Biphasic Modes Research Articles

Diabetic Foot Complications in Saudi Arabia: A Retrospective Study.

A common chronic health problem among Saudi Arabians is diabetes mellitus (DM). One of the most serious complications of diabetes is diabetic foot (DMF). The objective of this study was to identify the most common complications that develop among patients with DMF. In addition, we conducted a demographic analysis of chronic diabetic complications related to DMF. The study involved 100 DMF attending the Jeddah clinic of Dr Soliman Fakeeh Hospital. Several chronic complications associated with DMF were reported, including peripheral arterial disease (PAD), coronary artery disease (CAD), retinopathy, nephropathy, and neuropathy. We examined the feet for ulcers, gangrene, amputations, bone deformities, Charcot joints, osteoarthritis, septic arthritis, and osteomyelitis. By using B-mode ultrasound and spectral Doppler imaging, we imaged the posterior tibial and anterior tibial arteries. People with poorly controlled diabetes mellitus type 2 (T2DM) are more likely to develop diabetic feet. The most common foot complications were foot ulcers (81%), foot amputations (31%), foot gangrene (29%) (29/100), bone deformities (22%) (22/100), ingrown toenails (17%) (17/100), Charcot's foot (10%) (10/100), and calluses (9%) (9/100). The majority of the patients suffered from hypertension and half had anaemia. Diabetic peripheral neuropathy affected about half of the patients, diabetic nephropathy affected one-third, and diabetic retinopathy affected 14%. Approximately a quarter (25/100) of the patients had CAD and less than half had PAD. There was atherosclerosis in 43% (43/100) of popliteal/infra-popliteal arteries. Twenty-two percent (22/100) of the anterior tibial arteries and 25% (25/100) of the posterior tibial arteries were stenotic or occluded. A biphasic mode was observed in 21% (21/100) of anterior tibial arteries, a monophasic mode in 9% (9/100), and a non-flowing mode in 3% (3/100). Twenty-three percent (23/100) of the posterior tibial arteries displayed biphasic Doppler modes, 5% (5/100) displayed monophasic modes, and 6% (6/100) displayed non-flowing modes. Conclusion: Diabetes foot is common among older males with poorly controlled T2DM. The most common foot complications were amputations, gangrene, foot ulcers, bone deformities, ingrown toenails, Charcot's foot, and calluses. Most DMF patients were anemic and hypertensive. Diabetes-related microvascular complications, such as diabetic peripheral neuropathy, nephropathy, and retinopathy, as well as macrovascular complications, such as coronary artery disease and peripheral arterial disease, were associated with DMF.

Impact of tissue-electrode contact force on irreversible electroporation for atrial fibrillation in potato models

Background: Irreversible electroporation (IRE) is an emerging tissue ablation technique that offers advantages over traditional catheter ablation, such as minimal thermal damage and reduced treatment time. However, as this technique also involves delivering energy through a catheter to target tissue, there are still challenges regarding the contact between the catheter and the targeted tissue, and there is a lack of relevant studies. In this study, we examined this issue using potato models with three groups of experiments. Methods: First, the relationship between the effect of biphasic and monophasic output modes and contact force (CF) was studied. Next, the effect of different voltages on biphasic output mode was examined. Finally, impedance analysis was conducted to test the contact impedance under different CFs. Results: The IRE ablation efficacy increased with the increase of CF in both monophasic and biphasic output modes, and there was a strong correlation between the ablation efficacy and the CF. In addition, at three voltage levels, the IRE ablation efficacy increased with increasing CF, and there was a strong correlation between the ablation efficacy and the CF. Conclusion: The results indicate that, under common IRE electrical parameter configuration, the effect of IRE on the tissue has a positive response to the CF of the electrode in the potato model. This finding has important implications for the design of electrodes used in IRE for the treatment of atrial fibrillation.

Spectroscopic analysis and anti-inflammatory effects of Milicia excelsa (Moraceae) leaf and fractions

This study evaluated the spectroscopic and anti-inflammatory properties of the ethanol leaf extract of Milicia excelsa and fractions. The anti-inflammatory activities of the extract and various organic fractions were investigated using bovine erythrocyte membrane stabilizing assay. Ultraviolet‐visible (UV-VIS) and Fourier transform-infrared (FT-IR) methods were used to detect the characteristic peak values and their functional groups. The results showed that the crude extract and ethyl acetate fraction showed minimum percentage inhibitions of 0.88 ± 0.30 and 72.05 ± 0.45% and maximum percentage inhibitions of 81.66 ± 0.23% and 99.07 ± 0.30% respectively compared to the standard anti-inflammatory drug (Indomethacin) which exhibited minimum and maximum percentage inhibitions of 52.64 ± 0.83 and 75.51 ± 1.52% respectively. The UV-VIS profile showed the peaks ranging from 270 to 670 nm with the absorption values from 0.040 – 0.720 which could confirm the presence of aromatic compounds, alkaloids, flavonoids, unsaturated conjugated compounds in the plant. In addition, the FT-IR revealed diagnostic peaks around 3570-3200, 3000-2800, 2865-2845, 2850-2815, 2820-2780, 2070-2000, 1630-1750, 1640-1450, 1340-1250, 1200-1000, 800-700 nm-1 which could confirm the presence of phenols/alcohol/carboxylic acids, alkanes, diazocompounds, aldehyde /ketone/ amide/ester, alkenes/aromatic compounds, ethers/phosphate compounds, aliphatic/chloro compounds respectively in Milicia excelsa. This study therefore demonstrated that ethyl acetate fraction with the highest percentage inhibition contained bioactive principles that protected the erythrocyte membranes effectively from lyses and also exhibited both monophasic and biphasic modes. The study also produced the UV-VIS and FT-IR spectrum profile for Milicia excelsa leaf which could be used to identify the plant biomarkers and chemical markers.

Chirality Controls Mesenchymal Stem Cell Lineage Diversification through Mechanoresponses

Biogenesis and tissue development are based on the heterogenesis of multipotent stem cells. However, the underlying mechanisms of stem cell fate specification are unclear. Chirality is one of the most crucial factors that affects stem cell development and is implicated in asymmetrical cell morphology formation; however, its function in heterogeneous cell fate determination remains elusive. In this study, it is reported that the chirality of a constructed 3D extracellular matrix (ECM) differentiates mesenchymal stem cells to diverse lineages of osteogenic and adipogenic cells by providing primary heterogeneity. Molecular analysis shows that left-handed chirality of the ECM enhances the clustering of the mechanosensor Itgα5, while right-handed chirality decreases this effect. These differential adhesion patterns further activate distinct mechanotransduction events involving the contractile state, focal adhesion kinase/extracellular signal-regulated kinase 1/2 cascades, and yes-associated protein/runt-related transcription factor 2 nuclear translocation, which direct heterogeneous differentiation. Moreover, theoretical modeling demonstrates that diverse chirality mechanosensing is initiated by biphasic modes of fibronectin tethering. The findings of chirality-dependent lineage specification of stem cells provide potential strategies for the biogenesis of organisms and regenerative therapies.

Strain-specific effect on biphasic DNA binding by HIV-1 integrase.

: The oligomerization of HIV-1 integrase onto DNA is not well understood. Here we show that HIV-1 integrase binds the DNA in biphasic (high-affinity and low-affinity) modes. For HIV-1 subtype B, the high-affinity mode is ∼100-fold greater than the low-affinity mode (Kd.DNA = 37 and 3400 nmol/l, respectively). The Kd.DNA values of patient-derived integrases containing subtype-specific polymorphisms were affected two- to four-fold, suggesting that polymorphisms may have an influence on effective-concentrations of inhibitors, as these inhibitors preferably bind to integrase-DNA complex.

Probing the enzyme kinetics, allosteric modulation and activation of α1- and α2-subunit-containing AMP-activated protein kinase (AMPK) heterotrimeric complexes by pharmacological and physiological activators.

AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that serves as a pleotropic regulator of whole body energy homoeostasis. AMPK exists as a heterotrimeric complex, composed of a catalytic subunit (α) and two regulatory subunits (β and γ), each present as multiple isoforms. In the present study, we compared the enzyme kinetics and allosteric modulation of six recombinant AMPK isoforms, α1β1γ1, α1β2γ1, α1β2γ3, α2β1γ1, α2β2γ1 and α2β2γ3 using known activators, A769662 and AMP. The α1-containing complexes exhibited higher specific activities and lower Km values for a widely used peptide substrate (SAMS) compared with α2-complexes. Surface plasmon resonance (SPR)-based direct binding measurements revealed biphasic binding modes with two distinct equilibrium binding constants for AMP, ADP and ATP across all isoforms tested. The α2-complexes were ∼25-fold more sensitive than α1-complexes to dephosphorylation of a critical threonine on their activation loop (pThr(172/174)). However, α2-complexes were more readily activated by AMP than α1-complexes. Compared with β1-containing heterotrimers, β2-containing AMPK isoforms are less sensitive to activation by A769662, a synthetic activator. These data demonstrate that ligand induced activation of AMPK isoforms may vary significantly based on their AMPK subunit composition. Our studies provide insights for the design of isoform-selective AMPK activators for the treatment of metabolic diseases.

Adaptive support ventilation versus biphasic positive airway pressure in patients with acute exacerbation of chronic obstructive pulmonary disease

Introduction The goal of mechanical ventilation in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) is to maintain both adequate oxygenation and ventilation, reduce the work of breathing, and improve the comfort of the patient until the condition has been reversed or alleviated. Unlike conventional pressure-controlled ventilatory modes, biphasic modes [biphasic positive airway pressure (BIPAP)] allow for unrestricted spontaneous breathing. Adaptive support ventilation (ASV) is a new ventilatory mode that uses a closed-loop controlled mode between breaths. It can be used safely during initiation, maintenance, or weaning phases of the mechanical ventilation. Objective The aim of this work was to compare between BIPAP and ASV in the management of patients with AECOPD in terms of ventilatory parameters, lung mechanics, patient ventilator dys-synchrony, days of mechanical ventilation, and mortality. Patients and methods This double-blind randomized trial was conducted on 72 AECOPD adult patients admitted to the units of Critical Care Medicine Department in Alexandria Main University Hospital indicated for invasive mechanical ventilation. Patients were excluded for reasons such as pregnancy, hemodynamic instability, and severe neurological disease. They were categorized randomly as follows: group I included 36 patients who were ventilated using the BIPAP mode and group II included 36 patients who were ventilated using the ASV mode. Informed consent was obtained from patients' first of kin after approval from the Ethical Committee of Alexandria Faculty of Medicine. Ventilatory parameters (respiratory rate, tidal volume, peak airway pressure, and rapid shallow breathing index) and lung mechanics (static compliance and inspiratory resistance) were recorded. Patient ventilator dys-synchrony and asynchrony index were recorded daily. Days of mechanical ventilation, ICU stay, and mortality were calculated. Results In the ASV group, the respiratory rate was significantly lower, tidal volume was higher, and rapid shallow breathing index was lower. Significantly higher compliance and lower resistance were encountered in the ASV group, with better patient-ventilator synchronization. A significant reduction in days of mechanical ventilation in the ASV group was found with less ICU length of stay. Conclusion ASV may be safer in AECOPD patients and may have a better prognosis.

Reduced effects of thyroid hormone on gene expression and metamorphosis in a paedomorphic plethodontid salamander.

It has been over a century since Gudernatsch (1912, Wilhelm Roux Arch Entwickl Mech Org 35:457-483) demonstrated that mammalian thyroid gland extracts can stimulate tadpole metamorphosis. Despite the tremendous developmental diversity of amphibians, mechanisms of metamorphosis have mostly been studied in a few model systems. This limits our understanding of the processes that influence the evolution of developmental aberrations. Here we isolated thyroid hormone receptors alpha (TRα) and beta (TRβ) from Oklahoma salamanders (Eurycea tynerensis), which exhibit permanently aquatic (paedomorphic) or biphasic (metamorphic) developmental modes in different populations. We found that TRα and TRβ were upregulated by thyroid hormone (T3 ) in tail tissues of larvae from metamorphic populations, but basal levels of TR expression and T3 responsiveness were reduced in larvae from paedomorphic populations. Likewise, we found that T3 treatment resulted in complete loss of larval epibranchials in larvae from metamorphic populations, but little to no epibranchial remodeling occurred in larvae from paedomorphic populations over the same duration. This is the first study to directly demonstrate reduced gene expression and metamorphic responses to T3 in a paedomorphic plethodontid compared to metamorphic conspecifics, and the first salamander system to show differential expression of thyroid hormone receptors associated with alternative developmental patterns.

Arabidopsis floral phytomer development: auxin response relative to biphasic modes of organ initiation.

In the Arabidopsis inflorescence meristem (IM), auxin is considered a prepatterning signal for floral primordia, whereas a centripetal mode of positional information for floral organ identity is inherent to the ABCE model. However, spatio-temporal patterns of organ initiation in each whorl at the earliest initiation stages are largely unknown. Evidence suggests that initial flower development occurs along an abaxial/adaxial axis and conforms to phytomer theory. Use of the founder cell marker DORNRÖSCHEN-LIKE (DRNL) as a tool in leafy, puchi, and apetala 1 cauliflower mutant backgrounds suggests that bract founder cells are marked at the IM periphery. The DRNL transcription domain in the wild-type IM is spatially discrete from DR5 expression, suggesting that bract initiation is independent of canonical auxin response. When bracts develop in lfy and puchi mutant floral primordia the initiation of lateral sepals precedes the specification of medial sepals compared with wild type, showing an interplay between bract and abaxial sepal founder cell recruitment. In the perianthia (pan) mutant background, DRNL expression indicates that a radial outer whorl arrangement derives from splitting of sepal founder cell populations at abaxial and adaxial positions. This splitting of incipient sepal primordia is partially dependent on PRESSED FLOWER (PRS) activity and implies that sepal specification is independent of WUSCHEL and CLAVATA3 expression, as both marker genes only regain activity in stage-2 flowers, when patterning of inner floral organs switches to a centripetal mode. The transition from an initially abaxial/adaxial into a centripetal patterning programme, and its timing represent an adaptive trait that possibly contributes to variation in floral morphology, especially unidirectional organ initiation.

Nonconventional ventilation techniques

Mechanical ventilation is one of the most important life support tools in the ICU, but it may also be harmful by causing ventilator-induced lung injury (VILI) and other deleterious effects. Advances in ventilator technology have allowed the introduction of numerous ventilator modes in an effort to improve gas exchange, reduce the risk of VILI, and finally improve outcome. In this review, we will summarize the studies evaluating some of the nonconventional ventilation techniques and discuss their possible use in clinical practice. Proportional assist ventilation and neurally adjusted ventilator assist are able to improve patient-ventilator synchrony, possibly sleep, and may be better tolerated than pressure support ventilation; both integrate the physiological concept of respiratory variability like noisy ventilation. Experimental or short-term clinical studies have shown physiological benefits with the application of biphasic pressure modes. Some of the automated weaning algorithms may reduce time spent on ventilator and decrease ICU stay, especially in a busy environment. Apart from the physiological and clinical attractiveness demonstrated in animals and small human studies, most of the nonconventional ventilator modes must prove their clinical benefits in large prospective trials before being applied in daily clinical practice.

Tidal Volume Variability During Airway Pressure Release Ventilation: Case Summary and Theoretical Analysis

Airway pressure-release ventilation (APRV) is used in the management of patients with severe or refractory respiratory failure. In addition to reversal of inspiratory-expiratory ratios, this pressure control mode also allows unrestricted spontaneous breathing. The spontaneous tidal volume (V(T)), as well as the V(T) resulting from transition between the high and low airway pressures, is uncontrolled. There are limited data on the within-patient variation of actual V(T) and the safety of these modes. The authors present a patient with severe ARDS who was managed with biphasic modes (APRV and bi-level positive airway pressure). Serial V(T) measurements showed that V(T) ranged from 4 to 12 mL/kg predicted body weight. Computed tomography scan images and chest radiographs obtained before and following APRV showed lung parenchyma changes that may be related to ventilator-induced lung injury. We also present a mathematical model that is useful for simulating APRV and demonstrating the issues related to volume delivery for mandatory breaths during the transition between the 2 pressure levels. A key finding of this analysis is the interdependence of release volume, autoPEEP, and the T(low) time setting. Furthermore, it is virtually impossible to target a specific P(aCO(2)) with a desired level V(T) and autoPEEP in a passive model, emphasizing the importance of spontaneous breathing with this mode. This case report suggests caution when using these modes, and that end-inspiratory lung volumes and V(T) should be limited to avoid lung injury. The important point of this case study and model analysis is that the application of APRV is more complex than it appears to be. It requires a lot more knowledge and skill than may be apparent from descriptions in the literature.

Bioproduction of cis‐(1S,2R)‐indandiol, a chiral pharmaceutical intermediate, using a solid–liquid two‐phase partitioning bioreactor for enhanced removal of inhibitors

AbstractBACKGROUND: A solid‐liquid two‐phase partitioning bioreactor (TPPB) was used in the biotransformation of indene to cis‐(1S,2R)‐indandiol by Pseudomonas putida 421‐5 (ATCC 55687). Metered substrate feeding in single‐phase operation, or delivery from an immiscible liquid, have previously been employed to regulate the exposure of the biocatalyst to inhibitory concentrations of the substrate. In contrast, the solid‐liquid platform provided in situ substrate addition (ISSA) as well as simultaneous it in situ product removal (ISPR) as a means of overcoming substrate and product toxicity. Three different modes of operation were compared for their effects on the performance of this biotransformation: single‐phase, fed‐batch operation was carried out as a benchmark in 2.75 L aqueous medium, and subsequently with the inclusion of either 700 g liquid silicone oil or 700 g solid polymer beads.RESULTS: Biphasic modes achieved a 3‐fold productivity improvement with respect to single‐phase (30 to 90 mg L−1 h−1), and solid‐liquid productivity was similar to liquid‐liquid operation while achieving more extensive removal of inhibitory compounds resulting in a slightly higher product titer (1.29 vs 1.16 g L−1). The operability of the reactor was improved by the phase stability of the solid polymer beads relative to immiscible organic solvents, preventing emulsion formation and facilitating analytics.CONCLUSION: Solid polymer beads replaced the immiscible liquid auxiliary phase for substrate delivery while performing simultaneous inhibitory molecule sequestration. Copyright © 2011 Society of Chemical Industry

Candida albicans Biofilms Produce More Secreted Aspartyl Protease than the Planktonic Cells

By using a simple, low-cost system of polystyrene centrifuge tubes we compared the secreted aspartyl proteases (Saps) secretion during the biphasic growth modes of Candida albicans using twenty-one clinical isolates. Our results indicate that biofilms of C. albicans consistently secrete more Saps than their planktonic counterparts.

Glycerol as a green solvent for high product yields and selectivities

Organic synthesis is usually performed in solution to dissolve both reactants and catalysts and to deliver heat. Here, we show that glycerol, which is a non-toxic, biodegradable, and recyclable liquid manufactured from renewable sources, has a high potential to serve as alternative green solvent for organic reactions. Several catalytic and non-catalytic reactions were successfully performed in glycerol. High products yields and selectivities were achieved. Besides solubility of the reactants and the catalysts and easy separation of the product, glycerol offers several other benefits such as catalyst recycling, microwave assisting reaction, and biphasic and emulsion modes.

Fluorocarbon Soluble Copper(II) Carboxylate Complexes with Nonfluoroponytailed Nitrogen Ligands as Precatalysts for the Oxidation of Alkenols and Alcohols under Fluorous Biphasic or Thermomorphic Modes: Structural and Mechanistic Aspects

This fluorous biphasic catalysis (FBC) contribution was focused on the synthesis and characterization of new fluorous soluble R(f)-Cu(II) carboxylate complexes containing nonfluoroponytailed ligands and defines their role as precatalysts for the FBC oxidation of alkenols and alcohols in the presence of 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO)/O(2). In this FBC approach, we have utilized the phase-switching technique of Vincent et al. (J. Am. Chem. Soc. 2002, 124, 12942) to solubilize the nonfluoroponytailed ligands, N-1,4,7-Me(3)TACN, 2, and N-1,4,7-pentamethyldiethylenetriamine (PMDETA), 3, by reaction with a fluorous solvent-soluble copper (II) dimeric complex, [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2)](2), 1. Moreover, the reaction of nonfluoroponytailed ligands 2 and 3 with 1 afforded new perfluoroheptane-soluble Cu(II) complexes, [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2)(2)], 4, and [Cu({C(8)F(17)(CH(2))(2)}(2)CHCO(2))(2) (3)], 5, respectively. The known Cu(II) complex, 1, was further characterized by electron paramagnetic resonance (EPR) spectroscopy confirming its dimeric structure, while 4 and 5 were characterized by elemental analysis, IR, diffuse reflectance UV-vis, and EPR spectroscopy. Furthermore, 1, 4, and 5 were evaluated as precatalysts for alkenol and alcohol oxidation. The oxidation reactions of alkenols and alcohols in the presence of TEMPO/O(2) proceeded under FBC conditions for 1, 4, and 5, but 1-octanol was unreactive under single-phase FBC conditions at 90 degrees C with TEMPO/O(2). The thermomorphic property of 5, soluble in chlorobenzene/toluene at 90 degrees C but insoluble at room temperature, was also evaluated in the selective oxidation of p-nitrobenzyl alcohol to p-nitrobenzaldehyde. Plausible mechanisms concerning these FBC/thermomorphic oxidation reactions will be discussed.

Synthesis, characterization and catalytic activity of a Wilkinson's type metal-organic-polyoxometalate hybrid compound.

A metal-organic-polyoxometalate hybrid compound with two functional centers consisting of a rhodium(I)bis(diphenylphospine) unit connected through two alkylene bridging groups to a lacunary Keggin type polyoxometalate was synthesized and used as an effective, recyclable hydrogenation catalyst in monophasic and aqueous biphasic reaction modes.

Molecular recognition between oligopeptides and nucleic acids. DNA sequence specificity and binding properties of an acridine‐linked netropsin hybrid ligand

The binding to DNA of a mixed function ligand (NETGA) is described, in which a potential intercalating group, an acridine moiety, is incorporated at the carboxyl terminus of the minor groove binding oligopeptide netropsin skeleton. Scatchard analysis of absorption data provided evidence of two modes of binding to DNA with K1 = 9.1 x 10(5) M-1 at low r values (0.003-0.1), and a binding site size n = 10, indicative of binding of both moeities. At high binding ratios (greater than 0.1), K2 = 0.9 x 10(5) M-1 and n = 5 corresponding to external binding. Complementary strand MPE footprinting on a pBR322 restriction fragment showed NETGA binds to 5'-AAAT like netropsin. It causes enhanced cleavage by MPE, particularly at G-C rich sequences and remote from the preferred binding sites. Viscometry measurements provided evidence for biphasic modes of the two binding portions of NETGA. Fluorescence polarization and linear dichroism measurements were in accord with distinct modes of interaction of the acridine (intercalation) and oligopeptide (minor groove binding) portions of NETGA. LD measurements on NETGA indicate that the oligopeptide moiety (netropsin-like) has an orientation typical of minor groove binders, whereas the degree of intercalation of the acridine group is decreased by association of the oligopeptide moiety.