325 research outputs found

    Src Family Kinases and p38 Mitogen-Activated Protein Kinases Regulate Pluripotent Cell Differentiation in Culture

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    Multiple pluripotent cell populations, which together comprise the pluripotent cell lineage, have been identified. The mechanisms that control the progression between these populations are still poorly understood. The formation of early primitive ectoderm-like (EPL) cells from mouse embryonic stem (mES) cells provides a model to understand how one such transition is regulated. EPL cells form from mES cells in response to l-proline uptake through the transporter Slc38a2. Using inhibitors of cell signaling we have shown that Src family kinases, p38 MAPK, ERK1/2 and GSK3β are required for the transition between mES and EPL cells. ERK1/2, c-Src and GSK3β are likely to be enforcing a receptive, primed state in mES cells, while Src family kinases and p38 MAPK are involved in the establishment of EPL cells. Inhibition of these pathways prevented the acquisition of most, but not all, features of EPL cells, suggesting that other pathways are required. L-proline activation of differentiation is mediated through metabolism and changes to intracellular metabolite levels, specifically reactive oxygen species. The implication of multiple signaling pathways in the process suggests a model in which the context of Src family kinase activation determines the outcomes of pluripotent cell differentiation

    Carbon Stocks and Fluxes in Tropical Lowland Dipterocarp Rainforests in Sabah, Malaysian Borneo

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    Deforestation in the tropics is an important source of carbon C release to the atmosphere. To provide a sound scientific base for efforts taken to reduce emissions from deforestation and degradation (REDD+) good estimates of C stocks and fluxes are important. We present components of the C balance for selectively logged lowland tropical dipterocarp rainforest in the Malua Forest Reserve of Sabah, Malaysian Borneo. Total organic C in this area was 167.9 Mg C ha−1±3.8 (SD), including: Total aboveground (TAGC: 55%; 91.9 Mg C ha−1±2.9 SEM) and belowground carbon in trees (TBGC: 10%; 16.5 Mg C ha−1±0.5 SEM), deadwood (8%; 13.2 Mg C ha−1±3.5 SEM) and soil organic matter (SOM: 24%; 39.6 Mg C ha−1±0.9 SEM), understory vegetation (3%; 5.1 Mg C ha−1±1.7 SEM), standing litter (<1%; 0.7 Mg C ha−1±0.1 SEM) and fine root biomass (<1%; 0.9 Mg C ha−1±0.1 SEM). Fluxes included litterfall, a proxy for leaf net primary productivity (4.9 Mg C ha−1 yr−1±0.1 SEM), and soil respiration, a measure for heterotrophic ecosystem respiration (28.6 Mg C ha−1 yr−1±1.2 SEM). The missing estimates necessary to close the C balance are wood net primary productivity and autotrophic respiration

    The worldwide impact of telemedicine during COVID-19: current evidence and recommendations for the future.

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    During the COVID-19 pandemic, telemedicine has emerged worldwide as an indispensable resource to improve the surveillance of patients, curb the spread of disease, facilitate timely identification and management of ill people, but, most importantly, guarantee the continuity of care of frail patients with multiple chronic diseases. Although during COVID-19 telemedicine has thrived, and its adoption has moved forward in many countries, important gaps still remain. Major issues to be addressed to enable large scale implementation of telemedicine include: (1) establishing adequate policies to legislate telemedicine, license healthcare operators, protect patients' privacy, and implement reimbursement plans; (2) creating and disseminating practical guidelines for the routine clinical use of telemedicine in different contexts; (3) increasing in the level of integration of telemedicine with traditional healthcare services; (4) improving healthcare professionals' and patients' awareness of and willingness to use telemedicine; and (5) overcoming inequalities among countries and population subgroups due to technological, infrastructural, and economic barriers. If all these requirements are met in the near future, remote management of patients will become an indispensable resource for the healthcare systems worldwide and will ultimately improve the management of patients and the quality of care

    Telemonitoring Devices and Systems: Current Status and Future Trends

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    In the future, the number of elderly and chronically ill will be quite large. Additionally, pathologies will in many cases be in comorbidity. Alongside this reality, the health care resources will be insufficient for the population, thus the current research for solutions that can be fully implemented in the future. There are available several telemonitoring devices and systems for chronic diseases. Massive use of these devices will be essential to address the current and future lack of health system resources. Research on telemonitoring devices and systems for chronic diseases was con-ducted in academic and scientific databases. The technical specifications were collected in the manufacturers’ web page. The gathered data was analysed and compared in order to propose scenarios for the future trend of technical specifi-cations required in telemonitoring devices/system is performed. Telemonitoring for chronic diseases can bring great benefits to patient and health systems. Widening this practice will be a reality in the near future. This procedure will be fostered by the promotion and regulation of interoperability between de-vices/systems, as well as of front-end programs providing the link between health support systems. Interoperability issues are the main flaw of tedevicesring devices/systems on the market today.info:eu-repo/semantics/publishedVersio

    Telemonitoring Devices and Systems: Current Status and Future Trends

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    In the future, the number of elderly and chronically ill will be quite large. Additionally, pathologies will in many cases be in comorbidity. Along with this reality, the health care resources will be insufficient for the population, thus the current research for technological solutions needs to be implemented in the future. There are available several telemonitoring devices and systems for chronic diseases. Massive use of these devices will be essential to address the current and future lack of health system resources. Research on telemonitoring devices and systems for chronic diseases was conducted in academic and scientific databases. The technical specifications were collected from the manufacturers’ web page. The collected data was analysed and compared in order to propose scenarios for the future trend of technical specifications required in telemonitoring devices/system. Telemonitoring for chronic diseases can bring great benefits to patient and health systems. Widening this practice will be a reality in the near future. This procedure will be fostered by the promotion and regulation of interoperability between devices/systems, as well as of front-end programs providing the link between health support systems. Interoperability issues are the main flaws of telemonitoring devices/systems on the market today.info:eu-repo/semantics/publishedVersio

    Thermal discomfort with cold extremities in relation to age, gender, and body mass index in a random sample of a Swiss urban population

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    <p>Abstract</p> <p>Background</p> <p>The aim of this epidemiological study was to investigate the relationship of thermal discomfort with cold extremities (TDCE) to age, gender, and body mass index (BMI) in a Swiss urban population.</p> <p>Methods</p> <p>In a random population sample of Basel city, 2,800 subjects aged 20-40 years were asked to complete a questionnaire evaluating the extent of cold extremities. Values of cold extremities were based on questionnaire-derived scores. The correlation of age, gender, and BMI to TDCE was analyzed using multiple regression analysis.</p> <p>Results</p> <p>A total of 1,001 women (72.3% response rate) and 809 men (60% response rate) returned a completed questionnaire. Statistical analyses revealed the following findings: Younger subjects suffered more intensely from cold extremities than the elderly, and women suffered more than men (particularly younger women). Slimmer subjects suffered significantly more often from cold extremities than subjects with higher BMIs.</p> <p>Conclusions</p> <p>Thermal discomfort with cold extremities (a relevant symptom of primary vascular dysregulation) occurs at highest intensity in younger, slimmer women and at lowest intensity in elderly, stouter men.</p

    Human Nail Plate Modifications Induced by Onychomycosis : Implications for Topical Therapy

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    Open Access - This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are creditedConclusions: Onchomycotic nails presented a thicker but more porous barrier, and its eroded intracellular matrix rendered the tissue more permeable to topically applied chemicals when an aqueous vehicle was used.Purpose: Through the characterisation of the human onchomycotic nail plate this study aimed to inform the design of new topical ungual formulations.Methods: The mechanical properties of the human nail were characterised using a Lloyd tensile strength tester. The nail’s density was determined via pycnometry and the nail’s ultrastructure by electron microscopy. Raman spectroscopy analysed the keratin disulphide bonds within the nail and its permeability properties were assessed by quantifying water and rhodamine uptake.Results: Chronic in vivo nail plate infection increased human nailplate thickness (healthy 0.49 ± 0.15 mm; diseased 1.20 ± 0.67 mm), but reduced its tensile strength (healthy 63.7 ± 13.4 MPa; diseased 41.7 ± 5.0 MPa) and density (healthy 1.34 ± 0.01 g/cm3; diseased 1.29 ± 0.00 g/cm3). Onchomycosis caused cell-cell separation, without disrupting the nail disulfide bonds or desmosomes. The diseased and healthy nails showed equivalent water uptake profiles, but the rhodamine penetration was 4-fold higher in the diseased nails using a PBS vehicle and 3 -fold higher in an ethanol/PBS vehicle.Peer reviewe

    Nail lacquer films’ surface energies and in vitro water-resistance and adhesion do not predict their in vivo residence

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    The in vivo residence of nail lacquers (which are ideal topical drug carriers for the treatment of nail diseases) determines their frequency of application, and is thereby expected to influence patient adherence and success of treatment. Thus in vitro measurements to indicate lacquers’ in vivo residence are routinely conducted during formulation development. However the literature on in vitro-in vivo correlations is severely limited. Thus, the aim of the work discussed in this paper was to investigate correlations between in vivo residence and in vitro film resistance to water, in vitro film adhesion and surface energy of lacquer films. In vivo measurements were conducted on fingernails in six volunteers. Seven commercially available nail lacquers were tested in commonly-used measurements. Correlations between in vivo residence and in vitro water resistance and adhesion were found to be extremely poor. The surface energies of the lacquer films (which were between 33 and 39 mJ/m2) were also not predictive of in vivo residence. High density polyethylene (HDPE) sheet – whose surface energy was determined to be similar to that of the human nailplate – was found to be a suitable model for the nailplate (when investigating surface energy) and was used in a number of experiments
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