Stem Cells in Hypertension

Endothelial dysfunction and vascular remodeling are the hallmarks of pulmonary arterial hypertension (PAH). For PAH treatment, there is a rising demand of Stem cell therapy. Interestingly, research reveals that stem/progenitor cells may have an impact in disease progression and therapy in PAH patients. Clinical trials for stem cell therapy in cardiac cell regeneration for heart repair in PAH patients are now underway. The clinical potential of stem/progenitor cell treatment that offers to PAH patients helps in lesion formation which occurs through regaining of vascular cell activities. Majorly the stem cells which are specifically derived from bone marrow such as mesenchymal stem cells (MSCs), endothelial progenitor cells (EPCs) and induced pluripotent cells (iPSCs), adipose-derived stem cells (ADSCs), and cardiac stromal cells (CSCs) are among the subtypes that are proved to play a pivotal role in the repair of the heart. But with only MSCs and EPCs, have shown positive outcomes and act as therapeutically efficient in regaining cure for PAH in clinical trials. This chapter also seeks to explain the potential limitations and challenges with most recent achievements in stem/progenitor cell research in PAH

'I never leave my house without praying': a qualitative exploration of the psychospiritual experiences of ethnically diverse healthcare staff during the COVID-19 pandemic

The study aimed to understand the psychospiritual experiences and support needs of ethnically diverse healthcare staff during the COVID-19 pandemic. A qualitative study using focus groups conducted remotely on Microsoft Teams. The study took place across 10 National Health Service Trusts in England: 5 were Acute Hospital Trusts and 5 were Community and Mental Health Trusts. Fifty-five participants were recruited to the study across 16 focus group meetings. Participants were all National Health Service staff from ethnically diverse backgrounds. Psychospiritual concerns were central to participants' understanding of themselves and their work in the National Health Service. Participants felt there was limited recognition of spirituality within the health service. They described close links between their spirituality and their ethnicities and felt that the psychospiritual support offered within the healthcare setting was not reflective of diverse ethnic and spiritual needs. Improved psychospiritual care was viewed as an opportunity to connect more deeply with other colleagues, rather than using the more individualistic interventions on offer. Participants requested greater compassion and care from leadership teams. Participants described both positive and negative changes in their spirituality as a result of the COVID-19 pandemic. Culturally sensitive psychospiritual support is a key aspect of healthcare staff's well-being, despite identified gaps in this area. Aside from affecting physical, psychological, social and financial aspects of healthcare staff's lives, the pandemic has also had a significant impact on the ways that people experience spirituality. [Abstract copyright: © Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Purification, Characterization and in vitro Evaluation of Polymyxin A From Paenibacillus dendritiformis: An Underexplored Member of the Polymyxin Family

Nosocomial infections caused by antibiotic-resistant Gram-negative pathogens are of grave concern today. Polymyxins are considered as the last resorts of therapy to treat these multi-drug resistant (MDR) bacteria. But their associated nephrotoxicity and neurotoxicity calls for the development of safer polymyxin therapy until novel and less toxic antibiotics are discovered. No other polymyxin molecule except polymyxin B and E (colistin) is explored thoroughly in literature to demonstrate its clinical relevance. In the present study, we have isolated two antimicrobial compounds named P1 and P2 from the soil isolate Paenibacillus dendritiformis strain PV3-16, which we later identified as polymyxin A2 and A1 respectively. We tested their minimum inhibitory concentrations (MICs) against MDR clinical isolates, performed membrane permeabilization assays and determined their interaction with lipopolysaccharide (LPS). Finally, we studied their toxicity against human Leukemic monocyte cell line (THP-1) and embryonic kidney cell line (HEK 293). Both compounds displayed equal efficacy when compared with standard polymyxins. P1 was 2–4 fold more active in most of the clinical strains tested. Moreover, P1 showed higher affinity toward LPS. In cytotoxicity studies, P1 had IC50 value (>1000 μg/ml) similar to colistin against HEK cells but immune cells, i.e., THP-1 cell lines were more sensitive to polymyxins. P1 showed less toxicity in THP-1 cell line than all other polymyxins checked. To sum up, P1 (polymyxin A2) possessed better efficacy than polymyxin B and E and had least toxicity to immune cells. Since polymyxin A was not investigated thoroughly, we performed the comprehensive in vitro assessment of this molecule. Moreover, this is the first report of isolation and characterization of polymyxin A from P. dendritiformis. This compound should be further investigated for its in vivo efficacy and toxicity to develop it as a drug candidate

On an Analytical Model for Long-Range Financial Planning (2)

The inhibitor of the nuclear factor-kappa B (I kappa B) kinase (IKK) complex is a key regulator of the canonical NF-kappa B signalling cascade and is crucial for fundamental cellular functions, including stress and immune responses. The majority of IKK complex functions are attributed to NF-kappa B activation; however, there is increasing evidence for NF-kappa B pathway-independent signalling. Here we combine quantitative mass spectrometry with random forest bioinformatics to dissect the TNF-alpha-IKK beta-induced phosphoproteome in MCF-7 breast cancer cells. In total, we identify over 20,000 phosphorylation sites, of which similar to 1% are regulated up on TNF-alpha stimulation. We identify various potential novel IKK beta substrates including kinases and regulators of cellular trafficking. Moreover, we show that one of the candidates, AEG-1/MTDH/LYRIC, is directly phosphorylated by IKK beta on serine 298. We provide evidence that IKK beta-mediated AEG-1 phosphorylation is essential for I kappa B alpha degradation as well as NF-kappa B-dependent gene expression and cell proliferation, which correlate with cancer patient survival in vivo

Building for resilience

As the population, infrastructure and economies around the world are growing, some global issues - like climate change and natural disasters are hindering the social and economic growth in some developing countries, like Vanuatu. The focus of this research project is on designing an educational and research facility, which allows the people of Vanuatu to prepare for and overcome a natural disaster by providing training and emergency relief. The facility will work in two different phases a ‘pre-disaster phase’, and a ‘post-disaster phase’. The first phase will cater to the everyday life of people where the centre will function as an educational and research facility. The locals, government and disaster relief organisations will have a chance to collaborate and share knowledge in this phase. The second phase is after a disaster has occurred when the centre’s primary role is the emergency relief facility for the local people by local and international disaster relief organisations. There is another, very short phase, immediately after a disaster, in which the repairs to the damaged parts of the building can be quickly performed. The UNU-EHS (United Nations University’s Institute for Environment and Human Security) has ranked Vanuatu “the world’s most disaster prone country” in an annual World Risk Report four years in a row. The reason Vanuatu ranks at the top is not because it’s exposed to natural disasters excessively more but because of its lack of preparedness, overall vulnerability based on susceptibility, lack of coping and adaptive capacities. In this project, the Disaster Relief Centre is located in Port Villa, the capital of Vanuatu, near the USP campus. It will be the hub of a system of satellite relief station throughout the main settled island of the nation. The design solution has two scales: a master plan for the entire DRC compound, and the design of the main DRC building, and both of them are presented in three states: pre-, in- and post; disaster phase. The design is based on a mix of considerations: functional efficiency; cultural sensitivity; resource self-sufficiency (resilience) and efficiency (sustainability). The setting of this thesis might be for a specfic country but I am hoping that it can be taken as an example for other less developed countries which suffer majorly from natural disasters. The idea behind the project is that educating the people to prepare for a natural disaster is more important for resilience than anything else and should be able to be replicated anywhere. The role of architecture in this project is to create a design which is strong and should be able to withstand any natural event. Therefore, it will use modern construction methods but will also incorporate the cultural aspect in it for the locals to create a familiar environment. The influential factor behind the idea of incorporating the cultural aspect in modern architecture is to help provide ‘a sense of a safe place’ for the locals and also be educational and inspirational for them at the same time

Sex Hormones and Immune Dimorphism

The functioning of the immune system of the body is regulated by many factors. The abnormal regulation of the immune system may result in some pathological conditions. Sex hormones of reproductive system are one of the major factors that regulate immune system due to the presence of hormone receptors on immune cells. The interaction of sex hormones and immune cells through the receptors on these cells effect the release of cytokines which determines the proliferation, differentiation, and maturation of different types of immunocytes and as a result the outcome of inflammatory or autoimmune diseases. The different regulations of sex hormones in both sexes result in immune dimorphism. In this review article the mechanism of regulation of immune system in different sexes and its impact are discussed