Treating the full humanity of our patients by acknowledging our limitations

A reflection on a clinical experience with a severely anemic Jehovah\u27s Witness Patient who refused blood transfusion

Evaluating Split Timing Fertilizer Applications for Improving Bread Baking Quality of Soft Red Winter Wheat in Kentucky

There is growing interest among farmers to locally produce high protein and strong gluten wheat that is suitable for bread making and meet the demand of local artisanal bakers in Kentucky. The warm and humid weather in southeast region is ideal for soft red winter wheat (SRW) production which characterized by low protein content. The technique of splitting nitrogen (N) fertilization according to the growth stages has been suggested to improve protein content and its composition. This study evaluated the effect of split N application on yield and baking quality traits of two SRW wheat cultivars grown in the eastern U.S. region in conventional and organic cropping systems. One landrace (Purple Straw) and one modern cultivar (Pembroke 2014 ) were grown under three split N application treatments (ST1, ST2 and ST3). Late N applications (ST3) significantly increased protein content for both years by 5.45% and 6.11% respectively compared to a single application; however, this treatment decreased yield. The cropping system had consistent effects in that the conventional system exceeded organic system except for thousand kernel weight. Conventional system had greater yield by 16.11% and 20.17% respectively for both years than organic system. Similarly, sedimentation value (a baking quality trait) was greater by 14.27% and 11.12% respectively in conventional than organic system. This study has generally found improvement in protein content by N application on soft red winter wheat. In addition, more studies should be done on the organic systems to examine other baking quality traits

Effect of Biofertilizer in Organic and Conventional Systems on Growth, Yield and Baking Quality of Hard Red Winter Wheat

A two-year study (harvest years 2019 and 2020) was conducted to investigate the effect of a commercially available biofertilizer, in combination with variable nitrogen (N) rate, on bread baking quality and agronomic traits in hard winter wheat grown in conventional (CONV) and organic (ORG) farming systems in Kentucky, USA. The hard red winter wheat cultivar ‘Vision 45’ was used with three N rates (44, 89.6 and 134.5 kg/ha as Low, Med and High, respectively) and three biofertilizer spray regimes (no spray, one spray and two sprays). All traits measured were significantly affected by the agricultural production system (CONV or ORG) and N rate, although trends in their interactions were inconsistent between years. In Y2, yield was greatest in treatments with high N rates and in the ORG system. Biofertilizer treatments had a negative to neutral effect on grain yield. Baking quality traits such as protein content, lactic acid solvent retention capacity and sedimentation value (SV) were consistently greater in the CONV system and increased with the higher N application rates. Similarly, biofertilizer application had no effect on predictive baking quality traits, except for SV in year 1 of the study, where it increased with two sprays. Loaf volume was consistently greater from wheat grown in CONV treatments. From these results, we conclude that further research is warranted to evaluate the potential for biofertilizers to enhance N uptake and affect bread baking quality or other end-use traits. Additional research may be especially useful in organic production systems where biologically based N fertilizers are utilized, and treatments were not negatively affected by biofertilizer applications. Such strategies may be needed to increase protein quantity and gluten quality to optimize winter wheat production for bread baking qualities in the southeastern USA

Impact of Nitrogen Rate in Conventional and Organic Production Systems on Yield and Bread Baking Quality of Soft Red Winter Wheat

Soft red winter wheat (SRW) is characterized by high yield and relatively low protein content. In Kentucky, there is growing demand from local artisan bread bakers for regionally produced flour, requiring production of grain with increased protein content and/or strength. The objective of this two-year field experiment was to evaluate the effect of nitrogen (N) management on five cultivars of winter wheat on yield and bread baking quality traits of modern and landrace SRW cultivars (Triticum aestivum L.). All five cultivars were evaluated using two N application rates in conventional and organic production systems. All traits measured were significantly affected by the agricultural production system and N rate, although plant height and other quality traits varied by study year. Significantly higher yields were achieved in the conventional system at a relatively low N rate (67.2 kg ha−1) in both study years (2017–2019) (p \u3c 0.01). Results were variable by cultivar and a locally bred, high-yielding cultivar (Pembroke 2014) had the highest lactic acid solvent retention capacity score and thousand kernel weight of the cultivars evaluated. In addition, a landrace cultivar (Purple Straw) had the highest grain N and plant height. A French soft wheat, Soissons, had the highest sedimentation value and Pembroke 2016 achieved the highest yield. The findings from this study suggest the possibility of attaining a desirable grain with quality traits of SRW wheat that meets the needs of local bread wheat production in Kentucky through improving the optimization of cultivar selection, N management and specific considerations for conventional and organic systems

Desert palm date seeds as a biodiesel feedstock:Extraction, characterization, and engine testing

The development of alternative fuels is increasingly important in order to maintain ongoing global economic and technological progress in the face of fossil fuel depletion and increasing environmental damage. Desert palm date seeds have clear potential as feedstock for biodiesel production given their high oil content and availability as food waste that requires no further cultivation. In this study we investigated the optimum production processes and conditions for date seed oil biodiesel, including characterizing the intermediate product and correcting its composition to meet international fuel standards. Four biodiesel blends were prepared (B5, B10, B15, and B20) and tested in a compression ignition engine at engine speeds from 1600 to 3600 rpm (200 rpm increments) and three engine loads (50%, 75%, and 100%). The highest oil yield and biodiesel conversion achieved were 10.74 wt.% and 92%, respectively. The biodiesel properties conformed well with the standards; the values for brake power, brake thermal efficiency, and brake specific fuel consumption were comparable with petrol diesel, though the latter was slightly superior. All blends produced lower levels of CO2, CO, and HC but higher levels of NOx emissions. These results demonstrate the fundamental suitability of date seeds as biodiesel feedstock, deserving of further research

Bruton's Tyrosine Kinase Inhibition Attenuates the Cardiac Dysfunction Caused by Cecal Ligation and Puncture in Mice

Sepsis is one of the most prevalent diseases in the world. The development of cardiac dysfunction in sepsis results in an increase of mortality. It is known that Bruton's tyrosine kinase (BTK) plays a role in toll-like receptor signaling and NLRP3 inflammasome activation, two key components in the pathophysiology of sepsis and sepsis-associated cardiac dysfunction. In this study we investigated whether pharmacological inhibition of BTK (ibrutinib 30 mg/kg and acalabrutinib 3 mg/kg) attenuates sepsis associated cardiac dysfunction in mice. 10-week old male C57BL/6 mice underwent CLP or sham surgery. One hour after surgery mice received either vehicle (5% DMSO + 30% cyclodextrin i.v.), ibrutinib (30 mg/kg i.v.), or acalabrutinib (3 mg/kg i.v.). Mice also received antibiotics and an analgesic at 6 and 18 h. After 24 h, cardiac function was assessed by echocardiography in vivo. Cardiac tissue underwent western blot analysis to determine the activation of BTK, NLRP3 inflammasome and NF-\u3baB pathway. Serum analysis of 33 cytokines was conducted by a multiplex assay. When compared to sham-operated animals, mice subjected to CLP demonstrated a significant reduction in ejection fraction (EF), fractional shortening (FS), and fractional area change (FAC). The cardiac tissue from CLP mice showed significant increases of BTK, NF-\u3baB, and NLRP3 inflammasome activation. CLP animals resulted in a significant increase of serum cytokines and chemokines (TNF-\u3b1, IL-6, IFN-\u3b3, KC, eotaxin-1, eotaxin-2, IL-10, IL-4, CXCL10, and CXCL11). Delayed administration of ibrutinib and acalabrutinib attenuated the decline of EF, FS, and FAC caused by CLP and also reduced the activation of BTK, NF-\u3baB, and NLRP3 inflammasome. Both ibrutinib and acalabrutinib significantly suppressed the release of cytokines and chemokines. Our study revealed that delayed intravenous administration of ibrutinib or acalabrutinib attenuated the cardiac dysfunction associated with sepsis by inhibiting BTK, reducing NF-\u3baB activation and the activation of the inflammasome. Cytokines associated with sepsis were significantly reduced by both BTK inhibitors. Acalabrutinib is found to be more potent than ibrutinib and could potentially prove to be a novel therapeutic in sepsis. Thus, the FDA-approved BTK inhibitors ibrutinib and acalabrutinib may be repurposed for the use in sepsis

Effects of flavonoids on glycosaminoglycan synthesis: implications for substrate reduction therapy in Sanfilippo disease and other mucopolysaccharidoses

Sanfilippo disease (mucopolysaccharidosis type III, MPS III) is a severe metabolic disorder caused by accumulation of heparan sulfate (HS), one of glycosaminoglycans (GAGs), due to a genetic defect resulting in a deficiency of GAG hydrolysis. This disorder is characterized as the most severe neurological form of MPS, revealing rapid deterioration of brain functions. Among therapeutic approaches for MPS III, one of the most promising appears to be the substrate reduction therapy (SRT). Genistein (5, 7-dihydroxy-3- (4-hydroxyphenyl)-4H-1-benzopyran-4-one) is an isoflavone that has been used in SRT for MPS III. In this report, we tested effects of other flavonoids (apigenin, daidzein, kaempferol and naringenin) on GAG synthesis. Their cytotoxicity and anti-proliferation features were also tested. We found that daidzein and kaempferol inhibited GAG synthesis significantly. Moreover, these compounds were able to reduce lysosomal storage in MPS IIIA fibroblasts. Interestingly, although genistein is believed to inhibit GAG synthesis by blocking the tyrosine kinase activity of the epidermal growth factor receptor, we found that effects of other flavonoids were not due to this mechanism. In fact, combinations of various flavonoids resulted in significantly more effective inhibition of GAG synthesis than the use of any of these compounds alone. These results, together with results published recently by others, suggest that combination of flavonoids can be considered as a method for improvement of efficiency of SRT for MPS III

Similarity scaling of turbulence spectra and cospectra in a shallow tidal flow

Author Posting. © American Geophysical Union, 2011. This article is posted here by permission of American Geophysical Union for personal use, not for redistribution. The definitive version was published in Journal of Geophysical Research 116 (2011): C10019, doi:10.1029/2011JC007144.Measured turbulence power spectra, cospectra, and ogive curves from a shallow tidal flow were scaled using Monin-Obukhov similarity theory to test the applicability to a generic tidal flow of universal curves found from a uniform, neutrally stable atmospheric boundary layer (ABL). While curves from individual 10 min data bursts deviate significantly from similarity theory, averages over large numbers of sufficiently energetic bursts follow the general shape. However, there are several differences: (1) Variance in the measured curves was shifted toward higher frequencies, (2) at low frequencies, velocity spectra were significantly more energetic than theory while cospectra were weaker, and (3) spectral ratios of momentum flux normalized by turbulent kinetic energy (TKE) indicate decreased fluxes and/or elevated TKE levels. Several features of the turbulence structure may explain these differences. First, turbulent dissipation exceeded production, indicating nonequilibrium turbulence, possibly from advection of TKE. Indeed, using the production rate rather than dissipation markedly improves agreement in the inertial subrange. Second, spectral lag of the largest eddies due to inhomogeneous boundary conditions and decaying turbulence could explain spectral deviations from theory at low frequencies. Finally, since the largest eddies dominate momentum transfer, the consequence of the cospectra difference is that calculated ogive curves produced smaller total momentum fluxes compared to theory, partly because of countergradient fluxes. While ABL similarity scaling applied to marine bottom boundary layers (MBBLs) will produce curves with the general shape of the universal curves, care should be taken in determining details of turbulent energy and stress estimates, particularly in shallow and inhomogeneous MBBLs.The data were collected with support from NSF grant ECCS‐0308070 to SGM as part of the LOBO program (Ken Johnson, P.I.). The analysis presented here was supported by the Department of Defense (DoD) through the National Defense Science and Engineering Graduate Fellowship (NDSEG) Program and through ONR grant N00014‐ 10‐1‐0236 (Scientific officers: Thomas Drake, C. Linwood Vincent, and Terri Paluszkiewicz). Additional support was provided by the Stanford Graduate Fellowship (SGF)

Towards the clinical implementation of pharmacogenetics in bipolar disorder.

BackgroundBipolar disorder (BD) is a psychiatric illness defined by pathological alterations between the mood states of mania and depression, causing disability, imposing healthcare costs and elevating the risk of suicide. Although effective treatments for BD exist, variability in outcomes leads to a large number of treatment failures, typically followed by a trial and error process of medication switches that can take years. Pharmacogenetic testing (PGT), by tailoring drug choice to an individual, may personalize and expedite treatment so as to identify more rapidly medications well suited to individual BD patients.DiscussionA number of associations have been made in BD between medication response phenotypes and specific genetic markers. However, to date clinical adoption of PGT has been limited, often citing questions that must be answered before it can be widely utilized. These include: What are the requirements of supporting evidence? How large is a clinically relevant effect? What degree of specificity and sensitivity are required? Does a given marker influence decision making and have clinical utility? In many cases, the answers to these questions remain unknown, and ultimately, the question of whether PGT is valid and useful must be determined empirically. Towards this aim, we have reviewed the literature and selected drug-genotype associations with the strongest evidence for utility in BD.SummaryBased upon these findings, we propose a preliminary panel for use in PGT, and a method by which the results of a PGT panel can be integrated for clinical interpretation. Finally, we argue that based on the sufficiency of accumulated evidence, PGT implementation studies are now warranted. We propose and discuss the design for a randomized clinical trial to test the use of PGT in the treatment of BD