc. These organizations are occupied daily with accidents, each within their own areas of responsibility, and often in cooperation with each other.

Where people are hurt, medical care will have priority over damage of materials and property. So resuscitation and transport are basic factors in most accidents.

Second, according to the definition of disaster, the problems created by accidents of various types will exceed these daily operating resources. The community must take extraordinary steps to provide rescue and first aid to the victims, and provide fire control, police control, transportation, etc.
Three Fire Disasters
Authors: Layton Thomas R. , Elhauge Einer R.
Published: July 2016

In order to better understand the conditions permitting a fire disaster to occur and to better postulate methods of fire prevention, an historic analysis of three fire disasters was performed. Journalistic accounts, official investigative studies and documents were examined concerning 3 fire disasters: (1) The General Slocum Ship Fire of 1904; (2) the Triangle Shirtwaist Factory Fire of 1911; and (3) the Coconut Grove Nightclub Fire in Boston of 1942. Although the fires occurred on a ship, in a factory, and in a nightclub, several striking similarities were found.

(1) On June 15, 1904, the shipGeneral Slocumembarked on a voyage up New York's East River, that ended in death for 1031 people. The ship, which was constructed entirely of wood, had recently passed inspection. The ship's crew, mostly longshoremen with little sea experience, had never fought a fire at sea. The hatches and bulkheads were flammable, the fire hoses were old and rotten, the fire buckets were out of reach and empty.
The Three Mile Island (TMI) Accident
Authors: MacLeod Gordon K.
Published: July 2016

On March 28,1979, a near nuclear catastrophe occurred at Three Mile Island (TMI) near Harrisburgh, Pennsylvania, USA. I was at that time Pennsylvania's Secretary of Health. It was an accident that just “could not happen.” After all, nuclear power plants were built so safely that they could not possibly affect public health.

As a physician, lam compelled to say that I am unalterably opposed to nuclear warfare. I am sure that most physicians would agree that there can be no adequate preparedness for the devastating medical consequences of nuclear war. Prevention of nuclear war is the only reasonable medical response to the hazards posed by nuclear weapons.

By contrast, many of you may not share my position on nuclear power. Nuclear power can be made relatively safe if we do not ignore the public health lessons of the past. I belive that physicians need to increase and update their understandings of the medical consequences of radiation accidents and be trained to triage and to treat blast, radiation, and burn injuries.
Planning Response to Nuclear Accidents in Peacetime: An Approach which Addresses Recently Described Problems
Authors: Foulke Garrett E. , Hines Horace , Fisher Charles J.
Published: July 2016

The growing number of nuclear power, research, and industrial facilities places increasing numbers of people and places at risk from an accident involving radioactive material. Fortunately, such accidents are infrequent. Unfortunately, this rarity often results in very limited hospital and physician interest and awareness. The incident at the nuclear facility at Three Mile Island (TMI) in Pennsylvania, USA, has demonstrated that despite its rarity, a radiation accident may not only occur, but occur on a scale large enough to require more than the radiation accident protocol which each hospital is required to have. There is a need, therefore, for the incorporation of radiation accidents into disaster planning and triage systems. We address the considerations to be made in planning an emergency medical system's response to a large radiation accident. We describe the application of a triage team in such a plan.
Respiratory Injuries in Earthquakes in Latin America in the 1970's — A Personal Experience in Peru, 1970; Nicaragua, 1972–73; and Guatemala, 1976.
Authors: Hingson Robert A. , Hingson Luke
Published: July 2016

Of the more than one million earthquakes which occur each year on our planet, very few involve areas of major population concentration. During the last decade, however, a significantly large number of earthquakes involved populations in cities or areas of large population density. The injuries, therefore, are multiplied by the collapse of large buildings or of walls of houses of poor design and construction of adobe brick. Crashing upon people asleep, they entrap, entomb or mutilate defenseless and often aged, ill, and diseased and helpless pediatric victims. The three earthquakes we witnessed recently have resulted in 70,000 deaths inPeru;, 12,000 inManagua, Nicaragua;, and 22,000 inGuatemala Cityand large suburban cities.

Most of the injuries are orthopedic fractures. Fatalities often occur from compression and permanent restriction of respiratory movement. These megaton disruptions of the environment cause the following types of respiratory challenge: (l) The unbelievably large and dense dust clouds from falling buildings, created by pulverization of the walls of mud, straw, and limestone, create suffocating chemical damage of some degree to the nasal mucosa, the bronchial tree and the respiratory bronchioles, immediately initiating endothelial edema, airway obstruction and collapse, and irritational bronchitis.
Fatalities from Volcanic Activity
Authors: Dice William H. , Bascom James F.
Published: July 2016

The eruption of Mount Saint Helens in the Cascade Mountain Range of Washington State on 18 May 1980 resulted in a life-threatening and economically disruptive natural disaster that required the mobilization of supportive agencies from the State and Federal government for control. Because of the potential for further eruptions, the mechanism of death for those persons exposed to the initial blast was examined to aid in contingency planning.

Fatalities as a result of the eruption could be attributed to lack of understanding of the danger in the area of the mountain. Although several scientists were killed during the eruption, most were sight-seers who ignored the warning seismic activity and the precautionary blockade of the area. A few were outside of the well-publicized danger zone, but were caught in the rapidly moving mudslides or the ash cloud.
38. Incidence and Nature of Complaints Received in an Urban Fire Rescue System
Authors: LeDuc Todd J. , Goellner William E. , El Sanadi Nabil
Published: July 2016

Objective: To determine the frequency and nature of patient complaints in a large urban Fire Rescue system.

Methods: A two year retrospective review of all unsolicited patient complaints received from any source either internal or external, through our full-time customer service personnel. All customer complaints, concerns and interactions are documented on an interaction form which we reviewed. All complaints were resolved with disposition related to the customer prior to our retrospective study inclusion.

Results: During the study period our Fire Rescue system responded to a total of 169,651 calls for medical assistance. Our division customer service personnel received a total of 87 unsolicited customer complaints (n = 87) regarding the service encounter with Fire Rescue/EMS. This accounts for a 0.0005% rate of customer complaints captured in correlation to total incidents during the study period. The majority of complaints, 27% were related to lost or missing goods. Service that was perceived as uncourteous or inconsiderate after calling 911, accounted for 25% of complaints. Complaints regarding not being transported after calling 911 accounted for 18%. Uncourteous driving or noise of sirens accounted for 7% of complaints. 7% of complaints resulted from not being transported to the hospital of their choice. Actual care received concerns were only 3% of total. Leaving medical objects behind was 2% of the total volume and 4% fit no specific trend.
56. Managed Care Organization Enrollee Utilization of 911 Emergency Medical Services
Authors: Dickinson Edward T. , Verdile Vincent P. , Duncan Timothy B. , Bryant Kerry A.
Published: July 2016

Purpose: The accessibility of emergency medical services (EMS) for enrollees of managed care organizations (MCOs) is currently a topic of national debate. The mechanisms by which enrollees currently enter the EMS system have not been well described. The purpose of this study was to determine how these patients enter our EMS system.

Methods: All enrollees who belong to the region's largest MCO and who were transported to hospital EDs by the paramedic level municipal EMS department were identified from billing records. Members of the MCO are mandated to call the MCO prior to seeking any emergency care. Dispatch logs were then examined to determine the time and origin of the call to the 911 communications center. Patient care records were used to obtain patient age, the level of care (ALS vs. BLS), and whether the ALS patient received medications (ALS Meds).

Results: Over a six month period 195 enrollees were transported to EDs, Three modes of system entry were identified: Group I—enrollees who called 911 directly; Group II—enrollees who called the MCO triage center who then called 911 for the patient; and Group III—enrollees who were sent to the MCO center for evaluation and subsequently the MCO called 911 to transport the patient to the hospital.
02. Flight Paramedics Scope of Practice: Current Level and Breadth
Authors: Hatley Todd , Ma O. John , Weaver Nancy , Strong Donna
Published: July 2016

Objective: The scope of practice (SOP) for flight paramedics (FPs) remains a controversial issue for air medical directors. This study's objective was to determine the current level and breadth of FPs'SOP.

Methods: A 6-item survey of lead FPs in all 158 air medical programs throughout the U.S. The survey addressed five issues: 1)Certifications required of FPs above state certification; 2) Procedures included in SOP; 3) Medications FPs are allowed to administer; and 4) Requirements needed to expand FPs’ SOP. Views on establishing a National FP certification (NFPC) to alter their current SOP.

Results: Survey response was 57% (90/158). Ten responding programs (11%) did not utilize FPs. Of the 80 programs (89%) that utilize FPs, 76 programs (95%) required certification in ACLS, 65 (81%) in PALS, and 50 (63%) in BCLS. Paramedics were allowed to perform cricothyroidotomy in 68 programs (85%), pericardiocentesis in 24 programs (30%), and tube thoracostomy in 23 programs (29%). A wide spectrum of medications were approved for administration by FPs, including streptokinase in 37 programs (46%), r-TPA in 51 (64%), and succinylcholine in 50 (63%). In 61 programs (76%), the SOP was determined solely by the air medical director. Eighteen respondents (23%) believed that the development of a NFPC program would alter their SOP.
03. How Are We Doing? A Survey of Private Internists
Authors: Schneider SM. , Cobaugh DJ , Leahey NF
Published: July 2016

Objective: In our community the majority of patients presenting to the ED with acute chest pain come by car and do not recall their MD suggesting EMS. How do private MD's (our customers) view EMS?

Methods: Single mailing survey to all 238 physicians with admitting privileges in Medicine at an urban, tertiary care hospital (722 beds). EMS services provided by 2 private ALS systems and 35 volunteer ALS services operating under one physician medical director and identical protocols. Survey consisted of a scenario with a cardiac patient in the home of the MD, followed by opinions regarding EMS.

Results: 50% return. Respondents were 79% male, mean age 44 ±14yr, 68% internal medicine, 11% cardiologists. Given a patient with acute chest pain at the MD's home, 90% would call EMS, 10% would drive patient. 16% chose to drive for safety concerns, 83% because it was faster. Of those who chose EMS, 10% made negative comments regarding paramedics “playing doctor”. The following perceptions were noted: 3% of respondents indicated paramedics take “too long” to respond to calls, 26% indicated paramedics delay patient arrival to the hospital, and 6% indicated patients get too nervous if told to take an ambulance. On the other hand, 59% indicated EMS prevents cardiac arrests, 83% indicated paramedics can appropriately treat cardiac arrest, and 13% agreed paramedics can provide similar treatment for chest pain patients as hospitals.
21. Prolonged QT Intervals in Patients with Out-of-Hospital Ventricular Tachycardia Cardiac Arrest
Authors: Brady William , DeBehnke Daniel , Laundrie Dennis , Skiles Jeffrey A.
Published: July 2016

Objective: To determine the prevalence and outcome of out-of-hospital ventricular tachycardia (VT) cardiac arrest with a prolonged QT interval and to identify the subset with torsades de pointes (TdP).

Methods: Design: Retrospective review. Setting: Fire department-based paramedic system. Participants: Non-traumatic VT cardiac arrest (1/91-12/94) with a supraventricular perfusing rhythm (SVPR) and a measurable QT interval. Interventions: QT interval was measured from a SVPR and corrected QT interval (QTc) was calculated (prolonged if ≥0.45 sec). VT was classified as polymorphic or monomorphic.

Results: 190 patients met inclusion criteria. 51% of patients had a prolonged QTc (PQTc). The overall hospital discharge rate was 28.4%. No difference with respect to paramedic-witnessed arrests in each QTc group was found (25.8% normal QTc [NQTc] vs. 27.8% PQTc; p = 0.752). Patients with PQTc were less likely to be discharged from the hospital (19.6% vs. 37.6%; p = 0.01). Patients with PQTc were not more likely to have PVT (37% vs. 40%; p = 0.705). 16 (8.4%) patients had TdP. 27.8% of TdP and 26.8% of non-TdP patients were discharged (p = 0.912).
45. The Impact of an Alert Tone on On-Scene Time in Trauma Patients
Authors: Le Duc Todd J. , Goellner William E. , Sanadi Nabil E.
Published: July 2016

Objective: Determine whether radio alerts to paramedics after 7 minutes of on-scene time reduces total on-scene time for trauma patients.

Methods: Paramedics radio base once they determine ACS criteria were met. Paramedics were informed by radio when 7 minutes lapsed on-scene. Dispatch times were recorded.

Results: The control group (Nov. 1-30, 1995) of 135 consecutive patients were reviewed without a radio alert. The test group (Dec. 1-31, 1995) of 103 consecutive patients, with a radio alert message 7 minutes after scene arrival were also reviewed. Groups were matched for extrication times, blunt versus penetrating trauma, age, etc. We analyzed both groups for the interval of time from announcement of “trauma alert,” (when paramedics determined the patient met ACS criteria or from the time extrication was complete (if applicable) to the time en route to the hospital. Average on-scene time for the control group was 13.7 minutes [range 4-35] versus test group 9.3 minutes [range 2-26] (p <0.001).
49. Waveform Design Based on Cardiac Electrophysiology Can Improve Transchest Defibrillation
Authors: Brewer James , Olson Ken , Steinkogler Gary , Tay Sew-Wah
Published: July 2016

Introduction: Monophasic defibrillation waveforms are presently the standard of care in clinical use for trans-thoracic defibrillation. Recently, there has been renewed interest in biphasic waveforms. This interest reflects the superior performance demonstrated with biphasic waveforms in implantable defibrillators (ICD). External defibrillation research on two biphasic truncated exponential waveforms has been reported in which the waveforms were compared clinically to a damped sine waveform. A limitation of these transthoracic waveforms is the insufficiency of fundamental design principles used to determine the waveform characteristics.

Methods: We developed design principles to determine the optimal waveform characteristics of an external biphasic truncated exponential waveform based on myocardial cell response model. The cell response model incorporates critical transthoracic elements into a recently published and experimentally validated intracardiac model used to design ICD waveforms. We determined the optimal leading-edge voltage (LEV), phase durations (in milliseconds, Ph1 D, Ph2 D), and delivered energies (ED) for the reported external biphasic waveforms (WF) using the model with 78 W for trans-chest resistance. We compared our results against those reported for the biphasic waveforms.
Yale Natural Radiocarbon Measurements V
Authors: Stuiver Minze , Deevey Edward S. , Gralenski L. J.
Published: July 2016

The following list of dates, measured since the publication of Yale IV, includes a few repetitions of published dates, noted as such by the addition ofbisto their number. One of these (Y-140bis) was a new preparation of CO2from a sample previously measured as acetylene; the others are rechecks of repurified CO2, repeated because instrumental difficulties plagued our laboratory throughout the year beginning in September 1958 and might have affected some dates published in Yale IV. No important differences were found, however. Several measurements of geochemical interest, on lake water and other lacustrine materials for which C13analyses have been reported (Oana and Deevey, 1960), are not included here but will form the subject of a separate paper.
The unit of survival
Authors: Ballantyne Andrew
Published: July 2016

We live in ecologies in which the elements connect with one another. If we see elements in isolation then we can believe that we are doing well by proliferating or perfecting an element, but for the ecology to do well everything must be held in balance. We are part of the environment of others, just as they are part of ours. Buildings mediate our relations with one another and with the world. Even some buildings that seem visually isolated, such as the Farnsworth House, are connected to mains services and need the rest of a civilization to be in place if they are to be conceived and maintained. If we think of ourselves as participating in actor-networks, rather than as autonomous individuals with free will to act on our desires, then it becomes possible to articulate ways in which we are enmeshed in our milieu. Our connections in the world are an important part of who we are. The elements of our bodies work together to produce consciousness, but also much else besides. The conscious part of us can articulate how it feels, and what it thinks, so we give it a disproportionate level of attention. In turn, at a larger scale, we participate in entities that act as if they have a will of their own, but they do not necessarily articulate it, but we help them along without necessarily being aware of it. Buildings are involved in establishing functional connections and separations in networks, both domestically, in providing protection and shelter, and economically, in connecting us into the banking and property systems that do much to establish the pattern of our lives. The unit of survival is organism + habitat, and our habitats do not have easily defined local limits.
Machines for living in: Connections and contrasts between designed architecture and the development of living forms
Authors: Davies Jamie A.
Published: July 2016

There is a growing interest in applying principles of biological morphogenesis to architectural practice. Biological morphogenesis differs from conventional architectonics in several important ways; architecture is teleological, biology has no purpose; architecture is blueprinted and top-down, morphogenesis is bottom-up and emergent; construction uses external agents and skills (builders) whereas embryos build themselves from largely internal information; control of construction sites is hierarchical while morphogenesis uses rich feedback and distributed control; biological systems show adaptation and self-repair. Many materials are, however, common to the two, and both use techniques of scaffolding. There are several ways in which the fields can be brought together, either using biological systems directly (for example in synthetic biological approaches), or by engineering inorganic systems to realize the potentially useful processes characteristic of living things, such as automatic adaptation to the environment, and self-repair.
SolarLeaf: The world's first bioreactive façade
Authors: Wurm Jan , Pauli Martin
Published: July 2016

Photobioreactors (pbr) are transparent containers for the controlled cultivation of microorganisms such as algae. The BIQ house is the worlds first architectural project realised featuring flat panel pbr, generating biomass and heat as part of an integrated energy concept. The project is part of the International Building Exhibition (IBA) in Hamburg.

In order to implement this potential disruptive technological innovation, technical, ecological and social aspects have been looked at holistically to optimise and develop the system towards market maturity.

At the foreground of this monitoring project has been the intensive evaluation and optimisation of the energy efficiency of the technology in relation to the acceptance and reception of the building users.

After the successful implementation of the pilot project, a big step towards the market maturity of the system has been taken. Further improvements with respect to the efficiency and a closed value chain are required to demonstrate commercial feasibility and attract investors to implement the system more widely.
Is the Association between Vitamin D and Metabolic Syndrome Independent of Other Micronutrients?
Authors: Khosravi-Boroujeni Hossein , Ahmed Faruk , Sarrafzadegan Nizal
Published: July 2016

Abstract. The incidence of metabolic syndrome (MetS) has been increasing globally and it is recognized as a major public health problem because MetS is associated with increased risk of diabetes, stroke, cancer, and other chronic diseases. Recently, MetS has been linked to vitamin D deficiency. However, the evidence on the association between vitamin D deficiency and the risk of MetS remains inconclusive. This review therefore aims to depict the existing evidence related to MetS and vitamin D deficiency, and examined some of the possible confounders which may affect the association between vitamin D status and risk of MetS. Earlier studies on the association between vitamin D deficiency and MetS have adjusted for the effect of some confounders including, age, sex, body mass index, race, physical activity, smoking, alcohol consumption, and energy intake. However, these studies failed to consider other potential confounders. There is evidence that vitamin A, zinc (Zn), and magnesium (Mg) play important roles in the activation and function of vitamin D and interact with gene expression. Furthermore, these micronutrients are also related to several components of the MetS including glucose intolerance, dyslipidemia, and obesity. Thus, there could be an interaction between these micronutrients, vitamin D, and MetS. This review highlights the possible interactions of vitamin A, Zn, Mg, and vitamin D with MetS and its components. The findings reinforce the need for further well-designed studies that take into account all potential confounders, including other micronutrients such as vitamin A, Zn, and Mg status, to investigate the independent association of vitamin D status with MetS and its components, and also to scrutinize for possible interactions among other nutrients which may have similar confounding effects.
Hypoxia-driven splicing into noncoding isoforms regulates the DNA damage response
Authors: Memon Danish , Dawson Keren , Smowton Christopher SF , Xing Wei , Dive Caroline , Miller Crispin J
Published: July 2016

Tumour hypoxia is associated with poor patient outcome and resistance to therapy. It is accompanied by widespread changes in gene expression mediated largely through the transcription factors HIF1/2/3α. Hypoxia impacts on multiple pathways throughout the cell and has widespread effects on phenotype. Here we use sample-specific annotation approaches to determine the changes in transcript architecture that arise as result of alternative splicing in hypoxic cells. Using in vivo data generated from a time course in reduced oxygenation we identified genome-wide switching between coding and noncoding isoforms, including a significant number of components of the DNA damage response pathway. Notably, HDAC6, a master regulator of the cytotoxic response, and TP53BP1, which sits at the nexus of the double-strand break repair pathway, both underwent a marked transition towards an intron-retention pattern with a concomitant decline in protein levels. These transitions from coding to noncoding isoforms were recapitulated in a large and independent cohort of 499 colorectal samples taken from The Cancer Genome Atlas (TCGA). The set of altered genes was enriched for multiple components of the Fanconi Anaemia, nucleotide excision and double-strand break repair pathways, and together correlating with tumour status at last contact. Altogether, these data demonstrate a new role for hypoxia-driven alternative splicing in regulating DNA damage response, and highlight the importance of considering alternative splicing as a critical factor in our understanding of human disease.
Modulation Instability and Phase-Shifted Fermi-Pasta-Ulam Recurrence
Authors: Kimmoun O. , Hsu H. C. , Branger H. , Li M. S. , Chen Y. Y. , Kharif C. , Onorato M. , Kelleher E. J. R. , Kibler B. , Akhmediev N. , Chabchoub A.
Published: July 2016

Instabilities are common phenomena frequently observed in nature, sometimes leading to unexpected catastrophes and disasters in seemingly normal conditions. One prominent form of instability in a distributed system is its response to a harmonic modulation. Such instability has special names in various branches of physics and is generally known as modulation instability (MI). The MI leads to a growth-decay cycle of unstable waves and is therefore related to Fermi-Pasta-Ulam (FPU) recurrence since breather solutions of the nonlinear Schrödinger equation (NLSE) are known to accurately describe growth and decay of modulationally unstable waves in conservative systems. Here, we report theoretical, numerical and experimental evidence of the effect of dissipation on FPU cycles in a super wave tank, namely their shift in a determined order. In showing that ideal NLSE breather solutions can describe such dissipative nonlinear dynamics, our results may impact the interpretation of a wide range of new physics scenarios.
Co-regulation of the Notch and Wnt signaling pathways promotes supporting cell proliferation and hair cell regeneration in mouse utricles
Authors: Wu Jingfang , Li Wenyan , Lin Chen , Chen Yan , Cheng Cheng , Sun Shan , Tang Mingliang , Chai Renjie , Li Huawei
Published: July 2016

This work sought to determine the crosstalk between the Notch and Wnt signaling pathways in regulating supporting cell (SC) proliferation and hair cell (HC) regeneration in mouse utricles. We cultured postnatal day (P)3 and P60 mouse utricles, damaged the HCs with gentamicin, and treated the utricles with the γ-secretase inhibitor DAPT to inhibit the Notch pathway and with the Wnt agonist QS11 to active the Wnt pathway. We also used Sox2-CreER, Notch1-flox (exon 1), and Catnb-flox (exon 3) transgenic mice to knock out the Notch pathway and activate the Wnt pathway in Sox2+ SCs. Notch inhibition alone increased SC proliferation and HC number in both undamaged and damaged utricles. Wnt activation alone promoted SC proliferation, but the HC number was not significantly increased. Here we demonstrated the cumulative effects of Notch inhibition and Wnt activation in regulating SC proliferation and HC regeneration. Simultaneously inhibiting Notch and overexpressing Wnt led to significantly greater SC proliferation and greater numbers of HCs than manipulating either pathway alone. Similar results were observed in the transgenic mice. This study suggests that the combination of Notch inhibition and Wnt activation can significantly promote SC proliferation and increase the number of regenerated HCs in mouse utricle.
Self-Similar Random Process and Chaotic Behavior In Serrated Flow of High Entropy Alloys
Authors: Chen Shuying , Yu Liping , Ren Jingli , Xie Xie , Li Xueping , Xu Ying , Zhao Guangfeng , Li Peizhen , Yang Fuqian , Ren Yang , Liaw Peter K.
Published: July 2016

The statistical and dynamic analyses of the serrated-flow behavior in the nanoindentation of a high-entropy alloy, Al0.5CoCrCuFeNi, at various holding times and temperatures, are performed to reveal the hidden order associated with the seemingly-irregular intermittent flow. Two distinct types of dynamics are identified in the high-entropy alloy, which are based on the chaotic time-series, approximate entropy, fractal dimension and Hurst exponent. The dynamic plastic behavior at both room temperature and 200 °C exhibits a positive Lyapunov exponent, suggesting that the underlying dynamics is chaotic. The fractal dimension of the indentation depth increases with the increase of temperature and there is an inflection at the holding time of 10 s at the same temperature. A large fractal dimension suggests the concurrent nucleation of a large number of slip bands. In particular, for the indentation with the holding time of 10 s at room temperature, the slip process evolves as a self-similar random process with a weak negative correlation similar to a random walk.
Structural and thermodynamic basis of proline-induced transmembrane complex stabilization
Authors: Schmidt Thomas , Situ Alan J. , Ulmer Tobias S.
Published: July 2016

In membrane proteins, proline-mediated helix kinks are indispensable for the tight packing of transmembrane (TM) helices. However, kinks invariably affect numerous interhelical interactions, questioning the acceptance of proline substitutions and evolutionary origin of kinks. Here, we present the structural and thermodynamic basis of proline-induced integrin αIIbβ3 TM complex stabilization to understand the introduction of proline kinks in membrane proteins. In phospholipid bicelles, the A711P substitution in the center of the β3 TM helix changes the direction of adjacent helix segments to form a 35 ± 2° angle and predominantly repacks the segment in the inner membrane leaflet due to a swivel movement. This swivel repacks hydrophobic and electrostatic interhelical contacts within intracellular lipids, resulting in an overall TM complex stabilization of −0.82 ± 0.01 kcal/mol. Thus, proline substitutions can directly stabilize membrane proteins and such substitutions are proposed to follow the structural template of integrin αIIbβ3(A711P).
CEACAM1 mediates B cell aggregation in central nervous system autoimmunity
Authors: Rovituso Damiano M. , Scheffler Laura , Wunsch Marie , Kleinschnitz Christoph , Dörck Sebastian , Ulzheimer Jochen , Bayas Antonios , Steinman Lawrence , Ergün Süleyman , Kuerten Stefanie
Published: July 2016

B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1+ B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain −3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.
Myeloid Deletion of Nemo Causes Osteopetrosis in Mice Owing to Upregulation of Transcriptional Repressors
Authors: Swarnkar Gaurav , Shim Kyuhwan , Nasir Amjad M. , Seehra Kuljeet , Chen Hung-Po , Mbalaviele Gabriel , Abu-Amer Yousef
Published: July 2016

The transcription factor NF-κB is central to numerous physiologic processes including bone development, and its activation is controlled by IKKγ (also called NEMO), the regulatory subunit of IKK complex. NEMO is X-linked, and mutations in this gene result in Incontinentia Pigmenti in human hemizygous females. In mice, global deficiency causes embryonic lethality. In addition, certain point mutations in the NEMO (IKBKG) human gene manifest skeletal defects implicating NEMO in the regulation of bone homeostasis. To specifically investigate such role, we conditionally deleted Nemo from osteoclast and myeloid progenitors. Morphometric, histologic, and molecular analyses demonstrate that myeloid NEMO deletion causes osteopetrosis in mice. Mechanistically, NEMO deficiency hampered activation of IKK complex in osteoclast precursors, causing arrest of osteoclastogenesis and apoptosis. Interestingly, inhibiting apoptosis by genetic ablation of TNFr1 significantly increased cell survival, but failed to rescue osteoclastogenesis or reverse osteopetrosis. Based on this observation, we analyzed the expression of different regulators of osteoclastogenesis and discovered that NEMO deletion leads to increased RBPJ expression, resulting in a decrease of Blimp1 expression. Consequently, expression of IRF8 and Bcl6 which are targets of Blimp1 and potent osteoclastogenic transcriptional repressors, is increased. Thus, NEMO governs survival and osteoclast differentiation programs through serial regulation of multiple transcription factors.
Depressive symptoms as a side effect of Interferon-α therapy induced by induction of indoleamine 2,3-dioxygenase 1
Authors: Murakami Yuki , Ishibashi Takaaki , Tomita Eiichi , Imamura Yukio , Tashiro Tomoyuki , Watcharanurak Kanitta , Nishikawa Makiya , Takahashi Yuki , Takakura Yoshinobu , Mitani Satoko , Fujigaki Hidetsugu , Ohta Yoshiji , Kubo Hisako , Mamiya Takayoshi , Nabeshima Toshitaka , Kim Hyoung-Chun , Yamamoto Yasuko , Saito Kuniaki
Published: July 2016

Depression is known to occur frequently in chronic hepatitis C viral (HCV) patients receiving interferon (IFN)-α therapy. In this study, we investigated whether indoleamine 2,3-dioxygenase1 (IDO1)-mediated tryptophan (TRP) metabolism plays a critical role in depression occurring as a side effect of IFN-α therapy. Increases in serum kynurenine (KYN) and 3-hydroxykynurenine (3-HK) concentrations and in the ratios of KYN/TRP and 3-HK/kynurenic acid (KA) were much larger in depressive HCV patients than in non-depressed patients following therapy. Furthermore, transfection of a plasmid continuously expressing murine IFN-γ into normal mice significantly increased depression-like behavior. IFN-γ gene transfer also resulted in a decrease in serum TRP levels in the mice while KYN and 3-HK levels were significantly increased in both serum and frontal cortex. Genetic deletion of IDO1 in mice abrogated both the increase in depression-like behavior and the elevation in TRP metabolites’ levels, and the turnover of serotonin in the frontal cortex after IFN-γ gene transfer. These results indicate that the KYN pathway of IDO1-mediated TRP metabolism plays a critical role in depressive symptoms associated with IFN-α therapy.
The myocardial regenerative potential of three-dimensional engineered cardiac tissues composed of multiple human iPS cell-derived cardiovascular cell lineages
Authors: Masumoto Hidetoshi , Nakane Takeichiro , Tinney Joseph P. , Yuan Fangping , Ye Fei , Kowalski William J. , Minakata Kenji , Sakata Ryuzo , Yamashita Jun K. , Keller Bradley B.
Published: July 2016

Human induced pluripotent stem cells (hiPSCs) are a robust source for cardiac regenerative therapy due to their potential to support autologous and allogeneic transplant paradigms. The in vitro generation of three-dimensional myocardial tissue constructs using biomaterials as an implantable hiPSC-derived myocardium provides a path to realize sustainable myocardial regeneration. We generated engineered cardiac tissues (ECTs) from three cellular compositions of cardiomyocytes (CMs), endothelial cells (ECs), and vascular mural cells (MCs) differentiated from hiPSCs. We then determined the impact of cell composition on ECT structural and functional properties. In vitro force measurement showed that CM+EC+MC ECTs possessed preferential electromechanical properties versus ECTs without vascular cells indicating that incorporation of vascular cells augmented tissue maturation and function. The inclusion of MCs facilitated more mature CM sarcomeric structure, preferential alignment, and activated multiple tissue maturation pathways. The CM+EC+MC ECTs implanted onto infarcted, immune tolerant rat hearts engrafted, displayed both host and graft-derived vasculature, and ameliorated myocardial dysfunction. Thus, a composition of CMs and multiple vascular lineages derived from hiPSCs and incorporated into ECTs promotes functional maturation and demonstrates myocardial replacement and perfusion relevant for clinical translation.
Research on the printability of hydrogels in 3D bioprinting
Authors: He Yong , Yang FeiFei , Zhao HaiMing , Gao Qing , Xia Bing , Fu JianZhong
Published: July 2016

As the biocompatible materials, hydrogels have been widely used in three- dimensional (3D) bioprinting/organ printing to load cell for tissue engineering. It is important to precisely control hydrogels deposition during printing the mimic organ structures. However, the printability of hydrogels about printing parameters is seldom addressed. In this paper, we systemically investigated the printability of hydrogels from printing lines (one dimensional, 1D structures) to printing lattices/films (two dimensional, 2D structures) and printing 3D structures with a special attention to the accurate printing. After a series of experiments, we discovered the relationships between the important factors such as air pressure, feedrate, or even printing distance and the printing quality of the expected structures. Dumbbell shape was observed in the lattice structures printing due to the hydrogel diffuses at the intersection. Collapses and fusion of adjacent layer would result in the error accumulation at Z direction which was an important fact that could cause printing failure. Finally, we successfully demonstrated a 3D printing hydrogel scaffold through harmonize with all the parameters. The cell viability after printing was compared with the casting and the results showed that our bioprinting method almost had no extra damage to the cells.