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Klotho is a well-known tumor suppressor hormone that exhibits anti-cancer and anti-aging properties. Klotho levels are low or non-existent in cancer patients. Klotho protein levels decrease with aging; maintaining consistent levels may prevent disease and promote healthier aging. Metadichol is a nano emulsion of long-chain alcohols C26, C28, and C30, of which C-28 constitutes over 85%. Any small molecule that can elevate Klotho can, in principle, help reverse many diseases in which Klotho levels are low. Previously, we showed that treatment of the pancreatic cancer cell lines PANC1, MIA-PACA, and COLO-205, combined with Metadichol, a lipid emulsion consisting of long-chain alcohols at 1-100 pg/mL concentrations, resulted in a 4- to 10-fold increase in Klotho expression as determined by qRT-PCR, This study aimed to demonstrate that Metadichol promotes Klotho expression in a wide variety of cell lines, such as primary cancer, stem, and somatic cell lines. Cells were treated with various concentrations of Metadichol ranging from 1 pg to 1 µg. Three to fifteen fold increase in Klotho expression was observed compared with baseline, as measured by qRT-PCR and qualified by western blot analysis. Metadichol is a natural agonist of Klotho expression and is non-toxic at levels up to 5000 mg/kg in rats. and has a potential therapeutic role in cancer and reversing aging.

In this work, we report the hardness and corrosion behavior of a selective laser melted 17-4 PH steel. Microstructure analysis using a scanning electron microscope (SEM) revealed a fine-grained material with a grain size of 1 μm. Phase analysis using SEM-EBSD (electron backscatter diffraction) revealed a ferritic-austenitic microstructure with 96% ferrite and 4% austenite. The material was also found to bear a combination of and fiber texture. The grain boundary character distribution revealed 68% low-angle grain boundaries, 10% CSL boundaries with predominantly Σ3 boundaries, and 21% high-angle grain boundaries. The Vickers hardness of this material was found to be quite high at 3.66±0.17 GPa which is probably due to the fine-grained structure of the material. Potentiodynamic polarization tests in 3.5 wt% NaCl solution yielded a corrosion current density, icorr of 1.4 × 10−6 A/cm2 and corrosion potential, Ecorr of −55 mVAg/AgCl electrode. Immersion tests in salt water for a period of 96 h showed hardly any pit formation although an AISI 304 stainless steel bearing grain size of 29 μm showed significant pit formation during the same time period.

The phospholipid lecithin (L) and the nonionic surfactant Tween 80 (T) are used together in various contexts, including in drug delivery and oil spill remediation. There is hence a need to elucidate the nanostructures in LT mixtures, which is the focus of this paper. We study these mixtures using cryogenic transmission electron microscopy (cryo-TEM), coupled with dynamic light scattering and small-angle neutron scattering. As the concentration of Tween 80 is increased, the vesicles formed by lecithin are transformed into spherical micelles. We identify bicelles (i.e., disc-like micelles) as well as cylindrical micelles as the key stable nanostructures formed at intermediate L/T ratios. The bicelles have diameters ∼13-26 nm, and the bicelle size decreases as the Tween 80 content increases. We propose that the lecithin lipids form the body of the discs, while the Tween 80 surfactants occupy the rims. This hypothesis is consistent with geometric arguments because lecithin is double-tailed and favors minimal curvature, whereas the single-tailed Tween 80 molecules prefer curved interfaces. In the case of cylindrical micelles, cryo-TEM reveals that the micelles are short (length22 nm) and flexible. We are able to directly visualize the microstructure of the aggregates formed by lecithin-Tween 80 mixtures, thereby enhancing the understanding of morphological changes in the lecithin-Tween 80 system.

In nature, various structures such as fruits and vegetables have a water-rich core that is covered by a hydrophobic layer, i.e., their skin. The skin creates a barrier that prevents chemicals in the external environment from entering the core; at the same time, the skin also ensures that the water in the core is preserved and not lost by evaporation. Currently, for many applications involving hydrogels, especially in areas such as soft robotics or bioelectronic interfaces, it would be advantageous if the gel could be encased in a skin-like material. However, forming such a skin around a gel has proved challenging because the skin would need to be a hydrophobic material with a distinct chemistry from the hydrophilic gel core. Here, we present a simple solution to this problem, which allows any hydrogel of arbitrary composition and geometry to be encased by a thin, transparent "skin." Our synthesis technique involves an inside-out polymerization, where one component of the polymerization (the initiator) is present only in the gel core, while other components (the monomers) are present only in the external medium. Accordingly, a thin polymeric layer (∼10-100 µm in thickness) grows outward from the core, and the entire process can be completed in a few minutes. We show that the presence of the skin prevents the gel from swelling in water and also from drying in air. Likewise, hydrophilic solutes in the gel core are completely prevented by the skin from leaking out into the external solution, while harsh chemicals (e.g., acids, bases, and chelators) or harmful microbes are prevented from entering the gels. The properties of the skin are all tunable, including its thickness and its mechanical properties. When the monomer used is urethane diacrylate, the resulting polyurethane skin is elastomeric, transparent, and peelable from the core gel. Conversely, when polyethylene glycol dimethacrylate is used as the monomer, the skin is hard and brittle (glass-like). The ability to grow a skin readily around any given hydrogel is likely to prove useful in numerous applications, such as in maintaining the electrical functionality of gel-based wires or circuit elements.

Background Little is known about the effects of secondhand marijuana smoke on children. We aimed to determine caregiver marijuana use prevalence and evaluate any association between secondhand marijuana smoke, childhood emergency department (ED) or urgent care (UC) visitation, and several tobacco-related illnesses: otitis media, viral respiratory infections (VRIs), and asthma exacerbations. Methods This study was a cross-sectional, convenience sample survey of 1500 subjects presenting to a pediatric ED. The inclusion criteria were as follows: caregivers aged 21-85 years, English- or Spanish-speaking. The exclusion criteria were as follows: children who were critically ill, medically complex, over 11 years old, or using medical marijuana. Results Of 1500 caregivers, 158 (10.5%) reported smoking marijuana and 294 (19.6%) reported smoking tobacco. Using negative-binomial regression, we estimated rates of reported ED/UC visits and specific illnesses among children with marijuana exposure and those with tobacco exposure, compared to unexposed children. Caregivers who used marijuana reported an increased rate of VRIs in their children (1.31 episodes/year) compared to caregivers with no marijuana use (1.04 episodes/year) (p = 0.02). Conclusions Our cohort did not report any difference with ED/UC visits, otitis media episodes, or asthma exacerbations, regardless of smoke exposure. However, caregivers of children with secondhand marijuana smoke exposure reported increased VRIs compared to children with no smoke exposure. Impact Approximately 10% of caregivers in our study were regular users of marijuana. Prior studies have shown that secondhand tobacco smoke exposure is associated with negative health outcomes in children, including increased ED utilization and respiratory illnesses. Prior studies have shown primary marijuana use is linked to negative health outcomes in adults and adolescents, including increased ED utilization and respiratory illnesses. Our study reveals an association between secondhand marijuana smoke exposure and increased VRIs in children. Our study did not find an association between secondhand marijuana smoke exposure and increased ED or UC visitation in children.

Electroadhesion, i.e., adhesion induced by an electric field, occurs between non-sticky cationic and anionic hydrogels. Here, we demonstrate electroadhesion between cationic gels and animal (bovine) tissues. When gel and tissue are placed under an electric field (DC, 10 V) for 20 s, the pair strongly adhere, and the adhesion persists indefinitely thereafter. Applying the DC field with reversed polarity eliminates the adhesion. Electroadhesion works with the aorta, cornea, lung, and cartilage. We demonstrate the use of electroadhesion to seal cuts or tears in tissues or model anionic gels. Electroadhered gel-patches provide a robust seal over openings in bovine aorta, and a gel sleeve is able to rejoin pieces of a severed gel tube. These studies raise the possibility of using electroadhesion in surgery while obviating the need for sutures. Advantages include the ability to achieve adhesion on-command, and moreover the ability to reverse this adhesion in case of error., The authors demonstrate strong adhesion of cationic hydrogels to bovine tissues under a DC electric field. Such electroadhesion can be reversed by switching the polarity of the field. This approach could enable simpler surgeries, where sutures are not needed.

Marine oil dispersants typically contain blends of surfactants dissolved in solvents. When introduced to the crude oil-seawater interface, dispersants facilitate the breakup of crude oil into droplets that can disperse in the water column. Recently, questions about the environmental persistence and toxicity of commercial dispersants have led to the development of "greener" dispersants consisting solely of food-grade surfactants such as l-α-phosphatidylcholine (lecithin, L) and polyoxyethylenated sorbitan monooleate (Tween 80, T). Individually, neither L nor T is effective at dispersing crude oil, but mixtures of the two (LT blends) work synergistically to ensure effective dispersion. The reasons for this synergy remain unexplained. More broadly, an unresolved challenge is to be able to predict whether a given surfactant (or a blend) can serve as an effective dispersant. Herein, we investigate whether the LT dispersant effectiveness can be correlated with thermodynamic phase behavior in model systems. Specifically, we study ternary "DOW" systems comprising LT dispersant (D) + a model oil (hexadecane, O) + synthetic seawater (W), with the D formulation being systematically varied (across 0:100, 20:80, 40:60, 60:40, 80:20, and 100:0 L:T weight ratios). We find that the most effective LT dispersants (60:40 and 80:20 L:T) induce broad Winsor III microemulsion regions in the DOW phase diagrams (Winsor III implies that the microemulsion coexists with aqueous and oil phases). This correlation is generally consistent with expectations from hydrophilic-lipophilic deviation (HLD) calculations, but specific exceptions are seen. This study then outlines a protocol that allows the phase behavior to be observed on short time scales (ca. hours) and provides a set of guidelines to interpret the results. The complementary use of HLD calculations and the outlined fast protocol are expected to be used as a predictive model for effective dispersant blends, providing a tool to guide the efficient formulation of future marine oil dispersants.

Human nuclear receptors (NRs) involve 49 ligand-dependent transcription factors that are important for regulating the cell cycle and processes. There are many literature references to work on NR expression in many organs, abnormal cells, and tissues. However, a simple universal method to study the expression of NR is still missing. Here, we present systematic profiling of NRs in human umbilical cord stem cell lines and assess the expression of the 48 human NRs by quantitative real-time (qRT)-PCR using Metadichol, a nanoemulsion made of natural lipid alcohol. Metadichol-treated umbilical cord cells and fibroblasts, where all cells expressed NRs at a concentration range of 1 pg-100 ng/mL in a dependent manner, were detected by qRT-PCR and qualified by Western blotting. This method will allow the study of many organs and tissues and expand our understanding of the role of NRs and their role in mitigating diseases. HighlightsMetadichol treatment of somatic cells leads to nuclear receptor expressionDepending on the cell and concentration of Metadichol used, fold changes are differentThe method could be used to study many cells and disease cells to better understand NR expression patterns and implications.The results suggest that Metadichol is a universal ligand to all nuclear receptors.

The human nuclear receptor (NR) consists of 49 ligand-dependent transcription factors that play a critical role in development, metabolism, reproduction, cell cycle, differentiation, and diseases, e.g., cancer and cardiovascular disease, to name a few. Today, we have gene sequencing data on NR presence in many organs, disease cells, and tissues. We do not have a simple universal method to study the expression of NR that small molecules can induce in various cell diseased and non-diseased states. Here in we present systematic profiling of NRs in human umbilical cord stem cell lines and Expression of the 48 human NRs was assessed by quantitative real-time PCR. using Metadichol a nano-emulsion natural lipid alcohol treated Umbilical cord cells, Fibroblasts, cells expressed all the nuclear receptors at a concentration of 1 picogram per ml to 100 nanogram per ml in a concentration-dependent manner as seen by Q-RT-PCR and qualified by Western blot. This method will allow the study of many organs and tissues and expand our understanding of the role of NR in normal and disease states.

The conversion of somatic cells back into induced pluripotent stem cells (iPSCs) or embryonic-like stem cells involves the introduction of four genes commonly called Yamanaka factors, i.e., Sox2, Oct4, Klf4, and c-Myc, into the cells. Because these genes and the viral vectors used to introduce them into cells have the potential to cause cancer, iPSC lines are not clinically useful. Most instances of direct reprogramming have been achieved by the forced expression of defined factors using viral vectors. Here, we show that Metadichol® has the potential to generate iPSCs nonvirally and may be helpful in clinical applications. Metadichol is a nanoformulation of long-chain alcohols derived from food. Quantitative real-time PCR (qRT-PCR) and western blotting showed that OCT4, SOX2, and Nanog are expressed when fibroblasts were treated with Metadichol at one picogram to 100 nanograms. Reverse-transcription PCR (RT-PCR) also revealed that OCT4, KLF4, Nanog, and Sox2 levels increased compared to controls by 4.01-, 3.51- and 1.26-, and 2.5-fold, respectively, in A549 cancer cells. In Colo-205 cells, OCT4, KLF4, and Sox2 were increased by 1.79-, 13.17-, and 2.25-fold, respectively. Metadichol treatment with triple-negative primary breast cancer (HCAF-TNPBC) primary cancer cells led to multifold increases in OKSM factors by 19-, 6-, 8.07-, 2.45-, and 6.91-fold in concentration ranges of 1 picogram to 100 nanograms. Metadichol is a natural product that induces the expression of Yamanaka factors needed for reprogramming and Klotho, an antiaging gene, and curbs the expression of the TP53 gene, which is critical for reprogramming somatic cells into IPSCs. Metadichol increases endogenous vitamin C levels, leading to the efficient reprogramming of somatic cells into iPSCs. Metadichol is nontoxic and commercially available as a nutritional supplement. Thus, it can be directly tested in vivo in human subjects to confirm that cells can indeed be programmed into a state of induced pluripotency and cause the mitigation of disease conditions.

Recently, we have created ‘artificial cells’ with an architecture mimicking that of typical eukaryotic cells. Our design uses common biopolymers like alginate and chitosan to create multi-compartment capsules (MCCs) via oil-free microfluidics. MCCs (~ 500 μm in diameter) can be engineered with multiple inner compartments, each with a distinct payload. This mimics the distinct organelles in eukaryotic cells, each of which has unique properties. In this study, we encapsulate microbial cells from two distinct kingdoms — Pseudomonas aeruginosa (bacteria) and Candida albicans (fungi) — in the inner compartments of MCCs. The two microbes are commonly found in biofilms at sites of infection in humans. We first demonstrate that the MCC can serve as a simple platform to observe the comparative growth of the cells in real time. Unlike typical co-culture in solution or on agar plates, the cells can grow in their own compartments without direct physical contact. Moreover, the hydrogel matrix in the compartments mimics the three-dimensional (3-D) environment that cells naturally encounter during their growth. Small molecules added to the solution are shown to permeate through the capsule walls and affect cell growth: for example, cationic surfactants inhibit the fungi but not the bacteria. Conversely, low pH and kanamycin inhibit the bacteria but not the fungi. Also, when the bacteria are present in adjacent compartments, the fungal cells mostly stay in a yeast morphology, meaning as spheroidal cells. In contrast, in the absence of the bacteria, the fungi transition into hyphae, i.e., long multicellular filaments. The inhibition of this morphological switch in fungal cells is shown to be induced by signaling molecules (specifically, the quorum sensing autoinducer-1 or AI-1) secreted by the bacteria. Thus, the MCC platform can also be used to detect cross-kingdom signaling between the compartmentalized microbes.

Glycosaminoglycans (GAGs) are molecules that govern the load-bearing and frictional properties of cartilage and the lubricating properties of synovial fluid of joints. Most GAGs in the body form pr...

Trypanosoma evansi infection was diagnosed in 15 out of 17 adult dromedaries of a breeding herd in the Emirate of Dubai. The herd had a history of abortions in the previous years. Own observations on 16 adult females and one bull lasted 12 months and revealed trypanosomosis in 15 animals in monthly haematological and serological examinations. Despite three to four injections of the trypanocides melarsamine and/or quinapyramine, only one camel was cured. One camel aborted in the 8th month of pregnancy. Four other dams delivered healthy calves.

“Smart” fluids displaying large changes in their rheological properties in response to external stimuli have been of great interest in recent years. For example, “smart” wormlike micelles (WLMs) that respond to pH can be readily formulated by combining a cationic surfactant such as cetyltrimethylammonium bromide (CTAB) with an aromatic compound such as 1,2-dihydroxybenzene (DHB). Here, we show that a pH-responsive aqueous formulation as mentioned above can be simultaneously made responsive to ultraviolet (UV) light by incorporating a photoacid generator (PAG) into the system. A commercially available PAG, diphenyliodonium-2-carboxylate, is used here. Upon exposure to UV light, this PAG irreversibly photolyzes into iodobenzene (IB) and benzoic acid (BA), with the formation of BA, leading to a drop in pH. WLMs formed by mixtures of CTAB, DHB, and the PAG are systematically characterized before and after UV irradiation. As the PAG photolyzes, an increase in the viscosity of WLMs occurs by a factor of 1000. We show that the ratio of the zero-shear viscosity η0 (after UV/before UV) depends on the initial pH of the sample. The UV-induced increase in η0 can be attributed to the growth of WLMs in solution, which in turn is influenced by both the ionization state of DHB and the presence of IB and BA.

BACKGROUND African horse sickness (AHS) is a devastating viral disease of equids that was first recorded in 1327. Currently, prevention and control of the disease are based on attenuated vaccines and midge control. It has been shown that attenuated Orbivirus vaccines are not always safe as they may reverse to virulence. OBJECTIVES In the Emirate of Dubai, a vaccination experiment was carried out with an inactivated AHS vaccine produced at the Central Veterinary Research Laboratory (CVRL), Dubai, UAE to investigate the humoral antibody response of AHS-naive horses to this vaccine. Our vaccination experiment was performed to establish an AHS vaccine bank in the UAE to protect horses from the disease in case of an outbreak. Therefore, CVRL established an inactivated AHS vaccine containing all nine serotypes which induce high neutralising antibodies. STUDY DESIGN A total of 10 horses kept in a desert isolation area were subcutaneously and intramuscularly vaccinated with an inactivated vaccine containing all nine AHS serotypes previously isolated from Kenyan horse fatalities. Primary immunisation was followed by two booster immunisations 4 weeks and 6 months apart. After 13 months, an annual booster was administered. METHODS Blood samples were regularly withdrawn for ELISA and virus neutralisation testing. Additionally, EDTA blood was tested every second day for 14 days post each vaccination for the presence of AHS virus or its RNA. RESULTS Results show that ELISA and virus neutralising antibodies appeared after the first booster, declined after 4-6 months and therefore three vaccinations and an annual vaccination are necessary to achieve high protective virus neutralising antibodies. MAIN LIMITATIONS No challenge infection was carried out due to the lack of a safe facility in the UAE. CONCLUSION Before more advanced AHS vaccines become a reality, inactivated vaccines containing all nine serotypes should be used as they produce high ELISA and neutralising antibodies.

Hydrogels of biopolymers such as agar and gelatin are widely used in many applications, and in many cases, the gels are loaded with nanoparticles. The polymer chains in these gels are cross-linked by physical bonds into three-dimensional networks, with the mesh size of these networks typically being 10-100 nm. One class of "soft" nanoparticles are liposomes, which have an aqueous core surrounded by a lipid bilayer. Solutes encapsulated in the liposomal core can be delivered externally over time. In this paper, we create liposomes with diameters ∼150 nm from an unsaturated phospholipid (lecithin) and embed them in agar gels (the aqueous phase also contains 0-50% of glycerol, which is an active ingredient in cosmetic products). Upon placing this gel in quiescent water, we find that the liposomes release out of the gel into the water over a period of 1-3 days, even though the gel remains intact.

Wormlike micelles (WLMs) are polymer-like chains formed by surfactant self-assembly in water. Recently, we have shown that WLMs can also be self-assembled in polar organic liquids like glycerol using a cationic surfactant and an aromatic salt. In this work, we focus on the dynamic rheology of the WLMs in glycerol and demonstrate that their rheology is very different from that of WLMs in water. Aqueous WLMs that are entangled into transient networks exhibit the rheology of a perfect Maxwell fluid having a single relaxation time tR-thereby, their elastic modulus G' and viscous modulus G″ intersect at a crossover frequency ωc = 1/tR. WLMs in glycerol also form entangled networks, but they are not Maxwell fluids; instead, they exhibit a double-crossover of G' and G″ (at ωc1 and ωc2) within the ω-window accessible by rheometry (10-2 to 102 rad/s). The first crossover at ωc1 (∼1 rad/s) corresponds to the terminal relaxation time (i.e., the timescale for chains to disentangle from the transient network and relax by reptation). At the other extreme, at frequencies above ωc2 (which is ∼10 rad/s), the rheology is dominated by the segmental motion of the chains. This "breathing regime" has rarely been accessed via experiments for aqueous WLMs because it falls around 105 rad/s. We believe that glycerol, a solvent that is much more viscous than water, exerts a crucial influence in pushing ωc2 to 1000-fold lower frequencies. On the basis of the rheology, we also hypothesize that WLMs in glycerol are shorter and weakly entangled compared to WLMs in water. Moreover, we suggest that WLMs in glycerol are "unbreakable" chains-i.e., the chains remain mostly intact instead of breaking and re-forming frequently-and this polymer-like behavior explains why the samples are quite unlike Maxwell fluids.

A dromedary camel breeding herd consisting of 16 female and 2 male camels experienced an abortion storm over a period of 2 years. Fifteen (94%) of the 16 female camels aborted during the last stage of pregnancy. Trypanosoma evansi was directly identified by the buffy coat technique in 7 (39%) of the camels and in 15 (83%) with the indirect in-house antibody ELISA developed at the Central Veterinary Research Laboratory (CVRL). One bull and two newly introduced female camels were negative in both tests.

Recent success in extending the electrochemical stability window of aqueous electrolytes to 3.0 V by using 21 mol kg-1 “water-in-salt” (WiS) has raised a high expectation for developing safe aqueous Li-ion batteries. However, the most compatible Li4Ti5O12 anodes still cannot use WiS electrolyte due to the cathodic limit (1.9 V vs. Li/Li+). Herein, a UV-curable hydrophilic polymer is introduced to further extend the cathodic limit of WiS electrolytes and replace the separator. In addition, a localized strongly basic solid polymer electrolyte (SPE) layer is coated on the anode to promote the formation of an LiF-rich SEI. The synthetic impacts of UV-crosslinking and local alkaline SPE on the anodes extend the electrochemical stability window of the solid-state aqueous polymer electrolyte to ∼3.86 V even at a reduced salt concentration of 12 mol kg−1. It enables a separator-free LiMn2O4//Li4Ti5O12 aqueous full cell with a practical capacity ratio (P/N = 1.14) of the cathode and anode to deliver a steady energy density of 151 W h kg−1 at 0.5C with an initial Coulombic efficiency of 90.50% and cycled for over 600 cycles with an average Coulombic efficiency of 99.97%, which has never been reported before for an aqueous LiMn2O4//Li4Ti5O12 full cell. This flexible and long-duration aqueous Li-ion battery with hydrogel WiSE can be widely used as a power source in wearable devices and electrical transportations where both energy density and battery safety are of high priority. An ultra-thick LTO electrode with UV-curable polymer electrolyte as the binder is demonstrated as a solid state battery electrode. And a high-voltage (7.4 V) solid-state bipolar cell is assembled with a solid-state UV-curable polymer as the electrolyte.

Introduction ‘Do not attempt cardiopulmonary resuscitation’ (DNACPR) documentation is essential to communicate decisions regarding ceilings of care for patients to the clinical team. Patients admitted to hospital with a fractured neck of femur (#NOF) are often elderly with multiple comorbidities, and so robust and clear anticipatory care plans are especially indicated. Method All patients admitted to a large district general hospital in Scotland with a #NOF over a three-week period between 23/10/2020 and 12/11/2020 were identified prospectively and included in this audit. Patients’ demographic information, DNACPR status and the quality of their DNACPR documentation was recorded. Results 20 patients (85% Female, 15% Male) were identified and included. Median ASA grade was 3, with 77.8% of patients ASA grade 3 or 4. 63.2% of patients had DNACPR documentation in place, all of which were ASA grade 3 or above. Most DNACPR documentation had patient information clearly identifiable (91.7%), was completed preoperatively (90.9%), and involved either the patient or appropriate relative or power of attorney (91.6%). However, only 75% of patients’ documentation had the rationale for the DNACPR decision documented and only 25% of DNACPR decisions were reviewed by a senior clinician within 72 hours. No DNACPR decisions were documented as having been communicated to the wider healthcare team. Conclusions DNACPR documentation is a crucial for anticipatory care planning in #NOF patients. This audit shows improvement is needed in documenting whether decisions have been reviewed by senior clinicians, and if they have been communicated to the wider healthcare team.

OBJECTIVE We sought to measure trends in evaluation and management of children with simple febrile seizures (SFSs) before and after the American Academy of Pediatrics updated guidelines published in 2011. METHODS In this retrospective, cross-sectional analysis, we used the Pediatric Health Information System database comprising 49 tertiary care pediatric hospitals in the United States from 2005 to 2019. We included children aged 6 to 60 months with an emergency department visit for first SFS identified using codes from the International Classification of Diseases, Ninth Revision, and International Classification of Diseases 10th Revision. RESULTS We identified 142 121 children (median age 21 months, 42.4% female) with an emergency department visit for SFS. A total of 49 668 (35.0%) children presented before and 92 453 (65.1%) after the guideline. The rate of lumbar puncture for all ages declined from 11.6% (95% confidence interval [CI], 10.8% to 12.4%) in 2005 to 0.6% (95% CI, 0.5% to 0.8%) in 2019 (P < .001). Similar reductions were noted in rates of head computed tomography (10.6% to 1.6%; P < .001), complete blood cell count (38.8% to 10.9%; P < .001), hospital admission (19.2% to 5.2%; P < .001), and mean costs ($1523 to $601; P < .001). Reductions in all outcomes began before, and continued after, the publication of the American Academy of Pediatrics guideline. There was no significant change in delayed diagnosis of bacterial meningitis (preperiod 2 of 49 668 [0.0040%; 95% CI, 0.00049% to 0.015%], postperiod 3 of 92 453 [0.0032%; 95% CI, 0.00066% to 0.0094%]; P = .99). CONCLUSIONS Diagnostic testing, hospital admission, and costs decreased over the study period, without a concomitant increase in delayed diagnosis of bacterial meningitis. These data suggest most children with SFSs can be safely managed without lumber puncture or other diagnostic testing.

Management of patients with single ventricle physiology after surgical palliation is challenging. Arginine vasopressin has gained popularity in recent years as a non-catecholamine vasoactive medication due to its unique properties. However, data regarding its use in the pediatric population is limited. Therefore, we designed a survey to explore whether and how clinicians use this medication in intensive care units for the postoperative management of single ventricle patients. This international survey aimed to assess usage, practices, and concepts related to arginine vasopressin in pediatric intensive care units worldwide. Directors of pediatric intensive care units who are members of the following international professional societies: European Society of Pediatric Neonatal Intensive Care, Association for European Pediatric and Congenital Cardiology, and Pediatric Cardiac Intensive Care Society were invited to participate in this survey. Of the 62 intensive care unit directors who responded, nearly half use arginine vasopressin in the postoperative management of neonatal single ventricle patients, and 90% also use the drug in subsequent surgical palliation. The primary indications are vasoplegia, hemodynamic instability, and refractory shock, although it is still considered a second-line medication. Conceptual benefits include improved hemodynamics and end-organ perfusion and decreased incidence of low cardiac output syndrome. Those practitioners who do not use arginine vasopressin cite lack of availability, fear of potential adverse effects, unclear indication for use, and lack of evidence suggesting improved outcomes. Both users and non-users described increased myocardial afterload and extreme vasoconstriction as potential disadvantages of the medication. Despite the lack of conclusive data demonstrating enhanced clinical outcomes, our study found arginine vasopressin is used widely in the care of infants and children with single ventricle physiology after the first stage and subsequent palliative surgeries. While many intensive care units use this medication, few had protocols, offering an area for further growth and development.

The self-assembly of lipids into nanoscale vesicles (liposomes) is routinely accomplished in water. However, reports of similar vesicles in polar organic solvents like glycerol, formamide, and ethylene glycol (EG) are scarce. Here, we demonstrate the formation of nanoscale vesicles in glycerol, formamide, and EG using the common phospholipid lecithin (derived from soy). The samples we study are simple binary mixtures of lecithin and the solvent, with no additional cosurfactants or salt. Lecithin dissolves readily in the solvents and spontaneously gives rise to viscous fluids at low lipid concentrations (∼2-4%), with structures ∼200 nm detected by dynamic light scattering. At higher concentrations (>10%), lecithin forms clear gels that are strongly birefringent at rest. Dynamic rheology confirms the elastic response of gels, with their elastic modulus being ∼20 Pa at ∼10% lipid. Images from cryo-scanning electron microscopy (cryo-SEM) indicate that concentrated samples are "vesicle gels," where multilamellar vesicles (MLVs, also called "onions"), with diameters between 50 and 600 nm, are close-packed across the sample volume. This structure can explain both the elastic rheology as well as the static birefringence of the samples. The discovery of vesicles and vesicle gels in polar solvents widens the scope of systems that can be created by self-assembly. Interestingly, it is much easier to form vesicles in polar solvents than in water, and the former are stable indefinitely, whereas the latter tend to aggregate or coalesce over time. The stability is attributed to refractive index-matching between lipid bilayers and the solvents, i.e., these vesicles are relatively "invisible" and thus experience only weak attractions. The ability to use lipids (which are "green" or eco-friendly molecules derived from renewable natural sources) to thicken and form gels in polar solvents could also prove useful in a variety of areas, including cosmetics, pharmaceuticals, and lubricants.

Cytoadhesion of Plasmodium falciparum-infected erythrocytes (IEs) to the endothelial lining of blood vessels protects parasites from splenic destruction, but also leads to detrimental inflammation and vessel occlusion. Surface display of the P. falciparum erythrocyte membrane protein 1 (PfEMP1) adhesion ligands exposes them to host antibodies and serum proteins. PfEMP1 are important targets of acquired immunity to malaria, and through evolution, the protein family has expanded and diversified to bind a select set of host receptors through antigenically diversified receptor-binding domains. Here, we show that complement component 1s (C1s) in serum cleaves PfEMP1 at semiconserved arginine motifs located at interdomain regions between the receptor-binding domains, rendering the IE incapable of binding the two main PfEMP1 receptors, CD36 and endothelial protein C receptor (EPCR). Bioinformatic analyses of PfEMP1 protein sequences from 15 P. falciparum genomes found the C1s motif was present in most PfEMP1 variants. Prediction of C1s cleavage and loss of binding to endothelial receptors was further corroborated by testing of several different parasite lines. These observations suggest that the parasites have maintained susceptibility for cleavage by the serine protease, C1s, and provides evidence for a complex relationship between the complement system and the P. falciparum cytoadhesion virulence determinant.

Biodegradation of oil by marine bacteria is a significant pathway to oil spill remediation. Marine hydrocarbon degrading bacteria are known to form biofilms consisting of exopolymer and interconnected bacterial cells. This work indicates that microbial biofilm aids in the stabilization of dispersed oil droplets through the formation of biofilm at the oil–water interface and is therefore an environmentally benign and sustainable method to aid dispersion of spilled oil. Using a model hydrocarbon degrading organism Alcanivorax borkumensis, we show, through a combination of optical and high-resolution cryogenic scanning electron microscopy, that these microbes sequester into biofilm at the oil–water interface. We show that the bacterial culture incubated for 3 days and containing biofilm can disperse oil slicks moderately well (40–50%) as estimated by the baffled flask test and can thus be used as an environmentally benign response to oil spills. The dispersion occurs through bacterial adsorption at the oil–w...

Aqueous capsules made from polymers typically allow their encapsulated cargo (e.g., drugs, dyes, proteins) to slowly diffuse out into the solvent through the capsule shell. In many applications, there is a need for a ‘hermetic’ seal to protect the cargo from the solvent over extended periods of time. Ideally, this hermetic seal should also be capable of being broken on-demand to enable cargo release. We demonstrate a new design for capsules having the above combination of properties. The key is to create the capsule shell from wax materials (alkanes and fatty acids) with a defined melting temperature Tm. Capsules can be loaded with any desired material, including strong acids or bases, reactive or unstable reagents (such as H2O2), and biopolymer gels. When sealed capsules are placed in water, no leakage is observed for over six weeks. The capsules can also encapsulate volatile liquids and remain air-tight over at least three weeks. On the other hand, under mild heat (above Tm, e.g., to 45 °C), the shell melts, releasing the core contents into the surrounding solvent. This provides a convenient thermal on–off “switch” for delivering contents from the capsules. The utility of these capsules is shown by implementing a nitrate-detection assay using hazardous chemicals (including H2SO4) sealed in the capsules. These “smart” capsules thus constitute a modular, mass-producible platform that could be useful in diverse applications.

Microgels of biopolymers such as alginate are widely used to encapsulate cells and other biological payloads. Alginate is an attractive material for cell encapsulation because it is nontoxic and convenient: spherical alginate gels are easily created by contacting aqueous droplets of sodium alginate with divalent cations such as Ca2+. Alginate chains in the gel become cross-linked by Ca2+ cations into a 3-D network. When alginate gels are placed in a buffer, however, the Ca2+ cross-links are eliminated by exchange with Na+, thereby weakening and degrading the gels. With time, encapsulated cells are released into the external solution. Here, we describe a simple solution to the above problem, which involves forming alginate gels enveloped by a thin shell of a covalently cross-linked gel. The shell is formed via free-radical polymerization using conventional monomers such as acrylamide (AAm) or acrylate derivatives, including polyethylene glycol diacrylate (PEGDA). The entire process is performed in a single step at room temperature (or 37 °C) under mild, aqueous conditions. It involves combining the alginate solution with a radical initiator, which is then introduced as droplets into a reservoir containing Ca2+ and monomers. Within minutes of either simple incubation or exposure to ultraviolet (UV) light, the droplets are converted into alginate-polymer microcapsules with a core of alginate and a shell of the polymer (AAm or PEGDA). The microcapsules are mechanically more robust than conventional alginate/Ca2+ microgels, and while the latter swell and degrade when placed in buffers or in chelators like sodium citrate, the former remain stable under all conditions. We encapsulate both bacteria and mammalian cells in these microcapsules and find that the cells remain viable and functional over time. Lastly, a variation of the synthesis technique is shown to generate multilayered microcapsules with a liquid core surrounded by concentric layers of alginate and AAm gels. We anticipate that the approaches presented here will find application in a variety of areas including cell therapies, artificial cells, drug delivery, and tissue engineering.

Bleeding from injuries to the torso region is a leading cause of fatalities in the military and in young adults. Such bleeding cannot be stopped by applying direct pressure (compression) of a bandage. An alternative is to introduce a foam at the injury site, with the expansion of the foam counteracting the bleeding. Foams with an active hemostatic agent have been tested for this purpose, but the barrier created by these foams is generally not strong enough to resist blood flow. In this paper, we introduce a new class of foams with enhanced rheological properties that enable them to form a more effective barrier to blood loss. These aqueous foams are delivered out of a double-barrelled syringe by combining precursors that produce bubbles of gas (CO2) in situ. In addition, one barrel contains a cationic polymer (hydrophobically modified chitosan, hmC) and the other an anionic polymer (hydrophobically modified alginate, hmA). Both these polymers function as hemostatic agents due to their ability to connect blood cells into networks. The amphiphilic nature of these polymers also enables them to stabilize gas bubbles without the need for additional surfactants. hmC-hmA foams have a mousse-like texture and exhibit a high modulus and yield stress. Their properties are attributed to the binding of hmC and hmA chains (via electrostatic and hydrophobic interactions) to form a coacervate around the gas bubbles. Rheological studies are used to contrast the improved rheology of hmC-hmA foams (where a coacervate arises) with those formed by hmC alone (where there is no such coacervate). Studies with animal wound models also confirm that the hmC-hmA foams are more effective at curtailing bleeding than the hmC foams due to their greater mechanical integrity.