A Role of Myocardin Related Transcription Factor-A (MRTF-A) in Scleroderma Related Fibrosis.

In scleroderma (systemic sclerosis, SSc), persistent activation of myofibroblast leads to severe skin and organ fibrosis resistant to therapy. Increased mechanical stiffness in the involved fibrotic tissues is a hallmark clinical feature and a cause of disabling symptoms. Myocardin Related Transcription Factor-A (MRTF-A) is a transcriptional co-activator that is sequestered in the cytoplasm and translocates to the nucleus under mechanical stress or growth factor stimulation. Our objective was to determine if MRTF-A is activated in the disease microenvironment to produce more extracellular matrix in progressive SSc. Immunohistochemistry studies demonstrate that nuclear translocation of MRTF-A in scleroderma tissues occurs in keratinocytes, endothelial cells, infiltrating inflammatory cells, and dermal fibroblasts, consistent with enhanced signaling in multiple cell lineages exposed to the stiff extracellular matrix. Inhibition of MRTF-A nuclear translocation or knockdown of MRTF-A synthesis abolishes the SSc myofibroblast enhanced basal contractility and synthesis of type I collagen and inhibits the matricellular profibrotic protein, connective tissue growth factor (CCN2/CTGF). In MRTF-A null mice, basal skin and lung stiffness was abnormally reduced and associated with altered fibrillar collagen. MRTF-A has a role in SSc fibrosis acting as a central regulator linking mechanical cues to adverse remodeling of the extracellular matrix

HO-1 Upregulation Attenuates Adipocyte Dysfunction, Obesity, and Isoprostane Levels in Mice Fed High Fructose Diets

Background. Fructose metabolism is an unregulated metabolic pathway and excessive fructose consumption is known to activate ROS.HO-1 is a potent antioxidant gene that plays a key role in decreasing ROS and isoprostanes.We examinedwhether the fructosemediated increase in adipocyte dysfunction involves an increase in isoprostanes and that pharmacological induction ofHO-1would decrease both isoprostane levels and adipogenesis. Methods and Results. We examined the effect of fructose, on adipogenesis in human MSCs in the presence and absence of CoPP, an inducer of HO-1. Fructose increased adipogenesis and the number of large lipid droplets while decreasing the number of small lipid droplets ( \u3c 0.05). Levels of heme and isoprostane in fructose treated MSC-derived adipocytes were increased. CoPP reversed these effects andmarkedly increasedHO-1 and theWnt signaling pathway. Thehigh fructose diet increased heme levels in adipose tissue and increased circulating isoprostane levels ( \u3c 0.05 versus control). Fructose diets decreasedHO-1 and adiponectin levels in adipose tissue. Induction ofHO-1 by CoPP decreased isoprostane synthesis ( \u3c 0.05 versus fructose). Conclusion. Fructose treatment resulted in increased isoprostane production and adipocyte dysfunction, which was reversed by the increased expression of HO-1

Urban Park Characteristic as a Key Element for Mental Health Restoration in Malaysia

A recent study has reported that the Malaysian urban population faces mental health problems due to urbanisation. Nature environment has been expected to give restoration experience among people. Therefore, the objective of this study is to analyse the relationship between park characteristics and mental health restoration in an urban park. Survey questionnaires (n=382) were distributed among urban park users. The analysis was conducted using the Partial Least Square Structural Equation Model. Results show that the Serene and Nature dimensions are the significant factors that give a restorative experience among urban park users. These findings can assist landscape architects in advocating for creating the urban park for mental health restoration. Keywords: Mental health; restoration experience; perceived sensory dimension, restorative environment eISSN: 2398-4287 © 2022. The Authors. Published for AMER ABRA cE-Bs by e-International Publishing House, Ltd., UK. This is an open access article under the CC BYNC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). Peer–review under responsibility of AMER (Association of Malaysian Environment-Behaviour Researchers), ABRA (Association of Behavioural Researchers on Asians/Africans/Arabians) and cE-Bs (Centre for Environment-Behaviour Studies), Faculty of Architecture, Planning & Surveying, Universiti Teknologi MARA, Malaysia. DOI: https://doi.org/10.21834/ebpj.v7i20.337

Alternative solutions for challenging environments: a look at UNICEF-assisted ecosan projects worldwide

This paper summarises information from 20 UNICEF-assisted ecological sanitation projects in 12 countries. The projects varied widely in size from 95 users for a project with household urine diversion dehydration toilets (UDDTs) in Bangladesh up to 23,000 users under emergency conditions in Zimbabwe. They share characteristics of purpose, scope, challenges, opportunities and sanitation technologies, which were mainly UDDTs and composting toilets. Specific insights are given for the projects in Bangladesh and Rwanda where large-scale ecological sanitation „ecosan‟ programs are currently underway. We discuss the potential to scale-up initiatives by providing increased technical back-up support to users, greater linkages with community-led total sanitation and with income generation initiatives via higher agricultural yields. In the context of growing urbanisation and hydro-geological challenges, this paper highlights that “ecosan technologies” (such as UDDTs) can be a suitable technical solution where pit-based toilets are impossible to be implemented sustainably

Adiposity Predicts Pulse Pressure in Subjects with Chronic Kidney Disease: Data from the Modification of Diet in Renal Disease

Obesity is a known risk factor for hypertension, but the mechanisms by which this occurs are still unclear. As the body mass index (BMI) is frequently used to define obesity, but the BMI does not distinguish between adipose and other tissues, we sought to develop another index of obesity. We decided to look at the ratio of BMI to urinary creatinine excretion as the latter measurement is believed to be an index of muscle mass. We used data from the modification of diet in renal disease (MDRD) study as urinary creatinine collections and blood pressure measurements were readily available in this data set. The UCRV correlated well with lean body mass determined by anthropomorphic measurements available on this data set. We found that the BMI/UCRV ratio correlated with either percent body fat (PBF) or total body fat calculated as the product of PBF and weight. We also found that the BMI/UCRV ratio correlated significantly with systolic, diastolic and especially pulse pressure in this population. These data suggest that adipocyte mass has a relationship to blood pressure in subjects with renal disease. Should these data be confirmed in other populations, the BMI/UCRV ratio may prove to be a useful measurement in patients at risk for hypertension and other cardiovascular diseases

Prospective Study Evaluating Management of Hypertension Induced by anti-VEGF Therapy in Patients with Active Cancer: VEGFHTN Trial

https://openworks.mdanderson.org/sumexp23/1027/thumbnail.jp

Transition of Care in Inflammatory Bowel Disease

Abstract: The management of patients with chronic conditions, such as inflammatory bowel disease (IBD), requires specific attention and careful planning during the transition from pediatric to adult care. Early education about the transition process and the acquisition of self-management skills are crucial to fostering independent adolescents and young adults who have the knowledge and tools to manage life with a chronic disease. A growing body of literature describes the challenges and barriers to providing adolescent and transition care. Potential barriers to effective transition include the following: differences between adult-and pediatric-onset IBD; patients' lack of developmental maturity and readiness, self-efficacy, and knowledge of the disease; poor adherence to therapy; adolescent anxiety and depression; differences between pediatric and adult IBD care; and parental and provider reluctance to transition. Despite our ability to identify barriers and challenges, there remain significant gaps in our knowledge about how they should be addressed. Outcomes data on adolescents with IBD are limited, and there are even fewer data on how the transition of care affects long-term treatment and outcomes. More research is needed to truly understand the best way to facilitate care during transition and improve outcomes. Current research and transition guidelines acknowledge that providing support and guidance to patients and their families and establishing clear goals can ultimately equip patients with the skills needed to cope with a chronic disease as adults and can improve their long-term care. This paper provides an overview of the transition from pediatric to adult IBD care, a discussion of challenges and barriers, and recommendations and resources that can help patients, parents, and providers navigate this important process. T he management of patients with chronic conditions, such as inflammatory bowel disease (IBD), requires specific attention and careful planning during the transition from pediatric to adult care. Early education about the transition process and the acquisition of self-management skills are crucial to foster

Am I getting an accurate picture: a tool to assess clinical handover in remote settings?

BACKGROUND: Good clinical handover is critical to safe medical care. Little research has investigated handover in rural settings. In a remote setting where nurses and medical students give telephone handover to an aeromedical retrieval service, we developed a tool by which the receiving clinician might assess the handover; and investigated factors impacting on the reliability and validity of that assessment. METHODS: Researchers consulted with clinicians to develop an assessment tool, based on the ISBAR handover framework, combining validity evidence and the existing literature. The tool was applied 'live' by receiving clinicians and from recorded handovers by academic assessors. The tool's performance was analysed using generalisability theory. Receiving clinicians and assessors provided feedback. RESULTS: Reliability for assessing a call was good (G = 0.73 with 4 assessments). The scale had a single factor structure with good internal consistency (Cronbach's alpha = 0.8). The group mean for the global score for nurses and students was 2.30 (SD 0.85) out of a maximum 3.0, with no difference between these sub-groups. CONCLUSIONS: We have developed and evaluated a tool to assess high-stakes handover in a remote setting. It showed good reliability and was easy for working clinicians to use. Further investigation and use is warranted beyond this setting

pNaKtide inhibits Na/K-ATPase reactive oxygen species amplification and attenuates adipogenesis

Obesity has become a worldwide epidemic and is a major risk factor for metabolic syndrome. Oxidative stress is known to play a role in the generation and maintenance of an obesity phenotype in both isolated adipocytes and intact animals. Because we had identified that the Na/K-ATPase can amplify oxidant signaling, we speculated that a peptide designed to inhibit this pathway, pNaKtide, might ameliorate an obesity phenotype. To test this hypothesis, we first performed studies in isolated murine preadipocytes (3T3L1 cells) and found that pNaKtide attenuated oxidant stress and lipid accumulation in a dose-dependent manner. Complementary experiments in C57Bl6 mice fed a high-fat diet corroborated our in vitro observations. Administration of pNaKtide in these mice reduced body weight gain, restored systemic redox and inflammatory milieu, and, crucially, improved insulin sensitivity. Thus, we propose that inhibition of Na/K-ATPase amplification of oxidative stress may ultimately be a novel way to combat obesity, insulin resistance, and metabolic syndrome

Deletion of parasite immune modulatory sequences combined with immune activating signals enhances vaccine mediated protection against filarial nematodes

<p>Background: Filarial nematodes are tissue-dwelling parasites that can be killed by Th2-driven immune effectors, but that have evolved to withstand immune attack and establish chronic infections by suppressing host immunity. As a consequence, the efficacy of a vaccine against filariasis may depend on its capacity to counter parasite-driven immunomodulation.</p> <p>Methodology and Principal Findings: We immunised mice with DNA plasmids expressing functionally-inactivated forms of two immunomodulatory molecules expressed by the filarial parasite Litomosoides sigmodontis: the abundant larval transcript-1 (LsALT) and cysteine protease inhibitor-2 (LsCPI). The mutant proteins enhanced antibody and cytokine responses to live parasite challenge, and led to more leukocyte recruitment to the site of infection than their native forms. The immune response was further enhanced when the antigens were targeted to dendritic cells using a single chain Fv-αDEC205 antibody and co-administered with plasmids that enhance T helper 2 immunity (IL-4) and antigen-presenting cell recruitment (Flt3L, MIP-1α). Mice immunised simultaneously against the mutated forms of LsALT and LsCPI eliminated adult parasites faster and consistently reduced peripheral microfilaraemia. A multifactorial analysis of the immune response revealed that protection was strongly correlated with the production of parasite-specific IgG1 and with the numbers of leukocytes present at the site of infection.</p> <p>Conclusions: We have developed a successful strategy for DNA vaccination against a nematode infection that specifically targets parasite-driven immunosuppression while simultaneously enhancing Th2 immune responses and parasite antigen presentation by dendritic cells.</p&gt