Inverse baseline expression pattern of the NEP/neuropeptides and NFκB/proteasome pathways in androgen-dependent and androgen-independent prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Castration-resistance in prostate cancer (PC) is a critical event hallmarking a switch to a more aggressive phenotype. Neuroendocrine differentiation and upregulation of NFκB transcriptional activity are two mechanisms that have been independently linked to this process.</p> <p>Methods</p> <p>We investigated these two pathways together using <it>in vitro </it>models of androgen-dependent (AD) and androgen-independent (AI) PC. We measured cellular levels, activity and surface expression of Neutral Endopeptidase (NEP), levels of secreted Endothelin-1 (ET-1), levels, sub-cellular localisation and DNA binding ability of NFκB, and proteasomal activity in human native PC cell lines (LnCaP and PC-3) modelling AD and AI states.</p> <p>Results</p> <p>At baseline, AD cells were found to have high NEP expression and activity and low secreted ET-1. In contrast, they exhibited a low-level activation of the NFκB pathway associated with comparatively low 20S proteasome activity. The AI cells showed the exact mirror image, namely increased proteasomal activity resulting in a canonical pathway-mediated NFκB activation, and minimal NEP activity with increased levels of secreted ET-1.</p> <p>Conclusions</p> <p>Our results seem to support evidence for divergent patterns of expression of the NFκB/proteasome pathway with relation to components of the NEP/neuropeptide axis in PC cells of different level of androgen dependence. NEP and ET-1 are inversely and directly related to an activated state of the NFκB/proteasome pathway, respectively. A combination therapy targeting both pathways may ultimately prove to be of benefit in clinical practice.</p

Peptidergic modulation of motor neuron output via CART signaling at C bouton synapses

Funding: This work was supported by the General Secretariat for Research and Technology (ARISTEIA II 4257, L.Z.), Fondation SANTE (L.Z.), a Marie Curie Re-Integration Grant (268323, L.Z.), the Hellenic Foundation for Research and Innovation (spinMNALS, 4013, L.Z.) and by a St. Andrews Restarting Research Fund (S.A.S. and G.B.M.). S.A.S. was funded by a Royal Society Newton International Fellowship (NIF/R1/180091) and a Natural Sciences and Engineering Research Council of Canada (NSERC) Postdoctoral Fellowship (NSERC-PDF-517295-2018) and M.M. by the National Scholarship Foundation (IKY).The intensity of muscle contraction, and therefore movement vigour, needs to be adaptable to enable complex motor behaviors. This can be achieved by adjusting the properties of motor neurons, which form the final common pathway for all motor output from the central nervous system. Here we identify novel roles for a neuropeptide, Cocaine and Amphetamine Regulated Transcript (CART), in the control of movement vigour. We reveal distinct, but parallel mechanisms by which CART and acetylcholine, both released at C bouton synapses on motor neurons, selectively amplify the output of subtypes of motor neurons that are recruited during intense movement. We find that mice with broad genetic deletion of CART or selective elimination of acetylcholine from C boutons exhibit deficits in behavioral tasks that require higher levels of motor output. Overall, these data uncover novel spinal modulatory mechanisms that control movement vigour to support movements that require a high degree of muscle force.Publisher PDFPeer reviewe

Premature Birth, Management, Complications

In recent years an increase in premature births (PB) rate has been noticed, as this pregnancy complication that still remain an important cause of perinatal morbidity and mortality, is multifactorial and prediction is not easy in many cases. There are many bibliographic data supporting the view that PB have also genetic predisposition. The trend of “recurrence” of PB in women as well as its increased frequency in ethnic groups suggests its association with genetic factors, either as such or as an interaction of genes and environment. Immunomodulatory molecules and receptors as well as polymorphisms of various genes and/or single nucleotides (single nucleotide polymorphisms, SNPs) now allow with advanced methods of Molecular Biology the identification of genes and proteins involved in the pathophysiology of PB. From the history of a pregnant woman, the main prognostic factor is a previous history of prematurity, while an ultrasound assessment of the cervix between 18 and 24 weeks is suggested, both in the developed and the developing world. According to the latest data, an effective method of successful prevention of premature birth has not been found. The main interventions suggested for the prevention of premature birth are the cervical cerclage, the use of cervical pessary, the use of progesterone orally, subcutaneously or transvaginally, and for treatment administration of tocolytic medication as an attempt to inhibit childbirth for at least 48 hours to make corticosteroids more effective. Despite the positive results in reducing mortality and morbidity of premature infants, the need for more research in the field of prevention, investigation of the genital code and the mechanism of initiation of preterm birth is important

Antiphospholipid Syndrome and Pregnancy-Diagnosis, Complications and Management: An Overview

Antiphospholipid syndrome which is also known as APS is an autoimmune disease which represents an acquired form of thrombophilia. The etiology of APS remains unknown. This disorder occurs when the immune system mistakenly attacks some of the normal human proteins and manifests itself as recurrent arterial or venous thrombosis and it could emerge after abortions or in recurrent pregnancy loss. In APS, the body produces the wrong antibodies against phospholipid-binding proteins, that is present in the blood and plays an important role in coagulation. Antibodies are specific proteins that usually target and neutralize the body’s invaders, such as viruses and bacteria. When antibodies attack phospholipid-binding proteins, blood clots abnormally. Specifically, it could cause blood clots in veins or arteries leading to stroke and various pregnancy complications such as: endometrial death, miscarriage, preeclampsia, intrauterine growth restriction and prematurity. APS is divided into primary and secondary, which is associated with autoimmune diseases and more often with systemic lupus erythematosus (SLE), while antibodies against cardiolipin are detected in many other conditions (infections, malignancies, drugs, etc.). The symptoms of APS, in addition to arterial and/or venous thrombosis and pregnancy complications, are multisystemic and the differential diagnosis of the primary APS from the secondary, in the context of SLE, is of particular clinical interest and is subject of this literature review

Twin Pregnancies Labour Modus and Timing

Twin pregnancies are categorized according to three factors, zygosity, chorionicity and amnionicity. Dizygotic twins are always dichorionic and diamniotic, where each twin has its own chorionic and amniotic sac. Monozygotic twins account for 1/3 of twin pregnancies and show higher morbidity and mortality. In monozygotic twins, chorionicity and amnionicity are determined by the time of zygote division. Chorionicity and amnionicity determine the risks of twin pregnancy. Morbitidies are shown notable decreasing tendency depending on improving of high risk obstetric and neonatal care, however is still discussed the optimum labour management in twin pregnancies Vaginal delivery in twin pregnancies is possible when both have cephalic presentation and in the late weeks of pregnancy during which the risks of prematurity are minimized. The aim of this review was the assessment and evaluation the impact of the labour modus and timing of termination of twin pregnancies due to rise of their occurrence based on scientific aspects of the new published literature on perinatal outcome

Bacterial and fungal microflora in surgically removed lung cancer samples

<p>Abstract</p> <p>Background</p> <p>Clinical and experimental data suggest an association between the presence of bacterial and/or fungal infection and the development of different types of cancer, independently of chemotherapy-induced leukopenia. This has also been postulated for the development of lung cancer, however the prevalence and the exact species of the bacteria and fungi implicated, have not yet been described.</p> <p>Aim</p> <p>To determine the presence of bacterial and fungal microflora in surgically extracted samples of patients with lung cancer.</p> <p>Materials and methods</p> <p>In this single-center prospective, observational study, tissue samples were surgically extracted from 32 consecutive patients with lung cancer, and reverse-transcription polymerase chain reaction (RT-PCR) was used to identify the presence of bacteria and fungi strains.</p> <p>Results</p> <p>The analysis of the electrophoresis data pointed out diversity between the samples and the strains that were identified. Mycoplasma strains were identified in all samples. Strains that appeared more often were Staphylococcus epidermidis, Streptococcus mitis and Bacillus strains, followed in descending frequency by Chlamydia, Candida, Listeria, and Haemophilus influenza. In individual patients Legionella pneumophila and Candida tropicalis were detected.</p> <p>Conclusions</p> <p>A diversity of pathogens could be identified in surgically extracted tissue samples of patients with lung cancer, with mycoplasma strains being present in all samples. These results point to an etiologic role for chronic infection in lung carcinogenesis. Confirmation of these observations and additional studies are needed to further characterize the etiologic role of inflammation in lung carcinogenesis.</p

Global disparities in surgeons’ workloads, academic engagement and rest periods: the on-calL shIft fOr geNEral SurgeonS (LIONESS) study

: The workload of general surgeons is multifaceted, encompassing not only surgical procedures but also a myriad of other responsibilities. From April to May 2023, we conducted a CHERRIES-compliant internet-based survey analyzing clinical practice, academic engagement, and post-on-call rest. The questionnaire featured six sections with 35 questions. Statistical analysis used Chi-square tests, ANOVA, and logistic regression (SPSS® v. 28). The survey received a total of 1.046 responses (65.4%). Over 78.0% of responders came from Europe, 65.1% came from a general surgery unit; 92.8% of European and 87.5% of North American respondents were involved in research, compared to 71.7% in Africa. Europe led in publishing research studies (6.6 ± 8.6 yearly). Teaching involvement was high in North America (100%) and Africa (91.7%). Surgeons reported an average of 6.7 ± 4.9 on-call shifts per month, with European and North American surgeons experiencing 6.5 ± 4.9 and 7.8 ± 4.1 on-calls monthly, respectively. African surgeons had the highest on-call frequency (8.7 ± 6.1). Post-on-call, only 35.1% of respondents received a day off. Europeans were most likely (40%) to have a day off, while African surgeons were least likely (6.7%). On the adjusted multivariable analysis HDI (Human Development Index) (aOR 1.993) hospital capacity &gt; 400 beds (aOR 2.423), working in a specialty surgery unit (aOR 2.087), and making the on-call in-house (aOR 5.446), significantly predicted the likelihood of having a day off after an on-call shift. Our study revealed critical insights into the disparities in workload, access to research, and professional opportunities for surgeons across different continents, underscored by the HDI

Reducing the environmental impact of surgery on a global scale: systematic review and co-prioritization with healthcare workers in 132 countries

Abstract Background Healthcare cannot achieve net-zero carbon without addressing operating theatres. The aim of this study was to prioritize feasible interventions to reduce the environmental impact of operating theatres. Methods This study adopted a four-phase Delphi consensus co-prioritization methodology. In phase 1, a systematic review of published interventions and global consultation of perioperative healthcare professionals were used to longlist interventions. In phase 2, iterative thematic analysis consolidated comparable interventions into a shortlist. In phase 3, the shortlist was co-prioritized based on patient and clinician views on acceptability, feasibility, and safety. In phase 4, ranked lists of interventions were presented by their relevance to high-income countries and low–middle-income countries. Results In phase 1, 43 interventions were identified, which had low uptake in practice according to 3042 professionals globally. In phase 2, a shortlist of 15 intervention domains was generated. In phase 3, interventions were deemed acceptable for more than 90 per cent of patients except for reducing general anaesthesia (84 per cent) and re-sterilization of ‘single-use’ consumables (86 per cent). In phase 4, the top three shortlisted interventions for high-income countries were: introducing recycling; reducing use of anaesthetic gases; and appropriate clinical waste processing. In phase 4, the top three shortlisted interventions for low–middle-income countries were: introducing reusable surgical devices; reducing use of consumables; and reducing the use of general anaesthesia. Conclusion This is a step toward environmentally sustainable operating environments with actionable interventions applicable to both high– and low–middle–income countries

On the Selection of Process Mining Tools

Process mining is a research discipline that applies data analysis and computational intelligence techniques to extract knowledge from event logs of information systems. It aims to provide new means to discover, monitor, and improve processes. Process mining has gained particular attention over recent years and new process mining software tools, both academic and commercial, have been developed. This paper provides a survey of process mining software tools. It identifies and describes criteria that can be useful for comparing the tools. Furthermore, it introduces a multi-criteria methodology that can be used for the comparative analysis of process mining software tools. The methodology is based on three methods, namely ontology, decision tree, and Analytic Hierarchy Process (AHP), that can be used to help users decide which software tool best suits their needs

The symphony as a field of application of contemporary aesthetic concepts and a means of expression of new quests

The present work examines the symphony as a valuable and timeless compositional tool, as a field of application of contemporary aesthetic concepts, and as a means of expressing new quests. It focuses primarily on the original musical creation of a relevant work and its analysis. At the same time, it listens to global historical data of the evolutionary course of the genre and the position of contemporary Greek creation.Το παρόν πόνημα εξετάζει τη συμφωνία ως πολύτιμο και διαχρονικό συνθετικό εργαλείο, ως πεδίο εφαρμογής σύγχρονων αισθητικών αντιλήψεων, καθώς και ως μέσο έκφρασης νέων αναζητήσεων. Εστιάζει πρωτίστως στην πρωτότυπη μουσική δημιουργία σχετικού έργου και της ανάλυσής του. Παράλληλα, αφουγκράζεται παγκόσμια ιστορικά δεδομένα της εξελικτικής πορείας του είδους και τη θέση της σύγχρονης ελληνικής δημιουργίας