Impact of the β-Lactam Resistance Modifier (−)-Epicatechin Gallate on the Non-Random Distribution of Phospholipids across the Cytoplasmic Membrane of Staphylococcus aureus

The polyphenol (−)-epicatechin gallate (ECg) inserts into the cytoplasmic membrane (CM) of methicillin-resistant Staphylococcus aureus (MRSA) and reversibly abrogates resistance to β-lactam antibiotics. ECg elicits an increase in MRSA cell size and induces thickened cell walls. As ECg partially delocalizes penicillin-binding protein PBP2 from the septal division site, reduces PBP2 and PBP2a complexation and induces CM remodelling, we examined the impact of ECg membrane intercalation on phospholipid distribution across the CM and determined if ECg affects the equatorial, orthogonal mode of division. The major phospholipids of the staphylococcal CM, lysylphosphatidylglycerol (LPG), phosphatidylglycerol (PG), and cardiolipin (CL), were distributed in highly asymmetric fashion; 95%–97% of LPG was associated with the inner leaflet whereas PG (~90%) and CL (~80%) were found predominantly in the outer leaflet. ECg elicited small, significant changes in LPG distribution. Atomic force microscopy established that ECg-exposed cells divided in similar fashion to control bacteria, with a thickened band of encircling peptidoglycan representing the most recent plane of cell division, less distinct ribs indicative of previous sites of orthogonal division and concentric rings and “knobbles” representing stages of peptidoglycan remodelling during the cell cycle. Preservation of staphylococcal membrane lipid asymmetry and mode of division in sequential orthogonal planes appear key features of ECg-induced stress

Biophysical study of resin acid effects on phospholipid membrane 1 structure and properties

Hydrophobic resin acids (RAs) are synthesized by conifer trees as part of their defense mechanisms. One of the functions of RAs in plant defense is suggested to be the perturbation of the cellular membrane. However, there is a vast diversity of chemical structures within this class of molecules, and there are no clear correlations to the molecular mechanisms behind the RA's toxicity. In this study we unravel the molecular interactions of the three closely related RAs dehydroabietic acid, neoabietic acid, and the synthetic analogue dichlorodehydroabietic acid with dipalmitoylphosphatidylcholine (DPPC) model membranes and the polar lipid extract of soybeans. The complementarity of the biophysical techniques used (NMR, DLS, NR, DSC, Cryo-TEM) allowed correlating changes at the vesicle level with changes at the molecular level and the co-localization of RAs within DPPC monolayer. Effects on DPPC membranes are correlated with the physical chemical properties of the RA and their toxicity

Cesarean section versus vaginal delivery – state-of-the-art paper

Summary Aim of the study: The aim of the study was to perform a comparative analysis of complications after vaginal deliveries and cesarean sections and to introduce emotional status of the mother as an indication for a cesarean section. Material and methods: 406 patients after vaginal deliveries and cesarean sections, that took place in the first quarter of 2009, were enrolled into the study. Results: In the studied group of 406 patients, 200 women (49.2%) had cesarean section and 206 women (50.8%) delivered vaginally. In both groups there were no differences in the clinical state of newborns, which were assessed according to the Apgar score, and in umbilical cord blood pH. Hemoglobin concentration evaluated on the second day of puerperium was statistically significantly higher in the group of patients after cesarean section than after vaginal delivery. Episiotomy and laparotomy wound healing complications were observed in 2 (0.97%) and 3 (1.5%) cases, respectively. Conclusions: Due to lack of differences in complication rates between cesarean section and vaginal delivery patients, the emotional status of a pregnant woman should be considered as an indication for cesarean section

Sonoelastografia szyjki macicy jako nowa metoda diagnostyczna w ocenie stanu szyjki u kobiet ciężarnych – doniesienie wstępne

Objectives: The study aimed at determining whether there exists a correlation between the cervical cohesion parameters assessed in the elastography and the length of the cervix. Material and methods: Assessment of cervical cohesion parameters with the use of real-time sonoelastography was performed on 59 patients between 28 and 39 weeks of gestation. Results: The analysis showed that there exists a statistically significant (p=0.033) correlation between the cervical length and the elasticity of the front cervical labium (strain ratio A). Correlation coefficient (r) stood at (-) 0.28. Conclusions: 1. There exists a negative correlation between the condition on the front cervical labium in elastographic imaging and the length of the cervical canal in USG imaging. 2. Elastography of the uterine cervix may be helpful in assessing the risk of premature labour or cervical insufficiency. 3. There is a need to perform a study on a larger group of patients in order to determine whether elastography may find its place among routine obstetric diagnostic methods.Cel pracy: Celem pracy było zbadanie czy istnieje korelacja między spoistością szyjki macicy ocenianej metodą elastografii a długością szyjki macicy. Materiał i metody: Badaniu poddano 59 ciężarnych kobiet pomiędzy 28. i 39. tygodniem ciąży, u których oceniono parametry konsystencji szyjki macicy przy użyciu sonoelastografii w czasie rzeczywistym (real-time sonoelastography) . Wyniki: Analiza wykazała, iż istnieje istotna statystycznie (p=0.033) korelacja między długością szyjki macicy a konsystencją przedniej wargi szyjki macicy (strain ratio A). Współczynnik korelacji (r) wyniósł (-) 0.28. Wnioski: 1. Istnieje ujemna korelacja pomiędzy stanem przedniej wargi szyjki macicy ciężarnej ocenianej w badaniu elastograficznym z długością kanału szyjki macicy w obrazie USG. 2. Badanie elastograficzne szyjki macicy może być pomocne w prognozowaniu ryzyka porodu przedwczesnego oraz niewydolności szyjki macicy. 3. Potrzebne są badania na większej grupie pacjentek aby stwierdzić czy elastografia znajdzie miejsce wśród rutynowych położniczych metod diagnostycznych

Barriers for Access to New Medicines: Searching for the Balance Between Rising Costs and Limited Budgets

Introduction: There is continued unmet medical need for new medicines across countries especially for cancer, immunological diseases and orphan diseases. However, there are growing challenges with funding new medicines at ever increasing prices along with funding increased medicine volumes with the growing prevalence of both infectious diseases and non-communicable diseases across countries. This has resulted in the development of new models to better manage the entry of new medicines, new financial models being postulated as well as strategies to improve prescribing efficiency. However, more needs to be done. Consequently, the primary aim of this paper is to consider potential ways to optimise the use of new medicines balancing rising costs with increasing budgetary pressures to stimulate debate especially from a payer perspective. Methods: A narrative review of pharmaceutical policies and implications, as well as possible developments, based on key publications and initiatives known to the co-authors principally from a health authority perspective. Results: A number of initiatives and approaches have been identified including new models to better manage the entry of new medicines based on three pillars (pre-, peri-, and post-launch activities). Within this, we see the growing role of horizon scanning activities starting up to 36 months before launch, managed entry agreements and post launch follow-up. It is also likely there will be greater scrutiny over the effectiveness and value of new cancer medicines given ever increasing prices. This could include establishing minimum effectiveness targets for premium pricing along with re-evaluating prices as more medicines for cancer lose their patent. There will also be a greater involvement of patients especially with orphan diseases. New initiatives could include a greater role of multicriteria decision analysis, as well as looking at the potential for de-linking research and development from commercial activities to enhance affordability. Conclusion: There are a number of ongoing activities across countries to try and fund new valued medicines whilst attaining or maintaining universal healthcare. Such activities will grow with increasing resource pressures and continued unmet need

Towards quantum internet and non-local communication in position-based qubits

The Fifth International Conference on Quantum Technologies (ICQT-2019), Moscow, Russia, 15-19 July 2019Non-local communication between position-based qubits is described for a system of a quantum electromagnetic resonator entangled to two semiconductor electrostatic qubits via an interaction between matter and radiation by Jaynes-Cummings tight-binding Hamiltonian. Principle of quantum communication between position-dependent qubits is explained. Further prospects of the model development are given. The obtained results bring foundation for the construction of quantum internet and quantum communication networks between position-based qubits that are implementable in semiconductor single-electron devices that can be realized in current CMOS technologies. The case of two semiconductor position-dependent qubits interacting with quantum electromagnetic cavity is discussed and general form of tight-binding Hamiltonian is derived with renormalized tight-binding coefficients. The considerations also describe the situation of mutual qubit-qubit electrostatic interaction.Science Foundation IrelandInsight Research Centr