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2.
Anaesthesist ; 69(10): 726-732, 2020 Oct.
Article in German | MEDLINE | ID: mdl-32671429

ABSTRACT

BACKGROUND: The number of interhospital transfers is constantly increasing because of specialization of medical facilities, capacity balancing between intensive care units as well as earlier rehabilitation procedures. This leads to an increase in requests for emergency physicians to accompany patient transfers. This study investigated whether clarification of interhospital transport by an emergency physician at the dispatch center can optimize the use of emergency services resources. METHOD: All transport clarifications performed by a tele-emergency physician between 1 January 2018 and 31 December 2019 were retrospectively analyzed as well as the transport request forms. Furthermore, all data on the number and alarmed rescue resources for interhospital transfers in the city of Aachen from 2013 onwards were exported from the dispatch center databank and included in the evaluation. RESULTS: In total 2333 requests for interhospital patient transfers from 2018 and 2019 were analyzed as well as 10,923 transports recorded from 2013 to 2019. The number of patient transfers accompanied by an emergency physician from 2013 to 2019 was significantly reduced from 786 (68.2%) to 495 (30.5%, p > 0.001). The correct resources of rescue vehicles and staff was requested in 1816 cases (77.8%). The urgency of emergency patient transfers was correctly evaluated in 567 (89.2%) cases. In total 526 assignments were carried out without an emergency physician and 315 of these patients were accompanied by a tele-emergency physician during transfer. CONCLUSION: The immediate clarification of interhospital transport requests by an emergency physician at the dispatch center leads to a significant reduction in unnecessary medical accompaniment of patient transfers. The choice of an appropriate transfer vehicle and staff should not be left to the requesting hospital physician alone.


Subject(s)
Emergency Medical Services , Physicians , Humans , Patient Transfer , Resource Allocation , Retrospective Studies
3.
Mater Today Bio ; 7: 100061, 2020 Jun.
Article in English | MEDLINE | ID: mdl-32637910

ABSTRACT

Antagonistic fungi such as Trichoderma reesei are promising alternatives to conventional fungicides in agriculture. This is especially true for worldwide occurring grapevine trunk diseases, causing losses of US$1.5 billion every year, at which conventional fungicides are mostly ineffective or prohibited by law. Yet, applications of Trichoderma against grapevine trunk diseases are limited to preventive measures, suffer from poor shelf life, or uncontrolled germination. Therefore, we developed a mild and spore-compatible layer-by-layer assembly to encapsulate spores of a new mycoparasitic strain of T. reesei IBWF 034-05 in a bio-based and biodegradable lignin shell. The encapsulation inhibits undesired premature germination and enables the application as an aqueous dispersion via trunk injection. First injected into a plant, the spores remain in a resting state. Second, when lignin-degrading fungi infect the plant, enzymatic degradation of the shell occurs and germination is selectively triggered by the pathogenic fungi itself, which was proven in vitro. Germinated Trichoderma antagonizes the fungal pathogens and finally supplants them from the plant. This concept enables Trichoderma spores for curative treatment of esca, one of the most infective grapevine trunk diseases worldwide.

4.
Anaesthesist ; 68(10): 665-675, 2019 10.
Article in German | MEDLINE | ID: mdl-31489458

ABSTRACT

BACKGROUND: Acute pain is a common reason for calling emergency medical services (EMS) and can require medication depending on the pain intensity. German EMS personnel feel strong pressure to reduce a patient's pain but are restricted by law. Currently, German federal law only allows the administration of opioid-containing drugs by or on the order of a physician, while in other European countries (e.g. Switzerland and The Netherlands) the administration of opioid-based analgesia by trained and certified paramedics is common practice. Consequently, a patient in Germany experiencing acute pain needs the attendance of an emergency physician in EMS missions. According to international standards pain reduction on the numeric rating scale (NRS) score by ≥2 or a NRS score ≤4 at the end of the patient transport is considered to be adequate. OBJECTIVE: Comparison of two different algorithm-based concepts for analgesia with consultation of a physician analyzing the efficacy, tolerance and safety of application. MATERIAL AND METHODS: In a retrospective cohort study in two different regions, two physician-supported algorithm-based analgesia concepts, a call back-supported concept (EMS Schleswig-Holstein: RKiSH) and a tele-EMS physician-based concept (EMS Aachen: RDAC), were compared over 2 years. The call back-supported concept is based on specific algorithms and certification of EMS personnel. In Aachen, the tele-EMS physician is integrated into the routine EMS system and includes immediate vital data transmission. RESULTS: Over a period of 2 years call back-supported analgesia was administered in 878 cases (2016: 428, 2017: 450) and telemedically assisted analgesia was used in 728 cases (2015: 226, 2016: 502). Call back vs. telemedicine: initial NRS scores were 9 (8-10) and 8 (6-9), respectively (p < 0.0001); NRS scores were reduced by 4 (3-5) and 5 (3-6), respectively (p = 0.0002), leading to mean NRS scores of 4 (3-6) vs. 3 (2-4), respectively (p < 0.0001) at patient handover/emergency room arrival. Clinically relevant pain reduction was achieved in both groups. Complete NRS documentation was conducted in 753 (85.8%) vs. 673 (92.4%) cases, respectively, p = 0. Severe adverse events did not occur in either of the groups. CONCLUSION: The administration of analgesia by EMS personnel with teleconsultation of a physician is effective and has a low rate of complications, particularly morphine. Overall, algorithm-based call back-supported as well as telemedically supported analgesia concepts based on regular training improve the management of pain in the prehospital setting. In addition, the resources of the emergency physician remain available for life-threatening emergencies. The training, certification and supervision of EMS personnel is very important in both systems to ensure the best pain management care and patient safety. Adjustments to the federal law on the administration of analgesics would facilitate the realization of algorithm-based concepts by paramedics as pain reduction could be performed with delegation by a medical director without consulting another physician.


Subject(s)
Analgesia/methods , Emergency Medical Services/methods , Pain Management/methods , Remote Consultation , Allied Health Personnel , Analgesics/therapeutic use , Analgesics, Opioid/therapeutic use , Female , Germany , Humans , Male , Physicians , Retrospective Studies
5.
Anaesthesist ; 68(7): 476-482, 2019 07.
Article in German | MEDLINE | ID: mdl-31297543

ABSTRACT

Fortunately, mass casualty incidents involving a large number of children and adolescents are rare and the experience in this field, both in terms of medical as well as psychosocial emergency care is comparatively low. Children represent a vulnerable group and have a particularly high risk of developing posttraumatic stress disorder in the aftermath of experiencing disasters. A selective literature search was carried out in Medline. The peculiarity of damaging events with a large number of children and adolescents affected is that in addition to emergency medical care, an early approach to psychosocial emergency care must be provided. Accordingly, it makes sense to integrate such structures into the respective deployment concepts. A specific screening algorithm for children could so far not prevail but due to the physiological and anatomical characteristics appropriate emergency medical care concepts should be provided. Furthermore, hospitals must adapt to this patient group in a suitable manner.


Subject(s)
Emergency Medical Services , Mass Casualty Incidents , Adolescent , Child , Disaster Planning , Emergencies , Emergency Service, Hospital , Humans , Triage
6.
Anaesthesist ; 67(6): 452-457, 2018 06.
Article in German | MEDLINE | ID: mdl-29500580

ABSTRACT

Entrustable professional activities (EPAs) are characterized as self-contained units of work in a given typical clinical context, which may be entrusted to a trainee for independent execution at a certain point of training. An example could be the intraoperative anesthesia management of an ASA 1 patient for an uncomplicated surgical intervention as an EPA in early postgraduate anesthesia training. The EPAs can be described as an evolution of a competency-based medical educational concept, applying the concept of the competencies of a person to specific workplace contexts. In this way the expected level of skills and supervision at a certain stage of training have a more practical meaning and the danger of fragmentation of individual competencies in the competence-based model is avoided. It is a more holistic view of a trainee. Experience with this new concept is so far limited, therefore, further studies are urgently needed to determine whether and how EPAs can contribute to improvements in further training.


Subject(s)
Anesthesiology/education , Education, Medical, Continuing/trends , Clinical Competence , Competency-Based Education , Curriculum , Humans , Internship and Residency
7.
Eur J Pain ; 20(7): 1176-84, 2016 08.
Article in English | MEDLINE | ID: mdl-26914284

ABSTRACT

BACKGROUND: In German emergency medical services (EMS), the analgesia is restricted to physicians. In this prospective, interventional, multicentre trial, complications with and quality of telemedically delegated analgesia were evaluated. METHODS: If prehospital analgesia was necessary, five telemedically equipped paramedic ambulances from four different districts could consult a telemedicine centre. Analgesics were delegated based on a predefined algorithm. Telemedically assisted cases were compared with local historical regular EMS missions using matched pairs. The primary outcome was the frequency of therapeutic complications (respiratory/circulatory insufficiency, allergic reactions). Secondary outcomes were quality of analgesia (11-point numerical rating scale, NRS) and the frequency of nausea/vomiting. RESULTS: Analgesia was necessary in 106 telemedically assisted missions. In 23 cases, the telemedical procedure was used until an EMS physician arrived. Of the remaining 83 cases, 80 could be matched to comparable controls. Complications did not occur in either the study group or the control group (0 vs. 0; p = N/A). Complete NRS documentation was noted in 65/80 (study group) and 32/80 (control group) cases (p < 0.0001). Adequate initial pain reduction (quality indicator: reduction of NRS ≥ 2 points or NRS < 5 at end of mission) occurred in 61/65 versus 31/32 cases (p = 1.0); NRS reduction during mission was 3.78 ± 2.0 versus 4.38 ± 2.2 points (p = 0.0159). Nausea and vomiting occurred with equal frequency in both groups. CONCLUSIONS: Telemedical delegation of analgesics to paramedics was safe and led to a pain reduction superior to the published minimum standard in both groups. The documentation quality was better in the telemedicine group. WHAT DOES THIS STUDY ADD?: Little is known about the safety and quality of prehospital analgesia carried out by emergency medical services (EMS). Beside potential quality problems, in some countries meaningful pain reduction is limited by legal regulations that allow only physicians to administer analgesics. This first multicentre prospective trial for telemedically delegated analgesia demonstrates that remote analgesia is possible and safe and retains equivalent analgesic quality compared with that administered by onsite EMS physicians.


Subject(s)
Analgesics/administration & dosage , Emergency Medical Services , Pain/drug therapy , Telemedicine , Adolescent , Adult , Aged , Allied Health Personnel , Child , Child, Preschool , Female , Germany , Humans , Infant , Infant, Newborn , Male , Middle Aged , Pain/diagnosis , Pain/etiology , Prospective Studies , Young Adult
10.
Anaesthesist ; 64(6): 438-45, 2015 Jun.
Article in German | MEDLINE | ID: mdl-26036316

ABSTRACT

BACKGROUND: The demographic change and an increasing multimorbidity of patients represent increasing challenges for the adequate prehospital treatment of emergency patients. The incorporation of supplementary telemedical concepts and systems can lead to an improved guideline-conform treatment. Beneficial evidence of telemedical procedures is only known for isolated disease patterns; however, no mobile telemedical concept exists which is suitable for use in the wide variety of different clinical situations. AIM: This article presents a newly developed and evaluated total telemedical concept (TemRas) that encompasses organizational, medical and technical components. The use of intelligent and robust communication technology and the implementation of this add-on system allows the telemedical support of the rescue service for all emergencies. METHODS: After development of the telemedical rescue assistance system, which includes organizational, medical and technical components, a telemedical centre and six ambulances in five different districts in North-Rhine Westphalia were equipped with this new tool. During the evaluation phase of 1 year in the routine emergency medical service the rate of complications as well as differences between urban and rural areas were analyzed with respect to different target parameters. RESULTS: Between August 2012 and July 2013 a total of 401 teleconsultations were performed during emergency missions and 24 during secondary interhospital transfers. No complications due to teleconsultation were observed. The mean duration (±SD) of teleconsultations was longer in rural areas than in urban areas with 28.6±12.0 min vs. 25.5±11.1 min (p < 0.0001). In 63.2% of these missions administration of medications was delegated to the ambulance personnel (52.0% urban vs. 73.6% rural, p < 0.0001). The severity of ailments corresponded to scores of III and VI in the National Advisory Committee for Aeronautics (NACA) classification. CONCLUSION: Emergency medical care of patients with support by a telemedical system is technically feasible, safe for the patient and allows medical treatment independent of spatial availability of a physician in different emergency situations.


Subject(s)
Emergency Medicine/organization & administration , Rescue Work/organization & administration , Telemedicine/organization & administration , Ambulances , Communication , Documentation , Emergency Medicine/methods , Germany , Humans , Patient Transfer/organization & administration , Physicians/supply & distribution , Prospective Studies , Remote Consultation , Rescue Work/methods , Rural Population , Telemedicine/methods , Urban Population
11.
Anaesthesist ; 64(3): 183-9, 2015 Mar.
Article in German | MEDLINE | ID: mdl-25772604

ABSTRACT

Because of an ageing population and a relative lack of professionals, the German health system is under great pressure. In rural regions in particular, anesthesiology is also affected - nursing staff, anesthetists, intensive care physicians, and emergency physicians often have to be supported by freelancers from other regions and from abroad - at least periodically. In addition to the increasing number of treatments, the potential quality of therapy is also increasing owing to progress in medical research. Against this background the need for resources is increasing to ensure the optimal quality of treatment. This applies to all clinical disciplines, including all sections of anesthesiology - especially in economically underdeveloped regions where highly qualified experts are lacking. In various cases it is not the physical attendance or manual skills of experts that is primarily requested on-site, but rather their medical expertise and experience. Therefore, telemedicine systems are suitable for closing these gaps very effectively and efficiently. In the various anesthesiological sub-sections the number of scientific papers published to date varies. For anesthesia and pain therapy only a few telemedical applications or concepts have been reported in the literature. However, in tele-intensive care medicine and tele-emergency medicine several national and international research projects have successfully been carried out, leading to established routine systems in some cases.


Subject(s)
Anesthesiology/trends , Telemedicine/trends , Anesthesia , Critical Care/trends , Emergency Medicine/trends , Germany , Humans , Pain Management/trends
12.
Methods Inf Med ; 53(2): 99-107, 2014.
Article in English | MEDLINE | ID: mdl-24477815

ABSTRACT

OBJECTIVES: Demographic change, rising co-morbidity and an increasing number of emergencies are the main challenges that emergency medical services (EMS) in several countries worldwide are facing. In order to improve quality in EMS, highly trained personnel and well-equipped ambulances are essential. However several studies have shown a deficiency in qualified EMS physicians. Telemedicine emerges as a complementary system in EMS that may provide expertise and improve quality of medical treatment on the scene. Hence our aim is to develop and test a specific teleconsultation system. METHODS: During the development process several use cases were defined and technically specified by medical experts and engineers in the areas of: system administration, start-up of EMS assistance systems, audio communication, data transfer, routine tele-EMS physician activities and research capabilities. Upon completion, technical field tests were performed under realistic conditions to test system properties such as robustness, feasibility and usability, providing end-to-end measurements. RESULTS: Six ambulances were equipped with telemedical facilities based on the results of the requirement analysis and 55 scenarios were tested under realistic conditions in one month. The results indicate that the developed system performed well in terms of usability and robustness. The major challenges were, as expected, mobile communication and data network availability. Third generation networks were only available in 76.4% of the cases. Although 3G (third generation), such as Universal Mobile Telecommunications System (UMTS), provides beneficial conditions for higher bandwidth, system performance for most features was also acceptable under adequate 2G (second generation) test conditions. CONCLUSIONS: An innovative concept for the use of telemedicine for medical consultations in EMS was developed. Organisational and technical aspects were considered and practical requirements specified. Since technical feasibility was demonstrated in these technical field tests, the next step would be to prove medical usefulness and technical robustness under real conditions in a clinical trial.


Subject(s)
Emergency Medicine/organization & administration , Remote Consultation/organization & administration , Telemedicine/organization & administration , Ambulances/organization & administration , Computer Communication Networks/organization & administration , Germany , Health Services Needs and Demand/organization & administration , Humans , Quality Assurance, Health Care/organization & administration , Workforce
13.
Anaesthesist ; 63(1): 23-31, 2014 Jan.
Article in German | MEDLINE | ID: mdl-24399370

ABSTRACT

BACKGROUND: The handling of advance directives (AD) in prehospital emergency treatment in Germany is characterized by instability. In the project "Advance directives in preclinical emergency medical aid" ("Patientenverfügungen in der präklinischen Notfallmedizin") the frequency and quality of ADs in emergency situations was investigated. AIM: The aim of this study was to fill the gaps in research and to collate data on how consideration of the self-determination of patients in emergency situations can be optimized. MATERIAL AND METHODS: Over a period of 12 months from December 2007 to December 2008 a questionnaire was included in the emergency documentation of the medical emergency service in Aachen. Emergency patients were asked by emergency physicians to provide an AD and the quantitative as well as qualitative features of these ADs were examined. Furthermore, the study recorded what kinds of problems occurred with ADs in emergency situations and what measures were needed to correct this deficiency. The reactions of patients were documented on a numeral rating scale with a score of 1 reflecting a negative and 10 reflecting a positive reaction. In the 12-month period emergency doctors recorded 1,321 missions and after application of the exclusion criteria (e.g. missing signature, incomplete documentation and late delivery) 1,047 documented questionnaires were available for the analysis. RESULTS: A total of 127 out of 1,047 emergency patients provided an AD, 44 had a durable power of attorney and 27 had appointed a legal representative for healthcare. Of the emergency patients 20 had a legal attendant and 43 out of the 127 ADs could be presented to the emergency team during the emergency mission. The emergency team often encountered difficulties regarding the handling of the ADs due to the time factor and unclear wording. The latter included the following problems: misleading formulation (19.1 %), difficulty with the complexity (14.9 %) and contradicting information (4 %). Only 29 (61.7 %) of the durable powers of attorney were signed and legally binding. From the view of the emergency physicians the following information was lacking but would be helpful in emergency situations: emergency plan, hierarchy of those given power of attorney, knowledge of risks regarding ADs and medication requirements. CONCLUSION: The results show that for an AD to apply in an emergency situation certain standards are necessary that assure the practicability, especially if a patient does not wish to be resuscitated. Most difficulties with ADs occurred with imprecise formulation, text length and inconsistency of statements. The following instructions were usually missing: hierarchy of those given power of attorney and specification on medication, information about the scope of the ADs, statement about resuscitation, extent and limitations of the desired treatment, especially with patients certified as terminally ill and instructions on who should decide about medical treatment in a conflict situation. A so-called emergency instruction which gives on a single page the patient's statement on resuscitation would have been very helpful in individual cases. The results suggest that patients may need more information and education about AD to guarantee patients rights and self-determination.


Subject(s)
Advance Directives/statistics & numerical data , Emergency Medical Services/statistics & numerical data , Adult , Advance Directive Adherence , Age Factors , Aged , Aged, 80 and over , Germany , Hospital Rapid Response Team , Humans , Middle Aged , Physicians , Prospective Studies , Surveys and Questionnaires , Young Adult
14.
Stem Cell Rev Rep ; 10(2): 207-29, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24323281

ABSTRACT

Wnt signaling determines major developmental processes in the embryonic state and regulates maintenance, self-renewal and differentiation of adult mammalian tissue stem cells. Both ß-catenin dependent and independent Wnt pathways exist, and both affect stem cell fate in developing and adult tissues. In this review, we debate the response to Wnt signal activation in embryonic stem cells and human, adult stem cells of mesenchymal, hematopoetic, intestinal, gastric, epidermal, mammary and neural lineages, and discuss the need for Wnt signaling in these cell types. Due to the vital actions of Wnt signaling in developmental and maintenance processes, deregulation of the pathway can culminate into a broad spectrum of developmental and genetic diseases, including cancer. The way in which Wnt signals can feed tumors and maintain cancer stem stells is discussed as well. Manipulation of Wnt signals both in vivo and in vitro thus carries potential for therapeutic approaches such as tissue engineering for regenerative medicine and anti-cancer treatment. Although many questions remain regarding the complete Wnt signal cell-type specific response and interplay of Wnt signaling with pathways such as BMP, Hedgehog and Notch, we hereby provide an overview of current knowledge on Wnt signaling and its control over human stem cell fate.


Subject(s)
Stem Cells/metabolism , Wnt Signaling Pathway , Animals , Cell Differentiation , Cell Proliferation , Humans , Receptors, Wnt/metabolism , Stem Cells/physiology , Wnt Proteins/physiology
15.
Pediatr Obes ; 9(1): 36-42, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23325614

ABSTRACT

UNLABELLED: What is already known about this subject BDNF is involved in the regulation of food intake and body weight. BDNF deficient animal models are obese. Chromosomal abnormalities cause obesity in humans. What this study adds Evaluation of point mutations in BDNF. Identification of BDNF mutations in obese children. Point mutations in BDNF are not a common cause of childhood obesity. INTRODUCTION: There is ample evidence that BDNF has a role in the regulation of food intake and body weight. Study of various mouse models gave a clear indication that BDNF deficiency leads to the development of obesity. Functional loss of one copy of the BDNF gene, due to chromosomal rearrangements or microdeletions, can cause an obesity phenotype in humans. Therefore, we wanted to investigate whether point mutations in the gene also result in a comparable phenotype. METHODS: We screened 554 severely overweight and obese children and adolescents and 565 lean adults for mutations in the coding region of BDNF. Mutation screening was performed by high-resolution melting curve analysis and direct sequencing. RESULTS: Screening of obese patients led to the identification of two synonymous variations (V37V and H65H) and two non-synonymous coding mutations (T2I and V46M) in the BDNF gene. When we subsequently screened our control population, we found T2I with comparable frequency and confirmed that this is a rare and non-pathogenic variant. In addition, we found another non-synonymous mutation (N187S) in the control population. CONCLUSIONS: In silico analysis of the V46M variant did not support a clear disease-causing effect and no family data were available in order to determine whether the mutation segregates with obesity. However, we cannot rule out a possible pathogenic effect for this variant. In general, we tend to conclude that mutations in the coding region of BDNF are uncommon in obese patients and are therefore not likely to play an essential role in the pathogenesis of childhood obesity.


Subject(s)
Brain-Derived Neurotrophic Factor/genetics , Genetic Testing , Pediatric Obesity/genetics , Point Mutation , Adolescent , Adult , Child , Child, Preschool , Female , Genetic Variation , Humans , Male , Pediatric Obesity/diagnosis , Phenotype
16.
Endocrine ; 46(3): 477-84, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24287795

ABSTRACT

Considering the role of sFRP5 in Wnt signalling, an important group of pathways regulating adipogenesis and inflammation, we performed a genetic association study on sFRP5 polymorphisms in a population of obese and lean individuals. Using information from the HapMap, two tagSNPs were identified in the sFRP5 gene region and genotyped on a population of 1,014 obese, non-diabetic individuals and 606 lean controls. We performed logistic and linear regression analysis including a wide variety of obesity parameters (BMI, waist circumference, height, WHR, fat mass, fat mass percentage and visceral, subcutaneous and total abdominal fat), in addition to OGTT and HOMA-IR values. We were able to show a significant association of sFRP5 with both total abdominal and subcutaneous fat. The association signal was only seen in obese males, and in this population, the minor allele of rs7072751 explains 1.8 % of variance in total abdominal fat. In addition, we saw a trend towards an association of rs10748709 with glucose metabolism. Although further research is necessary, we can conclude that sFRP5 is a significant regulator of fat development and distribution in obese males. We postulate that altered transcription factor binding on the rs7072751 surrounding sequence might play a role in the associations we found with both total abdominal and subcutaneous fat. In addition, although no conclusive evidence was found, our results indicate that sFRP5 genetic variation may affect glucose metabolism and it would be interesting to investigate this further.


Subject(s)
Adiposity/genetics , Eye Proteins/genetics , Genetic Variation , Membrane Proteins/genetics , Obesity/genetics , Adaptor Proteins, Signal Transducing , Adult , Aged , Genetic Predisposition to Disease , Genotype , Humans , Male , Middle Aged , Sex Factors , Young Adult
17.
Int J Obes (Lond) ; 38(7): 1000-4, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24097297

ABSTRACT

BACKGROUND: The transcription factor SIM1 (Single-minded 1) is involved in the control of food intake and in the pathogenesis of obesity. In mice, Sim1 is involved in the development of the paraventricular nucleus, and Sim1 deficiency leads to severe obesity and hyperphagia. In humans, chromosomal abnormalities in the SIM1 gene region have been reported in obese individuals. Furthermore, recent data also suggest that loss-of-function point mutations in SIM1 are responsible for SIM1 haplo-insufficiency that is involved in causing human obesity. In this study, we therefore wanted to expand the evidence regarding the involvement of SIM1 mutations in the pathogenesis of severe early-onset obesity. METHODS: We screened 561 severely overweight and obese children and adolescents and 453 lean adults for mutations in the coding region of the SIM1 gene. Mutation screening in all patients and lean individuals was performed by high-resolution melting curve analysis combined with direct sequencing. To evaluate the effect of the mutations on SIM1 transcriptional activity, luciferase reporter assays were performed. RESULTS: Mutation analysis identified four novel nonsynonymous coding variants in SIM1 in four unrelated obese individuals: p.L242V, p.T481K, p.A517V and p.D590E. Five synonymous variants, p.P57P, p.F93F, p.I183I, p.V208V and p.T653T, were also identified. Screening of the lean control population revealed the occurrence of four other rare SIM1 variants: p.G408R, p.R471P, p.S492P and p.S622F. For variants p.T481K and p.A517V, which were found in obese individuals, a decrease in SIM1 transcriptional activity was observed, whereas the transcriptional activity of all variants found in lean individuals resembled wild type. CONCLUSIONS: In this study, we have demonstrated the presence of rare SIM1 variants in both an obese pediatric population and a population of lean adult controls. Further, we have shown that functional in vitro analysis of SIM1 variants may help in distinguishing benign variants of no pathogenic significance from variants which contribute to the obesity phenotype.


Subject(s)
Basic Helix-Loop-Helix Transcription Factors , Genetic Predisposition to Disease , Mutation, Missense , Obesity, Morbid/genetics , Repressor Proteins , Adolescent , Adult , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Child , DNA Mutational Analysis , Genes, Reporter , Genetic Association Studies , Humans , Mice , Phenotype , Repressor Proteins/genetics , Transcriptional Activation
18.
Obesity (Silver Spring) ; 21(10): 2138-45, 2013 Oct.
Article in English | MEDLINE | ID: mdl-23512881

ABSTRACT

OBJECTIVE: Mechanisms explaining the relationship in non-alcoholic fatty liver disease (NAFLD), obesity, and insulin resistance are poorly understood. A genetic basis has been suggested. We studied the association between the genes patatin-like phospholipase domain-containing protein 3 (PNPLA3) and apolipoprotein C3 (APOC3) and metabolic and histological parameters of NAFLD in obese patients. DESIGN AND METHODS: Overweight and obese patients underwent a metabolic and liver assessment. If NAFLD was suspected, liver biopsy was proposed. APOC3 variant rs2854117 and PNPLA3 variant rs738409 were genotyped. RESULTS: Four hundred seventy patients were included (61.1% had liver biopsy). The percentage of patients with non-alcoholic steatohepatitis (NASH) was significantly different according to the PNPLA3 variant. After adjustment for age and body mass index, the PNPLA3 variant was associated with alanine aminotransferase (P < 0.001) and aspartate aminotransferase (P < 0.001). The PNPLA3 variant was associated with more severe features of steatohepatitis: steatosis (P < 0.001), lobular inflammation (P < 0.001), and ballooning (P = 0.002), but not with liver fibrosis, anthropometry, or insulin resistance. No significant difference in liver histology, anthropometric, or metabolic parameters was found between carriers and non-carriers of the APOC3 variant. CONCLUSIONS: PNPLA3 polymorphism rs738409 was associated with NASH and the severity of necroinflammatory changes independently of metabolic factors. No association between APOC3 gene variant rs2854117 and histological or metabolic parameters of NAFLD was found.


Subject(s)
Apolipoprotein C-III/genetics , Fatty Liver/genetics , Genetic Predisposition to Disease , Lipase/genetics , Membrane Proteins/genetics , Obesity/genetics , Polymorphism, Single Nucleotide , Adult , Alanine Transaminase/genetics , Alanine Transaminase/metabolism , Apolipoprotein C-III/metabolism , Aspartate Aminotransferases/genetics , Aspartate Aminotransferases/metabolism , Body Mass Index , Cross-Sectional Studies , Female , Genotype , Humans , Intra-Abdominal Fat/metabolism , Lipase/metabolism , Lipid Metabolism/genetics , Liver/pathology , Male , Membrane Proteins/metabolism , Middle Aged , Non-alcoholic Fatty Liver Disease
19.
Endocrine ; 43(1): 120-6, 2013 Feb.
Article in English | MEDLINE | ID: mdl-22767440

ABSTRACT

AdipoR1 is one of the adiponectin receptors which are important for adiponectin signaling. Because adiponectin is a candidate gene for common obesity, it is also hypothesized that variations in AdipoR1 may be involved in the development of complex obesity. Therefore, we designed an association study for the AdipoR1 gene. We performed a case-control association study including 1,021 obese subjects (mean age 42 ± 12 years; mean BMI 38.2 ± 6.2 kg/m²) and 226 lean, healthy individuals (mean age 36 ± 7 years; mean BMI 22.1 ± 1.7 kg/m²). Nine tagSNPs were selected to cover the entire AdipoR1 gene and surrounding 7 kb region (based on HapMap data). TagSNPs were genotyped using AcycloPrime-Fluorescence Polarization (FP) SNP Detection kits and TaqMan Pre-Designed SNP Genotyping assays according to manufacturer's protocols. We found that the rs1075399 non-reference allele decreases obesity risk by 45 % in men only [odds ratio (OR) = 0.55, 95 % CI 0.35-0.87, nominal P = 0.010]. However, after Bonferroni correction for multiple testing, this association is lost. None of the other tagSNPs were associated with obesity when studying the entire population, nor when looking at men and women separately. Quantitative analysis of the effect of each SNP on height, weight, and BMI revealed that none of the tagSNPs are associated with weight or BMI. We report here that we found no decisive evidence for association between AdipoR1 tagSNPs and complex obesity in our Belgian Caucasian population.


Subject(s)
Obesity/genetics , Polymorphism, Single Nucleotide , Receptors, Adiponectin/genetics , 3' Untranslated Regions , 5' Untranslated Regions , Adult , Aged , Belgium , Body Mass Index , Case-Control Studies , Female , Gene Frequency , Genetic Association Studies , Hospitals, University , Humans , Linkage Disequilibrium , Male , Middle Aged , Obesity/metabolism , Obesity, Morbid/genetics , Obesity, Morbid/metabolism , Outpatient Clinics, Hospital , Receptors, Adiponectin/metabolism , Sequence Tagged Sites , Young Adult
20.
Med Klin Intensivmed Notfmed ; 107(7): 515-20, 2012 Oct.
Article in German | MEDLINE | ID: mdl-23076373

ABSTRACT

Endotracheal intubation is a standard procedure in anesthesiology as well as in intensive care medicine in many forms of assisted spontaneous breathing or controlled ventilation. In addition it continues to be the gold standard for airway protection in prehospital and in-hospital emergency medicine settings. Approaches will have to be considered to help prevent errors before they occur not only in the non-elective use of endotracheal intubation. The most common preventable situations are summarized in this paper.


Subject(s)
Intubation, Intratracheal/adverse effects , Intubation, Intratracheal/standards , Medical Errors/prevention & control , Critical Care/standards , Germany , Humans , Intubation, Intratracheal/methods , Noninvasive Ventilation/standards , Patient Positioning/methods , Patient Positioning/standards , Pulmonary Disease, Chronic Obstructive/therapy , Quality Assurance, Health Care/methods , Quality Assurance, Health Care/standards , Respiratory Insufficiency/therapy , Risk Factors
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