Mooring forces in horizontal interlaced multilayered Floating pipe breakwater with three layers

Source: ICHE Conference Archive - https://mdi-de.baw.de/icheArchiv

Is there a positive effect of participation on a clinical trial for patients with advanced non-small cell lung cancer?

Background: There is general belief that patients who enrolled on a clinical trial have better outcomes compared to those who are treated outside of a trial. We analyzed if there was a \u2032trial effect\u2032 for patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy. Materials and methods: A retrospective analysis of cohorts of patients with advanced NSCLC who received chemotherapy inside and outside of a clinical trial were analyzed for response rates (RR), progression free survival (PFS), overall survival (OS), 1 and 2 year survival. Results: There were 194 patients who received chemotherapy of which, 54 were on a clinical trial and 140 outside of it. For the whole group, the RR, median PFS, OS, one and two-year survivals were 35.4%, six months (range, 2-70), seven months (range, 2-72), 29.8% and 9.7% respectively. The differences in RR and PFS of patients who were treated inside and outside of a clinical trial were not significant (P=0.6164, 0.0881). The differences in median OS and one-year survivals between the groups were significant (P=0.0052, 0.022). For the whole group, patients who received II line chemotherapy had better OS (P\ua30.0001). More patients in the trial group received II line chemotherapy (P=0.0004).The difference in the median OS between the groups continued to be significant even after patients who received II line chemotherapy were censored (P=0.0437). Conclusion: Patients with advanced NSCLC who were treated inside of a clinical trial had better OS compared to those who were treated outside of it

N 3-[(E)-Morpholin-4-yl­methyl­idene]-1-phenyl-1H-1,2,4-triazole-3,5-diamine monohydrate

In the title compound, C13H16N6O·H2O, the mean planes of the benzene and 1,2,4-triazole rings form a dihedral angle of 54.80 (5)°. The N atom of the amino group adopts a trigonal–pyramidal configuration. Conjugation in the amidine N=C—N fragment results in sufficient shortening of the formal single bond. In the crystal, inter­molecular N—H⋯O and O—H⋯N hydrogen bonds link mol­ecules into double layers parallel to the bc plane

Altered synaptobrevin-II trafficking in neurons expressing a synaptophysin mutation associated with a severe neurodevelopmental disorder

textabstractFollowing exocytosis, synaptic vesicles (SVs) have to be reformed with the correct complement of proteins in the correct stoichiometry to ensure continued neurotransmission. Synaptophysin is a highly abundant, integral SV protein necessary for the efficient retrieval of the SV SNARE protein, synaptobrevin II (sybII). However the molecular mechanism underpinning synaptophysin-dependent sybII retrieval is still unclear. We recently identified a male patient with severe intellectual disability, hypotonia, epilepsy and callosal agenesis who has a point mutation in the juxtamembrane region of the fourth transmembrane domain of synaptophysin (T198I). This mutation had no effect on the activity-dependent retrieval of synaptophysin that was tagged with the genetically-encoded pH-sensitive reporter (pHluorin) in synaptophysin knockout hippocampal cultures. This suggested the mutant has no global effect on SV endocytosis, which was confirmed when retrieval of a different SV cargo (the glutamate transporter vGLUT1) was examined. However neurons expressing this T198I mutant did display impaired activity-dependent sybII retrieval, similar to that observed in synaptophysin knockout neurons. Interestingly this impairment did not result in an increased stranding of sybII at the plasma membrane. Screening of known human synaptophysin mutations revealed a similar presynaptic phenotype between T198I and a mutation found in X-linked intellectual disability. Thus this novel human synaptophysin mutation has revealed that aberrant retrieval and increased plasma membrane localisation of SV cargo can be decoupled in human disease

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes

Integration of Synaptic Vesicle Cargo Retrieval with Endocytosis at Central Nerve Terminals

Central nerve terminals contain a limited number of synaptic vesicles (SVs) which mediate the essential process of neurotransmitter release during their activity-dependent fusion. The rapid and accurate formation of new SVs with the appropriate cargo is essential to maintain neurotransmission in mammalian brain. Generating SVs containing the correct SV cargo with the appropriate stoichiometry is a significant challenge, especially when multiple modes of endocytosis exist in central nerve terminals, which occur at different locations within the nerve terminals. These endocytosis modes include ultrafast endocytosis, clathrin-mediated endocytosis (CME) and activity-dependent bulk endocytosis (ADBE) which are triggered by specific patterns of neuronal activity. This review article will assess the evidence for the role of classical adaptor protein complexes in SV retrieval, discuss the role of monomeric adaptors and how interactions between specific SV cargoes can facilitate retrieval. In addition it will consider the evidence for preassembled plasma membrane cargo complexes and their role in facilitating these endocytosis modes. Finally it will present a unifying model for cargo retrieval at the presynapse, which integrates endocytosis modes in time and space

Haemoglobinopathies encountered at Khoula Hospital, Oman: A retrospective study

Objective: The objective of this study was to find out the frequency of abnormal haemoglobins (Hb) in patients referred to Khoula Hospital, Oman and compare the data from other studies by assessing a large number of patients. Methods: The results of 27,403 patients, either admitted to Khoula Hospital or referred to it from different health centres during the 4 years of the study from January 2001 till December 2004, were analysed for haemoglobinopathies. The laboratory methods used for detection of abnormal haemoglobins were sickle cell solubility test and haemoglobin electrophoresis. Results: The frequency of sickle cell trait was 7.5%, sickle cell disease 0.46% and other Hb variants were 0.102%. The results correlate well with that of the National Genetic Blood Disorder Survey carried out by the research and studies department, Ministry of Health, Sultanate of Oman, during a 4 year period from January 2001 till December 2004. Conclusion: This retrospective study demonstrates the high prevalence of haemoglobinopathies among the studied group of patients. More attention to the importance of health education and genetic counselling is required for the prevention of this public health problem in the country.

Haemoglobinopathies encountered at Khoula Hospital, Oman A retrospective study

Objective: The objective of this study was to find out the frequency of abnormal haemoglobins (Hb) in patients referred to Khoula Hospital, Oman and compare the data from other studies by assessing a large number of patients. Methods: The results of 27,403 patients, either admitted to Khoula Hospital or referred to it from different health centres during the 4 years of the study from January 2001 till December 2004, were analysed for haemoglobinopathies. The laboratory methods used for detection of abnormal haemoglobins were sickle cell solubility test and haemoglobin electrophoresis. Results: The frequency of sickle cell trait was 7.5%, sickle cell disease 0.46% and other Hb variants were 0.102%. The results correlate well with that of the National Genetic Blood Disorder Survey carried out by the research and studies department, Ministry of Health, Sultanate of Oman, during a 4 year period from January 2001 till December 2004. Conclusion: This retrospective study demonstrates the high prevalence of haemoglobinopathies among the studied group of patients. More attention to the importance of health education and genetic counselling is required for the prevention of this public health problem in the country.

FIGURE 1 in A new species of the genus Lichenomima Enderlein, 1910 (Psocodea: 'Psocoptera' Myopsocidae) from India

FIGURE 1. Distribution of Lichenomima aldretei n. sp. in India.Published as part of <i>Ramesh, Gurusamy, Babu, Rajappa & Subramanian, Kumarapuram A., 2023, A new species of the genus Lichenomima Enderlein, 1910 (Psocodea: 'Psocoptera' Myopsocidae) from India, pp. 575-584 in Zootaxa 5374 (4)</i> on page 576, DOI: 10.11646/zootaxa.5374.4.8, <a href="http://zenodo.org/record/10158817">http://zenodo.org/record/10158817</a&gt