E-bike injuries: experience from an urban emergency department-a retrospective study from Switzerland.

Background. Between 2005 and 2012, annual sales of E-bikes in Switzerland increased from 1,792 to 52,941. This continuous and rapid transition from human-powered bicycles to an electric bicycle technology may indicate the increasing demand for low-cost transportation technology in combination with a healthy lifestyle. Material and Methods. In the present study, from April 2012 to September 2013, we retrospectively analysed E-bike accidents treated in the Emergency Department of our hospital by focusing on the following parameters: age, gender, time, period, and cause of the accident, as well as injury and outcome. Results. Patients were predominantly male. The mean age of injured E-cyclists was 47.5 years. The main causes of injury were self-accident. Most injuries were to the head/neck. The mean ISS was 8.48. The outcome showed that 9 patients were treated as outpatients, 9 were inpatients, and 5 patients were kept in the Intensive Care Unit (ICU). Only six patients underwent surgery (S). Discussion. This is the first attempt to evaluate E-bike injuries in Switzerland in an acute hospital setting. Since there is increasing popular preference for E-bikes as means of transportation and injuries to the head or neck are prevalent among E-cyclists, the hazard should not to be underestimated.

Application, tolerance and safety of fondaparinux therapy in a German hospital: a prospective single-centre experience.

INTRODUCTION The pentasaccharide fondaparinux is widely approved for prophylaxis and treatment of thromboembolic diseases and therapy of acute coronary syndrome. It is also used off-label in patients with acute, suspected or antecedent heparin-induced thrombocytopenia (HIT). The aim of this prospective observational cohort study was to document fondaparinux' prescription practice, tolerance and therapy safety in a representative mixed German single-centre patient cohort. PATIENTS AND METHODS Between 09/2008 - 04/2009, 231 consecutive patients treated with fondaparinux were enrolled. Medical data were obtained from patient's records. The patients were clinically screened for thrombosis (Wells score), sequelae of HIT (4T's score), and bleeding complications (ISTH-criteria) and subjected to further assessment (i.e. sonography, HIT-diagnostics), if necessary. The mortality rate was assessed 30 days after therapy start. RESULTS Overall, 153/231 patients had a prophylactic, 74/231 patients a therapeutic, and 4/231 patients a successive prophylactic/therapeutic indication. In 11/231 patients fondaparinux was used due to suspected/antecedent HIT, in 5/231 patients due to a previous cutaneous delayed-type hypersensitivity to heparins. Other indications were rare. Three new/progressive thromboses were detected. No cases of HIT, major bleedings, or fatalities occurred. CONCLUSIONS Fondaparinux was well tolerated and was safe in prophylaxis and therapy; prescriptions mostly followed the current approval guidelines and were rarely related to HIT-associated indications (<5% of prescriptions), which is in contrast to previous study results in the U.S. (>94% of prescriptions were HIT-associated). A trend towards an individualised fondaparinux use based on the compound's inherent properties and the patients' risk profiles, i.e., antecedent HIT, bone fractures, heparin allergy, was observed.

Visual Hallucinations in Eye Disease and Lewy Body Disease

Objective: Visual hallucinations (VH) most commonly occur in eye disease (ED), Parkinson’s disease (PD), and Lewy body dementia (LBD). The phenomenology of VH is likely to carry important information about the brain areas within the visual system generating them. Methods: Data from five controlled cross-sectional VH studies (164 controls, 135 ED, 156 PD, 79 (PDD 48 + DLB 31) LBD) were combined and analysed. The prevalence, phenomenology, frequency, duration, and contents of VH were compared across diseases and gender. Results: Simple VH were most common in ED patients (ED 65% vs. LBD 22% vs. PD 9%, Chi-square [χ2] test: χ2=31.43, df=2, p<0.001), whilst complex VH were more common in LBD (LBD 76% vs. ED 38%, vs PD 28%, Chi-square test: χ2=96.80, df=2, p<0.001). The phenomenology of complex VH was different across diseases and gender. ED patients reported more “flowers” (ED 21% vs. LBD 6% vs. PD 0%, Chi-square test: χ2=10.04, df=2, p=0.005) and “body parts” (ED 40% vs. LBD 17% vs. PD 13%, Chi-square test: χ2=11.14, df=2, p=0.004); in contrast LBD patients reported “people” (LBD 85% vs. ED 67% vs. PD 63%, Chi-square test: χ2=6.20, df=2, p=0.045) and “animals/insects” (LBD 50% vs. PD 42% vs. ED 21%, Chi-square test: χ2=9.76, df=2, p=0.008). Males reported more “machines” (13 % vs. 2%, Chi-square test: χ2=6.94, df=1, p=0.008), whilst females reported more “family members/children” (48% vs. 29%, Chi-square test: χ2=5.10, df=1, p=0.024). Conclusions: The phenomenology of VH is likely related to disease specific dysfunctions within the visual system and to past, personal experiences.

Immune cell trafficking across the barriers of the central nervous system in multiple sclerosis and stroke

Each year about 650,000 Europeans die from stroke and a similar number lives with the sequelae of multiple sclerosis (MS). Stroke and MS differ in their etiology. Although cause and likewise clinical presentation set the two diseases apart, they share common downstream mechanisms that lead to damage and recovery. Demyelination and axonal injury are characteristics of MS but are also observed in stroke. Conversely, hallmarks of stroke, such as vascular impairment and neurodegeneration, are found in MS. However, the most conspicuous common feature is the marked neuroinflammatory response, marked by glia cell activation and immune cell influx. In MS and stroke the blood-brain barrier is disrupted allowing bone marrow-derived macrophages to invade the brain in support of the resident microglia. In addition, there is a massive invasion of auto-reactive T-cells into the brain of patients with MS. Though less pronounced a similar phenomenon is also found in ischemic lesions. Not surprisingly, the two diseases also resemble each other at the level of gene expression and the biosynthesis of other proinflammatory mediators. While MS has traditionally been considered to be an autoimmune neuroinflammatory disorder, the role of inflammation for cerebral ischemia has only been recognized later. In the case of MS the long track record as neuroinflammatory disease has paid off with respect to treatment options. There are now about a dozen of approved drugs for the treatment of MS that specifically target neuroinflammation by modulating the immune system. Interestingly, experimental work demonstrated that drugs that are in routine use to mitigate neuroinflammation in MS may also work in stroke models. Examples include Fingolimod, glatiramer acetate, and antibodies blocking the leukocyte integrin VLA-4. Moreover, therapeutic strategies that were discovered in experimental autoimmune encephalomyelitis (EAE), the animal model of MS, turned out to be also effective in experimental stroke models. This suggests that previous achievements in MS research may be relevant for stroke. Interestingly, the converse is equally true. Concepts on the neurovascular unit that were developed in a stroke context turned out to be applicable to neuroinflammatory research in MS. Examples include work on the important role of the vascular basement membrane and the BBB for the invasion of immune cells into the brain. Furthermore, tissue plasminogen activator (tPA), the only established drug treatment in acute stroke, modulates the pathogenesis of MS. Endogenous tPA is released from endothelium and astroglia and acts on the BBB, microglia and other neuroinflammatory cells. Thus, the vascular perspective of stroke research provides important input into the mechanisms on how endothelial cells and the BBB regulate inflammation in MS, particularly the invasion of immune cells into the CNS. In the current review we will first discuss pathogenesis of both diseases and current treatment regimens and will provide a detailed overview on pathways of immune cell migration across the barriers of the CNS and the role of activated astrocytes in this process. This article is part of a Special Issue entitled: Neuro inflammation: A common denominator for stroke, multiple sclerosis and Alzheimer's disease, guest edited by Helga de Vries and Markus Swaninger.

Thrombosis during pregnancy: Risks, prevention, and treatment for mother and fetus--harvesting the power of omic technology, biomarkers and in vitro or in vivo models to facilitate the treatment of thrombosis

Maternal thromboembolism and a spectrum of placenta-mediated complications including the pre-eclampsia syndromes, fetal growth restriction, fetal loss, and abruption manifest a shared etiopathogenesis and predisposing risk factors. Furthermore, these maternal and fetal complications are often linked to subsequent maternal health consequences that comprise the metabolic syndrome, namely, thromboembolism, chronic hypertension, and type II diabetes. Traditionally, several lines of evidence have linked vasoconstriction, excessive thrombosis and inflammation, and impaired trophoblast invasion at the uteroplacental interface as hallmark features of the placental complications. "Omic" technologies and biomarker development have been largely based upon advances in vascular biology, improved understanding of the molecular basis and biochemical pathways responsible for the clinically relevant diseases, and increasingly robust large cohort and/or registry based studies. Advances in understanding of innate and adaptive immunity appear to play an important role in several pregnancy complications. Strategies aimed at improving prediction of these pregnancy complications are often incorporating hemodynamic blood flow data using non-invasive imaging technologies of the utero-placental and maternal circulations early in pregnancy. Some evidence suggests that a multiple marker approach will yield the best performing prediction tools, which may then in turn offer the possibility of early intervention to prevent or ameliorate these pregnancy complications. Prediction of maternal cardiovascular and non-cardiovascular consequences following pregnancy represents an important area of future research, which may have significant public health consequences not only for cardiovascular disease, but also for a variety of other disorders, such as autoimmune and neurodegenerative diseases.

Implant therapy in a surgical specialty clinic: an analysis of patients, indications, surgical procedures, risk factors, and early failures

PURPOSE The aim of this study was to analyze the patient pool referred to a specialty clinic for implant surgery over a 3-year period. MATERIALS AND METHODS All patients receiving dental implants between 2008 and 2010 at the Department of Oral Surgery and Stomatology were included in the study. As primary outcome parameters, the patients were analyzed according to the following criteria: age, sex, systemic diseases, and indication for therapy. For the inserted implants, the type of surgical procedure, the types of implants placed, postsurgical complications, and early failures were recorded. A logistic regression analysis was performed to identify possible local and systemic risk factors for complications. As a secondary outcome, data regarding demographics and surgical procedures were compared with the findings of a historic study group (2002 to 2004). RESULTS A total of 1,568 patients (792 women and 776 men; mean age, 52.6 years) received 2,279 implants. The most frequent indication was a single-tooth gap (52.8%). Augmentative procedures were performed in 60% of the cases. Tissue-level implants (72.1%) were more frequently used than bone-level implants (27.9%). Regarding dimensions of the implants, a diameter of 4.1 mm (59.7%) and a length of 10 mm (55.0%) were most often utilized. An early failure rate of 0.6% was recorded (13 implants). Patients were older and received more implants in the maxilla, and the complexity of surgical interventions had increased when compared to the patient pool of 2002 to 2004. CONCLUSION Implant therapy performed in a surgical specialty clinic utilizing strict patient selection and evidence-based surgical protocols showed a very low early failure rate of 0.6%.

Concise Asymmetric Synthesis and Pharmacological Characterization of All Stereoisomers of Glutamate Transporter Inhibitor TFB-TBOA and Synthesis of EAAT Photoaffinity Probes

Glutamate is the major excitatory neurotransmitter in the mammalian brain. Its rapid clearance after the release into the synaptic cleft is vital in order to avoid toxic effects and is ensured by several transmembrane transport proteins, so-called excitatory amino acid transporters (EAATs). Impairment of glutamate removal has been linked to several neurodegenerative diseases and EAATs have therefore received increased attention as therapeutic targets. O-benzylated L-threo-β-hydroxyaspartate derivatives have been developed previously as highly potent inhibitors of EAATs with TFB-TBOA ((2S,3S)-2-amino-3-((3-(4-(trifluoromethyl)benzamido)benzyl)oxy)succinic acid) standing out as low-nanomolar inhibitor. We report the stereoselective synthesis of all four stereoisomers of TFB-TBOA in less than a fifth of synthetic steps than the published route. For the first time, the inhibitory activity and isoform selectivity of these TFB-TBOA enantio- and diastereomers were assessed on human glutamate transporters EAAT1-3. Furthermore, we synthesized potent photoaffinity probes based on TFB-TBOA using our novel synthetic strategy.

Joining the dots - understanding the complex interplay between the values we place on wildlife, biodiversity conservation, human and animal health: A review.

The value of wildlife has long been ignored or under-rated. However, growing concerns about biodiversity loss and emerging diseases of wildlife origin have enhanced debates about the importance of wildlife. Wildlife-related diseases are viewed through these debates as a potential threat to wildlife conservation and domestic animal and human health. This article provides an overview of the values we place on wildlife (positive: socio-cultural, nutritional, economic, ecological; and negative: damages, health issues) and of the significance of diseases for biodiversity conservation. It shows that the values of wildlife, the emergence of wildlife diseases and biodiversity conservation are closely linked. The article also illustrates why investigations into wildlife diseases are now recognized as an integral part of global health issues. The modern One Health concept requires multi-disciplinary research groups including veterinarians, human physicians, ecologists and other scientists collaborating towards a common goal: prevention of disease emergence and preservation of ecosystems, both of which are essential to protect human life and well-being.

Experiences with a voluntary surveillance system for early detection of equine diseases in Switzerland

Clinical observations made by practitioners and reported using web- and mobile-based technologies may benefit disease surveillance by improving the timeliness of outbreak detection. Equinella is a voluntary electronic reporting and information system established for the early detection of infectious equine diseases in Switzerland. Sentinel veterinary practitioners have been able to report cases of non-notifiable diseases and clinical symptoms to an internet-based platform since November 2013. Telephone interviews were carried out during the first year to understand the motivating and constraining factors affecting voluntary reporting and the use of mobile devices in a sentinel network. We found that non-monetary incentives attract sentinel practitioners; however, insufficient understanding of the reporting system and of its relevance, as well as concerns over the electronic dissemination of health data were identified as potential challenges to sustainable reporting. Many practitioners are not yet aware of the advantages of mobile-based surveillance and may require some time to become accustomed to novel reporting methods. Finally, our study highlights the need for continued information feedback loops within voluntary sentinel networks.

Current United States stem cell policy considerations and a recommendation for an alternative policy based on guidelines from existing international policies

Embryonic stem cell research is a widely debated topic in modern politics and religion. Differing views on the fetal rights conflict with the rights of an embryo. Those who believe an embryo has the same human qualities as a fetus accordingly believe embryonic stem cell research is unethical because it destroys a potential human life. However, scientists advocate the embryo does not have human qualities and should be used for valuable research in the stem cell field. Stem cell research may lead to vast developments in medical treatments, including cancer and brain conditions and injuries that are currently incurable. ^ The current stem cell policy introduced by President Bush in 2001 in an attempt to balance the moral issues with the need for scientific research has broad negative implications on the furthering of stem cell research. There is a limited diversity of available stem cell lines, there may be constitutional issues, there is an increasing disparity between the public and private research spheres, and the U.S. is struggling to maintain its scientific community. The U.S. must develop a new stem cell research policy that will balance the interest of science and public health with the moral issues that concern the public. ^ The United Kingdom allows researchers great liberty in conducting research, permitting the creation of embryos for the sole purpose of research, while Germany is equally conservative in their laws, as their policies support the philosophy that all embryos deserve the protection of full life. The United States should adopt a policy that takes the "middle ground" approach and permit research on excess embryos created for IVF purposes, rather than simply discarding those potentially valuable research tools. ^

The eukaryotic cellular stress response: Biochemical and genetic analyses in Saccharomyces cerevisiae

All cells must have the ability to deal with a variety of environmental stresses. Failure to correctly adapt to and/or protect against adverse stress conditions can lead to cell death. In humans, stress response defects have been linked to a number of neurodegenerative diseases and cancer, underscoring the importance of developing a fundamental understanding of the eukaryotic stress response.^ In an effort to characterize cellular response to high temperature stress, I identified and described one member of a novel gene family— RTR1. I show that the RTR1 gene and its protein product genetically and biochemically interact with core subunits of the RNA polymerase II enzyme. Appropriately, loss of RTR1 results in defective transcription from multiple promoters. These data provide evidence that Rtr1, which is essential under stress conditions, acts as a key regulator of transcription.^ In addition to transcriptional regulation, cells deal with many stressors by inducing molecular chaperones. Molecular chaperones are ubiquitous in all living cells and bind unfolded or damaged proteins and catalyze refolding or degradation. Hsp90 is a unique chaperone because it targets specific clients—typically signaling proteins—for maturation. While it has been shown that Sse1, the yeast Hsp110, is a critical regulator of the Hsp90 chaperone cycle, this work describes the molecular basis for that regulation. I show that Sse1 modulates Hsp90 function through regulation of Hsp70 nucleotide exchange. Further, Hsp110-type nucleotide exchange factors (NEFs) appear to have a specific role in modulating Hsp90 function in this manner. Finally, in addition to Hsp110, the eukaryotic cytosol contains two other types of Hsp70 NEF: Snl1 (BAG-domain protein) and Fes1 (HspBP1-like protein). I investigated the cellular roles of these NEFs to better understand the reason that eukaryotic cells contain three distinct protein families that perform the same biochemical function. I show that while cytsolic Hsp70 NEFs have some degree of functional overlap, they also exhibit striking divergence. Taken together, the work presented in this dissertation provides a more detailed understanding of the eukaryotic stress response. ^

Occupational injuries among day laborers in Houston

Research has indicated that day laborers engage in higher risk occupations and suffer a high number of occupationally related fatal and non-fatal injuries. Although there have been some studies focusing on immigrant workers and their occupational injuries, none to our knowledge has studied Houston’s day laborers. An exploratory study of Houston’s day laborer population was conducted in 2008 by Dr. Fernández-Esquer from the University of Texas. ^ The aims of the current study are to analyze secondary data from this parent study and describe the prevalence of the self reported occupational injuries among Houston immigrant day laborers seeking work during the months of October through December 2008. The study also aims to determine if the reported injuries varied by age group, education level, length of time living in the U.S. and length of time working as day laborers and describe if injuries were more common by the number of different job types or job conditions reported or the use of personal protective equipment used (PPE). ^ This study analyzed 325 questionnaires that included job-related information from the parent study. One hundred and nine workers (35 %) reported an occupational injury or illness in the year before the interview. The most frequent injuries or illnesses reported were falls (26.7 %), cuts and lacerations (23.3 %) and being struck by an object (18.3 %). Over half of the workers (57 %) reported working 4 to 6 different jobs in the year before the interview, followed by 22.5 % reporting 1 to 3 different jobs. A combined 79 % of day laborers in Houston reported exposure to 7 or more of the job conditions listed and 69 % of those workers also reported an injury or illness. PPE use varied from 44 % of workers reporting using 4 to 6 PPE items to 6.8 % reporting not using any type of PPE. Thirty two percent of workers reporting not using any PPE also reported an injury or illness. ^ Injuries were found not to have varied significantly by age group, time living in the US, time working as a day laborer, numbers of different job types and the number of PPE used. Injuries did vary significantly by education level of the participants and the number of different job conditions reported (education, X2 (4, N = 315) = 12.651, p =0.013; and job conditions, X2 (3, N = 319) = 14.698, p = 0.002). ^ Although this first study of Houston’s day laborers was successful at engaging the population and getting background information regarding the occupational health of these workers, more studies are needed to further characterize the day laborers occupational experiences and injuries along with determining what specific job types and job conditions were present when injuries occurred and what kind of PPE was being used at the time. It is also clear that these workers need better safety training programs regarding working in potentially dangerous jobs and job conditions. They would also benefit from programs that would help empower them to negotiate for safer conditions.^

ALLERGEN SENSITIZATION AND IMMUNOMODULATION BY SYNTHETIC LIGANDS, PUL-042, IN AN ALLERGEN-INDUCED ASTHMA MURINE MODEL

Allergen-induced asthma is the leading form of asthma and a chronic condition worldwide. Common allergens are known to contribute to the pathogenesis of this disease. Murine models of allergic asthma have mostly used an intraperitoneal route of sensitization (not airway) to study this disease. Allergic asthma pathophysiology involves the activation of TH2-specific cells, which triggers production of IgE antibodies, the up-regulation of TH2-specific cytokines (i.e. IL-4, IL-5, IL-9 and IL-13), increased airway eosinophilia, and mucin hypersecretion. Although there are several therapeutics currently treating asthmatic patients, some of these treatments can result in drug tolerance and may be linked to increased mortality. CpG oligodeoxynucleotides (ODNs) is a synthetic ligand that targets Toll-like Receptor (TLR) 9. It has been evaluated as a therapeutic agent for the treatment of cancer, infectious diseases, and for treating allergy and asthma. PUL-042 is also a synthetic TLR ligand and is composed of two agonists against TLR2/6 heterodimer and TLR9. Previous studies have evaluated PUL-042 for its ability to confer resistance against bacterial and viral lung infection. These findings, combined with studies performed using CpG ODNs, led to speculation that PUL-042 dampens the immune response in allergen-induced asthma. My thesis research investigated airway route sensitization and airway delivery of PUL-042 to evaluate its effects in reducing an allergen-induced asthma phenotype in a murine model. The results of this study contribute to the foundation for future investigations to evaluate the efficacy of PUL-042 as a novel therapy in allergic-asthma disease.

Mind-body therapy use among U.S. children and adolescents

The use of complementary and alternative medicine (CAM) has increased dramatically in the United States in the past several decades. While botanicals and dietary supplements have received the majority of attention in the popular and scholarly literature on alternative therapies, mind-body therapies, such as biofeedback, meditation, hypnosis, massage and chiropractic care presently constitute a large portion of the American public's use of CAM. The present study explores the patterns and prevalence of such therapy use among an under-studied population of CAM users: children and adolescents. Using data from the 2007 National Health Interview Survey, this paper describes the prevalence, patterns, and predictors of mind-body therapy use among a nationally representative sample of children (n=9,417) using a multidimensional model of health care behavior. The contribution of predisposing, enabling, and medical factors to mind-body therapy use among children will be also examined. Results provide additional evidence to a growing body of literature documenting that children and adolescents increasingly turn to mind-body therapies to alleviate symptoms, cope with chronic or life-threatening diseases, and to promote overall well-being. ^