Intervention effects of Ganoderma lucidum spores on epileptiform discharge hippocampal neurons and expression of Neurotrophin-4 and N-Cadherin

Epilepsy can cause cerebral transient dysfunctions. Ganoderma lucidum spores (GLS), a traditional Chinese medicinal herb, has shown some antiepileptic effects in our previous studies. This was the first study of the effects of GLS on cultured primary hippocampal neurons, treated with Mg2+ free medium. This in vitro model of epileptiform discharge hippocampal neurons allowed us to investigate the anti-epileptic effects and mechanism of GLS activity. Primary hippocampal neurons from <1 day old rats were cultured and their morphologies observed under fluorescence microscope. Neurons were confirmed by immunofluorescent staining of neuron specific enolase (NSE). Sterile method for GLS generation was investigated and serial dilutions of GLS were used to test the maximum non-toxic concentration of GLS on hippocampal neurons. The optimized concentration of GLS of 0.122 mg/ml was identified and used for subsequent analysis. Using the in vitro model, hippocampal neurons were divided into 4 groups for subsequent treatment i) control, ii) model (incubated with Mg2+ free medium for 3 hours), iii) GLS group I (incubated with Mg2+ free medium containing GLS for 3 hours and replaced with normal medium and incubated for 6 hours) and iv) GLS group II (neurons incubated with Mg2+ free medium for 3 hours then replaced with a normal medium containing GLS for 6 hours). Neurotrophin-4 and N-Cadherin protein expression were detected using Western blot. The results showed that the number of normal hippocampal neurons increased and the morphologies of hippocampal neurons were well preserved after GLS treatment. Furthermore, the expression of neurotrophin-4 was significantly increased while the expression of N-Cadherin was decreased in the GLS treated group compared with the model group. This data indicates that GLS may protect hippocampal neurons by promoting neurotrophin-4 expression and inhibiting N-Cadherin expression

Glargine and degludec: solution behaviour of higher dose synthetic insulins

Single, double and triple doses of the synthetic insulins glargine and degludec currently used in patient therapy are characterised using macromolecular hydrodynamic techniques (dynamic light scattering and analytical ultracentrifugation) in an attempt to provide the basis for improved personalised insulin profiling in patients with diabetes. Using dynamic light scattering and sedimentation velocity in the analytical ultracentrifuge glargine was shown to be primarily dimeric under solvent conditions used in current formulations whereas degludec behaved as a dihexamer with evidence of further association of the hexamers (“multi-hexamerisation”). Further analysis by sedimentation equilibrium showed that degludec exhibited reversible interaction between mono- and-di-hexamer forms. Unlike glargine, degludec showed strong thermodynamic non-ideality, but this was suppressed by the addition of salt. With such large injectable doses of synthetic insulins remaining in the physiological system for extended periods of time, in some case 24–40 hours, double and triple dose insulins may impact adversely on personalised insulin profiling in patients with diabetes

Identifying educator behaviours for high quality verbal feedback in health professions education: literature review and expert refinement

Background Health professions education is characterised by work-based learning and relies on effective verbal feedback. However the literature reports problems in feedback practice, including lack of both learner engagement and explicit strategies for improving performance. It is not clear what constitutes high quality, learner-centred feedback or how educators can promote it. We hoped to enhance feedback in clinical practice by distinguishing the elements of an educator’s role in feedback considered to influence learner outcomes, then develop descriptions of observable educator behaviours that exemplify them. Methods An extensive literature review was conducted to identify i) information substantiating specific components of an educator’s role in feedback asserted to have an important influence on learner outcomes and ii) verbal feedback instruments in health professions education, that may describe important educator activities in effective feedback. This information was used to construct a list of elements thought to be important in effective feedback. Based on these elements, descriptions of observable educator behaviours that represent effective feedback were developed and refined during three rounds of a Delphi process and a face-to-face meeting with experts across the health professions and education. Results The review identified more than 170 relevant articles (involving health professions, education, psychology and business literature) and ten verbal feedback instruments in health professions education (plus modified versions). Eighteen distinct elements of an educator’s role in effective feedback were delineated. Twenty five descriptions of educator behaviours that align with the elements were ratified by the expert panel. Conclusions This research clarifies the distinct elements of an educator’s role in feedback considered to enhance learner outcomes. The corresponding set of observable educator behaviours aim to describe how an educator could engage, motivate and enable a learner to improve. This creates the foundation for developing a method to systematically evaluate the impact of verbal feedback on learner performance

Early Treatment with Basal Insulin Glargine in People with Type 2 Diabetes: Lessons from ORIGIN and Other Cardiovascular Trials

Dysglycemia results from a deficit in first-phase insulin secretion compounded by increased insulin insensitivity, exposing beta cells to chronic hyperglycemia and excessive glycemic variability. Initiation of intensive insulin therapy at diagnosis of type 2 diabetes mellitus (T2DM) to achieve normoglycemia has been shown to reverse glucotoxicity, resulting in recovery of residual beta-cell function. The United Kingdom Prospective Diabetes Study (UKPDS) 10-year post-trial follow-up reported reductions in cardiovascular outcomes and all-cause mortality in persons with T2DM who initially received intensive glucose control compared with standard therapy. In the cardiovascular outcome trial, outcome reduction with an initial glargine intervention (ORIGIN), a neutral effect on cardiovascular disease was observed in the population comprising prediabetes and T2DM. Worsening of glycemic control was prevented over the 6.7 year treatment period, with few serious hypoglycemic episodes and only moderate weight gain, with a lesser need for dual or triple oral treatment versus standard care. Several other studies have also highlighted the benefits of early insulin initiation as first-line or add-on therapy to metformin. The decision to introduce basal insulin to metformin must, however be individualized based on a risk-benefit analysis. The landmark ORIGIN trial provides many lessons relating to the concept and application of early insulin therapy for the prevention and safe and effective induction and maintenance of glycemic control in type 2 diabetes

Retinoic acid regulates avian lung branching through a molecular network

Retinoic acid (RA) is of major importance during vertebrate embryonic development and its levels need to be strictly regulated otherwise congenital malformations will develop. Through the action of specific nuclear receptors, named RAR/RXR, RA regulates the expression of genes that eventually influence proliferation and tissue patterning. RA has been described as crucial for different stages of mammalian lung morphogenesis, and as part of a complex molecular network that contributes to precise organogenesis; nonetheless, nothing is known about its role in avian lung development. The current report characterizes, for the first time, the expression pattern of RA signaling members (stra6, raldh2, raldh3, cyp26a1, rar alpha, and rar beta) and potential RA downstream targets (sox2, sox9, meis1, meis2, tgf beta 2, and id2) by in situ hybridization. In the attempt of unveiling the role of RA in chick lung branching, in vitro lung explants were performed. Supplementation studies revealed that RA stimulates lung branching in a dose-dependent manner. Moreover, the expression levels of cyp26a1, sox2, sox9, rar beta, meis2, hoxb5, tgf beta 2, id2, fgf10, fgfr2, and shh were evaluated after RA treatment to disclose a putative molecular network underlying RA effect. In situ hybridization analysis showed that RA is able to alter cyp26a1, sox9, tgf beta 2, and id2 spatial distribution; to increase rar beta, meis2, and hoxb5 expression levels; and has a very modest effect on sox2, fgf10, fgfr2, and shh expression levels. Overall, these findings support a role for RA in the proximal-distal patterning and branching morphogenesis of the avian lung and reveal intricate molecular interactions that ultimately orchestrate branching morphogenesis.The authors would like to thank Ana Lima for slide sectioning and Rita Lopes for contributing to the initiation of this project. This work has been funded by FEDER funds, through the Competitiveness Factors Operational Programme (COMPETE), and by National funds, through the Foundation for Science and Technology (FCT), under the scope of the Project POCI-01-0145-FEDER-007038; and by the Project NORTE-01-0145- FEDER-000013, supported by the Northern Portugal Regional Operational Programme (NORTE 2020), under the Portugal 2020 Partnership Agreement, through the European Regional Development Fund (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.info:eu-repo/semantics/publishedVersio

Sources and Sinks of Diversification and Conservation Priorities for the Mexican Tropical Dry Forest

Elucidating the geographical history of diversification is critical for inferring where future diversification may occur and thus could be a valuable aid in determining conservation priorities. However, it has been difficult to recognize areas with a higher likelihood of promoting diversification. We reconstructed centres of origin of lineages and identified areas in the Mexican tropical dry forest that have been important centres of diversification (sources) and areas where species are maintained but where diversification is less likely to occur (diversity sinks). We used a molecular phylogeny of the genus Bursera, a dominant member of the forest, along with information on current species distributions. Results indicate that vast areas of the forest have historically functioned as diversity sinks, generating few or no extant Bursera lineages. Only a few areas have functioned as major engines of diversification. Long-term preservation of biodiversity may be promoted by incorporation of such knowledge in decision-making

Epidemic infectious gastrointestinal illness aboard U.S. Navy ships deployed to the Middle East during peacetime operations – 2000–2001

BACKGROUND: Infectious gastrointestinal illness (IGI) outbreaks have been reported in U.S. Navy ships and could potentially have an adverse mission impact. Studies to date have been anecdotal. METHODS: We conducted a retrospective analysis of weekly reported disease and non-battle injury health data collected in 2000 – 2001 from 44 U.S. Navy ships while sailing in the 5(th )Fleet (Persian Gulf and nearby seas). RESULTS: During this period, 11 possible IGI outbreaks were identified. Overall, we found 3.3 outbreaks per 100 ship-weeks, a mean outbreak duration of 4.4 weeks, and a mean cumulative ship population attack rate of 3.6%. Morbidity, represented by days lost due to personnel being placed on sick-in-quarters status, was higher during outbreak weeks compared to non-outbreak weeks (p = 0.002). No clear seasonal distribution was identified. CONCLUSION: Explosive outbreaks due to viruses and bacteria with the potential of incapacitating large proportions of the crew raise serious concerns of mission impact and military readiness

Basal plus basal-bolus approach in type 2 diabetes

This is a copy of an article published in the Diabetes Technology and Therapeutics © 2011 [copyright Mary Ann Liebert, Inc.]; Diabetes Technology and Therapeutics is available online at: http://online.liebertpub.com.[EN] Type 2 diabetes is characterized by insulin resistance and progressive b-cell deterioration. As b-cell function declines, most patients with type 2 diabetes treated with oral agents, in monotherapy or combination, will require insulin therapy. Addition of basal insulin (glargine, detemir, or NPH/neutral protamine lispro insulin) to previous treatment is accepted as the simplest way to start insulin therapy in those patients. But even when basal insulin is adequately titrated, some patients will also need prandial insulin to achieve or maintain individual glycemic targets over time. Starting with premixed insulin is an effective option, but it is frequently associated with increased hypoglycemia risk, ¿xed meal schedules, and weight gain. As an alternative, a novel approached known as ``basal plus strategy¿¿ has been developed. This approach considers the addition of increasing injections of prandial insulin, beginning with the meal that has the major impact on postprandial glucose values. Finally, if this is not enough intensi¿cation to basal¿bolus will be necessary. In reducing hyperglycemia, this modality still remains the most effective option, even in people with type 2 diabetes. This article will review the currently evidence on the basal plus strategy and also its progression to basal¿bolus therapy. In addition, practical recommendations to start and adjust basal plus therapy will be provided.F.J.A.-B. has received honoraria as speaker and/or consultant from Abbott, AstraZeneca, Bristol-Myers Squibb, Glaxo-SmithKline, LifeScan, Lilly, Madaus, MannKind Corp., Medtronic, Menarini, Merch Farma y Quimica, SA, MSD, Novartis, Novo Nordisk, Pfizer, Roche, sanofi-aventis, Schering-Plough, and Solvay. In addition, F.J.A.-B. has participated in clinical trials supported totally or partially by AstraZeneca, Glaxo-SmithKline, LifeScan, Lilly, MSD, Novo Nordisk, Pfizer, sanofi-aventis, and Servier. P. R. has no potential conflicts of interest to declare. J.F.A. has received honoraria as speaker and/or consultant form AstraZeneca, Ferrer, Glaxo-SmithKline, Laboratorios Dr. Esteve, Lilly, MSD, and Solvay.Ampudia-Blasco, J.; Rossetti ., P.; Ascaso, JF. (2011). Basal plus basal-bolus approach in type 2 diabetes. Diabetes Technology & Therapeutics. 13:75-83. doi:10.1089/dia.2011.0001S75831