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Purpose: To investigate how well visually impaired individuals can learn to use mobility scooters and which parts of the driving task deserve special attention., Materials and Methods: A mobility scooter driving skill test was developed to compare driving skills (e.g. reverse driving, turning) between 48 visually impaired (very low visual acuity = 14, low visual acuity = 10, peripheral field defects = 11, multiple visual impairments = 13) and 37 normal-sighted controls without any prior experience with mobility scooters. Performance on this test was rated on a three-point scale. Furthermore, the number of extra repetitions on the different elements were noted., Results: Results showed that visually impaired participants were able to gain sufficient driving skills to be able to use mobility scooters. Participants with visual field defects combined with low visual acuity showed most problems learning different skills and needed more training. Reverse driving and stopping seemed to be most difficult., Conclusions: The present findings suggest that visually impaired individuals are able to learn to drive mobility scooters. Mobility scooter allocators should be aware that these individuals might need more training on certain elements of the driving task. Implications for rehabilitation Visual impairments do not necessarily lead to an inability to acquire mobility scooter driving skills. Individuals with peripheral field defects (especially in combination with reduced visual acuity) need more driving ability training compared to normal-sighted people - especially to accomplish reversing. Individual assessment of visually impaired people is recommended, since participants in this study showed a wide variation in ability to learn driving a mobility scooter.

Objectives: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany., Methods: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients., Results: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/μL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups)., Conclusions: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration., (© 2018 British HIV Association.)

Though cultural competence and inclusion of diverse identities are increasingly emphasized in psychological training and practice, sexual health and well-being among people with disabilities (PWD) continue to be underrecognized areas in which disability cultural competence is needed. The experience of disability is best conceptualized as an interaction between physical, sensory, or cognitive differences and environmental and sociocultural contexts that facilitate or impede adaptive functioning; these complex interactions, coupled with an individual's age, gender, ethnicity, religious background, and sexual orientation, often inform one's sexual health and well-being. Disability can be thought of as a minority cultural status-a marginalized and stigmatized identity. Given the imperative that psychologists must be culturally competent and self-aware, as well as the centrality of sexual health and well-being to quality of life including among PWD, assessment of sexuality as a facet of overall well-being among individuals with physical disabilities should be part of routine clinical practice. A discussion of disability cultural competence is offered as a foundation to explore disability sexual health and wellness competence in clinical assessment. The disability and sexuality health care competency model is introduced to address the need for evidence-based sexual health and wellness assessment of PWD. Specific conceptual and behavioral sexuality and disability competencies that correspond to the provision and facilitation of these services are delineated. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Background: Habitat fragmentation reduces genetic connectivity for multiple species, yet conservation efforts tend to rely heavily on single-species connectivity estimates to inform land-use planning. Such conservation activities may benefit from multi-species connectivity estimates, which provide a simple and practical means to mitigate the effects of habitat fragmentation for a larger number of species. To test the validity of a multi-species connectivity model, we used neutral microsatellite genetic datasets of Canada lynx ( Lynx canadensis ), American marten ( Martes americana ), fisher ( Pekania pennanti ), and southern flying squirrel ( Glaucomys volans ) to evaluate multi-species genetic connectivity across Ontario, Canada., Results: We used linear models to compare node-based estimates of genetic connectivity for each species to point-based estimates of landscape connectivity (current density) derived from circuit theory. To our knowledge, we are the first to evaluate current density as a measure of genetic connectivity. Our results depended on landscape context: habitat amount was more important than current density in explaining multi-species genetic connectivity in the northern part of our study area, where habitat was abundant and fragmentation was low. In the south however, where fragmentation was prevalent, genetic connectivity was correlated with current density. Contrary to our expectations however, locations with a high probability of movement as reflected by high current density were negatively associated with gene flow. Subsequent analyses of circuit theory outputs showed that high current density was also associated with high effective resistance, underscoring that the presence of pinch points is not necessarily indicative of gene flow., Conclusions: Overall, our study appears to provide support for the hypothesis that landscape pattern is important when habitat amount is low. We also conclude that while current density is proportional to the probability of movement per unit area, this does not imply increased gene flow, since high current density tends to be a result of neighbouring pixels with high cost of movement (e.g., low habitat amount). In other words, pinch points with high current density appear to constrict gene flow.

Objective: To investigate practical fitness to drive mobility scooters, comparing visually impaired participants with healthy controls., Design: Between-subjects design., Subjects: Forty-six visually impaired (13 with very low visual acuity, 10 with low visual acuity, 11 with peripheral field defects, 12 with multiple visual impairment) and 35 normal-sighted controls., Methods: Participants completed a practical mobility scooter test-drive, which was recorded on video. Two independent occupational therapists specialized in orientation and mobility evaluated the videos systematically., Results: Approximately 90% of the visually impaired participants passed the driving test. On average, participants with visual impairments performed worse than normal-sighted controls, but were judged sufficiently safe. In particular, difficulties were observed in participants with peripheral visual field defects and those with a combination of low visual acuity and visual field defects., Conclusion: People with visual impairment are, in practice, fit to drive mobility scooters; thus visual impairment on its own should not be viewed as a determinant of safety to drive mobility scooters. However, special attention should be paid to individuals with visual field defects with or without a combined low visual acuity. The use of an individual practical fitness-to-drive test is advised.

Background  Heart failure in a terminal stage is usually treated with a heart transplant or with implantation of ventricular assist devices (VAD). VAD treatment is increasingly chosen as a permanent therapy. Problem  The growing number of VAD implants leads to an increased need for rehabilitation programs. The development of standards is essential. So far only a few single center reports with a limited number of patients have been published. Guidelines on this subject are not available. Results  A working group of German rehabilitation physicians was installed in order to analyze the problems and to develop strategies for the process of rehabilitation of VAD-patients, ending in a consensus statement 1.The most important aspects of rehabilitation aiming at the safest possible participation in everyday life with a VAD are summarized here., (© Georg Thieme Verlag KG Stuttgart · New York.)

Purpose: To develop a fully automatic algorithm for abdominal organs and adipose tissue compartments segmentation and to assess organ and adipose tissue volume changes in longitudinal water-fat magnetic resonance imaging (MRI) data., Materials and Methods: Axial two-point Dixon images were acquired in 20 obese women (age range 24-65, BMI 34.9±3.8kg/m(2)) before and after a four-week calorie restriction. Abdominal organs, subcutaneous adipose tissue (SAT) compartments (abdominal, anterior, posterior), SAT regions along the feet-head direction and regional visceral adipose tissue (VAT) were assessed by a fully automatic algorithm using morphological operations and a multi-atlas-based segmentation method., Results: The accuracy of organ segmentation represented by Dice coefficients ranged from 0.672±0.155 for the pancreas to 0.943±0.023 for the liver. Abdominal SAT changes were significantly greater in the posterior than the anterior SAT compartment (-11.4%±5.1% versus -9.5%±6.3%, p<0.001). The loss of VAT that was not located around any organ (-16.1%±8.9%) was significantly greater than the loss of VAT 5cm around liver, left and right kidney, spleen, and pancreas (p<0.05)., Conclusion: The presented fully automatic algorithm showed good performance in abdominal adipose tissue and organ segmentation, and allowed the detection of SAT and VAT subcompartments changes during weight loss., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

The assessment of body fat distribution and characteristics using magnetic resonance (MR) methods has recently gained significant attention as it further extends our pathophysiological understanding of diseases including obesity, metabolic syndrome, or type 2 diabetes mellitus, and allows more detailed insights into treatment response and effects of lifestyle interventions. Therefore, the purpose of this study was to review the current literature on MR-based assessment of body fat distribution and characteristics. PubMed search was performed to identify relevant studies on the assessment of body fat distribution and characteristics using MR methods. T1-, T2-weighted MR Imaging (MRI), Magnetic Resonance Spectroscopy (MRS), and chemical shift-encoding based water-fat MRI have been successfully used for the assessment of body fat distribution and characteristics. The relationship of insulin resistance and serum lipids with abdominal adipose tissue (i.e. subcutaneous and visceral adipose tissue), liver, muscle, and bone marrow fat content have been extensively investigated and may help to understand the underlying pathophysiological mechanisms and the multifaceted obese phenotype. MR methods have also been used to monitor changes of body fat distribution and characteristics after interventions (e.g. diet or physical activity) and revealed distinct, adipose tissue-specific properties. Lastly, chemical shift-encoding based water-fat MRI can detect brown adipose tissue which is currently the focus of intense research as a potential treatment target for obesity. In conclusion, MR methods reliably allow the assessment of body fat distribution and characteristics. Irrespective of the promising findings based on these MR methods the clinical usefulness remains to be established., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Bone consists of the mineralized component (i.e., cortex and trabeculae) and the non-mineralized component (i.e., bone marrow). Most of the routine clinical bone imaging uses X-ray-based techniques and focuses on the mineralized component. However, bone marrow adiposity has been also shown to have a strong linkage with bone health. Specifically, multiple previous studies have demonstrated a negative association between bone marrow fat fraction (BMFF) and bone mineral density. Magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) are ideal imaging techniques for non-invasively investigating the properties of bone marrow fat. In the present work, we first review the most important MRI and MRS methods for assessing properties of bone marrow fat, including methodologies for measuring BMFF and bone marrow fatty acid composition parameters. Previous MRI and MRS studies measuring BMFF and fat unsaturation in the context of osteoporosis are then reviewed. Finally, previous studies investigating the relationship between bone marrow fat, other fat depots, and bone health in patients with obesity and type 2 diabetes are presented. In summary, MRI and MRS are powerful non-invasive techniques for measuring properties of bone marrow fat in osteoporosis, obesity, and type 2 diabetes and can assist in future studies investigating the pathophysiology of bone changes in the above clinical scenarios.

Magnetic resonance-based assessment of quadriceps muscle fat has been proposed as surrogate marker in sarcopenia, osteoarthritis, and neuromuscular disorders. We presently investigated the association of quadriceps muscle fat with isometric strength measurements in healthy males using chemical shift encoding-based water-fat magnetic resonance imaging. Intermuscular adipose tissue fraction and intramuscular proton density fat fraction correlated significantly (P < 0.05) with isometric strength (up to r = -0.83 and -0.87, respectively). Reproducibility of intermuscular adipose tissue fraction and intramuscular proton density fat fraction was 1.5% and 5.7%, respectively.

The increasing use of ventricular assist devices (VADs) in terminal heart failure patients provides new challenges to cardiac rehabilitation physicians. Structured cardiac rehabilitation strategies are still poorly implemented for this special patient group. Clear guidance and more evidence for optimal modalities are needed. Thereby, attention has to be paid to specific aspects, such as psychological and social support and education (e.g., device management, INR self-management, drive-line care, and medication).In Germany, the post-implant treatment and rehabilitation of VAD Patients working group was founded in 2012. This working group has developed clear recommendations for the rehabilitation of VAD patients according to the available literature. All facets of VAD patients' rehabilitation are covered. The present paper is unique in Europe and represents a milestone to overcome the heterogeneity of VAD patient rehabilitation.

Purpose: To determine changes in the bone marrow fat fraction (BMFF) in obesity after dietary intervention in comparison with changes in abdominal fat, liver fat, and serum lipids., Materials and Methods: Twenty obese (BMI 34.92 ± 3.8 kg/m(2) ) women participated in a 4-week dietary intervention of 800 kcal/d plus additional vegetables. They underwent anthropometric and blood value measurements before and after the intervention. Abdominal 3T MRI was performed to measure changes in subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) volume and single-voxel magnetic resonance spectroscopy (MRS) to measure fat content changes in the liver and L5 vertebral body., Results: The greatest relative change after dietary intervention was found in the liver (-40.3%), followed by VAT volume (-15.1%), serum lipids (-12.6 to -14.5%), and SAT volume (-8.5%). There were no statistically significant changes in BMFF after dietary intervention (P = 0.39), but absolute changes in the BMFF were positively associated with SAT volume (r = 0.489) and negatively associated with nonadipose tissue volume (r = -0.493) before dietary intervention., Conclusion: Bone marrow behaves differently compared to SAT volume, VAT volume, liver fat, and serum lipids after a 4-week dietary intervention in obesity and BMFF changes depend on abdominal tissue volumes before intervention., (© 2015 Wiley Periodicals, Inc.)

Context: Emergency 911 calls are often made when the end stage of an advanced illness is accompanied by alarming symptoms and substantial anxiety for family caregivers, particularly when an approaching death is not anticipated. How prehospital providers (paramedics and emergency medical technicians) manage emergency calls near death influences how and where people will die, if their end-of-life choices are upheld and how appropriately health care resources are used., Objectives: The purpose of this study was to explore and describe how prehospital providers assess and manage end-of-life emergency calls., Methods: In-depth and in-person interviews were conducted with 43 prehospital providers. Interviews were audiotaped, transcribed, and entered into ATLAS.ti for data management and coding. Qualitative data analysis involved systematic and axial coding to identify and describe emergent themes., Results: Four themes illustrate the nature and dynamics of emergency end-of-life calls: 1) multifocal assessment (e.g., of the patient, family, and environment), 2) family responses (e.g., emotional, behavioral), 3) conflicts (e.g., missing do-not-resuscitate order, patient-family conflicts), and 4) management of the dying process (e.g., family witnessed resuscitation or asking family to leave, decisions about hospital transport). After a rapid comprehensive multifocal assessment, family responses and the existence of conflicts mediate decision making about possible interventions., Conclusion: The importance of managing symptom crises and stress responses that accompany the dying process is particularly germane to quality care at life's end. The results suggest the importance of increasing prehospital providers' abilities to uphold advance directives and patients' end-of-life wishes while managing family emotions near death., (Copyright © 2015 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Vertebral bone marrow fat quantification using single-voxel MRS is confounded by overlapping water-fat peaks and the difference in T2 relaxation time between water and fat components. The purposes of the present study were: (i) to determine the proton density fat fraction (PDFF) of vertebral bone marrow using single-voxel multi-TE MRS, addressing these confounding effects; and (ii) to investigate the implications of these corrections with respect to the age dependence of the PDFF. Single-voxel MRS was performed in the L5 vertebral body of 86 subjects (54 women and 32 men). To reliably extract the water peak from the overlying fat peaks, the mean bone marrow fat spectrum was characterized based on the area of measurable fat peaks and an a priori knowledge of the chemical triglyceride structure. MRS measurements were performed at multiple TEs. The T2 -weighted fat fraction was calculated at each TE. In addition, a T2 correction was performed to obtain the PDFF and the T2 value of water (T2w ) was calculated. The implications of the T2 correction were investigated by studying the age dependence of the T2 -weighted fat fractions and the PDFF. Compared with the PDFF, all T2 -weighted fat fractions significantly overestimated the fat fraction. Compared with the age dependence of the PDFF, the age dependence of the T2 -weighted fat fraction showed an increased slope and intercept as TE increased for women and a strongly increased intercept as TE increased for men. For women, a negative association between the T2 value of bone marrow water and PDFF was found. Single-voxel MRS-based vertebral bone marrow fat quantification should be based on a multi-TE MRS measurement to minimize confounding effects on PDFF determination, and also to allow the simultaneous calculation of T2w , which might be considered as an additional parameter sensitive to the composition of the water compartment., (Copyright © 2015 John Wiley & Sons, Ltd.)

Catalytic generation of hydrogen from aqueous ethanol solution proceeds in the presence of pincer-type transition metal catalysts. Optimal results are obtained applying a [Ru(H)(Cl)(CO)(iPr2PEtN(H)EtPiPr2)] complex (catalyst TON 80,000) in the presence of water and base. This dehydrogenation reaction provides up to 70% acetic acid in a selective manner. For the first time, it is shown that bioethanol obtained from fermentation processes can be used directly in this protocol without the need for water removal. The produced hydrogen can be directly utilized in proton exchange membrane (PEM) fuel cells, since very low amounts of CO are formed., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

For starter culture production, fluidized bed drying is an efficient and cost-effective alternative to the most frequently used freeze drying method. However, fluidized bed drying also poses damaging or lethal stress to bacteria. Therefore, investigation of impact of process variables and conditions on viability of starter cultures produced by fluidized bed drying is of major interest. Viability of bacteria is most frequently assessed by plate counting. While reproductive growth of cells can be characterized by the number of colony-forming units, it cannot provide the number of viable-but-nonculturable cells. However, in starter cultures, these cells still contribute to the fermentation during food production. In this study, flow cytometry was applied to assess viability of Lactobacillus plantarum starter cultures by membrane integrity analysis using SYBR®Green I and propidium iodide staining. The enumeration method established allowed for rapid, precise and sensitive determination of viable cell concentration, and was used to investigate effects of fluidized bed drying and storage on viability of L. plantarum. Drying caused substantial membrane damage on cells, most likely due to dehydration and oxidative stress. Nevertheless, high bacterial survival rates were obtained, and granulates contained in the average 2.7 × 10(9) viable cells/g. Furthermore, increased temperatures reduced viability of bacteria during storage. Differences in results of flow cytometry and plate counting suggested an occurrence of viable-but-nonculturable cells during storage. Overall, flow cytometric viability assessment is highly feasible for rapid routine in-process control in production of L. plantarum starter cultures, produced by fluidized bed drying.

Background: Antibody responses to hepatitis C virus (HCV) occur delayed and overly decline after viral clearance indicating that the B-cell response to HCV is abnormal. Virus-specific memory B-cells have recently been found in infected individuals, but the viral exposure requirements for the generation of these cells is unknown., Objectives: The primary goal of this study was to quantify and compare the HCV-specific memory B-cell response between chronic and resolved HCV-infected individuals. A secondary goal was to examine if HIV-specific memory B-cell responses are maintained during HCV co-infection., Study Design: HCV core protein- and HIV-specific memory B-cell responses were examined in HIV/HCV-infected individuals treated 4-30 weeks after HCV diagnosis. Memory B-cell frequencies were compared between chronically and transiently infected individuals., Results: Chronically infected individuals had vigorous HCV-specific memory B-cell responses and antibodies, whereas subjects with transient viremia showed low or undetectable virus-specific B-cell responses. In addition, chronically HIV/HCV-infected subjects had robust HIV-specific memory B-cell responses., Conclusions: Whereas chronic HCV infection induces virus-specific antibodies and memory B-cells, transient infection in individuals with sustained viral response to therapy does not stimulate a durable HCV-specific B-cell response indicating that the formation of long-lived virus-specific B-cells is suppressed in the early phase of infection. This may contribute to the inability to spontaneously clear HCV infection., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Background: Genome-wide association studies found low plasma levels of 25-hydroxyvitamin D and vitamin D receptor (VDR) polymorphisms associated with a higher prevalence of pathological changes in the intestine such as chronic inflammatory bowel diseases., Methods: In this study, a proteomic approach was applied to understand the overall physiological importance of vitamin D in the small intestine, beyond its function in calcium and phosphate absorption., Results: In total, 569 protein spots could be detected by two-dimensional-difference in-gel electrophoresis (2D-DIGE), and 82 proteins were considered as differentially regulated in the intestinal mucosa of VDR-deficient mice compared to that of wildtype (WT) mice. Fourteen clearly detectable proteins were identified by MS/MS and further analyzed by western blot and/or real-time RT-PCR. The differentially expressed proteins are functionally involved in cell proliferation, cell adhesion and cell migration, stress response and lipid transport. Mice lacking VDR revealed higher levels of intestinal proteins associated with proliferation and migration such as the 37/67 kDa laminin receptor, collagen type VI (alpha 1 chain), keratin-19, tropomyosin-3, adseverin and higher levels of proteins involved in protein trafficking and stress response than WT mice. In contrast, proteins that are involved in transport of bile and fatty acids were down-regulated in small intestine of mice lacking VDR compared to WT mice. However, plasma and liver concentrations of cholesterol and triglycerides were not different between the two groups of mice., Conclusion: Collectively, these data imply VDR as an important factor for controlling cell proliferation, migration and stress response in the small intestine.

Molecularly well-defined iron pincer complexes promote the aqueous-phase reforming of methanol to carbon dioxide and hydrogen, which is of interest in the context of a methanol and hydrogen economy. For the first time, the use of earth-abundant iron complexes under mild conditions for efficient hydrogen generation from alcohols is demonstrated., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

A better and regular control of the production chain of fresh fruits and vegetables is necessary, because a contamination of the product by human- and phyto-pathogenic microorganisms may result in high losses during storage and poses a threat to human health. Therefore, detailed knowledge about the occurrence and the diversity of microorganisms within single processing steps is required to allow target-oriented produce safety control. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was successfully used to identify bacterial colonies. Bacteria can be identified with high accuracy by comparing them with generated spectra of a reference database. In this study, spinach and wash water samples were taken of the complete process line of a spinach-washing plant. Bacteria in the samples were grown on plate-count, Arcobacter selective, marine and blood agar. In total, 451 colonies were evaluated by MALDI-TOF MS, 16S rRNA gene sequence and phylogenetic analysis. 50% of the detected species belonged to the class of Gammaproteobacteria. Firmicutes were present with 22%. Mostly, the detected species showed 16S rRNA gene sequence dissimilarities larger than 1% to known reference species and, hence, could not be assigned to a distinct species. However, many isolated species belonged to genera which contain pathogenic or opportunistic pathogenic bacteria. In addition, the bacterial diversity on the spinach surface increased after the first washing step indicating a process-borne contamination of the spinach., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objectives: Once-daily (qd) antiretroviral therapies improve convenience and adherence. If found to be effective, nevirapine extended release (NVP XR) will confer this benefit. The TRANxITION trial examined the efficacy and safety of switching virologically suppressed patients from NVP immediate release (NVP IR) 200 mg twice daily to NVP XR 400 mg qd., Methods: An open-label, parallel-group, noninferiority, randomized (2:1 NVP XR:NVP IR) study was performed. Adult HIV-1-infected patients receiving NVP IR plus a fixed-dose nucleoside reverse transcriptase inhibitor (NRTI) combination of lamivudine (3TC)/abacavir (ABC), tenofovir (TDF)/emtricitabine (FTC) or 3TC/zidovudine (ZDV) with undetectable viral load (VL) were enrolled in the study. The primary endpoint was continued virological suppression with VL < 50 HIV-1 RNA copies/mL up to week 24 (calculated using a time to loss of virological response algorithm). Cochran's statistic (background regimen adjusted) was used to test noninferiority. Adverse events (AEs) were recorded., Results: Among 443 randomized patients, continued virological suppression was observed in 93.6% (276 of 295) of NVP XR- and 92.6% (137 of 148) of NVP IR-treated patients, an observed difference of 1% [95% confidence interval (CI) -4.3, 6.0] at 24 weeks of follow-up. Noninferiority (adjusted margin of -10%) of NVP XR to NVP IR was robust and further supported by SNAPSHOT analysis. Division of Acquired Immunodeficiency Syndrome (DAIDS) grade 3 and 4 events were similar for the NVP XR and NVP IR groups (3.7 vs. 4.1%, respectively), although overall AEs were higher in the NVP XR group (75.6 vs. 60.1% for the NVP-IR group)., Conclusions: NVP XR administered once daily resulted in continued virological suppression at week 24 that was noninferior to that provided by NVP IR, with similar rates of moderate and severe AEs. The higher frequency of overall AEs with NVP XR may be a consequence of the open-label design., (© 2011 British HIV Association.)

Micro-RNAs (miRNAs) are short, non-coding RNAs that regulate gene expression post transcriptionally. Several studies have demonstrated the relevance of miRNAs for a wide range of cellular mechanisms, however, the current knowledge on how miRNAs respond to relevant external stimuli, e.g. in disease scenarios is very limited. To generate a descriptive picture of the miRNA network associated to inflammatory responses, we quantified the levels of 330 miRNAs upon stimulation with a panel of pro-inflammatory components such as microbial pattern molecules (flagellin, diacylated lipopeptide lipopolysaccharide, muramyl dipeptide), infection with Listeria monocytogenes and TNF-α as pro-inflammatory control in primary human monocytes using real time PCR. As a result, we found distinct miRNA response clusters for each stimulus used. Additionally, we identified potential target genes of three selected miRNAs miR-129-5p, miR-146a and miR-378 which were part of PAMP-specific response clusters by transfecting THP1 monocytes with the corresponding pre- or anti-miRNAs and microfluidic PCR arrays. The miRNAs induced distinct transcriptomal signatures, e.g. overexpression of miRNA129-5p, which was selectively upregulated by the NOD2-elicitor MDP, led to an upregulation of DEFB1, IRAK1, FBXW7 and IKK γ (Nemo). Our findings on highly co-regulated clusters of miRNAs support the hypothesis that miRNAs act in functional groups. This study indicates that miRNAs play an important role in fine-tuning inflammatory mechanisms. Further investigation in the field of miRNA responses will help to understand their effects on gene expression and may close the regulatory gap between mRNA and protein expression in inflammatory diseases.

Objective: The sexual lives of returning Operation Enduring Freedom (OEF), Operation Iraqi Freedom (OIF), and Operation New Dawn (OND) veterans have only been discussed minimally in the psychological literature. Given the nature of military social and cultural contexts, the potential for exposure to combat-related stressors that may lead to posttraumatic stress disorder (PTSD), and the risk of traumatic brain injury secondary to physical injury, the potential for significant psychological and relational ramifications exists. This article focuses on the intimate relationships and sexuality of returning OIF/OEF/OND veterans within the context of their personal cultural variables and the diverse experience of being a part of military life., Conclusions: Culturally competent assessment and evidenced-based treatment approaches are highlighted to offer clinicians initial strategies to begin treatment of sexuality issues within the returning Veteran population. These clinical tools are discussed within a positive psychology approach that emphasizes healthy sexuality as a part of overall satisfactory quality of life.

Head and neck squamous cell carcinomas (HNSCC) represent the sixth largest group among all human malignancies. However, the exact molecular mechanisms inducing the genesis and the progression of metastasis in these tumors are poorly understood. The identification of molecular alterations involved in metastasis of HNSCC might influence the value of clinical diagnostics, impact therapy strategies and finally improve the prognosis of the patients. The purpose of this study was to identify clinically relevant alterations at the transcriptional and translational levels, when comparing metastatic (N+) and non-metastatic (N0) primary HNSCC. Three transcripts HERPUD1, SLPI and RAD51 were selected for further validation based on their association with carcinogenesis and metastasis. Quantitative real-time-PCR was performed to determine the mRNA expression levels. For subsequent confirmation of the results, immunohistochemistry was performed applying a monoclonal anti-SLPI antibody on 121 HNSCC tumor specimens (N0, n=40; N+, n=81). In metastatic primary cancer, SLPI mRNA showed 5.9-fold lower expression in comparison with non-metastatic primary cancer (p=0.0092). Immunohistochemical staining revealed a fold change of -1.79 between the N+ and the N0 group (p=0.0002). The results presented here clearly indicate the repression of SLPI, measurable on both, mRNA and protein levels in metastatic primary HNSCC as compared to non-metastatic HNSCC. Therefore, it can be assumed that SLPI might have a substantial protective effect on the metastasis process of HNSCC.

Objectives: Outbreaks of sexually transmitted acute HCV infection have been described recently in several cities in the western world. The epidemic affects mainly MSM who are coinfected with HIV and is supposably linked to certain sexual risk practices. Here, we compared our findings with current knowledge and recommendations., Methods: HIV-positive patients with the diagnosis of acute HCV infection were included in the retrospective analysis. The patients came from outpatient infectious disease centers in northern German cities. We looked at markers of HIV and HCV infection and compared patients who received treatment and those who did not. Treated patients were followed up to 72 weeks., Results: Three hundred nineteen HIV-positive patients with the diagnosis of acute hepatitis C between 2001 and 2008 and were included in the analysis. All patients were male, 315 (99%) patients were of caucasian origin, 296 (93%) declared homosexual contacts as a risk factor for HCV infection, intravenous drug use was declared in 3 (1%) cases. Median age at HCV diagnosis was 40 years (range 20-69 years). Median HCV viral load was 1.2 x 106 IU/mL, 222 patients (70%) had HCV genotype 1, 59 (18%) genotype 4. The median time of HIV infection was 5.5 years (range 0 to 22.4 years). Median HIV viral load was 110 copies/mL (range 25 to 10x106 copies/mL). The median CD 4 count was 461 cells/mm3 (range 55-1331 cells/mm3). Two hundred and fourty-six patients (77%) received anti-HCV treatment, and 175 (55%) had completed therapy by the time of the analysis. Median treatment duration was 33 weeks (IQR 24.1-49.9). 93 of the 175 treated patients (53%) reached a sustained virological response (SVR). In the multivariate analysis, ART at diagnosis, HCV RNA drop at week 12, hemoglobin levels and higher platelets were associated with SVR. Treatment duration was significantly higher in the SVR group (40.6 weeks vs 26.6 weeks, p<0.0001). Seventy-three patients (23%) did not receive anti-HCV treatment. In 19 of the untreated patients (26%) the hepatitis C virus was cleared spontaneously., Conclusions: Our findings confirm that acute hepatitis C in HIV infected patients affects mainly MSM who acquire HCV sexually. Patients had a short duration of HIV infection and a stable immunological situation. In this real-life setting from urban regions in northern Germany, treatment rates appear to be high and effective.

Problems/objectives: Epstein-Barr virus (EBV) is commonly associated with nasopharyngeal carcinoma and Burkitt's lymphoma, but association with hypopharyngeal and laryngeal tumours is rare. To the best of our knowledge, this is the first case report of an EBV-associated diffuse large B-cell lymphoma (DLBCL) of the hypopharynx., Methodology: A 63-year-old male patient suffering from chronic lymphocytic leukemia presented with swallowing disorders and a sore throat. Panendoscopy with laser surgical resection of tissue specimens was performed., Results: Immunohistochemical and molecular genetic diagnostics, including EBV-encoded small RNA in situ hybridization, confirmed the diagnosis of an EBV-associated DLBCL of the hypopharynx. Ten weeks after the diagnosis, the patient died of disease related to multiple complications., Conclusions: We hypothesize that the EBV infection was triggered by long-term immunosuppressive therapy that led secondarily to the development of a DLBCL. Otorhinolaryngologists should keep in mind that lymphomas might develop in the entire pharynx.

Background: There is a clear correlation between proliferative activity and the biological behavior of cancer, which might have an impact on the patients' prognosis and consequences for the individual therapy concept. REPP86 (restrictedly expressed proliferation-associated protein 86) is a proliferation-associated protein expressed in S-, G(2)- and M-phases of the cell cycle, regarded as a promising proliferation marker and has not yet been examined in squamous cell carcinoma of the larynx (SCCL)., Materials and Methods: REPP86 was analyzed retrospectively in 104 SCCL using the monoclonal antibody Ki-S2. Proliferative activity was correlated with tumor stage, histopathological grading, patients' survival and the results we recently published on Ki-67 staining in SCCL. Median follow-up time was 47 months., Results: A significant correlation (p<0.05) between histopathological grading, N-status and proliferation activity was observed. The patient group consisting of low proliferating laryngeal cancer showed a statistically longer absolute (p<0.05) and relapse-free (p=0.001) 5-year survival time than the group with a high proliferating tumor. Compared to the Ki-67 staining results, the REPP86 antibody better predicts the relapse-free 5-year-survival., Conclusion: Our results indicate that REPP86 staining of SCCL with Ki-S2 is a helpful prognostic indicator for SCCL and better predicts the relapse-free survival than Ki-67 staining in SCCL.

In various biotechnological processes, filamentous fungi, e.g. Aspergillus niger, are widely applied for the production of high value-added products due to their secretion efficiency. There is, however, a tangled relationship between the morphology of these microorganisms, the transport phenomena and the related productivity. The morphological characteristics vary between freely dispersed mycelia and distinct pellets of aggregated biomass. Hence, advantages and disadvantages for mycel or pellet cultivation have to be balanced out carefully. Due to this inadequate understanding of morphogenesis of filamentous microorganisms, fungal morphology, along with reproducibility of inocula of the same quality, is often a bottleneck of productivity in industrial production. To obtain an optimisation of the production process it is of great importance to gain a better understanding of the molecular and cell biology of these microorganisms as well as the approaches in biochemical engineering and particle technique, in particular to characterise the interactions between the growth conditions, cell morphology, spore-hyphae-interactions and product formation. Advances in particle and image analysis techniques as well as micromechanical devices and their applications to fungal cultivations have made available quantitative morphological data on filamentous cells. This chapter provides the ambitious aspects of this line of action, focussing on the control and characterisation of the morphology, the transport gradients and the approaches to understand the metabolism of filamentous fungi. Based on these data, bottlenecks in the morphogenesis of A. niger within the complex production pathways from gene to product should be identified and this may improve the production yield.

The tumour suppressor protein p53 (wild-type = wt-p53) is of major importance in the genetic integrity of the cell. Mutations of the p53-gene (mt-p53) are the most frequent genetic aberrations identified in different tumour entities. As analyzed in a wide variety of human malignomas, mt-p53 evokes a specific immune response. Yet, the possible occurrence of p53-autoantibodies in patients with head and neck squamous cell carcinomas (HNSCC) correlated to p53-mutations, p53 in sera and p53-overexpression in tissue has not been previously investigated. For the first time, the p53 status in 24 HNSCC patients was analyzed in the present study. The following parameters were investigated: analysis of mutation frequency of the p53-gene by direct sequencing of the exons 5-9, immunohistochemical detection of p53, measurement of the wt- and mt-p53-protein in sera by ELISA and p53-autoantibodies in sera by ELISA. Mutations of the p53-gene were detected in four (17%) patients. Overexpression of wt-p53 was detected by immunohistochemistry in 18 out of 24 (75%) tumours. In 8 (33%) patients the p53-protein was also detectable in sera, whereas in just one of these eight patients p53-autoantibodies were detectable simultaneously. Overall 6 out of 24 (25%) patients were found to be positive for serum p53-autoantibodies. Of these 6 cases, 5 could be assigned to tumours with immunohistochemically measurable wt-p53-overexpression. There was no correlation between p53-overexpression in tissue and p53-protein levels in sera or between p53-autoantibody levels in sera, nor in mutation frequency of the p53-gene and p53-overexpression in tissue. The results presented herein support the hypothesis that strong accumulation of p53 in the tissue is an important prerequisite for development of p53-autoantibodies. However, there must be further, yet unknown factors that influence the p53-autoantibody production because p53-autoantibodies were not identified in sera in each case of p53-accumulation in the tissue.

Purpose: Patient survival after resection of non-small cell lung cancer (NSCLC) strongly correlated with the occurrence of distant metastasis. Cathepsins are members of the lysosomal cysteine proteases family and can support the metastatic process by degrading the extracellular matrix. The purpose of this study was to identify members of the Cathepsin family that correlate with recurrence-free and overall survival of NSCLC patients., Patients and Methods: The expression of 13 Cathepsins was examined using DNA-microarray technology in tumor tissues of 89 surgically treated NSCLC patients. All NSCLC samples were classified according to median Cathepsin expression value into either a high or a low expression group. All Cathepsin expression groups were subjected to clinical prognostic analyses regarding survival and local as well as distant recurrences., Results: Patients with high Cathepsin C tumor expression showed higher tumor recurrence rate compared to patients with low Cathepsin C expression (p = 0.02). The tumor expression of Cathepsins K and B significantly correlated with recurrence-free and overall survival as determined by multivariate analysis. A high expression of Cathepsin B or K was associated with a considerable reduction of recurrence-free as well as overall survival. NSCLC patients with a high expression of both Cathepsin B and K had a significantly (p = 0.001) poorer outcome (5-year survival rate: 13%) than patients with low expression of both genes (5-year survival rate: 75%)., Conclusions: The combined expression level of Cathepsins B and K identifies high-risk NSCLC patients. A selection of gene expression panels is theoretically superior to established clinical and pathological criteria.

Background: Proliferative activity has been shown to be of prognostic significance for several malignancies. Ki-67, a cell cycle associated antigen, is regarded as a promising proliferation marker. Very few results on the proliferative activity of head and neck cancer and their potential prognostic value are available., Materials and Methods: The proliferative activity of 104 squamous cell carcinomas of the larynx (SCCL) was analyzed retrospectively with the monoclonal antibody Ki-S11 which specifically detects the Ki-67 antigen. Median follow-up time was 47 months., Results: There was a statistically significant correlation (p<0.05) between histopathological grading, N-status and proliferative activity. There was also a significant difference for the 5-year survival between low and highly proliferating tumours. The patient group with low proliferating laryngeal cancer had a statistically (p<0.05) longer absolute and recurrence-free 5-year-survival time than patients with a highly proliferating cancer., Conclusion: These results show that Ki-67 staining of SCCL with Ki-S11 is a helpful prognostic indicator for squamous cell carcinoma of the larynx with a potential clinical application.

Objectives: This cross-sectional study was designed to pilot the analysis of clinical data, knowledge about and attitudes towards HIV/AIDS, and prevention and risk behaviour in persons recently infected with HIV., Methods: Blood samples and demographic, laboratory, clinical and behavioural data were collected from patients with newly diagnosed HIV infections. The BED IgG-capture ELISA (BED-CEIA) was used to determine the recency of infection., Results: Recent HIV infections contributed 54% [95% confidence interval (CI) 45; 64%] of infections in men who have sex with men (MSM) and 16% (95% CI 0; 39%) of infections in patients with other transmission risks (P=0.041). Recently infected MSM were characterized by younger age and higher viral load as compared with MSM who had longstanding infections (P=0.011 and 0.005, respectively). Symptoms during primary infection and patients' assumptions with regard to time of infection were significantly correlated with test results indicating whether or not the HIV infection was recently acquired (P<0.001)., Conclusions: Cross-sectional surveillance of recent HIV infections proved to be relevant to the identification of current risks for acquiring HIV infection. The high proportion of recent HIV infections in MSM and the even higher proportion in MSM younger than 30 years indicate ongoing HIV transmission in this group. The method will be used in future national HIV surveillance in Germany.

To identify genes that are involved in ischemia response of the brain, we have evaluated changes of gene expression in rat cerebrum after 15 min complete global ischemia, followed by reperfusion for 1 h, 6 h or 24 h. The expression profiles of approximately 30,000 transcripts from three subjects in each group (including sham-operated controls) were monitored employing oligonucleotide microarrays. About 20,000 transcripts were detectable in rat brains. The levels of 576 transcripts (approximately 2.9%) were significantly altered in response to experimental ischemia. 419 transcripts were up- and 157 downregulated; 39 transcripts changed after 1 h reperfusion, 174 after 6 h and 462 after 24 h. Results from quantitative real-time reverse transcription PCR of 18 selected genes showed excellent agreement with the microarray data. There is surprisingly little overlap between gene regulation patterns at different reperfusion times (only seven genes displayed significant changes in transcript levels at all reperfusion times. Several genes that were previously unknown to be involved in ischemia-response have been identified. Analyses of gene ontology patterns and the most strongly regulated transcripts showed that the immediate response to an ischemia/reperfusion is mediated by the induction of specific transcription factors and stress genes. Delayed gene expression response is characterised by inflammation and immune-related genes. These results support the hypothesis that the brain's response to ischemia is an active, specific and coordinated process.

Selective up-regulation of the mRNA of LOXL4, a member of the LOX matrix amine oxidase family, significantly correlated with lymph node metastases and higher tumour stages in head and neck squamous cell carcinomas (HNSCC). To evaluate the diagnostic and prognostic value of the protein we produced an antibody specific for LOXL4 and assessed the expression in 317 human HNSCC specimens. The LOXL4 protein was detected in 92.7% of primary tumours, in 97.8% of lymph node metastases and in affected oral mucosa with high-grade dysplasia, but was absent in various non-neoplastic tissues of the head and neck. TNM categories and overall survival did not link to grades of immunoreactivity. Studies in cultured primary hypopharyngeal HTB-43 carcinoma cells detected perinuclear and cell surface expression of LOXL4, but no nuclear localisation. Therefore, its interactive SRCR-domains and catalytic activity combined with tumour cell specific expression and cell surface associated location indicate multiple functions in tumour cell adhesion and interactions with the extracellular matrix. Our data suggest that LOXL4 is useful both as tumour marker and target in the treatment of HNSCC.

In this study, the feasibility of fluorescence lifetime imaging (FLIM) for measurement of RNA:DNA ratios in microorganisms was assessed. The fluorescence lifetime of a nucleic acid-specific probe (SYTO 13) was used to directly measure the RNA:DNA ratio inside living bacterial cells. In vitro, SYTO 13 showed shorter fluorescence lifetimes in DNA solutions than in RNA solutions. Growth experiments with bacterial monocultures were performed in liquid media. The results demonstrated the suitability of SYTO 13 for measuring the growth-phase-dependent RNA:DNA ratio in Escherichia coli cells. The fluorescence lifetime of SYTO 13 reflected the known changes of the RNA:DNA ratio in microbial cells during different growth phases. As a result, the growth rate of E. coli cells strongly correlated with the fluorescence lifetime. Finally, the fluorescence lifetimes of SYTO 13 in slow- and fast-growing biofilms were compared. For this purpose, biofilms developed from activated sludge were grown as autotrophic and heterotrophic communities. The FLIM data clearly showed a longer fluorescence lifetime for the fast-growing heterotrophic biofilms and a shorter fluorescence lifetime for the slow-growing autotrophic biofilms. Furthermore, starved biofilms showed shorter lifetimes than biofilms supplied with glucose, indicating a lower RNA:DNA ratio in starved biofilms. It is suggested that FLIM in combination with SYTO 13 represents a useful tool for the in situ differentiation of active and inactive bacteria. The technique does not require radioactive chemicals and may be applied to a broad range of sample types, including suspended and immobilized microorganisms.

The sensitivity and specificity of the human immunodeficiency virus (HIV) type 1-specific immunoglobulin G capture enzyme-linked immunosorbent assay (BED-CEIA) were compared with those of the avidity index method to identify recent HIV infection using a panel of 148 samples (81 patients) representing durations of infection ranging from 0 to 222 weeks. The results from the two tests were similar (sensitivity of 80% versus 74% [P = 0.53]; specificity of 86% versus 82% [P = 0.67]).

Aspergillus niger is a widely used expression host for homologous and heterologous protein production in biotechnological processes. In order to increase product yields, a thorough optimisation of these cultivation processes is necessary. Considering mRNA as the key molecule, which transports the genetic information between DNA and protein production side, the quantification of product specific gene expression provides useful information about product formation already on the level of transcription. Quantitative reverse transcription polymerase chain reaction (qRT-PCR) is a powerful tool to obtain data about gene transcription. However, using this technique the choice of an appropriate reference system is a crucial aspect to provide optimal data normalisation. A prominent approach is the use of so called housekeeping genes as internal references. However, validation of the usability of these reference genes is the fundamental step before starting with qRT-PCR experiments. Adequate reference genes for A. niger have not been published so far. Therefore, 10 possible candidate genes from different functional classes were selected and their applicability as internal references validated. Transcript levels of these genes were compared in sets of 9, 41 and 19 samples from diverse cultivations of A. niger. Under the chosen experimental conditions, the genes act, sarA and cox5 have been identified as genes with the most stable gene expression. The three reference genes were used to normalise qRT-PCR data for glaA gene expression which showed a high correlation with glucoamylase production in continuous cultivations.

The molecular mechanisms causing the development of squamous cell carcinomas in the head and neck region are mostly unknown. Identification of molecular changes which are involved in carcinogenesis might play a key role in improving the diagnosis, therapy and prognosis of patients with carcinomas in the head and neck. The purpose of the study was to identify transcriptional alterations of apoptosis associated genes between normal mucosa and tumor tissue. We measured the mRNA expression of 408 apoptosis associated genes by microarray-technique in normal upper aerodigestive tract mucosa (n=4), and in cancer tissue (n=8) of squamous cell carcinomas of the upper aerodigestive tract. RT-PCR was performed to confirm the microarray results. A hierarchial cluster analysis, based on 22 selected marker-genes showing a separation of the two tissue types supports the hypothesis of a specific expression pattern associated with tumor development. Additionally, we found 11 genes associated with anti-apoptotic processes to be upregulated while 12 genes associated with proapoptotic functions as well as 5 DNA-replication and chromosome cycle associated genes were found to be downregulated in the tumor tissue. Furthermore 6 of 8 genes which are known to be associated with lymphocyte activation were upregulated in tumor edge tissue. These results represent a first step for the diagnostic use of microarrays in squamous cell carcinomas of the head and neck region and might improve the understanding of the molecular mechanisms of carcinogenesis in the head and neck region.

The quality of a phytomedicine is defined by the quality of the herbal drug, the manufacturing of the drug preparations and the properties of the finished product, taking into account the special requirements of the individual herbal species in accordance with Good Manufacturing Practice (GMP) standards [2003. Medicinal Products for Human and Veterinary Use. Eudralex, vol. 4 (2003/94/EC)]. The quality control of the complete process is based on pharmacognostic methods, characteristic fingerprint chromatograms, defined amounts of marker substances, physicochemical characteristics and microbiological monitoring. For a herbal multi-component preparation used in multi-target therapy, these pharmaceutical prerequisites have to be ensured for all components and for their combination, as is exemplified by Iberogast((R)) (STW 5) a fixed combination of hydroethanolic extracts of bitter candytuft (Iberis amara), angelica root (Angelicae radix), milk thistle fruit (Silybi mariani fructus), celandine herb (Chelidonii herba), caraway fruit (Carvi fructus), liquorice root (Liquiritiae radix), peppermint herb (Menthae piperitae folium), balm leaf (Melissae folium) and chamomile flower (Matricariae flos) using in the therapy of gastrointestinal complaints (Rösch et al., 2006). The prerequisites for the quality of each of its components according to actual standards are at first the cultivation of the plant material according to the Guidelines for Good Agricultural Practice (GAP) conditions of Medicinal and Aromatic Plants [1998. Z. Arzn. Gew. Pfl. 3, 166-178] to yield a defined raw material of high quality. Characteristic compounds of the extracts had to be identified and different analytical methods such as HPLC, with low coefficients of variation had to be developed to analyze each of the standardized ethanolic extracts and the finished product. At the example of the extract of I. amara these necessary investigations are described. The variability of the plant material in its natural habitats, the identification of characteristic compounds and exemplary chromatograms for fingerprint evaluation and quantification are shown. These data are required for characterization of the profile of the active substances in the finished product.

Methadone is metabolized by various isoforms of the cytochrome P450 family, which can be induced by many drugs, including nevirapine. The objective of the present study was to determine the effects of coadministration of nevirapine and methadone on the dose-adjusted areas under the concentration-time curves (AUCs) of racemic and (R)-methadone. Twenty-five human immunodeficiency virus-infected subjects taking stable single daily doses of racemic methadone or (R)-methadone were included in this prospective, single-crossover trial. At the baseline, nevirapine was either started as part of a new regimen containing two nucleoside reverse transcriptase inhibitors (NRTIs) or added to an ongoing NRTI regimen. Patients could increase their methadone doses if withdrawal symptoms developed. Twelve-hour pharmacokinetic profiles were obtained before and 28 days after the start of nevirapine treatment. The total concentrations of methadone and its inactive metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), in serum were determined by liquid chromatography-tandem mass spectrometry. Among the 20 evaluable patients, coadministration of nevirapine significantly decreased the mean dose-adjusted AUC of methadone by 41%. AUC reductions were similar for patients taking racemic methadone (37%; n = 11) and (R)-methadone (44%; n = 9). AUC changes ranged from mild increases in three patients to decreases of up to 70%. Fourteen of 20 patients required additional methadone due to withdrawal symptoms. However, the median dose increase was only 15%, which was less than that which would have been expected from the pharmacokinetic data. The AUC of EDDP increased significantly, by 35%. Methadone dose adjustments are justified when methadone is coadministered with nevirapine. Due to extensive variability, the adjustments must be tailored to the individual patient's needs.

Objectives: Prognosis and course of severe left ventricular dysfunction have been shown to be influenced positively by exercise training. Yet, physicians have been reluctant to include exercise into therapeutic concepts due to widespread uncertainty about the acceptable intensity of cardiac stress. Standardized exercise programs with proven safety may promote acceptance of this approach., Patients and Methods: 25 patients with severe heart failure were enrolled in a PC-controlled interval exercise training on cycle ergometer, lasting 21 minutes five times a week for a 4-week inpatient period. After discharge patients performed incremental daily walking for 3 months. Associated educational measures concerned life-style changing and self-controls., Results: None of the patients had to interrupt the training because of side effects. 3 weeks and 3 months after starting exercise training there was an increase of peak VO2 from 13.4 +/- 2.8 to 14.5 +/- 3.8 (p < 0.05) and 15.3 +/- 3.2 ml/kg/min (p < 0.01), respectively, and an increase of ventilatory anaerobic threshold (VAT) from 9.3 +/- 1.9 to 10.0 +/- 2.3 (p < 0.05) and 11.3 +/- 2.2 ml/kg/min (p < 0.001), respectively. The improved aerobic capacity corresponded to a 9.3% increase in the results of the 6-minute walk test in the 4th week (n.s.). During out-patient period, the walking could be increased from 37 to 58 minutes daily. The physical quality of life was significantly improved after 3 months. There was no hospital admission due to heart failure., Conclusion: Exercise training in the therapy of severe heart failure is safe and increases the aerobic capacity. Associated educational measures may be able to minimize the danger of wrong exercise techniques and to reduce the rate of hospital readmissions.

To evaluate the incidence and survival time for AIDS-patients affected by different stages of nontuberculous mycobacterial (NTM) infection we performed a retrospective study. Data of 1540 hospitalised AIDS-patients was analyzed with respect to survival time and incidence rates. The overall incidence rate of NTM following AIDS was 16.6/100 person-years (PY), with an increase from 12.1/100PY (1987-1990) to 18.9/100PY (1991-1994). Antiretroviral therapy (ART) and toxoplasmosis prophylaxis reduced the risk of NTM disease whereas CD4 cells <40/ microl at time of the first AIDS defining illness led to a 2.5 fold higher risk. Pneumocystis carinii pneumonia (PCP), wasting syndrome and PCP prophylaxis increased the risk of progression from colonization to dissemination. Cryptococcus neoformans infection, wasting syndrome, PCP prophylaxis and CD4 cells <40/ microl were linked to immediate NTM dissemination. Though the incidence of NTM dissemination increased by the factor 1.56 in 1991-1994, survival did not differ between patients with and without NTM infection.

In the observation of various opportunistic pathogens in HIV-positive persons, co-infection by Cryptococcus neoformans together with Mycobacterium avium intracellulare was found if there was a CD4 lymphocyte count as low as 3-20/microliters. In 1540 HIV-positive patients under treatment at a Berlin hospital (Auguste-Viktoria-Krankenhaus) during 1985-1994, all AIDS-relevant diseases were examined in a multivariate analysis as variables of influence on the manifestation of a systemic Mycobacterium avium complex (MAC) infection. The analysis involved data on 36 cases of cryptococcosis and 202 cases with a typical clinical course in whom MAC had been detected at sterile body sites. As significant and independent factors of influence, the following were identified: C. neoformans infection, wasting syndrome, lower age, low CD4 lymphocyte count and preceding Pneumocystis carinii pneumonia (PcP) prophylaxis. Cryptococcosis ranged first with an ods ratio of 2.75. The concomitant manifestation of cryptococcosis and systemic MAC infection in six patients is shown. Because both opportunists, C. neoformans and avian mycobacteria, may have their common habitat in droppings of defined species of pet birds, a common source of infection deserves further clinical and epidemiological attention.

The rabbit tooth-pulp assay is well established as a method for measuring the efficacy and potency of parenteral analgesic drugs. We describe a method for administration of local anesthetic drugs into the maxillary arch and subsequent measurements of antinociceptive action. It was possible to use two different methods of ED50 estimation and to provide measures of the potency, efficacy, and duration of local anesthetic drugs. These measurements corresponded with in vitro estimates of potency and duration and with intrinsic observations of the clinical actions.

Corynebacterium glutamicum is an industrially important bacterium for the manufacture of amino acids. We constructed genomic libraries of this Gram+ bacterium and screened for clones carrying isoleucine biosynthesis genes (ilv) by complementation of Escherichia coli mutants. Clones complementing ilvA, ilvB, and ilvC were isolated. As based on the functional analysis of the corresponding plasmids in C. glutamicum, the DNA fragments isolated encode threonine dehydratase, acetohydroxy acid synthase, and isomeroreductase, catalyzing three subsequent reactions in Ile synthesis. Subcloning and transposon mutagenesis revealed that ilvB and ilvC reside on a 7-kb chromosomal fragment and that these genes are transcribed in the same direction. A shuttle vector was constructed to allow exonuclease treatment and assay subsets of plasmids for gene expression in the original C. glutamicum background. These constructs and their enzyme activity determinations revealed that despite close linkage ilvC is expressed independently from ilvB. Using Southern blots, a 15-kb fragment of chromosomal DNA carrying the ilvBC cluster was characterized. This fragment does not contain ilvA, demonstrating the entirely different organization of the isoleucine biosynthesis genes in C. glutamicum from that in enterobacteria.