Improvement in Oxygenation Utilizing Transpulmonary Pressure Monitoring for Optimal Positive End-Expiratory Pressure in Pediatric Acute Respiratory Distress Syndrome: A Case Report.

In severe pediatric acute respiratory distress syndrome, data are lacking on methods to measure and set optimal positive end-expiratory pressure. We present a 2-year-old girl with Trisomy 21 who developed severe pediatric acute respiratory distress syndrome and refractory hypoxemia from human metapneumovirus pneumonia. Esophageal manometry was utilized to measure transpulmonary pressure, and positive end-expiratory pressure was increased to 19 cm H2O, resulting in rapid improvement in oxygenation. Hemodynamics remained adequate without intervention. The patient improved and survived without sequelae. Our case suggests that transpulmonary pressure monitoring should be studied as an adjunct to improve outcomes in pediatric acute respiratory distress syndrome.

A rationale for universal tranexamic acid in major joint arthroplasty: overall efficacy and impact of risk factors for transfusion.

BACKGROUND: Tranexamic acid (TXA) therapy is effective in reducing postoperative red blood cell (RBC) transfusion in total joint arthroplasty (TJA), yet uncertainty persists regarding comparative efficacy and safety among specific patient subgroups. We assessed the impact of a universal TXA protocol on RBC transfusion, postoperative hemoglobin (Hb), and adverse outcomes to determine whether TXA is safe and effective in TJA, both overall and in clinically relevant subgroups. STUDY DESIGN AND METHODS: A retrospective observational study was performed on patients undergoing TJA at our institution spanning 1 year before and after the implementation of a universal protocol to administer intravenous (IV) TXA. The primary outcome was percentage of patients transfused, and secondary outcomes were perioperative Hb and occurrence of adverse events (death, myocardial infarction, stroke, seizure, pulmonary embolism, deep vein thrombosis, and acute kidney injury ). Outcomes were compared in pre- and post-protocol groups with χ2 analysis. Logistic regression compared risk of transfusion in pre- and post-protocol subgroups of patients with differing risk for transfusion (anemia, body mass index [BMI], and sex). RESULTS: No differences were found in baseline patient characteristics across pre- and post-protocol groups (n = 1084 and 912, respectively). TXA use increased from 32.3% to 92.2% while transfusion rates decreased from 10.3% to 4.8% (p < 0.001). Postoperative Day 3 Hb increased from 95.8 to 101.4 g/L (p < 0.001). Logistic regression demonstrated reduced transfusion in post-protocol subgroups regardless of sex, anemia, or BMI (p < 0.001). No increase in adverse events was observed (p = 0.8451). CONCLUSIONS: Universal TXA was associated with a reduction of RBC transfusion, overall and in clinically relevant subgroups, strengthening the rationale for universal therapy.

Nanophotonic trapping: precise manipulation and measurement of biomolecular arrays.

Optical trapping is a powerful and widely used laboratory technique in the biological and materials sciences that enables rapid manipulation and measurement at the nanometer scale. However, expanding the analytical throughput of this technique beyond the serial capabilities of established single-trap microscope-based optical tweezers remains a current goal in the field. In recent years, advances in nanotechnology have been leveraged to create innovative optical trapping methods that increase the number of available optical traps and permit parallel manipulation and measurement of arrays of optically trapped targets. In particular, nanophotonic trapping holds significant promise for integration with other lab-on-a-chip technologies to yield compact, robust analytical devices. In this review, we highlight progress in nanophotonic manipulation and measurement, as well as the potential for implementing these on-chip functionalities in biological research and biomedical applications. WIREs Nanomed Nanobiotechnol 2018, 10:e1477. doi: 10.1002/wnan.1477 This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Recognition-mediated particle detection under microfluidic flow with waveguide-coupled 2D photonic crystals: towards integrated photonic virus detectors.

Label-free biodetection schemes compatible with standard CMOS fabrication methods constitute an important goal, as these are enabling tools for the mass production of high-sensitivity biosensors. Two-dimensional slab photonic crystal (2D slab-PhC) sensors have been posited as ultrahigh-sensitivity detection components, but to date recognition-mediated detection of viruses or simulants under flow has not been demonstrated. We report the design and optimization of a new W1 waveguide-coupled 2D slab-PhC sensor, with a geometry well suited to virus detection. Proof of concept experiments with fluorescent latex particles verified that the sensor could respond to infiltration of a single particle, both in air and under an aqueous cover layer. Subsequent experiments with antibody-functionalized sensors and virus simulants confirmed the ability of the device to detect virus-sized particles under flow via a recognition-mediated process. This work sets the stage for incorporation of 2D slab-PhC sensors into fully integrated photonic sensor systems.

Universal tranexamic acid therapy to minimize transfusion for major joint arthroplasty: a retrospective analysis of protocol implementation.

PURPOSE: Tranexamic acid (TXA) therapy can reduce red blood cell (RBC) transfusion; however, this therapy remains underutilized in many surgical patient populations. We assessed whether implementation of a protocol to facilitate universal administration of TXA in patients undergoing total hip or knee arthroplasty would reduce the incidence of RBC transfusion without increasing adverse clinical outcomes. METHODS: We implemented a quality of care policy to provide universal administration of intravenous TXA at a dose of 20 mg·kg(-1) iv to all eligible patients undergoing total hip or knee arthroplasty from October 21, 2013 to April 30, 2014. We compared data from an equal number of patients before and after protocol implementation (n = 422 per group). The primary outcome was RBC transfusion with secondary outcomes including postoperative hemoglobin concentration (Hb) and length of hospital stay. Adverse events were identified from the electronic medical records. Data were analyzed by a Chi square test and adjusted logistic and linear regression analysis. RESULTS: Implementation of the protocol resulted in an increase in TXA utilization from 45.8% to 95.3% [change 49.5%; 95% confidence interval (CI), 44.1 to 54.5; P < 0.001]. This change was associated with a reduction in the rate of RBC transfusion from 8.8% to 5.2%, (change -3.6%; 95% CI, -0.1 to -7.0; P = 0.043). Pre- and post-protocol mean [standard deviation (SD)] Hb values were similar, including the nadir Hb prior to RBC transfusion [72 (8) g·L(-1) vs 70 (8) g·L(-1), respectively; mean difference -1 g·L(-1); 95% CI, -3 to 5; P = 0.569]. Length of stay was not altered, and no increase in adverse events was observed. CONCLUSIONS: Implementation of a perioperative TXA protocol was associated with both an increase in TXA use and a reduction in RBC transfusion following hip or knee arthroplasty. Adverse events and length of hospital stay were not influenced by the protocol.

Discrimination of "specific" and "nonspecific" binding in two-dimensional photonic crystals.

In this paper, we propose a design for a 2D slab photonic crystal (PhC) virus sensor and an associated signal analysis methodology that together enable single-virus detection while rejecting false positives that occur due to non-specific interactions of serum proteins and small molecules with the sensor surface. The slab-PhC design takes advantage of both the optical and geometrical properties of its incorporated structures by physically limiting virus infiltration to only the most sensitive region of the PhC sensor, while allowing simultaneous measurement of both site-selective virus infiltration and non-specific small molecule accumulation across the device. Notably, the proposed sensor transducer is compatible with both standard semiconductor fabrication procedures and lab-on-a-chip style microfluidic delivery systems. 3D finite-difference time-domain electromagnetic field computation results are presented, the outcomes of which indicate that both specific (target) virus capture and non-specific (non-target) binding can be simultaneously measured and discerned from one another. This type of capacity for background-corrected, single-pathogen target detection would provide a new and novel advancement toward sensitive, label-free virus diagnostics.

Two-dimensional photonic crystals for sensitive microscale chemical and biochemical sensing.

Photonic crystals - optical devices able to respond to changes in the refractive index of a small volume of space - are an emerging class of label-free chemical- and bio-sensors. This review focuses on one class of photonic crystal, in which light is confined to a patterned planar material layer of sub-wavelength thickness. These devices are small (on the order of tens to hundreds of microns square), suitable for incorporation into lab-on-a-chip systems, and in theory can provide exceptional sensitivity. We introduce the defining characteristics and basic operation of two-dimensional photonic crystal sensors, describe variations of their basic design geometry, and summarize reported detection results from chemical and biological sensing experiments.

Selective virus detection in complex sample matrices with photonic crystal optical cavities.

Rapid, sensitive, and selective detection of viruses is critical for applications in medical diagnostics, biosecurity, and environmental safety. In this article, we report the application of a point-defect-coupled W1 photonic crystal (PhC) waveguide biosensor to label-free optical detection of viruses. Fabricated on a silicon-on-insulator (SOI) substrate using electron-beam (e-beam) lithography and reactive-ion-etching, the PhC sensing platform allows optical detection based on resonant mode shifts in response to ambient refractive index changes produced by infiltration of target biomaterial within the holes of the PhC structure. Finite difference time domain (FDTD) calculations were performed to assist with design of the sensor, and to serve as a theoretical benchmark against which experimental results could be compared. Using Human Papillomavirus virus-like particles (VLPs) spiked in 10% fetal bovine serum as a model system, we observed a limit of detection of 1.5 nM in simple (buffer only) or complex (10% serum) sample matrices. The use of anti-VLP antibodies specific for intact VLPs with the PhC sensors provided highly selective VLP detection.

Assessment and treatment of preoperative anemia: Continuing Professional Development.

PURPOSE: The purpose of this continuing professional development (CPD) module is to review the risk of anemia and transfusion in perioperative patients and to propose an approach for the diagnosis and treatment of preoperative anemia. PRINCIPAL FINDINGS: Preoperative anemia has been associated with increased transfusion of red blood cells, organ injury, and mortality. Postoperative anemia has also been associated with impaired recovery from surgery. Transfusion also increases the risk of infection, organ injury, and mortality. Preoperatively, iron deficiency anemia can be corrected with oral or intravenous iron; certain types of patients might respond to administration of erythrocyte stimulating agents (ESAs). With ESAs, the increased risk of thrombosis should be balanced against the expected benefit. CONCLUSIONS: Preoperative diagnosis and treatment of anemia may reduce the risk of morbidity and mortality associated with both anemia and transfusion.

Combination of a Beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor for the treatment of obesity.

We report the novel combination of a selective beta adrenoceptor modulator and a norepinephrine-serotonin uptake inhibitor (sibutramine) with potential for the treatment of obesity. The synthesis and characterization of 6-[4-[2-[[(2S)-3-(9H-carbazol-4-yloxy)-2-hydroxypropyl]amino]-2-methylpropyl]phenoxy]pyridine-3-carboxamide (LY377604), a human ß3-adrenergic receptor agonist and ß1- and ß2-adrenergic receptor antagonist with no sympathomimetic activity at the ß1- and ß2-adrenergic receptors, is reported. Some in vivo data in both rats and humans is presented.

Phenoloxidase in larvae of Plodia interpunctella (Lepidoptera: Pyralidae): molecular cloning of the proenzyme cDNA and enzyme activity in larvae paralyzed and parasitized by Habrobracon hebetor (Hymenoptera: Braconidae).

Phenoloxidase (PO) is a major component of the insect immune system. The enzyme is involved in encapsulation and melanization processes as well as wound healing and cuticle sclerotization. PO is present as an inactive proenzyme, prophenoloxidase (PPO), which is activated via a protease cascade. In this study, we have cloned a full-length PPO1 cDNA and a partial PPO2 cDNA from the Indianmeal moth, Plodia interpunctella (Hubner) (Lepidoptera: Pyralidae) and documented changes in PO activity in larvae paralyzed and parasitized by the ectoparasitoid Habrobracon hebetor (Say) (Hymenoptera: Braconidae). The cDNA for PPO1 is 2,748 bp and encodes a protein of 681 amino acids with a calculated molecular weight of 78,328 and pI of 6.41 containing a conserved proteolytic cleavage site found in other PPOs. P. interpunctella PPO1 ranges from 71-78% identical to other known lepidopteran PPO-1 sequences. Percent identity decreases as comparisons are made to PPO-1 of more divergent species in the orders Diptera (Aa-48; As-49; and Sb-60%) and Coleoptera (Tm-58; Hd-50%). Paralyzation of host larvae of P. interpunctella by the idiobiont H. hebetor results in an increase in phenoloxidase activity in host hemolymph, a process that may protect the host from microbial infection during self-provisioning by this wasp. Subsequent parasitization by H. hebetor larvae causes a decrease in hemolymph PO activity, which suggests that the larval parasitoid may be secreting an immunosuppressant into the host larva during feeding.

Insect fragments in flour: relationship to lesser grain borer (Coleoptera: Bostrichidae) infestation level in wheat and rapid detection using near-infrared spectroscopy.

We determined that the number of insect fragments, quantified using the standard flotation method, in flour milled from wheat infested with larvae, pupae, or preemergent adults of the lesser grain borer, Rhyzopertha dominica (F.), was proportional to infestation level. Wheat infested with a single preemergent adult contributed 28 and 10x as many fragments as wheat infested with a single larva or pupa, respectively. Using regression models that were developed from these data, we predicted that the maximum infestation level that would result in flour with fragment counts below the Food and Drug Administration defect action level (75 fragments/50 g of flour) was 0.95 and 1.5% (380-640 infested kernels/kg of wheat) for pupae and larvae, but it decreased to 0.05% (20 infested kernels/kg) when the grain was infested with preemergent adults. We also reexamined the accuracy and sensitivity of near-infrared spectroscopy (NIRS) for detecting insect fragments in flour by testing three different NIR spectrometers. NIRS-predicted numbers of insect fragments were correlated with the actual number of fragments. NIRS is less precise than the standard flotation method, but it is rapid, nondestructive, does not require extensive sample preparation, and could easily be automated for a more sophisticated sampling protocol for flour based on prescreening samples with NIRS followed up by use of the standard flotation method when necessary.

Chronological age-grading of three species of stored-product beetles by using near-infrared spectroscopy.

The accuracy of near-infrared spectroscopy (NIRS) for predicting the chronological age of adults of the rice weevil, Sitophilus oryzae (L.); the lesser grain borer, Rhyzopertha dominica (F.); and the red flour beetle, Tribolium castaneum (Herbst), three pests of stored grain, was examined. NIRS-predicted age correlated well with actual age of these three species. Age predictions in S. oryzae by using the NIRS method are not dependent upon adult sex or temperatures to which adult weevils are exposed. Results indicated that water content decreased with increasing age in rice weevil adults, and excluding wavelengths at which water absorbs NIR radiation reduced the accuracy of correct classification. Additionally, removing cuticular lipids from insects resulted in a significant decrease in classification accuracy of weevils, indicating that these compounds may be partly responsible for the ability of NIRS to differentiate young from old beetles. NIRS is a nondestructive technique that can be used to age-grade large numbers of adult stored-product beetles, information that could help to increase the accuracy of population models for these pest species.

Stage-specific surface chemicals of Plodia interpunctella: 2-acyl-1,3-cyclohexanediones from larval mandibular glands serve as cuticular lipids.

Cuticular lipid compositions of all life stages of the stored product moth Plodia interpunctella have been determined. Eggs and adults of P. interpunctella have cuticular lipids consisting solely of hydrocarbons. The composition of eggs and adult females is qualitatively nearly identical with ca. 86 hydrocarbons (11 n-alkanes, 39 monomethyl alkanes, 19 dimethyl alkanes, 11 trimethyl alkanes and 6 monoenes) except females lack the 2-methyl alkanes found in eggs. Adult males have a hydrocarbon composition qualitatively nearly identical to females with the exception that they lack the monoenes. Larval and pupal cuticular lipids are dominated by a mixture of ca. 20 previously described 2-acyl-1,3-cyclohexanediones, with only minute amounts of n-alkanes on the larvae and pupae. The 2-acyl-1,3-cyclohexanediones are continuously secreted onto their silk webbing and food particles by the paired mandibular glands found in all larvae. Extracts from dissected mandibular glands have a qualitatively identical composition to larval cuticular extracts. The pupal stage (which does not have mandibular glands) is enclosed in a silk cocoon also coated with 2-acyl-1,3-cyclohexanediones laid down while the wandering stage larvae spin the cocoon. The 2-acyl-1,3-cyclohexanediones have physical properties which closely mimic those of cuticular hydrocarbons, including melting point and boiling point range and hydrophobicity. This is the first report of an insect with a life stage that does not use conventional cuticular lipids for conservation of water.

Innate immunity in a pyralid moth: functional evaluation of domains from a beta-1,3-glucan recognition protein.

Invertebrates, like vertebrates, utilize pattern recognition proteins for detection of microbes and subsequent activation of innate immune responses. We report structural and functional properties of two domains from a beta-1,3-glucan recognition protein present in the hemolymph of a pyralid moth, Plodia interpunctella. A recombinant protein corresponding to the first 181 amino-terminal residues bound to beta-1,3-glucan, lipopolysaccharide, and lipoteichoic acid, polysaccharides found on cell surfaces of microorganisms, and also activated the prophenoloxidase-activating system, an immune response pathway in insects. The amino-terminal domain consists primarily of an alpha-helical secondary structure with a minor beta-structure. This domain was thermally stable and resisted proteolytic degradation. The 290 residue carboxyl-terminal domain, which is similar in sequence to glucanases, had less affinity for the polysaccharides, did not activate the prophenoloxidase cascade, had a more complicated CD spectrum, and was heat-labile and susceptible to proteinase digestion. The carboxyl-terminal domain bound to laminarin, a beta-1,3-glucan with beta-1,6 branches, but not to curdlan, a beta-1,3-glucan that lacks branching. These results indicate that the two domains of Plodia beta-1,3-glucan recognition protein, separated by a putative linker region, bind microbial polysaccharides with differing specificities and that the amino-terminal domain, which is unique to this class of pattern recognition receptors from invertebrates, is responsible for stimulating prophenoloxidase activation.

Profound hypoxemia resulting from shunting across an inadvertent atrial septal tear after left ventricular assist device placement.

UNLABELLED: Defects within the interatrial septum (IAS) can be a source of significant right-to-left shunting and hypoxemia, particularly after placement of a left ventricular assist device (LVAD). We report a case of LVAD placement in which an unrecognized IAS tear occurred intraoperatively, leading to profound arterial desaturation. Transesophageal echocardiography (TEE) was instrumental in making the diagnosis. Certain intraoperative events increased the pressure gradient between the right and left atria, aggravating hypoxemia. We recommend that patients undergoing LVAD placement be screened intraoperatively with TEE for unrecognized IAS defects. Re-examination of the IAS should occur on weaning from cardiopulmonary bypass. IMPLICATIONS: A traumatic atrial septal defect after atrial cannulation caused a right-to-left intracardiac shunt on initiation of left ventricular assist device support that was further aggravated by chest closure and pleural suction, culminating in severe hypoxemia.

RNAi-induced silencing of embryonic tryptophan oxygenase in the Pyralid moth, Plodia interpunctella.

Gene silencing through the introduction of double-stranded RNA (RNA interference, RNAi) provides a powerful tool for the elucidation of gene function in many systems, including those where genomics and proteomics are incomplete. The use of RNAi technology for gene silencing in Lepidoptera has lacked significant attention compared to other systems. To demonstrate that RNAi can be utilized in the lepidopteran, Plodia interpunctella, we cloned a cDNA for tryptophan oxygenase, and showed that silencing of tryptophan oxygenase through RNAi during embryonic development resulted in loss of eye-color pigmentation. The complete amino acid sequence of Plodia tryptophan oxygenase can be accessed through NCBI Protein Database.