Factors associated with non-utilization of postnatal care among newborns in the first 2 days after birth in Pakistan: a nationwide cross-sectional study.

BACKGROUND: Recent data indicated that approximately four in every ten newborns in Pakistan do not receive postnatal care (PNC) services in the first 48 hours after delivery. OBJECTIVES: This study aimed to identify factors associated with the non-utilization of PNC for newborns in Pakistan using the 2017-18 Pakistan Demographic and Health Survey (PDHS). METHODS: This was a cross-sectional analytical study utilizing data from 3887 live-born newborns recorded in the 2017-18 PDHS. Non-utilization of PNC was assessed against a set of independent factors using multilevel logistic regression analysis, and the population attributable risk estimates of factors associated with non-utilization of PNC were also calculated. RESULTS: There were 1443 newborns (37%) in Pakistan whose mothers did not utilize PNC check-ups in the first 2 days after delivery. The non-utilization of PNC was largely attributable to newborns delivered at non-health facilities 53% (47% to 59%) and those born to uneducated women 27% (13% to 38%). Adjusted analyses indicated that newborns with higher birth order and with a birth interval of more than 2 years, women who perceived their baby to be small at birth, women with no formal education and those living in regional areas of Khyber Pakhtunkhwa and Federally Administered Tribal Areas were significantly associated with non-utilization of PNC services. CONCLUSIONS: Tailored health messages by community health workers, including door-to-door visits on utilizing health facilities through pregnancy to the postnatal periods, are needed and should target places of low socioeconomic status, including educationally disadvantaged women from regional areas of Pakistan.

Climate change and the health of older people in Australia: A scoping review on the role of mobile applications (apps) in ameliorating impact.

OBJECTIVES: Due to the impact of climate change, mobile applications (apps) providing information about the external environment have the potential to improve the health of older people. The purpose of this research was to undertake a scoping review of the evidence on the usability, feasibility and effectiveness of mobile apps to encourage access to activities outside the home in older people. METHODS: A search of databases was undertaken with relevant keywords. Selected manuscripts were judged for relevance to the inclusion criteria and assessed for quality. RESULTS: Very few published studies examined mobile apps specifically designed to prevent, or to treat, chronic disease in ageing populations, and fewer had rigorous designs. No study addressed accessing the external environment in the context of climate change. CONCLUSION: This study demonstrates that there is a gap in the evidence about the mobile apps designed for healthy ageing and, more specifically, to improve access to the external environment.

Factors influencing suicide in older rural males: a review of Australian studies.

INTRODUCTION: Suicide remains an important public health issue in Australia, responsible for around 2500 deaths each year. Although suicide only accounts for around 1.7% of total mortality in Australia per year, 75% of suicide deaths are in males. This article reviews the factors contributing to suicide in older rural males in Australia and then categorises the papers into themes for ease of explanation. Living with experiences of drought, dramatic weather change, lower employment opportunities, out-migration, changing family dynamics, ageism in the community, economic change and competitive labour markets, all add to the diverse experience for an older person who is ageing in a rural setting. METHODS: A literature search was conducted in March 2015, using the terms 'elderly' and 'older males' and then combined with 'rural', 'suicide' and 'Australia', to investigate the amount of research that has been conducted on the factors relating to suicide in older rural Australian males. RESULTS: Reviewed articles consisted of research using either quantitative or qualitative approaches, which investigated suicide in older Australians published between 1950 and 2014. With strict adherence to the selection criteria, articles (21 in total) were removed because they were a literature review; a narrative review; they focused predominantly on youth or suicide risk, suicidal ideation or suicide attempts; or they discussed reasons for living. This article discusses the researcher's recommendations for further research into employment transitions for older Australian males, and the need to review policy change for further intervention in the future. CONCLUSIONS: This article highlights factors that may cause older rural Australians to be placed at a higher risk of suicide than their urban-dwelling counterparts. With the impact of the changing economy, unpredictable climatic conditions and dynamic changes in rural Australian families, there is a need to highlight research that has been conducted in this area. Future research should focus on identification of misclassification of suicide deaths, investigation of the possible effect that retirement pathways may have on older Australian males, suicide prevention strategies, mental wellbeing and the risk of suicidal behaviour. This will ascertain any compounding or protective factors that could influence this current trend.

Climate adversity and resilience: the voice of rural Australia.

INTRODUCTION: Over the past decade, Australia has experienced prolonged drought and extensive flooding. It is argued that such events impact more significantly on rural communities than urban. Although there is a body of research investigating the effects of drought on mental and physical health in rural Australia, little research has examined the effects of flood and drought on wellbeing. This article explores the influence of drought and flood on the wellbeing of rural residents in New South Wales (NSW), Australia. METHODS: Forty-six individuals living in four rural communities in NSW were recruited and asked their experience of flood and drought using in-depth semi-structured face to face interviews or focus groups. The study used a grounded hermeneutic approach to contextualise participants' experiences within a rural social and cultural construct. RESULTS: Weather was found to be at the core of rural life, with flood and drought contributing to decreased wellbeing from stress, anxiety, loss and fear. Social connectedness was found to promote resilience in rural communities buffering the effects of flood and drought. CONCLUSIONS: Flood and drought have negative impacts on an individual's wellbeing. Although these negative effects were seen to be buffered by individual and community resilience, the long term emotional impact of flood and drought on rural communities needs to be further considered.

Ets-1 regulates energy metabolism in cancer cells.

Cancer cells predominantly utilize glycolysis for ATP production even in the presence of abundant oxygen, an environment that would normally result in energy production through oxidative phosphorylation. Although the molecular mechanism for this metabolic switch to aerobic glycolysis has not been fully elucidated, it is likely that mitochondrial damage to the electron transport chain and the resulting increased production of reactive oxygen species are significant driving forces. In this study, we have investigated the role of the transcription factor Ets-1 in the regulation of mitochondrial function and metabolism. Ets-1 was over-expressed using a stably-incorporated tetracycline-inducible expression vector in the ovarian cancer cell line 2008, which does not express detectable basal levels of Ets-1 protein. Microarray analysis of the effects of Ets-1 over-expression in these ovarian cancer cells shows that Ets-1 up-regulates key enzymes involved in glycolysis and associated feeder pathways, fatty acid metabolism, and antioxidant defense. In contrast, Ets-1 down-regulates genes involved in the citric acid cycle, electron transport chain, and mitochondrial proteins. At the functional level, we have found that Ets-1 expression is directly correlated with cellular oxygen consumption whereby increased expression causes decreased oxygen consumption. Ets-1 over-expression also caused increased sensitivity to glycolytic inhibitors, as well as growth inhibition in a glucose-depleted culture environment. Collectively our findings demonstrate that Ets-1 is involved in the regulation of cellular metabolism and response to oxidative stress in ovarian cancer cells.

Mechanisms associated with mitochondrial-generated reactive oxygen species in cancer.

The mitochondria are unique cellular organelles that contain their own genome and, in conjunction with the nucleus, are able to transcribe and translate genes encoding components of the electron transport chain (ETC). To do so, the mitochondria must communicate with the nucleus via the production of reactive oxygen species (ROS) such as hydrogen peroxide (H2O2), which are produced as a byproduct of aerobic respiration within the mitochondria. Mitochondrial signaling is proposed to be altered in cancer cells, where the mitochondria are frequently found to harbor mutations within their genome and display altered functional characteristics leading to increased glycolysis. As signaling molecules, ROS oxidize and inhibit MAPK phosphatases resulting in enhanced proliferation and survival, an effect particularly advantageous to cancer cells. In terms of transcriptional regulation, ROS affect the phosphorylation, activation, oxidation, and DNA binding of transcription factors such as AP-1, NF-kappaB, p53, and HIF-1alpha, leading to changes in target gene expression. Increased ROS production by defective cancer cell mitochondria also results in the upregulation of the transcription factor Ets-1, a factor that has been increasingly associated with aggressive cancers.

VHL promotes E2 box-dependent E-cadherin transcription by HIF-mediated regulation of SIP1 and snail.

The product of the von Hippel-Lindau gene (VHL) acts as the substrate-recognition component of an E3 ubiquitin ligase complex that ubiquitylates the catalytic alpha subunit of hypoxia-inducible factor (HIF) for oxygen-dependent destruction. Although emerging evidence supports the notion that deregulated accumulation of HIF upon the loss of VHL is crucial for the development of clear-cell renal cell carcinoma (CC-RCC), the molecular events downstream of HIF governing renal oncogenesis remain unclear. Here, we show that the expression of a homophilic adhesion molecule, E-cadherin, a major constituent of epithelial cell junctions whose loss is associated with the progression of epithelial cancers, is significantly down-regulated in primary CC-RCC and CC-RCC cell lines devoid of VHL. Reintroduction of wild-type VHL in CC-RCC (VHL(-/-)) cells markedly reduced the expression of E2 box-dependent E-cadherin-specific transcriptional repressors Snail and SIP1 and concomitantly restored E-cadherin expression. RNA interference-mediated knockdown of HIFalpha in CC-RCC (VHL(-/-)) cells likewise increased E-cadherin expression, while functional hypoxia or expression of VHL mutants incapable of promoting HIFalpha degradation attenuated E-cadherin expression, correlating with the disengagement of RNA polymerase II from the endogenous E-cadherin promoter/gene. These findings reveal a critical HIF-dependent molecular pathway connecting VHL, an established "gatekeeper" of the renal epithelium, with a major epithelial tumor suppressor, E-cadherin.

ets-1 is transcriptionally up-regulated by H2O2 via an antioxidant response element.

Expression of the transcription factor Ets-1 is increasingly associated with the progression of several human cancers. A tumor-derived factor is expected to be involved in the inappropriate up-regulation of ets-1 in tumor and surrounding cells. A link between hydrogen peroxide (H2O2) and increased Ets-1 expression has also been suggested, leading to the proposal that this reactive oxygen species (ROS) may be an important factor in directly regulating the expression of ets-1 in tumor cells. Ets-1 expression in response to H2O2 was examined in an ovarian carcinoma cell model, and the genes promoter region was analyzed in order to identify putative elements involved in redox responsiveness. The up-regulation of Ets-1 by H2O2 was confirmed in the cells tested. Luciferase assays using constructs generated to test the contribution of specific promoter elements indicated that an antioxidant response element (ARE) is primarily involved in the H2O2-mediated induction. Gel shift analysis confirmed the increased binding of an Nrf2 containing protein complex to the ets-1 ARE after H2O2 treatment. This study has delineated a key element involved in the transcriptional regulation of ets-1 under basal and induced conditions. Ets-1 has obvious deleterious effects in many cancer cells, and thus, the identification of this regulatory pathway has provided possible targets for manipulating its expression.

Role of the transcription factor Ets-1 in cisplatin resistance.

Cisplatin is a DNA damaging agent widely used as a chemotherapeutic agent. A major limitation of the use of this agent is the development of drug resistance within tumors. Several in vitro models exist which enable the investigation of resistance mechanisms, including 2008/C13* ovarian carcinoma cells. C13* cells are variants of 2008 cells, displaying cisplatin resistance following 13 consecutive cisplatin treatments. This model system has led to the identification of several mechanisms that play parts in the multifactorial nature of cisplatin resistance. In this study, we have examined the contribution of a transcription factor, Ets-1, to the cisplatin resistance of C13* cells. Ets-1 is up-regulated in C13* cells as compared with the cisplatin-sensitive 2008 cells and overexpression of this protein in 2008 cells led to a 7-fold increase in resistance. Further studies on a colorectal carcinoma cell line overexpressing Ets-1 indicated that this phenomenon is not cell specific-increased cisplatin resistance correlated to Ets-1 expression. The mechanism of cisplatin resistance elicited by Ets-1 is potentially via transcriptional activation of genes whose products have well-described functions in reducing cisplatin toxicity. Examples, identified via microarray analysis, include metallothioneins and DNA repair enzymes. This is the first report to our knowledge associating expression of Ets-1, a transcription factor whose expression often signals poor prognosis in various cancer types, to cisplatin resistance.