The Effect of Structured Exercise Compared with Education on Neuropathic Signs and Symptoms in People at Risk of Neuropathic Diabetic Foot Ulcers: A Randomized Clinical Trial

Background and Objectives: Lifestyle interventions such as exercise prescription and education may play a role in the management of peripheral neuropathy in people with diabetes. The aim of this study was to determine the effect of undertaking an exercise program in comparison with an education program on the signs and symptoms of peripheral neuropathy in people with diabetes at risk of neuropathic foot ulceration. Materials and Methods: Twenty-four adult participants with diabetes and peripheral neuropathy were enrolled in this parallel-group, assessor blinded, randomised clinical trial. Participants were randomly allocated to one of two 8-week lifestyle interventions, exercise or education. The primary outcome measures were the two-part Michigan Neuropathy Screening Instrument (MNSI) and vibratory perception threshold (VPT). Secondary outcome measures included aerobic fitness, balance and lower limb muscular endurance. Results: Participants in both lifestyle interventions significantly improved over time for MNSI clinical signs (MD: −1.04, 95% CI: −1.68 to −0.40), MNSI symptoms (MD: −1.11, 95% CI: −1.89 to −0.33) and VPT (MD: −4.22, 95% CI: −8.04 to −0.40). Although the interaction effects did not reach significance, changes in values from pre to post intervention favoured exercise in comparison to control for MNSI clinical signs (MD −0.42, 95% CI −1.72 to 0.90), MNSI clinical symptoms (MD −0.38, 95% CI −1.96 to 1.2) and VPT (MD −4.22, 95% CI −12.09 to 3.65). Conclusions: Eight weeks of exercise training or lifestyle education can improve neuropathic signs and symptoms in people with diabetes and peripheral neuropathy. These findings support a role for lifestyle interventions in the management of peripheral neuropathy

Detection of Genetically Altered Copper Levels in Drosophila Tissues by Synchrotron X-Ray Fluorescence Microscopy

Tissue-specific manipulation of known copper transport genes in Drosophila tissues results in phenotypes that are presumably due to an alteration in copper levels in the targeted cells. However direct confirmation of this has to date been technically challenging. Measures of cellular copper content such as expression levels of copper-responsive genes or cuproenzyme activity levels, while useful, are indirect. First-generation copper-sensitive fluorophores show promise but currently lack the sensitivity required to detect subtle changes in copper levels. Moreover such techniques do not provide information regarding other relevant biometals such as zinc or iron. Traditional techniques for measuring elemental composition such as inductively coupled plasma mass spectroscopy are not sensitive enough for use with the small tissue amounts available in Drosophila research. Here we present synchrotron x-ray fluorescence microscopy analysis of two different Drosophila tissues, the larval wing imaginal disc, and sectioned adult fly heads and show that this technique can be used to detect changes in tissue copper levels caused by targeted manipulation of known copper homeostasis genes

American mastodon extirpation in the Arctic and Subarctic predates human colonization and terminal Pleistocene climate change

Existing radiocarbon ((14)C) dates on American mastodon (Mammut americanum) fossils from eastern Beringia (Alaska and Yukon) have been interpreted as evidence they inhabited the Arctic and Subarctic during Pleistocene full-glacial times (∼ 18,000 (14)C years B.P.). However, this chronology is inconsistent with inferred habitat preferences of mastodons and correlative paleoecological evidence. To establish a last appearance date (LAD) for M. americanum regionally, we obtained 53 new (14)C dates on 36 fossils, including specimens with previously published dates. Using collagen ultrafiltration and single amino acid (hydroxyproline) methods, these specimens consistently date to beyond or near the ∼ 50,000 y B.P. limit of (14)C dating. Some erroneously "young" (14)C dates are due to contamination by exogenous carbon from natural sources and conservation treatments used in museums. We suggest mastodons inhabited the high latitudes only during warm intervals, particularly the Last Interglacial [Marine Isotope Stage (MIS) 5] when boreal forests existed regionally. Our (14)C dataset suggests that mastodons were extirpated from eastern Beringia during the MIS 4 glacial interval (∼ 75,000 y ago), following the ecological shift from boreal forest to steppe tundra. Mastodons thereafter became restricted to areas south of the continental ice sheets, where they suffered complete extinction ∼ 10,000 (14)C years B.P. Mastodons were already absent from eastern Beringia several tens of millennia before the first humans crossed the Bering Isthmus or the onset of climate changes during the terminal Pleistocene. Local extirpations of mastodons and other megafaunal populations in eastern Beringia were asynchrononous and independent of their final extinction south of the continental ice sheets

Enhanced El Nino-Southern Oscillation Variability in Recent Decades

The El Nino-Southern Oscillation (ENSO) represents the largest source of year-to-year global climate variability. While Earth system models suggest a range of possible shifts in ENSO properties under continued greenhouse gas forcing, many centuries of preindustrial climate data are required to detect a potential shift in the properties of recent ENSO extremes. Here we reconstruct the strength of ENSO variations over the last 7,000 years with a new ensemble of fossil coral oxygen isotope records from the Line Islands, located in the central equatorial Pacific. The corals document a significant decrease in ENSO variance of similar to 20% from 3,000 to 5,000 years ago, coinciding with changes in spring/fall precessional insolation. We find that ENSO variability over the last five decades is similar to 25% stronger than during the preindustrial. Our results provide empirical support for recent climate model projections showing an intensification of ENSO extremes under greenhouse forcing. Plain Language Summary Recent modeling studies suggest that El Nino will intensify due to greenhouse warming. Here new coral reconstructions of the El Nino-Southern Oscillation (ENSO) record sustained, significant changes in ENSO variability over the last 7,000 years and imply that ENSO extremes of the last 50 years are significantly stronger than those of the preindustrial era in the central tropical Pacific. These records suggest that El Nino events already may be intensifying due to anthropogenic climate change

American mastodon extirpation in the Arctic and Subarctic predates human colonization and terminal Pleistocene climate change

Existing radiocarbon ((14)C) dates on American mastodon (Mammut americanum) fossils from eastern Beringia (Alaska and Yukon) have been interpreted as evidence they inhabited the Arctic and Subarctic during Pleistocene full-glacial times (∼18,000 (14)C years B.P.). However, this chronology is inconsistent with inferred habitat preferences of mastodons and correlative paleoecological evidence. To establish a last appearance date (LAD) for M. americanum regionally, we obtained 53 new (14)C dates on 36 fossils, including specimens with previously published dates. Using collagen ultrafiltration and single amino acid (hydroxyproline) methods, these specimens consistently date to beyond or near the ∼50,000 y B.P. limit of (14)C dating. Some erroneously “young” (14)C dates are due to contamination by exogenous carbon from natural sources and conservation treatments used in museums. We suggest mastodons inhabited the high latitudes only during warm intervals, particularly the Last Interglacial [Marine Isotope Stage (MIS) 5] when boreal forests existed regionally. Our (14)C dataset suggests that mastodons were extirpated from eastern Beringia during the MIS 4 glacial interval (∼75,000 y ago), following the ecological shift from boreal forest to steppe tundra. Mastodons thereafter became restricted to areas south of the continental ice sheets, where they suffered complete extinction ∼10,000 (14)C years B.P. Mastodons were already absent from eastern Beringia several tens of millennia before the first humans crossed the Bering Isthmus or the onset of climate changes during the terminal Pleistocene. Local extirpations of mastodons and other megafaunal populations in eastern Beringia were asynchrononous and independent of their final extinction south of the continental ice sheets