Upregulation of dual-specificity phosphatase-26 is required for transforming growth factor ß1(TGFß1)-induced Epithelial-mesenchymal transition in A549 and PANC1 cells.

BACKGROUND: Transforming Growth Factor ß (TGFß) proteins are potent inducers of the epithelial-mesenchymal transition (EMT) in tumor cells. Although mitogen-activated protein kinase (MAPK) family has been shown to be involved in TGFß-induced EMT, role of Dual Specificity Phosphatases (DUSP), key regulators of MAPK activity, in TGFß-induced EMT is largely unkonwn. METHODS AND RESULTS: Real-time qPCR analyses were performed to determine the effect of TGFß1 on expression of EMT genes and DUSP proteins in the non-small cell lung cancer model A549 and pancreatic adenocarcinoma model PANC1 cells. Western blot analyses were conducted to study the changes in protein levels of EMT proteins and select DUSP proteins, as well as phosphorylations of MAPK proteins upon TGFß1 stimulation. Small interfering RNA (siRNA) was utilized to reduce expressions of DUSP genes. We observed that the EMT phenotype coincided with increases in phosphorylations of the MAPK proteins ERK1/2, p38MAPK, and JNK upon TGFß1 stimulation. Real-time qPCR analysis showed increases in DUSP15 and DUSP26 mRNA levels and Western blot analysis confirmed the increase in DUSP26 protein levels in both A549 and PANC1 cells treated with TGFß1 relative to control. Silencing of DUSP26 expression by siRNA markedly suppressed the effect of TGFß1 on E-cadherin and mesenchymal genes in the cells. CONCLUSIONS: Data provided suggest that TGFß1 modulates the expression of DUSP genes and that upregulation of DUSP26 may be required for TGFß1-promoted EMT in A549 and PANC1 cells. Further studies should be carried out to elucidate the requirement of individual DUSPs in TGFß1-associated EMT in tumor cells.

The Diagnostic Value of Fine Needle Aspiration Biopsy in Parotid Tumors.

The aim of this study was to investigate the diagnostic accuracy rates of the patients who underwent an operation for parotid mass, by comparing their fine needle aspiration biopsy (FNAB) cytology results with the final pathology. A total of 136 patient files of those who applied to Otorhinolaryngology clinic due to parotid mass and underwent parotidectomy procedure between 2010 and 2020 at a tertiary center were scanned retrospectively. Database on patient age, gender, preoperative FNAB results, and final surgical histopathology results was created. The mean age of the patients was 48.26 ± 17.37 Superficial parotidectomy was performed to 108 (79.4%) and total parotidectomy to 28 (20.6%) of the patients. The sensitivity of FNAB was found as 85.2%, specificity as 96.2%, positive predictive value as 85.2%, negative predictive value as 96.2% and accuracy as 94.0%. It is found that FNAB has the high specificity and high negative predictive value with high diagnostic accuracy on detecting preoperative malignancy in parotid gland. We think that FNAB is a significant, necessary and safe method in the diagnosis of parotid lesions in preoperative sense.

Insights from targeting transferrin receptors to develop vaccines for pathogens of humans and food production animals.

While developing vaccines targeting surface transferrin receptor proteins in Gram-negative pathogens of humans and food production animals, the common features derived from their evolutionary origins has provided us with insights on how improvements could be implemented in the various stages of research and vaccine development. These pathogens are adapted to live exclusively on the mucosal surfaces of the upper respiratory or genitourinary tract of their host and rely on their receptors to acquire iron from transferrin for survival, indicating that there likely are common mechanisms for delivering transferrin to the mucosal surfaces that should be explored. The modern-day receptors are derived from those present in bacteria that lived over 320 million years ago. The pathogens represent the most host adapted members of their bacterial lineages and may possess factors that enable them to have strong association with the mucosal epithelial cells, thus likely reside in a different niche than the commensal members of the bacterial lineage. The bacterial pathogens normally lead a commensal lifestyle which presents challenges for development of relevant infection models as most infection models either exclude the early stages of colonization or subsequent disease development, and the immune mechanisms at the mucosal surface that would prevent disease are not evident. Development of infection models emulating natural horizontal disease transmission are also lacking. Our aim is to share our insights from the study of pathogens of humans and food production animals with individuals involved in vaccine development, maintaining health or regulation of products in the human and animal health sectors.

Risk Stratification in Chest Pain: Impact on the Diagnosis of Acute Coronary Syndrome

Abstract Background The implementation of institutional protocols in the emergency department (ED) for risk stratification in patients with chest pain has been recommended. Objective To assess the sensitivity, specificity and predictive value of an institutional risk stratification protocol for chest pain suggestive of acute coronary syndrome (ACS). Method Cross-sectional study conducted based on the computerized records of patients treated with the use of a chest pain protocol adapted from the Manchester protocol. The level of risk was stratified by applying five colors representing the respective levels. Each color represents a level of severity and a maximum waiting time for receiving medical care. Red and orange were considered to be high priority, while patients with yellow, green or blue indications were considered to represent a low priority. To compare the type of diagnosis and the classification of priority for receiving care, the Pearson's chi-square test was used, considering a significance level of p< 0.05 for all tests. Results The records of 1,074 patients admitted to the cardiology ED were analyzed. Men (54%), with a mean age of 60 ± 15 years, with complaints of chest pain (44%) of moderate intensity (80%) were predominant the study. Of these patients, 19% were classified as high priority, while 81% were considered to represent a low priority. ACS was confirmed in 23% of the patients, with 34% of them being classified as high priority and 66% as low priority. The sensitivity of the risk stratification protocol for chest pain was 33.7% and the specificity was 86.0%, with a positive and negative predictive value of 41.7% and 81.3%, respectively. Conclusion The Institutional risk stratification protocol for chest pain suggestive of ACS presented satisfactory specificity and a low degree of sensitivity. Int J Cardiovasc Sci. 2020; [online].ahead print, PP.0-0

CirRNAPL: A web server for the identification of circRNA based on extreme learning machine.

Circular RNA (circRNA) plays an important role in the development of diseases, and it provides a novel idea for drug development. Accurate identification of circRNAs is important for a deeper understanding of their functions. In this study, we developed a new classifier, CirRNAPL, which extracts the features of nucleic acid composition and structure of the circRNA sequence and optimizes the extreme learning machine based on the particle swarm optimization algorithm. We compared CirRNAPL with existing methods, including blast, on three datasets and found CirRNAPL significantly improved the identification accuracy for the three datasets, with accuracies of 0.815, 0.802, and 0.782, respectively. Additionally, we performed sequence alignment on 564 sequences of the independent detection set of the third data set and analyzed the expression level of circRNAs. Results showed the expression level of the sequence is positively correlated with the abundance. A user-friendly CirRNAPL web server is freely available at http://server.malab.cn/CirRNAPL/.

Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) and its soluble in the plasma form (sTREM-1) as a diagnostic biomarker in neonatal sepsis.

Neonatal sepsis, defined as sepsis occurring within the first 28 days of life, is associated with significant morbidity and mortality. It is undeniable that finding and appliance of biomarkers in clinical practice is of great importance, aiming at the early recognition of the impending clinical deterioration and the prompt and targeted therapeutic intervention. A er systematic and thorough research of the limited relevant literature, we attempt to present a documented point-of-view on the diagnostic value of TREM-1 and its soluble form both in early and late onset neonatal sepsis.

Conversion of aliphatic nitriles by the arylacetonitrilase from Pseudomonas fluorescens EBC191.

The conversion of aliphatic nitriles by the arylacetonitrilase from Pseudomonas fluorescens EBC191 (NitA) was analyzed. The nitrilase hydrolysed a wide range of aliphatic mono- and dinitriles and showed a preference for unsaturated aliphatic substrates containing 5-6 carbon atoms. In addition, increased reaction rates were also found for aliphatic nitriles carrying electron withdrawing substituents (e.g. chloro- or hydroxy-groups) close to the nitrile group. Aliphatic dinitriles were attacked only at one of the nitrile groups and with most of the tested dinitriles the monocarboxylates were detected as major products. In contrast, fumarodinitrile was converted to the monocarboxylate and the monocarboxamide in a ratio of about 65:35. Significantly different relative amounts of the two products were observed with two nitrilase variants with altered reaction specifities. NitA converted some aliphatic substrates with higher rates than 2-phenylpropionitrile, which is one of the standard substrates for arylacetonitrilases. This indicated that the traditional classification of nitrilases as "arylacetonitrilases", "aromatic" or "aliphatic" nitrilases might require some corrections. This was also suggested by the construction of some variants of NitA which were modified in an amino acid residue which was previously suggested to be essential for the conversion of aliphatic substrates by a homologous nitrilase.

Differential recognition of natural and remodeled glycotopes by three Diocleae lectins.

The carbohydrate specificities of Dioclea grandiflora lectins DGL-I1 and DGL-II, and Galactia lindenii lectin II (GLL-II) were explored by use of remodeled glycoproteins as well as by the lectin hemagglutinating activity against erythrocytes from various species with different glycomic profiles. The three lectins exhibited differences in glycan binding specificity but also showed overlapping recognition of some glycotopes (i.e. Tα glycotope for the three lectins; IIß glycotope for DGL-II and GLL-II lectins); in many cases the interaction with distinct glycotopes was influenced by the structural context, i.e., by the neighbouring sugar residues. Our data complement and expand the existing knowledge about the binding specificity of these three Diocleae lectins, and taken together with results of previous studies, allow us to suggest a functional map of the carbohydrate recognition which illustrate the impact of modification of basic glycotopes enhancing, permiting, or inhibiting their recognition by each lectin.

[Bayesian tragedy, from clinical iatrogenesis to biotechnology]. / La tragedia bayesiana desde la iatrogenia clínica hasta la biotecnología.

Diagnostic algorithms, as well as the biotechnological design, require the calculation of conditional probability, given the presence of certain positive data, in the context of prevalence, sensitivity and specificity; It is necessary to estimate the probability that the patient has a certain disease. Sometimes, with a test of scrutiny, it goes from a probability of 1/1000 to 1/20, constituting a great diagnostic advance, reducing the uncertainty spectacularly; However, the tragedy is that most doctors believe that the probability changed from 0.1% (1/1000) to more than 90%, which is outrageously wrong. Iatrogeny arises from the error in answering the question: "given that the test is positive, what is the probability that the patient has the disease?" In other cases, tragedy is to apply a test to an individual belonging to a subpopulation for which it was not designed. In addition, it is evident that the fascination for the sensitivity avoids the application of less sensitive methods in populations that are abandoned; It is not a matter of making better tests than those that the State does to the patients it attends, but of making less accurate tests for the patients that the State does not attend.

Los algoritmos diagnósticos así como el diseño biotecnológico, requieren del cálculo de la probabilidad condicional, dada la presencia de ciertos datos positivos en el contexto de la prevalencia, de la sensibilidad y de la especificidad, se necesita estimar la probabilidad de que el paciente tenga una determinada enfermedad. A veces, con una prueba de escrutinio se pasa de una probabilidad de 1/1000 a 1/20, constituyendo un gran avance diagnóstico, reduciendo la incertidumbre espectacularmente; sin embargo, la tragedia consiste en que la mayoría de los médicos creen que la probabilidad cambió de 0.1% (1/1000) a más del 90%, lo que es escandalosamente errado. La iatrogenia nace del error al contestar a la pregunta: "Dado que la prueba es positiva, ¿cuál es la probabilidad de que el paciente tenga la enfermedad?" En otros casos lo trágico consiste en aplicar una prueba a un individuo que pertenece a una subpoblación para la que esta no fue diseñada. Adicionalmente, se pone en evidencia que la fascinación por la sensibilidad evita que se apliquen métodos menos sensibles en poblaciones que están abandonadas, pues no se trata de hacer mejores pruebas que las que hace el Estado a los pacientes que atiende, sino de hacer pruebas de menor exactitud a los pacientes que no atiende el Estado.

[The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion].

Objective: To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion. Methods: Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion. Results: The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P<0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA (r=0.670, P=0.001 in MPE and r=0.002, P=0.001 in BEP). Conclusions: B7-H4 is a potential tumor marker in diagnosing the benign and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.

The value of B7-H4 and carcinoembryonic antigen in diagnosing the benign and malignant pleural effusion / 中华肿瘤杂志

Objective@#To evaluate the value of combined detection of negative costimulatory molecule B7-H4 and carcinoembryonic antigen (CEA) in diagnosing malignant and benign pleural effusion.@*Methods@#Ninety-seven pleural effusion specimen were collected, 55 of which were diagnosed as malignant pleural effusion and 42 were benign pleural effusion. Enzyme-linked immunosorbent assay(ELISA) was used to examine the concentration of B7-H4 and CEA in pleural effusion. Electro-chemiluminescence immunoassay was used to detect the CEA level in pleural effusion. Receiver operating characteristic (ROC) curve was established to analyze and evaluate the single or combined detection of B7-H4 and CEA in diagnosing malignant and benign pleural effusion.@*Results@#The concentrations of B7-H4 and CEA in malignant pleural effusion (MPE) group were (60.08±35.04) ng/ml and (41.49±37.16) ng/ml, respectively, obviously higher than (27.26±9.55) ng/ml and (2.41±0.94) ng/ml of benign pleural effusion (BPE) group (both P<0.01). Area under curve (AUC) of B7-H4 was 0.884 in MPE groupand the diagnostic sensitivity and specificity were 81.8% and 90.5%, respectively, at the optimized cut off value of 37.25 ng/ml. Likewise, area under curve (AUC) of CEA was 0.954 and the sensitivity and specificity were 87.3% and 95.2%, respectively, at the cut off value of 4.18 ng/ml. When B7-H4 >37.25 ng/ml or CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 90.9% and the specificity was elevated to 88.1%. When B7-H4 >37.25 ng/ml and CEA>4.18 ng/ml, the sensitivity of diagnosis as MPE was down-regulated to 78.2% and the specificity was elevated to 97.6%. The sensitivity and specificity of combined detection of B7-H4 and CEA to diagnose MPE were elevated to 90.9% and 97.6%, respectively. The level of B7-H4 in MPE and BPE were both positively correlated with CEA (r=0.670, P=0.001 in MPE and r=0.002, P=0.001 in BEP).@*Conclusions@#B7-H4 is a potential tumor marker in diagnosing the benign and malignant pleural effusion. Although the diagnostic value of B7-H4 may not precede to CEA, the combined detection of B7-H4 and CEA can improve the diagnostic sensitivity and specificity of MPE.

Inespecificidad persistente en amplificación isotérmica mediada por loop para diagnóstico de malaria / Persistent non-specificity in loop-mediated insothermal amplication for malaria diagnosis

Objetivo. Describir el ensayo realizado para la estandarización de la técnica de diagnóstico para malaria, denominada amplificación isotérmica mediada por loop (LAMP). Métodos. Se extrajeron 48 muestras divididas en 22 muestras para P. falciparum, 20 de P. vivax y 6 negativas para las mismas especies. Resultados. Se observaron falsos positivos, amplificaciones específicas que evidencian la inespecificidad de la técnica. Se propone estudiar los amplicones obtenidos por medio de restricción de fragmentos y secuenciación para elucidar el origen del problema.

Objetive. The present study describes the assay performed to standardize a malaria diagnostic DNA test, called loop-mediated isothermal amplification (LAMP). Methods. Extractions from 48 Plasmodium-infected blood samples (22 P.falciparum-positive samples, 20 P. vivax-positive samples and 6 negative control samples). Results. The data show false positives, unspecific amplifications that demonstrate the low specificity of the test. We propose to study the amplicons obtained by restriction fragment and sequencing to investigate the underlying cause of the problem.

A patient with partial trisomy 21 and 7q deletion expresses mild Down syndrome phenotype.

BACKGROUND: Down syndrome (DS) is the most common aneuploidy in live-born individuals and it is well recognized with various phenotypic expressions. Although an extra chromosome 21 is the genetic cause for DS, specific phenotypic features may result from the duplication of smaller regions of the chromosome and more studies need to define genotypic and phenotypic correlations. CASE REPORT: We report on a 26 year old male with partial trisomy 21 presenting mild clinical symptoms relative to DS including borderline intellectual disability. In particular, the face and the presence of hypotonia and keratoconus were suggestive for the DS although the condition remained unnoticed until his adult age array comparative genomic hybridization (aCGH) revealed a 10.1 Mb duplication in 21q22.13q22.3 and a small deletion of 2.2 Mb on chromosomal band 7q36 arising from a paternal translocation t(7;21). The 21q duplication encompasses the gene DYRK1. CONCLUSION: Our data support the evidence of specific regions on distal 21q whose duplication results in phenotypes recalling the typical DS face. Although the duplication region contains DYRK1, which has previously been implicated in the causation of DS, our patient has a borderline IQ confirming that their duplication is not sufficient to cause the full DS phenotype.

Preparation of Novel Biocompatible Macromolecular Magnetic Resonance Imaging Contrast Agent / 分析化学

Poly ( aspartic acid-co-leucine) was synthesized, modified via ethylenediamine, conjugated with 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) and finally chelated with gadoliniumⅢ, yielding PL-A2-DOTA-Gd. The T1-relaxivity (15. 3 mmol-1 ·L·s-1 ) of PL-A2-DOTA-Gd was 2. 6 times than that of Gd-DOTA (5. 8 mmol-1·L·s-1) in D2O. The results of magnetic resonance imaging experiments showed significant enhancement in the rat liver after intravenous administration of PL-A2-DOTA-Gd, which persisted longer than Gd-DOTA. The mean percentage enhancements of liver parenchyma were 65. 1%±5. 2%and 21. 3%±4. 9%, for PL-A2-DOTA-Gd and Gd-DOTA, respectively.

Trefoil factor 2 expression and its significance as a predictor of severity of sepsis in children.

Intestinal injury significantly contributes to critical illness, sepsis and multiorgan failure. TFF2 (Trefoil Factor 2) is expressed and secreted preferentially by gastric mucous neck cells. TFF2 gene expression is promptly increased after gut injury, and its expression profile broadens to include the regenerative epithelia of virtually the entire gastrointestinal tract. The first objective of our study was an analysis of TFF2 levels dynamics in patients with Systemic Inflammatory Response Syndrome (SIRS) or septic condition during a 5-day period after admission. The second objective was to determine optimal cut-off value and quantify diagnostic characteristics of TFF2 between controls and patients with various septic states. The study included 57 children aged 0-19 years, with expected or proven SIRS and septic condition. The degree of severity was evaluated according to PELOD Score (Pediatric Logistic Organ Dysfunction). Blood samples to determine levels of TFF2 factor were taken during the time patient met the criteria of SIRS or sepsis. Control group samples to determine the serum levels of TFF2 were taken from patients undergoing elective surgery. Analysis of TFF2 levels dynamics revealed that TFF2 levels kept steady state during the 5-day period. Significantly higher levels of TFF2 were in patients with Multiple Organ Dysfunction Syndrome (MODS). The difference was noticed also in ROC analysis.

Bone graft substitutes for the treatment of traumatic fractures of the extremities.

UNLABELLED: HEALTH POLITICAL AND SCIENTIFIC BACKGROUND: Bone graft substitutes are increasingly being used as supplements to standard care or as alternative to bone grafts in the treatment of traumatic fractures. RESEARCH QUESTIONS: The efficacy and cost-effectiveness of bone graft substitutes for the treatment of traumatic fractures as well as the ethical, social and legal implications of their use are the main research questions addressed. METHODS: A systematic literature search was conducted in electronic medical databases (MEDLINE, EMBASE etc.) in December 2009. Randomised controlled trials (RCT), where applicable also containing relevant health economic evaluations and publications addressing the ethical, social and legal aspects of using bone graft substitutes for fracture treatment were included in the analysis. After assessment of study quality the information synthesis of the medical data was performed using metaanalysis, the synthesis of the health economic data was performed descriptively. RESULTS: 14 RCT were included in the medical analysis, and two in the heath economic evaluation. No relevant publications on the ethical, social and legal implications of the bone graft substitute use were found. In the RCT on fracture treatment with bone morphogenetic protein-2 (BMP-2) versus standard care without bone grafting (RCT with an elevated high risk of bias) there was a significant difference in favour of BMP-2 for several outcome measures. The RCT of calcium phosphate (CaP) cement and bone marrow-based composite materials versus autogenous bone grafts (RCT with a high risk of bias) revealed significant differences in favour of bone graft substitutes for some outcome measures. Regarding the other bone graft substitutes, almost all comparisons demonstrated no significant difference. The use of BMP-2 in addition to standard care without bone grafting led in the study to increased treatment costs considering all patients with traumatic open fractures. However, cost savings through the additional use of BMP-2 were calculated in a patient subgroup with high-grade open fractures (Gustilo-Anderson grade IIIB). Cost-effectiveness for BMP-2 versus standard care with autologous bone grafts as well as for other bone graft substitutes in fracture treatment has not been determined yet. DISCUSSION: Although there were some significant differences in favour of BMP-2, due to the overall poor quality of the studies the evidence can only be interpreted as suggestive for efficacy. In the case of CaP cements and bone marrow-based bone substitute materials, the evidence is only weakly suggestive for efficacy. From an overall economic perspective, the transferability of the results of the health economic evaluations to the current situation in Germany is limited. CONCLUSIONS: The current evidence is insufficient to evaluate entirely the use of different bone graft substitutes for fracture treatment. From a medical point of view, BMP-2 is a viable alternative for treatment of open fractures of the tibia, especially in cases where bone grafting is not possible. Autologous bone grafting is preferable comparing to the use of OP-1. Possible advantages of CaP cements and composites containing bone marrow over autogenous bone grafting should be taken into account in clinical decision making. The use of the hydroxyapatite material and allograft bone chips compared to autologous bone grafts cannot be recommended. From a health economic perspective, the use of BMP-2 in addition to standard care without bone grafting is recommended as cost-saving in patients with high-grade open fractures (Gustilo-Anderson grade IIIB). Based on the current evidence no further recommendations can be made regarding the use of bone graft substitutes for the treatment of fractures. To avoid legal implications, use of bone graft substitutes outside their approved indications should be avoided.

The effectiveness of interventions in workplace health promotion as to maintain the working capacity of health care personal.

BACKGROUND: The increasing proportion of elderly people with respective care requirements and within the total population stands against aging personnel and staff reduction in the field of health care where employees are exposed to high load factors. Health promotion interventions may be a possibility to improve work situations and behavior. METHODS: A systematic literature search is conducted in 32 databases limited to English and German publications since 1990. Moreover, internet-searches are performed and the reference lists of identified articles are scanned. The selection of literature was done by two reviewers independently according to inclusion and exclusion criteria. Data extraction and tables of evidence are verified by a second expert just like the assessment of risk of bias by means of the Cochrane Collaboration's tool. RESULTS: We identified eleven intervention studies and two systematic reviews. There were three randomized controlled trials (RCT) and one controlled trial without randomization (CCT) on the improvement of physical health, four RCT and two CCT on the improvement of psychological health and one RCT on both. Study duration ranged from four weeks to two years and the number of participants included from 20 to 345, with a median of 56. Interventions and populations were predominantly heterogeneous. In three studies intervention for the improvement of physical health resulted in less complaints and increased strength and flexibility with statistically significant differences between groups. Regarding psychological health interventions lead to significantly decreased intake of analgesics, better stress management, coping with workload, communication skills and advanced training. DISCUSSION: Taking into consideration the small to very small sample sizes, other methodological flaws like a high potential of bias and poor quality of reporting the validity of the results has to be considered as limited. Due to the heterogeneity of health interventions, study populations with differing job specializations and different lengths of study durations and follow-up periods, the comparison of results would not make sense. CONCLUSIONS: Further research is necessary with larger sample sizes, with a sufficient study duration and follow-up, with a lower risk of bias, by considering of relevant quality criteria and with better reporting in publications.

Individual health services.

BACKGROUND: The German statutory health insurance (GKV) reimburses all health care services that are deemed sufficient, appropriate, and efficient. According to the German Medical Association (BÄK), individual health services (IGeL) are services that are not under liability of the GKV, medically necessary or recommendable or at least justifiable. They have to be explicitly requested by the patient and have to be paid out of pocket. RESEARCH QUESTIONS: The following questions regarding IGeL in the outpatient health care of GKV insurants are addressed in the present report: What is the empirical evidence regarding offers, utilization, practice, acceptance, and the relation between physician and patient, as well as the economic relevance of IGeL?What ethical, social, and legal aspects are related to IGeL? FOR TWO OF THE MOST COMMON IGEL, THE SCREENING FOR GLAUCOMA AND THE SCREENING FOR OVARIAN AND ENDOMETRIAL CANCER BY VAGINAL ULTRASOUND (VUS), THE FOLLOWING QUESTIONS ARE ADDRESSED: What is the evidence for the clinical effectiveness?Are there sub-populations for whom screening might be beneficial? METHODS: The evaluation is divided into two parts. For the first part a systematic literature review of primary studies and publications concerning ethical, social and legal aspects is performed. In the second part, rapid assessments of the clinical effectiveness for the two examples, glaucoma and VUS screening, are prepared. Therefore, in a first step, HTA-reports and systematic reviews are searched, followed by a search for original studies published after the end of the research period of the most recent HTA-report included. RESULTS: 29 studies were included for the first question. Between 19 and 53% of GKV members receive IGeL offers, of which three-quarters are realised. 16 to 19% of the insurants ask actively for IGeL. Intraocular tension measurement is the most common single IGeL service, accounting for up to 40% of the offers. It is followed by ultrasound assessments with up to 25% of the offers. Cancer screening and blood or laboratory services are also frequent and represent a major proportion of the demand. The ethical, social, and legal aspects discussed in the context of IGeL concern eight subject areas: autonomous patient decisions versus obtrusion,commercialization of medicine, duty of patient information, benefit, evidence, and (quality) control, role and relation of physicians and patients,relation to the GKV, social inequality,formally correct performance. For glaucoma screening, no randomized controlled trial (RCT) is identified that shows a patient relevant benefit. For VUS three RCT are included. However, they do not yet present mortality data concerning screened and non-screened persons. VUS screening shows a high degree of over-diagnosis in turn leading to invasive interventions. To diagnose one invasive carcinoma, 30 to 35 surgical procedures are necessary. CONCLUSION: IGeL are a relevant factor in the German statutory health care system. To provide more transparency, the requests for evidence-based and independent patient information should be considered. Whether official positive and negative-lists could be an appropriate instrument to give guidance to patients and physicians, should be examined. Generally, IGeL must be seen in the broader context of the discussions about the future design and development of the German health care system.

Prevention of alcohol misuse among children, youths and young adults.

BACKGROUND: Despite many activities to prevent risky alcohol consumption among adolescents and young adults there is an increase of alcohol intoxications in the group of ten to twenty year old juveniles. OBJECTIVES: This report gives an overview about the recent literature as well as the German federal prevention system regarding activities concerning behavioral and policy prevention of risky alcohol consumption among children, adolescents and young adults. Furthermore, effective components of prevention activities are identified and the efficiency and efficacy of ongoing prevention programs is evaluated. METHODS: A systematic literature review is done in 34 databases using Bool'sche combinations of the key words alcohol, prevention, treatment, children, adolescents and young adults. RESULTS: 401 studies were found and 59 studies were selected for the health technology assessment (HTA). Most of the studies are done in USA, nine in Germany. A family strengthening program, personalized computer based intervention at schools, colleges and universities, brief motivational interventions and policy elements like increase of prices and taxes proved effective. DISCUSSION: Among the 59 studies there are three meta-analyses, 15 reviews, 17 randomized controlled trials (RCT) and 18 cohort studies. Despite the overall high quality of the study design, many of them have methodological weaknesses (missing randomization, missing or too short follow-ups, not clearly defined measurement parameters). The transferability of US-results to the German context is problematic. Only a few prevention activities reach a sustainable reduction of frequency and/or amount of alcohol consumption. CONCLUSION: The HTA-report shows the need to develop specific and target group focused prevention activities for the German situation. Essential for that is the definition of target goals (reduction of consumption, change of behaviour) as well as the definition and empirical validation of risky alcohol consumption. The efficacy of prevention activities should be proven before they are launched. At present activities for the reduction or prevention of risky alcohol consumption are not sufficiently evaluated in Germany concerning their sustainable efficacy.