Electronic Structure, Phonons and Dielectric Anomaly in Ferromagnetic Insulating Double Perovskite La2NiMnO6

Using first-principles density functional calculations, we study the electronic and magnetic properties of ferromagnetic insulating double-perovskite compound La2NiMnO6, which has been reported to exhibit interesting magnetic field sensitive dielectric anomaly as a function of temperature. Our study reveals existence of very soft infra-red active phonons that couple strongly with spins at the Ni and Mn sites through modification of the super-exchange interaction. We suggest that these modes are the origin for observed dielectric anomaly in La2NiMnO6.Comment: 4 pages,3 figure

Characterization and evaluation of the performance of starch and cellulose as excipients for direct compression technique

Purpose: To investigate the influence of two often-used excipients (starch and microcrystalline cellulose) on the physical properties of powder blends and tablets that contain mannitol as diluent.Methods: Powder and powder mixtures of three commonly used excipients (starch, mannitol and microcrystalline cellulose) were thoroughly examined using the angle of repose for flowability, particle size analyzer to determine the diameter of the particles, scanning electron microscopy (SEM) for morphological assessment, and x-ray diffraction to determine crystalline/amorphous characteristics. Tablets were prepared by direct compression technique and were evaluated for mechanical strength and disintegration behavior as part of quality control test.Results: The results showed that increase in MCC concentration of the mixture leads to significantly enhanced flowability (p < 0.05) when compared to starch. The angle of repose for mannitol/MCC powder mixture with 70 % w/w MCC was approximately 29°, indicating good flow properties of thepowder mix. Moreover, starch tablets containing MCC exhibited better mechanical strength and longer disintegration time, while, at 1:1 ratio of MCC and mannitol, tablet disintegration was faster (33.0 ± 5.2s)Conclusion: MCC (at 30 %w/w in the blend) produces optimal flow of the powder blend and superior mechanical strength, Keywords: Tablet disintegration, Flowability, Starch, Hardness, Mechanical strengt

Clinical approach to the diagnosis of autoimmune encephalitis in the pediatric patient

Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. Diagnosis of AE in a developing child is challenging because of overlap in clinical presentations with other diseases and complexity of normal behavior changes. Existing diagnostic criteria for adult AE require modification to be applied to children, who differ from adults in their clinical presentations, paraclinical findings, autoantibody profiles, treatment response, and long-term outcomes.A subcommittee of the Autoimmune Encephalitis International Working Group collaborated through conference calls and email correspondence to consider the pediatric-specific approach to AE. The subcommittee reviewed the literature of relevant AE studies and sought additional input from other expert clinicians and researchers.Existing consensus criteria for adult AE were refined for use in children. Provisional pediatric AE classification criteria and an algorithm to facilitate early diagnosis are proposed. There is also discussion about how to distinguish pediatric AE from conditions within the differential diagnosis.Diagnosing AE is based on the combination of a clinical history consistent with pediatric AE and supportive diagnostic testing, which includes but is not dependent on antibody testing. The proposed criteria and algorithm require validation in prospective pediatric cohorts.Copyright © 2020 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology

International Consensus Recommendations for the Treatment of Pediatric NMDAR Antibody Encephalitis.

OBJECTIVE: To create an international consensus treatment recommendation for pediatric NMDA receptor antibody encephalitis (NMDARE). METHODS: After selection of a panel of 27 experts with representation from all continents, a 2-step Delphi method was adopted to develop consensus on relevant treatment regimens and statements, along with key definitions in pediatric NMDARE (disease severity, failure to improve, and relapse). Finally, an online face-to-face meeting was held to reach consensus (defined as ≥75% agreement). RESULTS: Corticosteroids are recommended in all children with NMDARE (pulsed IV preferred), with additional IV immunoglobulin or plasma exchange in severe patients. Prolonged first-line immunotherapy can be offered for up to 3-12 months (oral corticosteroids or monthly IV corticosteroids/immunoglobulin), dependent on disease severity. Second-line treatments are recommended for cases refractory to first-line therapies (rituximab preferred over cyclophosphamide) and should be considered about 2 weeks after first-line initiation. Further immunotherapies for refractory disease 1-3 months after second-line initiation include another second-line treatment (such as cyclophosphamide) and escalation to tocilizumab. Maintenance immune suppression beyond 6 months (such as rituximab redosing or mycophenolate mofetil) is generally not required, except for patients with a more severe course or prolonged impairments and hospitalization. For patients with relapsing disease, second-line and prolonged maintenance therapy should be considered. The treatment of NMDARE following herpes simplex encephalitis should be similar to idiopathic NMDARE. Broad guidance is provided for the total treatment duration (first line, second line, and maintenance), which is dictated by the severity and clinical course (i.e., median 3, 9 and 18 months in the best, average, and worst responders, respectively). Recommendations on the timing of oncologic searches are provided. CONCLUSION: These international consensus recommendations for the management of pediatric NMDARE aim to standardize the treatment and provide practical guidance for clinicians, rather than absolute rules. A similar recommendation could be applicable to adult patients

Global health partnerships for continuing medical education: Lessons from successful partnerships

The past decade has witnessed an increase in global partnerships created to strengthen health systems and provide training to health professionals in low- and middle-income countries. These partnerships are complex interventions. This study focused on unpacking the characteristics of global partnerships that provide continuing education for health professionals. A realist approach underpinned the research design to identify the mechanisms that shape successful global partnerships. Two case studies focusing on global continuing medical education (CME) were studied longitudinally using a realist evaluation approach. To complement that finding, published research reports of global CME partnerships were synthesized using a realist synthesis approach. Data were collected over a three-year period and included interviews, participant observations, document reviews, and surveys. A hybrid thematic approach guided the data analysis. The study results suggested that global CME partnerships are highly dependent on human factors. On the one hand, motivational factors related to individual players help to shape the partnership goals, directions, and outcomes. On the other hand, relational factors such as trust, communication, and understanding play a key role in developing and sustaining global partnerships. As such, these partnerships highly rely on the individuals who champion the partnership at the country level or at the partnership level and in their ability to build relationships as well as empower key stakeholders

Climate Process Team on internal wave–driven ocean mixing

Author Posting. © American Meteorological Society, 2017. This article is posted here by permission of American Meteorological Society for personal use, not for redistribution. The definitive version was published in Bulletin of the American Meteorological Society 98 (2017): 2429-2454, doi:10.1175/BAMS-D-16-0030.1.Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean and, consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Away from ocean boundaries, the spatiotemporal patterns of mixing are largely driven by the geography of generation, propagation, and dissipation of internal waves, which supply much of the power for turbulent mixing. Over the last 5 years and under the auspices of U.S. Climate Variability and Predictability Program (CLIVAR), a National Science Foundation (NSF)- and National Oceanic and Atmospheric Administration (NOAA)-supported Climate Process Team has been engaged in developing, implementing, and testing dynamics-based parameterizations for internal wave–driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here, we review recent progress, describe the tools developed, and discuss future directions.We are grateful to U.S. CLIVAR for their leadership in instigating and facilitating the Climate Process Team program. We are indebted to NSF and NOAA for sponsoring the CPT series.2018-06-0

Valproic Acid Induces Hair Regeneration in Murine Model and Activates Alkaline Phosphatase Activity in Human Dermal Papilla Cells

Alopecia is the common hair loss problem that can affect many people. However, current therapies for treatment of alopecia are limited by low efficacy and potentially undesirable side effects. We have identified a new function for valproic acid (VPA), a GSK3β inhibitor that activates the Wnt/β-catenin pathway, to promote hair re-growth in vitro and in vivo.Topical application of VPA to male C3H mice critically stimulated hair re-growth and induced terminally differentiated epidermal markers such as filaggrin and loricrin, and the dermal papilla marker alkaline phosphatase (ALP). VPA induced ALP in human dermal papilla cells by up-regulating the Wnt/β-catenin pathway, whereas minoxidil (MNX), a drug commonly used to treat alopecia, did not significantly affect the Wnt/β-catenin pathway. VPA analogs and other GSK3β inhibitors that activate the Wnt/β-catenin pathway such as 4-phenyl butyric acid, LiCl, and BeCl(2) also exhibited hair growth-promoting activities in vivo. Importantly, VPA, but not MNX, successfully stimulate hair growth in the wounds of C3H mice.Our findings indicate that small molecules that activate the Wnt/β-catenin pathway, such as VPA, can potentially be developed as drugs to stimulate hair re-growth

Climate Process Team on Internal-Wave Driven Ocean Mixing

Diapycnal mixing plays a primary role in the thermodynamic balance of the ocean, and consequently, in oceanic heat and carbon uptake and storage. Though observed mixing rates are on average consistent with values required by inverse models, recent attention has focused on the dramatic spatial variability, spanning several orders of magnitude, of mixing rates in both the upper and deep ocean. Climate models have been shown to be very sensitive not only to the overall level but to the detailed distribution of mixing; sub-grid-scale parameterizations based on accurate physical processes will allow model forecasts to evolve with a changing climate. Spatio-temporal patterns of mixing are largely driven by the geography of generation, propagation and destruction of internal waves, which are thought to supply much of the power for turbulent mixing. Over the last five years and under the auspices of US CLIVAR, a NSF and NOAA supported Climate Process Team has been engaged in developing, implementing and testing dynamics-base parameterizations for internal-wave driven turbulent mixing in global ocean models. The work has primarily focused on turbulence 1) near sites of internal tide generation, 2) in the upper ocean related to wind-generated near inertial motions, 3) due to internal lee waves generated by low-frequency mesoscale flows over topography, and 4) at ocean margins. Here we review recent progress, describe the tools developed, and discuss future directions

Carbohydrate Metabolism Is Essential for the Colonization of Streptococcus thermophilus in the Digestive Tract of Gnotobiotic Rats

Streptococcus thermophilus is the archetype of lactose-adapted bacterium and so far, its sugar metabolism has been mainly investigated in vitro. The objective of this work was to study the impact of lactose and lactose permease on S. thermophilus physiology in the gastrointestinal tract (GIT) of gnotobiotic rats. We used rats mono-associated with LMD-9 strain and receiving 4.5% lactose. This model allowed the analysis of colonization curves of LMD-9, its metabolic profile, its production of lactate and its interaction with the colon epithelium. Lactose induced a rapid and high level of S. thermophilus in the GIT, where its activity led to 49 mM of intra-luminal L-lactate that was related to the induction of mono-carboxylic transporter mRNAs (SLC16A1 and SLC5A8) and p27Kip1 cell cycle arrest protein in epithelial cells. In the presence of a continuous lactose supply, S. thermophilus recruited proteins involved in glycolysis and induced the metabolism of alternative sugars as sucrose, galactose, and glycogen. Moreover, inactivation of the lactose transporter, LacS, delayed S. thermophilus colonization. Our results show i/that lactose constitutes a limiting factor for colonization of S. thermophilus, ii/that activation of enzymes involved in carbohydrate metabolism constitutes the metabolic signature of S. thermophilus in the GIT, iii/that the production of lactate settles the dialogue with colon epithelium. We propose a metabolic model of management of carbohydrate resources by S. thermophilus in the GIT. Our results are in accord with the rationale that nutritional allegation via consumption of yogurt alleviates the symptoms of lactose intolerance