Health Status and Associated factors of middle-aged and Older Adult Cancer Survivors in India : Results from the Longitudinal Ageing Study in India

Funding This study was funded by the Scottish Funding council’s Global Challenges Research Fund Pump Priming Grant (SF10206–53). The funders had no role in the data analysis or decision to publish.Peer reviewedPublisher PD

An Antagomir to MicroRNA Let7f Promotes Neuroprotection in an Ischemic Stroke Model

We previously showed that middle-aged female rats sustain a larger infarct following experimental stroke as compared to younger female rats, and paradoxically, estrogen treatment to the older group is neurotoxic. Plasma and brain insulin-like growth factor-1 (IGF-1) levels decrease with age. However, IGF-1 infusion following stroke, prevents estrogen neurotoxicity in middle-aged female rats. IGF1 is neuroprotective and well tolerated, but also has potentially undesirable side effects. We hypothesized that microRNAs (miRNAs) that target the IGF-1 signaling family for translation repression could be alternatively suppressed to promote IGF-1-like neuroprotection. Here, we report that two conserved IGF pathway regulatory microRNAs, Let7f and miR1, can be inhibited to mimic and even extend the neuroprotection afforded by IGF-1. Anti-mir1 treatment, as late as 4 hours following ischemia, significantly reduced cortical infarct volume in adult female rats, while anti-Let7 robustly reduced both cortical and striatal infarcts, and preserved sensorimotor function and interhemispheric neural integration. No neuroprotection was observed in animals treated with a brain specific miRNA unrelated to IGF-1 (anti-miR124). Remarkably, anti-Let7f was only effective in intact females but not males or ovariectomized females indicating that the gonadal steroid environment critically modifies miRNA action. Let7f is preferentially expressed in microglia in the ischemic hemisphere and confirmed in ex vivo cultures of microglia obtained from the cortex. While IGF-1 was undetectable in microglia harvested from the non-ischemic hemisphere, IGF-1 was expressed by microglia obtained from the ischemic cortex and was further elevated by anti-Let7f treatment. Collectively these data support a novel miRNA-based therapeutic strategy for neuroprotection following stroke

A Dominant Negative ERβ Splice Variant Determines the Effectiveness of Early or Late Estrogen Therapy after Ovariectomy in Rats

The molecular mechanisms for the discrepancy in outcome of initiating estrogen therapy (ET) around peri-menopause or several years after menopause in women are unknown. We hypothesize that the level of expression of a dominant negative estrogen receptor (ER) β variant, ERβ2, may be a key factor determining the effectiveness of ET in post-menopausal women. We tested this hypothesis in ovariectomized nine month-old (an age when irregular estrous cycles occur) female Sprague Dawley rats. Estradiol treatment was initiated either 6 days (Early ET, analogous to 4 months post-menopause in humans), or 180 days (Late ET, analogous to 11 years post-menopause in humans) after ovariectomy. Although ERβ2 expression increased in all OVX rats, neurogenic and neuroprotective responses to estradiol differed in Early and Late ET. Early ET reduced ERβ2 expression in both hippocampus and white blood cells, increased the hippocampal cell proliferation as assessed by Ki-67 expression, and improved mobility in the forced swim test. Late ET resulted in either no or modest effects on these parameters. There was a close correlation between the degree of ERβ2 expression and the preservation of neural effects by ET after OVX in rats, supporting the hypothesis that persistent elevated levels of ERβ2 are a molecular basis for the diminished effectiveness of ET in late post-menopausal women. The correlation between the expression of ERβ2 in circulating white blood cells and brain cells suggests that ERβ2 expression in peripheral blood cells may be an easily accessible marker to predict the effective window for ET in the brain

The Immune System in Stroke

Stroke represents an unresolved challenge for both developed and developing countries and has a huge socio-economic impact. Although considerable effort has been made to limit stroke incidence and improve outcome, strategies aimed at protecting injured neurons in the brain have all failed. This failure is likely to be due to both the incompleteness of modelling the disease and its causes in experimental research, and also the lack of understanding of how systemic mechanisms lead to an acute cerebrovascular event or contribute to outcome. Inflammation has been implicated in all forms of brain injury and it is now clear that immune mechanisms profoundly influence (and are responsible for the development of) risk and causation of stroke, and the outcome following the onset of cerebral ischemia. Until very recently, systemic inflammatory mechanisms, with respect to common comorbidities in stroke, have largely been ignored in experimental studies. The main aim is therefore to understand interactions between the immune system and brain injury in order to develop novel therapeutic approaches. Recent data from clinical and experimental research clearly show that systemic inflammatory diseases -such as atherosclerosis, obesity, diabetes or infection - similar to stress and advanced age, are associated with dysregulated immune responses which can profoundly contribute to cerebrovascular inflammation and injury in the central nervous system. In this review, we summarize recent advances in the field of inflammation and stroke, focusing on the challenges of translation between pre-clinical and clinical studies, and potential anti-inflammatory/immunomodulatory therapeutic approaches

Socioeconomic patterns of underweight and its association with self-rated health, cognition and quality of life among older adults in India

<div><p>Background</p><p>Underweight defined as body mass index (BMI) < 18.5 is associated with negative health and quality of life outcomes including mortality. Yet, little is known about the socioeconomic differentials in underweight and its association with health and well-being among older adults in India. This study examined the socioeconomic differentials in underweight among respondents aged ≥50 in India. Consequently, three outcomes of the association of underweight were studied. These are poor self-rated health, cognition and quality of life.</p><p>Methods</p><p>Cross-sectional data on 6,372 older adults derived from the first wave of the WHO’s Study on global AGEing and adult health (SAGE), a nationally representative survey conducted in six states of India during 2007–8, were used. Bivariate and multivariate regression analyses were applied to fulfil the objectives.</p><p>Results</p><p>The overall prevalence of underweight was 38 percent in the study population. Further, socioeconomic status showed a significant and negative association with underweight. The association of underweight with poor self-rated health (OR = 1.60; <i>p</i> < .001), cognition (β = –0.95; <i>p</i> < .001) and quality of life (β = –1.90; <i>p</i> < .001) were remained statistically significant after adjusting for age, sex, place of residence, marital status, years of schooling, wealth quintile, sleep problems, chronic diseases, low back pain and state/province.</p><p>Conclusion</p><p>The results indicated significant socioeconomic differentials in underweight and its association with poor self-rated health, cognition and quality of life outcomes. Interventions focussing on underweight older adults are important to enhance the overall wellbeing of the growing older population in India.</p></div

Multivariable regression analysis of the association of underweight with poor self-rated health, cognition and quality of life.

<p>Multivariable regression analysis of the association of underweight with poor self-rated health, cognition and quality of life.</p

Sociodemographic characteristics of the study population by body mass index category (Weighted %).

<p>Sociodemographic characteristics of the study population by body mass index category (Weighted %).</p

Weighted prevalence of poor self-rated health (SRH), mean cognition and quality of life (QoL) scores by body mass index category.

<p>Weighted prevalence of poor self-rated health (SRH), mean cognition and quality of life (QoL) scores by body mass index category.</p

Multinomial logistic regression coefficient and confidence interval of BMI by socioeconomic and demographic characteristics.

<p>Multinomial logistic regression coefficient and confidence interval of BMI by socioeconomic and demographic characteristics.</p