Functional interplay of visual, sensitizing and screening pigments in the eyes of Drosophila and other red-eyed dipteran flies.

Several fly species have distinctly red-coloured eyes, meaning that the screening pigments that provide a restricted angular sensitivity of the photoreceptors may perform poorly in the longer wavelength range. The functional reasons for the red transparency and possible negative visual effects of the spectral properties of the eye-colouring screening pigments are discussed within the context of the photochemistry, arrestin binding and turnover of the visual pigments located in the various photoreceptor types. A phylogenetic survey of the spectral properties of the main photoreceptors of the Diptera indicates that the transition of the brown eye colour of the Nematocera and lower Brachycera to a much redder eye colour of the higher Brachycera occurred around the emergence of the Tabanidae family.

Photoreceptor spectral tuning by colorful, multilayered facet lenses in long-legged fly eyes (Dolichopodidae).

The facet lenses of the compound eyes of long-legged flies (Dolichopodidae) feature a striking, interlaced coloration pattern, existing of alternating rows of green-yellow and orange-red reflecting facets, due to dielectric multilayers located distally in the facet lenses (Bernard and Miller. Invest Ophthalmol 7:416-434 (1968). We investigated this phenomenon in the dolichopodid Dolichopus nitidus by applying microspectrophotometry, electron microscopy and optical modeling. The measured narrow-band reflectance spectra, peaking at ~540 and ~590 nm with bandwidth ~105 nm, are well explained by a refractive index oscillating sinusoidally in six periods around a mean value of about 1.44 with amplitude 0.6. The facet lens reflectance spectra are associated with a spectrally restricted, reduced transmittance, which causes modified spectral sensitivities of the underlying photoreceptors. Based on the modeling and electroretinography of the dolichopodid Condylostylus japonicus we conjecture that the green and orange facets narrow the spectral bandwidths of blue and green central photoreceptors, respectively, thus possibly improving color and/or polarization vision.

[Non-opioid pain medication in the elderly]. / Pharmakotherapie des Schmerzes bei älteren Patienten mit Nichtopioiden.

Non-opioid analgesics are frequently used to control chronic pain in elderly patients; however some of these drugs show high rates of adverse drug reactions. Among these are significant clinical problems which impede an effective and safe pain control. This review provides recent data concerning non-steroidal anti-inflammatory drugs (NSAID), acetaminophen, metamizol and flupirtin. Due to their risk profile NSAIDs are less appropriate due to high incidence rates and drug-related risk patterns. Acetaminophen, metamizol and flupirtin may be recommended instead; however a shortcoming of acetaminophen in comparison to NSAIDs is its weaker action to control pain. Metamizol is still banned in some countries due to rare but potentially severe hematological side effects and flupirtin frequently causes unfavorable sedation.

[Optimal stroke prevention in the geriatric patient with atrial fibrillation: position paper of an interdisciplinary expert panel]. / Optimale Schlaganfallprävention bei geriatrischen Patienten mit Vorhofflimmern. Konsensbericht eines interdiszipIinären Expertengremiums.

BACKGROUND: The optimal approach to stroke prevention in geriatric patients with atrial fibrillation (AF) has not been adequately clarified. Despite their high risk of stroke and clear indication for anticoagulation according to established risk scores, in practice geriatric AF patients often are withheld treatment because of comorbidities and comedications, concerns about low treatment adherence or fear of bleeding events, in particular due to falls. METHOD: The present position paper summarises the outcomes of an expert panel discussion held by hospital-based and office-based physicians with ample experience in the treatment of geriatric patients. RESULTS AND CONCLUSIONS: The panel agreed that geriatric patients should receive oral anticoagulation as a rule, unless a comprehensive neurological and geriatric assessment (including clinical examination, gait tests and validated instruments such as Modified Rankin Scale, Mini-mental state examination or Timed Test of Money Counting) provides sound reasons for refraining from treatment AII patients with a history of falls should be thoroughly evaluated for further evaluation of the causes. Patients with CHADS2 score ≥ 2 should receive anticoagulation even if at high risk for falls. The novel oral anticoagulants (NOAC) facilitate management in the geriatric population with AF (no INR monitoring needed, easier bridging during interventions) and have an improved benefit-risk ratio compared to vitamin K antagonists. Drugs with predominantly non-renal elimination are safer in geriatric

[Paracetamol. Efficacious and safe for all ages]. / Paracetamol. Wirksam und sicher bis ins hohe Alter.

Paracetamol has become a focus of attention as being unsafe due to hepatic toxicity and market withdrawal or prescription status is presently under discussion in Germany. This drug is, however, effective and safe if notes of caution are applied. In Germany 38 fatal cases of analgesic poisoning were observed in 2010, only 4 of which were due to paracetamol and 16 were caused by diclofenac and ibuprofen. Alternative pain medications are obviously much less safe, in particular given the additional risk of sometimes fatal gastrointestinal bleeding and cardiovascular side effects. This review extensively analyzes the safety record of paracetamol and applies these findings to the treatment of elderly people. Even very elderly patients may be safely treated with this compound, although a dose limit of 3 g/day should be instituted. This renewed discussion was triggered by the uncontrolled availability of paracetamol in the USA but observations from this country should not be generalized and applied to the German situation and objective reasoning should be re-installed.

Improving the health care of geriatric patients: management of urinary incontinence: a position paper.

A multidisciplinary German expert group met in 2012 to discuss the current status and prospects of health care of geriatric patients with urinary incontinence in Germany. The purpose of this position paper is to raise awareness among health care providers for the challenges associated with adequate management of urinary incontinence in frail elderly. The experts agree that a multidisciplinary collaboration is essential for the successful treatment of urinary incontinence symptoms which are often associated with loss of autonomy and social isolation. For most geriatric patients, usually the general practitioner is the first contact when seeking help. Hence, the general practitioner plays a crucial role in the coordination of diagnosis and treatment. The involved health care providers should have adequate education and training in their respective disciplines and should be networked allowing quick turnaround times. Non-pharmacological treatments (e.g. behavioural interventions) should have been tried before any pharmacotherapy is initiated. If pharmacological treatment of urinary incontinence involves the use of anticholinergic agents, cognitive performance should be monitored regularly. If indicated, anticholinergic agents with a documented efficacy and safety profile, explicitly assessed in the elderly population, should be preferred.

[Medication in the elderly : cognitive impairment by drugs]. / Medikation im Alter : Kognitionseinschränkende Pharmaka.

Cognitive impairment is a growing problem in aging societies, and dementia is turning into an epidemic. Modifiable conditions are of major interest, as a causal treatment of dementia is still unknown. Drugs represent a major reversible contributor to cognitive deficits and delirium which is seen in 12-50% of elderly in-hospital patients. A third of patients with delirium is being attributed to drugs, and age-related multimorbidity and subsequent polypharmacy are dominant risk factors. The anticholinergic mechanism is not sufficient to explain delirant drug side effects. Most prevalent in the induction of delirium are psychotropic drugs, in particular benzodiazepines, opiates, tricyclic antidepressants, and typical neuroleptics. In addition, "peripheral" drugs such as oxybutynin or fluorquinolones are involved. Rationalization of drug therapy is the clue for the prevention of cognitive impairment and delirium; most causative drugs are contained in negative lists (e.g., Beers list) and should be replaced by positively labelled drugs (e.g., by virtue of the FORTA classification). On top of the treatment of other modifiable causes for delirium (such as dehydration, infections, and fever), the avoidance or at least optimization of psychotropic drug prescriptions are key elements of the prevention of cognitive impairment in the elderly.

Lepirudin dose-dependently increases thrombelastography parameters at therapeutic plasma concentrations as measured with ROTEM® - a pilot study.

BACKGROUND: The aim of this in-vitro pilot study was to assess the usefulness of the thrombelastograph ROTEM® for determining the anticoagulant activity of lepirudin. METHODS: The ROTEM® parameters, clotting-time, clot formation time and maximum clot firmness were measured in the presence of increasing concentrations of lepirudin (10-4 µg/ml - 10 µg/ml). Citrated blood was obtained from 16 healthy male subjects. RESULTS: Clotting-time increased from 79.1 ± 53.4 s at baseline to 194.1 ± 151.9 s at a drug concentration of 1µg/ml as measured with EXTEM (p < 0.0001). Borderline significance was found for the difference between maximum clot firmness at baseline (60.2 ± 4.3 mm) and after drug application (55.5 ± 6.5 mm). CONCLUSIONS: This pilot investigation shows that the ROTEM® device may be suitable for monitoring lepirudin at low concentrations but the results should be confirmed in a larger study and the ROTEM® device validated against standard methods.

Coagulation status in patients with coronary artery disease taking 100 mg aspirin and healthy volunteers using PFA-100® and ROTEM®.

Previous investigation revealed that age is a major risk factor for thomboembolic events. Earlier studies with thrombelastography have demonstrated procoagulant activity in elderly patients with coronary artery disease. The aim of the present study was to investigate age-related differences in the coagulation status of patients with documented coronary artery disease, healthy elderly and healthy young volunteers with the rotation thrombelastography (ROTEM®) and PFA-100®. Measured with ROTEM®, mean clot formation time (CFT (EXTEM)) in healthy young volunteers (120.8 ± 73.5 s) was significantly longer than in healthy elderly (78.3 ± 36.7 s, p < 0.05) and in patients with coronary artery disease (74.3 ± 59.1 s, p < 0.05). No difference was found between healthy elderly and patients with coronary artery disease. The lowest value for mean maximum clot formation (MCF (EXTEM)) was seen in healthy young volunteers (57.0 ± 6.1 mm) which was significantly different to healthy elderly (61.9 ± 4.8 mm, p < 0.05) and patients with coronary artery disease (65.3 ± 8.4 mm, p < 0.05). No difference could be found between healthy elderly and patients with coronary artery disease, although a trend to higher mean MCF (EXTEM) and lower mean CFT (EXTEM)in patients with coronary artery disease was found. Measured with the collagen/epinephrine cartridge of the PFA-100®, healthy young volunteers (166.4 ± 59.5 s) had numerical but insignificantly longer mean closure times compared to healthy elderly (138.5 ± 53.3 s). These findings point to agerelated differences in thrombelastographic parameters. The ROTEM® analysis indicates an increased coagulability in patients with coronary artery disease and healthy elderly compared to healthy young volunteers.

Coagulation status in coronary artery disease patients with type II diabetes mellitus compared with non-diabetic coronary artery disease patients using the PFA-100® and ROTEM®.

Previous investigations in patients with coronary artery disease (CAD) revealed differences in thromboelastographic parameters indicating different states of coagulability. The aim of the present study was to investigate the coagulation status of patients with documented CAD and type II diabetes mellitus (DM) and non-diabetic patients with coronary artery disease with the PFA-100® and the ROTEM®. No differences were found in platelet function as measured with collagen/epinephrine (263.6 ± 70.6 s vs. 254.6 ± 65.3 s) and collagen/ADP cartridges (105.3 ± 63.2 s vs. 90.6 ± 47.3 s) in CAD patients with DM and CAD patients without DM. Measured with the EXTEM reagent of the ROTEM®, mean maximum clot elasticity (MCE) in patients with CAD and DM (233.6 ± 86.9) was significantly longer than in CAD patients without DM (186.7 ± 54.5), (p = 0.03). A similar result was seen using the INTEM reagent; patients with CAD and DM (234.4 ± 83.9) showed a higher value for MCE than CAD patients without DM (190.8 ± 57.8) which was of borderline significance (p = 0.053). Moreover, a weak trend for higher maximum clot firmness (MCF) was seen in CAD patients with DM compared with CAD patients without DM with the EXTEM reagent (68.1 ± 7.5 vs. 63.6 ± 8.6, p = 0.08) and the INTEM reagent (68.4 ± 7.2 vs. 64.1 ± 8.2, p = 0.09). The ROTEM® analysis indicates increased coagulability in patients with coronary artery disease and diabetes mellitus compared to non-diabetic CAD patients. Moreover, the ROTEM® device seems to be an appropriate and easy-to-use tool to describe the coagulation status in these patients groups.

The PFA-100R cannot detect blood group-dependent inhibition of platelet function by eptifibatide or abciximab at therapeutic plasma concentrations.

Previous investigations revealed that AB0 blood groups are associated with divergent concentrations of several coagulation factors. Concentrations of von Willebrand factor (vWF) and factor VIII are lower in individuals with blood group 0 compared to subjects with blood group A, B or AB, which might in turn result in a reduced inhibition of platelet aggregation in individuals with blood group 0. The aim of the present in vitro investigation was to elucidate the impact of AB0 blood group-dependent vWF concentrations on eptifibatide and abciximab mediated inhibition of GPIIb/IIIa function. Platelet function was measured with the platelet function analyzer PFA-100(R) at baseline and at increasing concentrations of eptifibatide and abciximab. It was stratified for blood group 0 vs A. If measured with the collagen/ADP cartridge, blood group 0 was associated with a prolonged mean baseline closure time in comparison with blood group A (94.3 +/- 14.6 s vs. 74.6 +/- 9.9 s, p = 0.007) which was paralleled by reduced concentrations of vWF and factor VIII. In contrast, no statistically significant differences in closure times (167.4 +/- 83.9 s vs. 140.1 +/- 99.0 s, p = 0.562) could be found in the presence of eptifibatide (0.1 microg/ml). Higher concentrations of abciximab (1 microg/ml) than those of eptifibatide were needed to increase the closure times in both cartridges of the PFA-100, but at this concentration of abciximab differences in closure times could not be detected most probably due to higher variability at these drug concentrations. The PFA-100(R) is not suitable for monitoring abciximab or eptifibatide within the therapeutic concentration range because the highest concentrations where the PFA-100(R) had measurable closure times of below 300 s is much too low to lead to the necessary platelet inhibition and, consequently, does not resemble the in vivo situation.

[Difficulties in pharmacotherapy of the elderly]. / Probleme bei der Pharmakotherapie älterer Patienten.

Pharmacotherapy in the elderly is a challenge as the real risk-benefit ratio of many drugs and treatment strategies often remains unknown in these patients. Furthermore there are some special adverse drug reactions such as falls and delirium not only occurring more often but also causing an increased proportion of adverse outcomes. Finally there is the phenomenon of multimorbidity and polypharmacy responsible for treatment errors and inadequate drug treatment. A comprehensive risk-benefit analysis is needed to avoid both under- and over-treatment. This analysis should cover patients preferences, vulnerability, resources and functionality. Some simple treatment rules may improve drug treatment in the elderly, but an improved characterization of drugs and treatment strategies with regard to the elderly is essential.

[Anticoagulation in the elderly]. / Antikoagulation im Alter.

The recommendations for anticoagulation in over 80 years old patients are based on the thromboembolic/bleeding risk relation. They add to the published recommendations for the specific indications. Low-molecular-weight heparin (LMWH) is used to prevent thromboembolism postoperatively. Compression stockings and/or intermittent pneumatic compression are used if bleeding risk is very high. The dose is increased starting at day two if the thromboembolic risk is very high. Bleeding and thromboembolic risks are re-evaluted daily. The antithrombotic therapy is adjusted accordingly. Prophylaxis of thromboembolism in patients with acute illnesses and bedrest is performed according postoperative care. Two-thirds of therapeutic doses of low-molecular-weight heparin are used to treat acute venous thromboembolism. Reduced renal function (creatinine clearance <30 ml/ min for most LMWHs or <20 ml/min for tinzaparin) should result in a further reduction of dose. Intensity and duration of prophylaxis of recurrent events with vitamin K antagonist or LMWH in malignancy follow current or herein described recommendations. Patients with atrial fibrillation are treated with vitamin K antagonists adjusted to an INR of 2-3 for prophylaxis of embolism. Further details of anticoagulant therapy should be in agreement with the national or international recommendations.

Imaging scatterometry of butterfly wing scales.

We describe an imaging scatterometer allowing hemispherical reflectance measurements as a function of the angle of incidence. The heart of the scatterometer is an ellipsoidal reflector, which compresses the hemispherical reflection into a cone-shaped beam that can be imaged by a normal optical system. The instrument's performance is illustrated by measurements of the scattering profiles of the blue-iridescent dorsal wing scales of the nymphalid Morpho aega and the matte-green ventral wing scales of the lycaenid Callophrys rubi.

A nitric oxide synthase transgene ameliorates muscular dystrophy in mdx mice.

Dystrophin-deficient muscles experience large reductions in expression of nitric oxide synthase (NOS), which suggests that NO deficiency may influence the dystrophic pathology. Because NO can function as an antiinflammatory and cytoprotective molecule, we propose that the loss of NOS from dystrophic muscle exacerbates muscle inflammation and fiber damage by inflammatory cells. Analysis of transgenic mdx mice that were null mutants for dystrophin, but expressed normal levels of NO in muscle, showed that the normalization of NO production caused large reductions in macrophage concentrations in the mdx muscle. Expression of the NOS transgene in mdx muscle also prevented the majority of muscle membrane injury that is detectable in vivo, and resulted in large decreases in serum creatine kinase concentrations. Furthermore, our data show that mdx muscle macrophages are cytolytic at concentrations that occur in dystrophic, NOS-deficient muscle, but are not cytolytic at concentrations that occur in dystrophic mice that express the NOS transgene in muscle. Finally, our data show that antibody depletions of macrophages from mdx mice cause significant reductions in muscle membrane injury. Together, these findings indicate that macrophages promote injury of dystrophin-deficient muscle, and the loss of normal levels of NO production by dystrophic muscle exacerbates inflammation and membrane injury in muscular dystrophy.

Body rate decoupling using haltere mid-stroke measurements for inertial flight stabilization in Diptera.

Halteres, the modified rear wings of Diptera, have long been recognized as sensory organs necessary for basic flight stability. These organs, which act as vibrating structure gyroscopes, are known to sense strains proportional to Coriolis accelerations. While compensatory responses have been demonstrated that indicate the ability of insects to distinguish all components of the body rate vector, the specific mechanism by which the halteres are able to decouple the body rates has not been clearly understood. The research documented in this report describes a potential mechanism, using averaged strain and strain rate at the center of the haltere stroke, to decouple the inertial rate components. Through dynamic simulation of a nonlinear model of the haltere 3-dimensional trajectory, this straightforward method was demonstrated to provide an accurate means of generating signals that are proportional to three orthogonal body rate components. Errors associated with residual nonlinearity and rate-coupling were quantified for a bilaterally reconstructed body rate vector over a full range of pitch and yaw rates and two roll rate conditions. Models that are compatible with insect physiology are proposed for performing necessary signal averaging and bilateral processing.

Circadian variation of platelet function measured with the PFA-100.

The circadian rhythm plays an important role in the physiology and pathophysiology of the human being. Previous investigations revealed a circadian rhythm also in platelet function but these investigations have been limited to optical aggregometry with platelet-rich plasma and low shear stress. The aim of the present study was to further elucidate the impact of the circadian rhythm on platelet function using whole blood at high shear rates. Platelet function determined with the platelet function analyzer PFA-100 and concentration of fibrinogen and factor VIII activity were measured in healthy volunteers during day and night time, and even at shorter intervals (8:00, 12:00, 16:00, 20:00, 22:00, 0:00, 2:00, 4:00, 6:00 h). The mean peak closure time of the collagen/epinephrine cartridge of the PFA-100 was maximal at 2:00 h (192.0 +/- 57.4 s) and declined to the trough value at 8:00 h (140.1 +/- 33.4 s) (p = 0.004). This was paralleled by data from the collagen/ADP cartridge (22:00 h: 99.1 +/- 38.5 s/2:00 h: 81.3 +/- 16.7 s; p = 0.049). Concentration of fibrinogen and factor VIII activity were lowest during night time (22:00-4:00 h). These findings demonstrate a circadian rhythm in platelet function as measured with the PFA-100. The PFA-100 seems to be an appropriate tool to describe circadian alterations and is easier to use than optical aggregometry in analogous studies.

EuGMS Task and Finish group on Fall-Risk-Increasing Drugs (FRIDs): Position on Knowledge Dissemination, Management, and Future Research.

Falls are a major public health concern in the older population, and certain medication classes are a significant risk factor for falls. However, knowledge is lacking among both physicians and older people, including caregivers, concerning the role of medication as a risk factor. In the present statement, the European Geriatric Medicine Society (EuGMS) Task and Finish group on fall-risk-increasing drugs (FRIDs), in collaboration with the EuGMS Special Interest group on Pharmacology and the European Union of Medical Specialists (UEMS) Geriatric Medicine Section, outlines its position regarding knowledge dissemination on medication-related falls in older people across Europe. The EuGMS Task and Finish group is developing educational materials to facilitate knowledge dissemination for healthcare professionals and older people. In addition, steps in primary prevention through judicious prescribing, deprescribing of FRIDs (withdrawal and dose reduction), and gaps in current research are outlined in this position paper.