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Open Reading Frame brings together a selection of recent publication highlights from elsewhere in the open access ecosystem. This week we take a look at the past few weeks in medicine.


Age, physical activity and prediabetes
The prevalence of prediabetes – often described as the ’grey area’ between normal blood sugar and diabetic levels – has increased substantially in the USA in the past 20 years. Low levels of physical activity (PA) have been identified as a key driver of hyperglycemia in type 2 diabetes. Now, new research has been carried out in the US to examine the link between PA and prediabetes. The researchers separated PA levels into three groups and found that participants in the highest PA tertile group were significantly less likely to have prediabetes than those in the lowest tertile. Adjusted analyses indicated that this association is independent of adiposity, but confounded by age and body mass index. In light of the close link between age and physical inactivity, the authors conclude that early PA interventions should be prioritized to decrease the risk of prediabetes and prevent the onset of physical disability in older people.
Farni et al. PeerJ


Managing pediatric UTIs
Urinary tract infections (UTIs) are common in children, affecting seven percent of girls and two percent of boys under six years of age. In addition to causing acute symptoms, it has been suggested that childhood UTIs could be linked to renal scarring and dysfunction later in life. In a review article, doctors from the UK and Trinidad and Tobego discuss the different antibiotic options for treating pediatric UTIs, considering the balance between resolving the infection and reducing antibiotic resistance and the side effects of treatment. The authors highlight that it is important to rationalize antibiotic choice to prevent the emergence of antibiotic-resistant UTI pathogens.
Ramlakhan et al. Clinical Medicine Insights: Pediatrics


ALK7: a new anti-obesity target?
Researchers have identified a possible new link between nutrient overload and lipid accumulation in obesity. β-adrenoceptor-mediated lipolysis, a chemical reaction that breaks down lipids, is impaired in those with obesity, but the mechanisms behind this are not well understood. The new study, carried out in mice lacking the Alk7 gene, revealed that a loss of ALK7 leads to increased lipolysis and resistance to diet-induced obesity. Furthermore, inhibition of ALK7 using a chemical-genetic approach reduced weight gain and fat accumulation in overfed mice. Together, these results suggest that ALK7-mediated signaling contributes to lipid accumulation, indicating that this protein could be targeted in pharmacological interventions against obesity.
Guo et al. eLife


Endothelial dysfunction: a marker of osteoporosis development?
Accumulating evidence suggests a link between coronary artery atherosclerosis and osteoporosis in women. Now, a study of almost 200 postmenopausal women suggests that coronary microvascular endothelial dysfunction (CMED), a marker of early coronary atherosclerosis, could predict the development of osteoporosis. Women with CMED were found to be twice as likely to develop osteoporosis compared with those without endothelial dysfunction, and this association remained significant after adjusting for confounding factors. These findings suggest that endothelial dysfunction could be an important mechanism linking cardiovascular disease and osteoporosis, and monitoring CMED could predict osteoporosis development in those with endothelial dysfunction.
Prasad et al. Vascular Health and Risk Management


microRNA predictions of chemotherapy response
Breast cancer patients with the luminal A disease type – one of the estrogen receptor-positive breast cancer subtypes – generally respond well to hormonal treatment, but there is a great deal of variety in responses to chemotherapy. It is therefore important to identify which patients are likely to respond well to chemotherapy to avoid the toxic side effects in those unlikely to benefit. In a study of luminal A type breast cancer patients receiving  chemotherapy, women were classified into two groups depending on treatment response, and a number of microRNAs associated with chemosensitivity were identified. miRNA -19a and miRNA-205 had significantly different expression levels across the two groups, and the authors used these microRNAs to create a predictive model of chemotherapy response. These findings suggest that measuring miRNA-19a and miRNA-205a levels in the blood could predict individual patients’ response to chemotherapy, allowing prioritization of chemotherapy for those likely to benefit.
Li et al. PLOS One


Overcoming resistance to targeted lung cancer therapy
Targeted therapies have greatly impacted the treatment of advanced non-small cell lung cancer (NSCLC), which accounts for around 85 percent of lung cancer cases. Epidermal growth factor receptor (EGFR) inhibitors and anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors are used to treat NSCLC patients with mutations in the corresponding genes, but therapeutic resistance often occurs within a year of starting treatment. There are many strategies currently underway to overcome EGFR and ALK inhibitor resistance; in a mini review, Johanna Spaans and Glenwood Goss outline clinical trials of novel agents to overcome resistance to these targeted therapies, including the angiokinase inhibitor afatinib and second generation EGFR inhibitors such as dacomitinib. The authors highlight that knowledge gained from investigating EGFR and ALK inhibitors can be applied to testing future therapies targeting newly discovered genetic alterations in NSCLC.
Spaans and Goss. Frontiers in Oncology


Written by Claire Barnard, Senior Editor for BMC Medicine.


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