Proteomics of Galápagos Marine Iguanas Links Function of Femoral Gland Proteins to the Immune System.

Communication between individuals via molecules, termed chemosignaling, is widespread among animal and plant species. However, we lack knowledge on the specific functions of the substances involved for most systems. The femoral gland is an organ that secretes a waxy substance involved in chemical communication in lizards. Although the lipids and volatile substances secreted by the femoral glands have been investigated in several biochemical studies, the protein composition and functions of secretions remain completely unknown. Applying a proteomic approach, we provide the first attempt to comprehensively characterize the protein composition of femoral gland secretions from the Galápagos marine iguana. Using samples from several organs, the marine iguana proteome was assembled by next-generation sequencing and MS, resulting in 7513 proteins. Of these, 4305 proteins were present in the femoral gland, including keratins, small serum proteins, and fatty acid-binding proteins. Surprisingly, no proteins with discernible roles in partner recognition or inter-species communication could be identified. However, we did find several proteins with direct associations to the innate immune system, including lysozyme C, antileukoproteinase (ALP), pulmonary surfactant protein (SFTPD), and galectin (LGALS1) suggesting that the femoral glands function as an important barrier to infection. Furthermore, we report several novel anti-microbial peptides from the femoral glands that show similar action against Escherichia coli and Bacillus subtilis such as oncocin, a peptide known for its effectiveness against Gram-negative pathogens. This proteomics data set is a valuable resource for future functional protein analysis and demonstrates that femoral gland secretions also perform functions of the innate immune system.

Dental pathologies in tumor patients with bone metastases or multiple myeloma scheduled for antiresorptive therapy.

Background: Medication-related osteonecrosis of the jaw (MRONJ) is a potentially severe complication of mainly antiresorptive drugs. We evaluated the frequency of dentoalveolar pathologies in patients scheduled for antiresorptive therapy in a 'real-world' setting, also including patients with poor oral health potentially requiring tooth extractions and/or other dentoalveolar surgery. This approach is in contrast to the setting of recent randomized trials with restrictive exclusion criteria. Patients & methods: We prospectively included patients suffering from solid tumors with osseous metastases or multiple myeloma. Screening for dentoalveolar pathologies was done prior to initiation of antiresorptive therapy at the specialized MRONJ clinic of the University Hospital for Cranio-Maxillofacial and Oral Surgery, Innsbruck, Austria. Results: 119 subjects could be included. In 76 patients (63.9%), a dental focus was revealed including deep caries (24.4% of patients), chronic apical periodontitis (26.9%), periodontal disease (45.8%), root remnants (16%), jaw cysts (2.5%), partially impacted teeth (5.0%) and peri-implantitis (5.0%). Conclusion: Considering the high number of dentoalveolar pathologies (63.9%), systematic dental focus screening prior to initiation of antiresorptive therapy is of utmost importance to lower the risk for MRONJ.

[Neurointensive Care: Aneurysmal Subarachnoid Hemorrhage - State of the Art]. / Neurointensivmedizin: aneurysmatische Subarachnoidalblutung ­ State of the Art.

The aneurysmal subarachnoid hemorrhage is a life threatening disorder associated with high morbidity and mortality. Identification and treatment of the bleeding source is mandatory within the first 24 hours to prevent rebleeding. Patients suffering from subarachnoid hemorrhage should be managed on an intensive care unit experienced in the treatment of this condition. Most frequent complications in the clinical course are hydrocephalus, requiring temporary or permanent shunting, and delayed cerebral ischemia. Consequent monitoring of the patients including transcranial doppler sonography and undelayed treatment of complications can improve the outcome of the patient substantially. Longterm neuropsychological sequelae may hamper the patient and thwart his reconstitution, thus requiring psychological intervention.

Identification of the Campanian Ignimbrite in the Dead Sea and consequent time-transgressive hydroclimatic shifts in the Eastern Mediterranean.

Robust chronologies and time equivalent tephra markers are essential to better understand spatial palaeoenvironmental response to past abrupt climatic changes. Identification of well-dated and widely dispersed volcanic ash by tephra and cryptotephra (microscopic volcanic ash) provides time synchronous tie-points and strongly reduces chronological uncertainties. Here, we present the major, minor and trace element analyses of cryptotephra shards in the Dead Sea Deep Drilling sedimentary record (DSDDP 5017-1A) matching the Campanian Ignimbrite (CI). This geochemical identification expands the known dispersal range of the CI to the southeastern Mediterranean, over 2300 km from the volcanic source. Due to the CI eruption occurring near-synchronous with North Atlantic ice surge of Heinrich Event 4 (HE4), this tephra provides insights into regional responses to large-scale climatic change in the Mediterranean. In the Dead Sea, the CI layer is associated with wetter climatic conditions. This contrasts with the contemporaneous occurrence of the CI deposition and dry conditions in the central and eastern Mediterranean suggesting a possible climate time-transgressive expansion of HE4. Our finding underscores the temporal and spatial complexity of regional climate responses and emphasises the importance of tephra as a time marker for studying large-scale climatic changes verses regional variations.

Functional cooperation between human adenovirus type 5 early region 4, open reading frame 6 protein, and cellular homeobox protein HoxB7.

Human adenovirus type 5 (HAdV5) E4orf6 (early region 4 open reading frame 6 protein) is a multifunctional early viral protein promoting efficient replication and progeny production. E4orf6 complexes with E1B-55K to assemble cellular proteins into a functional E3 ubiquitin ligase complex that not only mediates proteasomal degradation of host cell substrates but also facilitates export of viral late mRNA to promote efficient viral protein expression and host cell shutoff. Recent findings defined the role of E4orf6 in RNA splicing independent of E1B-55K binding. To reveal further functions of the early viral protein in infected cells, we used a yeast two-hybrid system and identified the homeobox transcription factor HoxB7 as a novel E4orf6-associated protein. Using a HoxB7 knockdown cell line, we observed a positive role of HoxB7 in adenoviral replication. Our experiments demonstrate that the absence of HoxB7 leads to inefficient viral progeny production, as HAdV5 gene expression is highly regulated by HoxB7-mediated activation of various adenoviral promoters. We have thus identified a novel role of E4orf6 in HAdV5 gene transcription via regulation of homeobox protein-dependent modulation of viral promoter activity.

Antibiofilm assay for antimicrobial peptides combating the sulfate-reducing bacteria Desulfovibrio vulgaris.

In medical, environmental, and industrial processes, the accumulation of bacteria in biofilms can disrupt many processes. Antimicrobial peptides (AMPs) are receiving increasing attention in the development of new substances to avoid or reduce biofilm formation. There is a lack of parallel testing of the effect against biofilms in this area, as well as in the testing of other antibiofilm agents. In this paper, a high-throughput screening was developed for the analysis of the antibiofilm activity of AMPs, differentiated into inhibition and removal of a biofilm. The sulfate-reducing bacterium Desulfovibrio vulgaris was used as a model organism. D. vulgaris represents an undesirable bacterium, which is considered one of the major triggers of microbiologically influenced corrosion. The application of a 96-well plate and steel rivets as a growth surface realizes real-life conditions and at the same time establishes a flexible, simple, fast, and cost-effective assay. All peptides tested in this study demonstrated antibiofilm activity, although these peptides should be individually selected depending on the addressed aim. For biofilm inhibition, the peptide DASamP1 is the most suitable, with a sustained effect for up to 21 days. The preferred peptides for biofilm removal are S6L3-33, in regard to bacteria reduction, and Bactenecin, regarding total biomass reduction.

Flexible biofilm monitoring device.

Biofilms and their analysis are increasingly attracting the attention of the scientific community due to the immense importance and impact of biofilms in various natural, technical and medical fields. For these purposes, an optimized and extended antibiofilm assay system based on the Calgary Biofilm Device (MBEC Assay® system) consisting of microtiter plate and PCR tubes was established. Its implementation was used to study the growth characteristics of the sessile phenotype of Pseudomonas fluorescens exposed to antimicrobial peptides. Inhibitory effects of an antimicrobial peptide on P. fluorescens biofilm formation could be determined at a concentration of 250 µg/ml (biofilm prevention concentration (BPC)) using the modified biofilm assay. Similarly, the biofilm bactericidal concentration (BBC) at 125 µg/ml and the minimum biofilm elimination concentration to remove 90% of the total biofilm mass (MBEC90) were measured at a concentration range of 15.625-1.95 µg/ml. In conclusion, this optimized system provides a highly variable, simple, and cost-effective alternative to high-throughput screening based on the Calgary Biofilm Device (CBD).

Phases of stability during major hydroclimate change ending the Last Glacial in the Levant.

In-depth understanding of the reorganization of the hydrological cycle in response to global climate change is crucial in highly sensitive regions like the eastern Mediterranean, where water availability is a major factor for socioeconomic and political development. The sediments of Lake Lisan provide a unique record of hydroclimatic change during the last glacial to Holocene transition (ca. 24-11 ka) with its tremendous water level drop of ~ 240 m that finally led to its transition into the present hypersaline water body-the Dead Sea. Here we utilize high-resolution sedimentological analyses from the marginal terraces and deep lake to reconstruct an unprecedented seasonal record of the last millennia of Lake Lisan. Aragonite varve formation in intercalated intervals of our record demonstrates that a stepwise long-term lake level decline was interrupted by almost one millennium of rising or stable water level. Even periods of pronounced water level drops indicated by gypsum deposition were interrupted by decades of positive water budgets. Our results thus highlight that even during major climate change at the end of the last glacial, decadal to millennial periods of relatively stable or positive moisture supply occurred which could have been an important premise for human sedentism.

Anti-Listeria activities of Galleria mellonella hemolymph proteins.

We report the use of antimicrobial hemolymph proteins from the model host Galleria mellonella as an inhibitor for various Listeria strains, providing a novel source for antilisterial therapeutics. We also have shown that specific virulence-associated genes known to mediate antimicrobial resistance of Listeria in mammalian models indicated a similar function in Galleria.

PaCO2-management in the neuro-critical care of patients with subarachnoid hemorrhage.

The partial pressure of carbon dioxide (PaCO2) in the arterial blood is a strong vasomodulator affecting cerebral blood flow and the risk of cerebral edema and ischemia after acute brain injury. In turn, both complications are related to poor outcome in patients with aneurysmal subarachnoid hemorrhage (aSAH). We aimed to analyze the effect of PaCO2 levels on the course and outcome of aSAH. All patients of a single institution treated for aSAH over 13.5 years were included (n = 633). Daily PaCO2 values from arterial blood gas measurements were recorded for up to 2 weeks after ictus. The study endpoints were: delayed cerebral ischemia (DCI), need for decompressive craniectomy due to increased intracranial pressure > 20 mmHg refractory to conservative treatment and poor outcome at 6-months follow-up (modified Rankin scale > 2). By correlations with the study endpoints, clinically relevant cutoffs for the 14-days mean values for the lowest and highest daily PaCO2 levels were defined by receiver operating characteristic curve analysis. Association with the study endpoints for the identifies subgroups was analyzed using multivariate analysis. The optimal range for PaCO2 values was identified between 30 and 38 mmHg. ASAH patients with poor initial condition (WFNS 4/5) were less likely to show PaCO2 values within the range of 30-38 mmHg (p < 0.001, OR = 0.44). In the multivariate analysis, PaCO2 values between 30 and 38 mmHg were associated with a lower risk for decompressive craniectomy (p = 0.042, aOR = 0.27), DCI occurrence (p = 0.035; aOR = 0.50), and poor patient outcome (p = 0.004; aOR = 0.42). The data from this study shows an independent positive association between low normal mean PaCO2 values during the acute phase of aSAH and patients' outcome. This effect might be attributed to the reduction of intracranial hypertension and alterations in the cerebral blood flow.

Interaction between cognitive status, fear of falling, and balance in elderly persons.

OBJECTIVE: Evaluate the cognitive function and its relationship with balance, history of falls, and fear of falling in the elderly. METHODS: We evaluated 250 elderly persons aged at least 60 years, who answered a sociodemographic questionnaire about the occurrence of falls in the last year. The cognitive function, balance, and fear of falling were assessed using the Mini-Mental State Examination (MMSE), Berg Balance Scale (BBS), and Falls Efficacy Scale (FES-I) scores, respectively. Participants were allocated into two groups based on the Mini-Mental State Examination (MMSE) score, the Group with Possible Cognitive Decline (GPCD) and the group with no cognitive decline (GNCD). We performed Student's t-test and Pearson's correlation for independent samples. RESULTS: The Group with Possible Cognitive Decline (GPCD) showed lower balance (p=0.003) and greater fear of falling (p=0.008) (BBS=50.98±4.68; FES-I=26.06±8.78) compared to the GNCD (BBS=52.53±3.047; FES-I=23.21±7.74). CONCLUSION: Elderly persons with cognitive decline have lower balance, greater fear of falling, and greater recurrence of falls.

New peptolides from the cyanobacterium Nostoc insulare as selective and potent inhibitors of human leukocyte elastase.

Eight new cyanopeptolins (insulapeptolides A-H) were obtained from the cyanobacterium Nostoc insulare. Their isolation was guided by their bioactivity toward the target enzyme human leukocyte elastase, molecular biological investigations, and MALDI-TOF analysis. These peptides are selective inhibitors of human leukocyte elastase with activities in the nanomolar range. Insulapeptolide D was the most potent compound with an IC(50) value of 85 nM (K(i) value of 36 nM).

Staging procedures in primary breast cancer.

BACKGROUND: In consideration of increasing incidence by introduction of screening mammography, the prevalence of distant metastases and necessity of staging procedures in early breast cancer should be proved. PATIENTS AND METHODS: A retrospective review was undertaken of 466 patients with newly diagnosed breast cancer in the period from 2003 to 2006. RESULTS: Distant metastases were found in 22 (4.8%) patients at the time of primary diagnosis of breast cancer. None of these patients had a tumour < or =1 cm and the percentage of metastatic disease increased with local extension (pT1 1.4%; pT2 7.9%; pT3 14.3%; pT4 23.1%; p<0.001) and nodal status (pN0 1.7%; pN1 3.8%; pN2 21.7%; pN3 17.6%; p<0.001) CONCLUSION: Indication for bone scan, liver ultrasound and chest x-ray should be limited to patients with tumours >2 cm, or tumours >1 cm with lymph node involvement (N1-3).

Brunsvicamides A-C: sponge-related cyanobacterial peptides with Mycobacterium tuberculosis protein tyrosine phosphatase inhibitory activity.

The cyanobacterium Tychonema sp. produces the new cyclic hexapeptides brunsvicamide A-C (1-3). Brunsvicamide B (2) and C (3) selectively inhibit the Mycobacterium tuberculosis protein tyrosine phosphatase B (MptpB), a potential drug target for tuberculosis therapy for which no inhibitors are known to date. Brunsvicamide C contains an N-methylated N'-formylkynurenine moiety, a unique structural motif in cyclic peptides. The new peptides are related to the sponge-derived mozamides, supporting the suggestion that secondary metabolites of certain marine invertebrates are produced by associated microorganisms. Thus, microorganisms phylogenetically related to symbionts of marine invertebrates can be judged as a means to supply "marine-like" compounds for drug development.

[Influenza vaccination in Germany. A population-based cross-sectional analysis of three seasons between 2002 and 2005]. / Grippeimpfung in Deutschland : Eine bevölkerungsbezogene Querschnittsanalyse der drei Influenzasaisons von 2002 bis 2005.

BACKGROUND AND PURPOSE: Influenza represents a considerable worldwide health problem. Vaccination is the only preventive measure, capable of reducing mortality and morbidity of influenza in all age groups. The objective of this study was to assess the extent of influenza vaccination coverage in the seasons 2002/2003, 2003/2004 and 2004/2005 in Germany, to understand the driving forces and barriers to vaccination, and to determine vaccination intentions for the subsequent winter. METHODS: The authors conducted a random-sampling, telephone-based household survey among noninstitutionalized individuals representative of the population aged > or =14. The surveys for the different seasons used the same questionnaire and were subsequently pooled. Four target groups were determined for analysis: (1) persons aged > or =60; (2) people working in the medical field; (3) persons suffering from chronic illness; and (4) a composite group made up of persons aged > or =60 or working in the medical field or suffering from a chronic illness. RESULTS: The overall sample consisted of 5,990 people. The influenza vaccination coverage rate in Germany increased from 22.3% in season 2002/2003 to 25.1% in season 2003/2004 and increased again to 26.5% in season 2004/2005. This increase is statistically significant (p = 0.007). The composite group coverage rate increased from 40.0% (2002/2003) to 42.2% (2004/2005). The driving forces and barriers to vaccination did not change over the years. The most frequent reasons for being vaccinated given by vaccinees were: influenza considered to be a serious illness which people wanted to avoid, having received advice from the family doctor or nurse to be vaccinated, and not wanting to infect family and friends. Reasons for not being vaccinated mentioned by people who have never been vaccinated were: thinking about it, however, not being vaccinated in the end, not expecting to catch influenza, and not having received a recommendation from the family doctor to be vaccinated. Major encouraging factors to influenza vaccination were: recommendation by the family doctor or nurse, more available information on the vaccine regarding efficacy and tolerance, and more information available about the disease. CONCLUSION: The vaccination coverage rate increased by 4.2% over the three seasons. The family doctor is the most important source of encouragement for people to be vaccinated against influenza. It seems that the public would be more likely to be vaccinated if they had more information on the efficacy and tolerance of the vaccine, as well as the disease. The authors therefore suggest that family doctors be better informed on influenza vaccine and the disease itself, so that they can actively inform their patients on these topics.

Influenza vaccination coverage rates in Germany a population-based cross-sectional analysis of the seasons 2002/2003 and 2003/2004.

BACKGROUND AND PURPOSE: Influenza continues to be a considerable health problem in Europe. Vaccination is the only preventive measure, reducing mortality and morbidity of influenza in all age groups. The objectives of this survey were to assess the level of influenza vaccination coverage in the 2002/2003 season compared with the 2003/2004 season in Germany, to understand the driving forces and barriers to vaccination, and to determine vaccination intentions for the following winter. METHODS: The authors conducted a random-sampling, telephone-based household survey among noninstitutionalized individuals representative of the population aged > or = 14. The surveys for 2002/2003 and 2003/2004 used the same questionnaire and were subsequently pooled. Four target groups were determined for analysis: (1) persons aged > or = 60; (2) people working in the medical field; (3) persons suffering from chronic illness; and (4) a group composed of persons aged > or = 60 or working in the medical field or suffering from a chronic illness. RESULTS: The overall sample consisted of 4,011 people. The influenza vaccination coverage rate in Germany increased from 22.3% in 2002/2003 to 25.1% in 2003/2004. This increase is not significant. The most frequent reasons for being vaccinated given by vaccinees were: influenza considered to be a serious illness, which people wanted to avoid (90.1%), having received advice from the family doctor or nurse to be vaccinated (71.3%), and not wanting to infect family and friends (70.4%). Reasons for not being vaccinated mentioned by people who have never been vaccinated were: thinking about it, however, not being vaccinated in the end (47.7%), not expecting to catch influenza (43.6%), and not having received a recommendation from the family doctor to be vaccinated (36.6%). Options encouraging influenza vaccination are: recommendation by the family doctor or nurse (66.6%), more available information on the vaccine regarding efficacy and tolerance (54.2%), and more information available about the disease (52.4%). CONCLUSION: The vaccination coverage in the 2003/2004 season increased in comparison to the 2002/2003 season, although not significantly. The family doctor is the most important source of encouragement for people to be vaccinated against influenza. It seems that the public would be more likely to be vaccinated if they had more information on the efficacy and tolerance of the vaccine, as well as the disease. It is therefore suggested that family doctors be better informed on influenza vaccine and the disease itself, so that they can actively inform their patients on these topics.

Streptozocin-Based Chemotherapy in Patients with Advanced Neuroendocrine Neoplasms--Predictive and Prognostic Markers for Treatment Stratification.

BACKGROUND AND AIM: Chemotherapy with streptozocin (STZ) in combination with 5-FU or doxorubicin (Dox) represents a standard of care for patients with metastatic pancreatic neuroendocrine neoplasms (pNEN). However, predictive markers for patient selection are still missing. The aim of this study was a retrospective evaluation of the clinicopathological characteristics of pNEN patients receiving STZ-based chemotherapies and to identify predictive and prognostic markers. PATIENTS AND METHODS: We retrospectively analyzed 77 patients treated at our center between 1995 and 2013. The median overall survival (OS) and progression-free survival (PFS) were calculated using Kaplan-Meier and Cox regression methods, respectively. Uni- and multivariate analyses were performed. RESULTS: The median PFS (mPFS) in patients receiving STZ/5-FU/Dox was 16 months with a median OS (mOS) of 28 months. Objective response rate (ORR) and disease control rate (DCR) were 34% and 72%, respectively. Biochemical response and positive octreotide scintigraphy predicted objective response. Univariate analysis revealed Ki-67 > 10% and the absence of biochemical or objective response by imaging as independent risk factors for shorter PFS. Additionally, performance status (PS) and resection of the primary tumor were observed to influence mOS. Treatment was well tolerated with less than 10% grade 3 and 4 toxicities. CONCLUSIONS: STZ-based chemotherapy is an effective and well-tolerated treatment option in patients with well differentiated neuroendocrine neoplasms. Positive octreotide scintigraphy and biochemical response predict objective response.

Interaction between cognitive status, fear of falling, and balance in elderly persons

OBJECTIVE: Evaluate the cognitive function and its relationship with balance, history of falls, and fear of falling in the elderly. METHODS: We evaluated 250 elderly persons aged at least 60 years, who answered a sociodemographic questionnaire about the occurrence of falls in the last year. The cognitive function, balance, and fear of falling were assessed using the Mini-Mental State Examination (MMSE), Berg Balance Scale (BBS), and Falls Efficacy Scale (FES-I) scores, respectively. Participants were allocated into two groups based on the Mini-Mental State Examination (MMSE) score, the Group with Possible Cognitive Decline (GPCD) and the group with no cognitive decline (GNCD). We performed Student's t-test and Pearson's correlation for independent samples. RESULTS: The Group with Possible Cognitive Decline (GPCD) showed lower balance (p=0.003) and greater fear of falling (p=0.008) (BBS=50.98±4.68; FES-I=26.06±8.78) compared to the GNCD (BBS=52.53±3.047; FES-I=23.21±7.74). CONCLUSION: Elderly persons with cognitive decline have lower balance, greater fear of falling, and greater recurrence of falls.