Rural-Urban Transition and Food Security in India (MiFood Paper No. 12)

As a growing proportion of world’s population lives in cities and towns, food security is increasingly acquiring an urban character. The locus of food security research and policy agendas has correspondingly expanded from rural areas to include cities and towns in the past few years. However, the dominant discourse on urbanization-food security relationship appears to be shaped by perspectives from the Global North and large cities, and shows a lack of adequate understanding of the urbanization-food security nexus in the small towns of the Global South. This paper aims to correct this bias. With a focus on India where urban growth is increasingly concentrated in small, former rural regions, this paper reviews the food and nutrition security implications of the country’s rural-urban transition. It identifies three conceptual pathways through which to understand the bearing of rural-urban transition on food and nutrition security that include: livelihood change, land use change, and dietary change. The evidence reviewed suggests the overall worsening of food and nutrition security for people in this rural-urban transition, particularly for the poor populations. The paper also identifies several key research questions and calls for more research on the urbanization-food security nexus in India

Dynamic association of the H3K64 trimethylation mark with genes encoding exported proteins in Plasmodium falciparum

Epigenetic modifications have emerged as critical regulators of virulence genes and stage-specific gene expression in Plasmodium falciparum. However, the specific roles of histone core epigenetic modifications in regulating the stage-specific gene expression are not well understood. In this study, we report an unconventional trimethylation at lysine 64 on histone 3 (H3K64me3) and characterize its functional relevance in P. falciparum. We show that PfSET4 and PfSET5 proteins of P. falciparum methylate H3K64 and that they prefer the nucleosome as a substrate over free histone 3 proteins. Structural analysis of PfSET5 revealed that it interacts with the nucleosome as a dimer. The H3K64me3 mark is dynamic, being enriched in the ring and trophozoite stages and drastically reduced in the schizont stages. Stage-specific global chromatin immunoprecipitation -sequencing analysis of the H3K64me3 mark revealed the selective enrichment of this methyl mark on the genes of exported family proteins in the ring and trophozoite stages and a significant reduction of the same in the schizont stages. Collectively, our data identify a novel epigenetic mark that is associated with the subset of genes encoding for exported proteins, which may regulate their expression in different stages of P. falciparum.</p

Temporal Trends and Factors Associated with Bisphosphonate Discontinuation and Restart

Adverse events related to long-term use of bisphosphonates have raised interest in temporary drug discontinuation. Trends in bisphosphonate discontinuation and restart, as well factors associated with these decisions, are not fully understood at a population level. We investigated temporal trends of bisphosphonate discontinuation from 2010 to 2015 and identified factors associated with discontinuation and restart of osteoporosis therapy. Our cohort consisted of long-term bisphosphonate users identified from 2010 to 2015 Medicare data. We defined discontinuation as 6512\u2009months without bisphosphonate prescription claims. We used conditional logistic regression to compare factors associated with alendronate discontinuation or osteoporosis therapy restart in the 120-day period preceding discontinuation or restart referent to the 120-day preceding control periods. Among 73,800 long-term bisphosphonate users, 59,251 (80.3%) used alendronate, 6806 (9.2%) risedronate, and 7743 (10.5%) zoledronic acid, exclusively. Overall, 26,281 (35.6%) discontinued bisphosphonates for at least 12\u2009months. Discontinuation of bisphosphonates increased from 1.7% in 2010, reaching a peak of 14% in 2012 with levels plateauing through 2015. The factors most strongly associated with discontinuation of alendronate were: benzodiazepine prescription (adjusted odds ratio [aOR] = 2.5; 95% confidence interval [CI] 2.1, 3.0), having a dual-energy X-ray absorptiometry (DXA) scan (aOR = 1.8; 95% CI 1.7, 2.0), and skilled nursing facility care utilization (aOR = 1.8; 95% CI 1.6, 2.1). The factors most strongly associated with restart of osteoporosis therapy were: having a DXA scan (aOR = 9.9; 95% CI 7.7, 12.6), sustaining a fragility fracture (aOR = 2.8; 95% CI 1.8, 4.5), and an osteoporosis or osteopenia diagnosis (aOR = 2.5; 95% CI 2.0, 3.1). Our national evaluation of bisphosphonate discontinuation showed that an increasing proportion of patients on long-term bisphosphonate therapy discontinue medications. The factors associated with discontinuation of alendronate were primarily related to worsening of overall health status, whereas traditional factors associated with worsening bone health were associated with restarting osteoporosis medication. \ua9 2019 American Society for Bone and Mineral Research

Head CT is of limited diagnostic value in critically ill patients who remain unresponsive after discontinuation of sedation

<p>Abstract</p> <p>Background</p> <p>Prolonged sedation is common in mechanically ventilated patients and is associated with increased morbidity and mortality. We sought to determine the diagnostic value of head computed tomography (CT) in mechanically ventilated patients who remain unresponsive after discontinuation of sedation.</p> <p>Methods</p> <p>A retrospective review of adult (age >18 years of age) patients consecutively admitted to the medical intensive care unit of a tertiary care medical center. Patients requiring mechanical ventilation for management of respiratory failure for longer than 72 hours were included in the study group. A group that did not have difficulty with awakening was included as a control.</p> <p>Results</p> <p>The median time after sedation was discontinued until a head CT was performed was 2 days (interquartile range 1.375–2 days). Majority (80%) of patients underwent head CT evaluation within the first 48 hours after discontinuation of sedation. Head CT was non-diagnostic in all but one patient who had a small subarachnoid hemorrhage. Twenty-five patients (60%) had a normal head CT. Head CT findings did not alter the management of any of the patients. The control group was similar to the experimental group with respect to demographics, etiology of respiratory failure and type of sedation used. However, while 37% of subjects in the control group had daily interruption of sedation, only 19% in the patient group had daily interruption of sedation (p < 0.05).</p> <p>Conclusion</p> <p>In patients on mechanical ventilation for at least 72 hours and who remain unresponsive after sedative discontinuation and with a non-focal neurologic examination, head CT is performed early and is of very limited diagnostic utility. Routine use of daily interruption of sedation is used in a minority of patients outside of a clinical trial setting though it may decrease the frequency of unresponsiveness from prolonged sedation and the need for head CT in patients mechanically ventilated for a prolonged period.</p

LKB1/KRAS mutant lung cancers constitute a genetic subset of NSCLC with increased sensitivity to MAPK and mTOR signalling inhibition

LKB1/STK11 is a multitasking tumour suppressor kinase. Germline inactivating mutations of the gene are responsible for the Peutz-Jeghers hereditary cancer syndrome. It is also somatically inactivated in approximately 30% of non-small-cell lung cancer (NSCLC). Here, we report that LKB1/KRAS mutant NSCLC cell lines are sensitive to the MEK inhibitor CI-1040 shown by a dose-dependent reduction in proliferation rate, whereas LKB1 and KRAS mutations alone do not confer similar sensitivity. We show that this subset of NSCLC is also sensitised to the mTOR inhibitor rapamycin. Importantly, the data suggest that LKB1/KRAS mutant NSCLCs are a genetically and functionally distinct subset and further suggest that this subset of lung cancers might afford an opportunity for exploitation of anti-MAPK/mTOR-targeted therapies