Strukturelle und funktionelle Untersuchungen von membranaktiven Peptiden/Peptaibolen in Lipid-Modellmembranen

In dieser Arbeit wurden Wechselwirkungen zwischen membranaktiven Peptiden und Lipidmembranen untersucht. Es wurde gezeigt, dass die stabilen archaealen Diphytanoyl-Lipide polymorphes Phasenverhalten besitzen, welches von Temperatur, Hydration und Lipidform abhängig ist. Das kurze Peptaibol Harzianin konnte entgegen der Erwartungen in Lipidmembranen keine Poren bilden und unterscheidet sich daher von längeren Peptaibolen. Es besitzt außerdem eine exotische Struktur aus beta-Spiralen

Membrane Thinning and Thickening Induced by Membrane-Active Amphipathic Peptides

Membrane thinning has been discussed as a fundamental mechanism by which antimicrobial peptides can perturb cellular membranes. To understand which factors play a role in this process, we compared several amphipathic peptides with different structures, sizes and functions in their influence on the lipid bilayer thickness. PGLa and magainin 2 from X. laevis were studied as typical representatives of antimicrobial cationic amphipathic α-helices. A 1:1 mixture of these peptides, which is known to possess synergistically enhanced activity, allowed us to evaluate whether and how this synergistic interaction correlates with changes in membrane thickness. Other systems investigated here include the α-helical stress-response peptide TisB from E. coli (which forms membrane-spanning dimers), as well as gramicidin S from A. migulanus (a natural antibiotic), and BP100 (designer-made antimicrobial and cell penetrating peptide). The latter two are very short, with a circular β-pleated and a compact α-helical structure, respectively. Solid-state 2H-NMR and grazing incidence small angle X-ray scattering (GISAXS) on oriented phospholipid bilayers were used as complementary techniques to access the hydrophobic thickness as well as the bilayer-bilayer repeat distance including the water layer in between. This way, we found that magainin 2, gramicidin S, and BP100 induced membrane thinning, as expected for amphiphilic peptides residing in the polar/apolar interface of the bilayer. PGLa, on the other hand, decreased the hydrophobic thickness only at very high peptide:lipid ratios, and did not change the bilayer-bilayer repeat distance. TisB even caused an increase in the hydrophobic thickness and repeat distance. When reconstituted as a mixture, PGLa and magainin 2 showed a moderate thinning effect which was less than that of magainin 2 alone, hence their synergistically enhanced activity does not seem to correlate with a modulation of membrane thickness. Overall, the absence of a typical thinning response in the case of PGLa, and the increase in the repeat distance and membrane thickening observed for TisB, demonstrate that the concept of peptide-induced membrane thinning cannot be generalized. Instead, these results suggest that different factors contribute to the resulting changes in membrane thickness, such as the peptide orientation in the bilayer, and/or bilayer adaptation to hydrophobic mismatch

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

KAÇARAK VE KAÇIRILARAK EVLENEN KADINLAR: NİTELİKSEL BİR ÇALIŞMA.

Bu çalışmanın amacı, kaçarak ya da kaçırılarak evlenen kadınların deneyimlerini, aile ilişkilerini ve duygu durumlarını anlamaktır. Türkiye’nin çeşitli illerinde yaşayan, 7’si kaçırılarak, 11’i de kaçarak evlenen, yaşları 21-66 arasında değişen 18 kadın katılımcı, çalışma grubunu oluşturmaktadır. Çalışmada kadınların deneyimlerinin, anlatımlarının çeşitliliğinden ve zenginliğinden faydalanılarak ortaya konulabilmesi amacıyla fenomonolojik yaklaşıma dayalı niteliksel araştırma yöntemi kullanılmıştır. Görüşmelerde, yapılandırılmışgörüşme formu kullanılmıştır. Veriler Maxqda 12 yazılımıileanaliz edilmiştir. Kaçma/ kaçırılma öncesi deneyimlerde; eğitimden yoksunluk, evlilik kararında söz sahibi olamama, kaçma/kaçırılma sonrası deneyimlerde ise; aile erkekleri tarafından reddedilme, evlilik ritüellerinin yapılmaması, ekonomik bağımlılık,şiddet gibi durumlar bulgulanmıştır. Katılımcıların çoğunluğunun kaçma ya da kaçırılmaya ilişkin duygularında pişmanlığın yer aldığı görülmüştür

VERBASCUM OZTURKII (SCROPHULARIACEAE), A NEW SPECIES FROM EAST ANATOLIA, TURKEY

WOS: 000260158200025A new species Verbascum ozturkii Karavel., Uzunh. & S. Celik sp. nov. (Sect. Bothrosperma Murb.), has been described here. It was collected from East Anatolia in Turkey The species is related to V. oocarpum Murb. and thus a comparison was made. It differs from V. oocarpum Murb. Mainly in its hair Situation, basal leaves, inflorescence. pedicels, calyx. corolla, stamens and capsule features.TUBITAKTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [TBAG-2282]The authors thank to Curators of Herbaria ANK and HUB, who allowed US to Study their Verbascum specimens, to Karel Sutory for sending some papers, to G herbaria for allowing, us to take some photos of the type specimens, Dr. Mehmet Sagiroglu for his help during our fieldwork. We are grateful to Secil Gungor for the illustrations. We also thank TUBITAK (Project Number TBAG-2282), for their support