Fold Improvement Research Articles

Abstract 3676: Influence of early toxicology assessment on the selection of azd9291

Abstract Discovery toxicology is the concept of evaluating the safety of molecules early in the drug development process when there is chemical scope to refine candidate drug quality. The aim is to identify and mitigate safety liabilities to maximize the chance of clinical success. This poster describes the impact of discovery toxicology on the selection of AZD9291, an irreversible inhibitor of both EGFR-TKI sensitising and resistance mutations. Although, maintaining a margin of selectivity to wild type EGFR was a key medicinal chemistry goal, early in vitro selectivity evaluation of the lead series compounds revealed significant off-target inhibition against the insulin and insulin-like growth factor receptors (IR/IGFR). Further exploration of this liability in a rat in vivo study revealed that our early lead compound (Cmpd 1) was associated with severe hyperglycemia, rapid body weight loss and evidence of reduced gastric emptying. The reduction in bodyweight and the inhibition of gastric emptying was dose limiting and we hypothesized this was caused by the hyperglycaemia. A broader selection of compounds based on the same scaffold was tested both in vitro and in vivo in the hope of identifying one or more compounds without this liability. Compounds were tested in a modified single dose rat study, exploring insulin and glucose homeostasis and effects on gastric emptying. Compounds within the shortlist caused increases in insulin of up to 80-fold, 3-fold increases in glucose and up to a 60% reduction in gastric emptying. There was a clear link between in vitro IR/IGF inhibition, hyperinsulinemia and inhibition of gastric emptying. One of the shortlisted candidates (now selected as AZD9291), had up to a 30 fold improvement in in vitro IGFR cellular potency compared to previous candidates and had no effect on insulin/glucose homeostasis in vivo. AZD9291 has demonstrated tumor shrinkage in patients at doses that have been very well tolerated and to date, no effect on glucose homeostasis has been reported. Cmpd 1Cmpd 2Cmpd 3Cmpd 4Cmpd 5 (AZD9291)EGFRm+sensitising mutationcell IC50 (pEGF μM)0.390.0160.0210.0020.017EGFRm+/T790Mdouble mutationcell IC50 (pEGF μM)0.0910.0020.0040.00070.015EGFR wildtypecell IC50 (pEGF μM)23.00.360.940.150.48IGFRcell IC50 (pIGF μM)0.0990.160.490.103.3SM/IGFR selectivity0.25102348194 Citation Format: Mark J. Anderton, Richard A. Ward, Paula Daunt, Anne Galer, Darren A. E. Cross, Louise Marks, M. Raymond V. Finlay. Influence of early toxicology assessment on the selection of azd9291. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3676. doi:10.1158/1538-7445.AM2014-3676

Enhanced Visible-Light Photoelectrochemical Performance of Titana Nanotubes Modified by Atomic Layer Deposited Cobalt Oxide

TiO2 is widely considered as one of the promising materials to fulfill photoelectrochemical water splitting requirements for its low cost, nontoxicity, photostablity, and strong photo oxidation ability. Several synthesis approaches have been reported to fabricate TiO2 nanostructures, including template assisted hydrothermal, anodization, and sol-gel. Among them, anodization method is capable of producing highly ordered, well aligned TiO2 nanotubes (NTs) with controlled diameters and tube length. The unidirectional tubular structure provides the charge transport channels from electrolyte/photoanode interface to conductive substrate. The intrinsic band gap of TiO2 (3.2eV for anatase and 3.0eV for rutile), however, limits its optical absorption only within UV region. The rapid recombination rate of photo-excited electrons and holes also severely hinders its practical application.1 Many approaches have been developed to promote the photo response of TiO2 in visible light region. For example, by hetero coupling, the holes and electrons can be photo excited from the narrow-gap semiconductor and separated effectively, which significantly promotes the visible light response. To form hetero coupling, cobalt oxide, a typical P-type semiconductor with band gap of ~2.1eV is chosen. Recent report shows cobalt oxide coupled with TiO2 exhibit could enhance the photo oxidation activity under visible light illumination.2 CoOx/TiO2 nanoparticles also show great photocatalytic activity on water splitting.Here we report the formation of CoOx/TiO2 NTs hetero coupling by atomic layer deposition (ALD). ALD is ultrathin film deposition technique to have sub-nanometer control of film thickness. As a promising method to passivate and modify photoanode,3 ALD could form chemical bonds on substrate and operate at a relatively low temperature. We will show that by uniformly depositing a layer of cobalt oxide film onto the TiO2 nanotubes, CoOx/TiO2 NTs system exhibits one fold improvement on photocurrent response under visible light illumination compared with pristine TiO2 NTs, and about two times the efficiency of CoOx/TiO2 synthesized via wet-chemistry method. The structure was detailed studied and optimized, and mechanism will also be discussed.

A Fluoroimmunoassay Method Using Quantum Dot Labels for Detection of Melamine

An indirect competitive immunoassay using quantum dots (QDs) as the fluorescent label has been developed for detection of melamine in milk products. The method exhibited a response for melamine with IC50 value of 11.3 ng mL-1 and a detection limit of 0.27 ng mL-1. Milk and milk powder samples spiked with melamine have been analyzed, and the method provided recoveries ranging from 84.2% to 108.0%, and a CV of 12.8%. The implementation of QDs provides for at least 30 fold improvement of detection limit when compared with optically-based ELISA screening methods that have been reported. The analytical performance in combination with simplicity of sample and antibody preparation provides the basis for a practical method for melamine detection.

Solid lipid nanoparticles enhance oral bioavailability of resveratrol, a natural polyphenol

Nanotechnology has provided remarkable prospects for the efficient delivery of food molecules which usually suffer from low aqueous solubility, insufficient bioavailability and stability issues. The objective of the present investigation was to explore the potential of the solid lipid nanoparticles (SLNs) for oral delivery of resveratrol, a natural polyphenol that faces problems of low and variable oral bioavailability. Resveratrol loaded stearic acid-based SLNs (RLNs) coated with poloxamer 188 were produced successfully by solvent diffusion–solvent evaporation method. RLNs had smooth surface with an average diameter of 134±7.6nm with a zeta potential of −34.3±2.5mV. The encapsulation efficiency of resveratrol in RLNs was found to be 88.9±3.1%, showed prolonged drug release in vitro up to ~120h and followed Higuchi kinetics. Pharmacokinetic parameters were evaluated using reverse-phase high-performance liquid chromatography (RP-HPLC) after oral administration of RLNs and a resveratrol control in Wistar male rats. The lipid formulation produced a significant 8.035 fold improvement in the oral bioavailability of resveratrol as compared to drug suspension. Thus, stearic acid-based RLNs could act as promising sustained release system with enhanced bioavailability for resveratrol after oral administration.

Characterization and evaluation of multi-component crystals of hydrochlorothiazide.

The present work aims at improving the physicochemical properties of hydrochlorothiazide, a poorly water soluble antihypertensive drug by preparing its multi-component crystals with nicotinic acid (HCT-NA) and 2-picolinic acid (HCT-PIC). The crystals prepared by solution crystallization were investigated by thermoanalytical techniques. The crystal structures of HCT-NA (1) and HCT-PIC (2) were determined by the single crystal X-ray diffraction and were assessed for their aqueous solubility, antihypertensive activity and acute toxicity in rats. Both 1 and 2 crystallized in the orthorhombic space group P212121 and formation of salts were confirmed. The solubility profiles of 1 and 2 in basic media showed a maximum release of 2.5mg/ml and 1.9mg/ml, respectively, in comparison to the drug (0.82mg/ml). The in-vivo antihypertensive activity of 1 in deoxycorticosterone acetate salt induced hypertensive rats showed 1.5 fold improvement. No increase in the signs of toxicity were revealed in rats during the acute toxicity studies even at doses of 2,000mg/kg by body weight in comparison to the free drug. Histopathological findings supported the safety of these multi-component crystals. The new solid phases exhibit potential to be explored for the oral drug delivery of HCT with improved solubility and therapeutic outcome.

Studies on single and duplex aging of metastable beta titanium alloy Ti–15V–3Cr–3Al–3Sn

This paper presents the age hardening behavior of metastable beta titanium alloy Ti–15V–3Cr–3Al–3Sn subjected to various single and duplex aging treatments. Single aging was carried out in the range 200–550°C for times up to 150h (h). For duplex aging first step was performed in two different ways: (i) 250°C for 24h (ii) 300°C for 10h; second step was carried in the range 350–500°C, for times up to 150h. The decomposition of alpha (α) phase during aging was monitored by hardness measurements, tensile testing, different microscopic techniques and X-ray diffraction. Duplex aging treatments resulted in higher hardness and strength compared to single aging. There was a good balance of tensile strength and ductility after two duplex aging treatments 300°C/10h+500°C/10h and 250°C/24h+500°C/8h. Precipitate free zones (PFZs) were observed when aged at ⩽450°C in the microstructure; aging at ⩾500°C gave freedom from such zones. Duplex aging resulted in a finer size and higher density of α precipitates compared to single aging. Duplex aging 250°C/24h+500°C/8h led to a four to five fold improvement in high cycle fatigue (HCF) life compared to single aging at 500°C/10h. The observed improvement in HCF life could thus be related to smaller size and larger density of α precipitates resulting from duplex aging. Optical microscopy and X-ray diffraction studies clearly revealed that preaging for 10h at 300°C accelerated the α-phase precipitation reaction during aging.

Simultaneous Saccharification and Fermentation of Waste Textiles for Ethanol Production

Ethanol production in a simultaneous saccharification and fermentation (SSF) process using waste textiles as feedstock was studied. The dissolution pretreatment of waste textiles in ortho-phosphoric acid resulted in at least 2 fold improvement in enzymatic hydrolysis rate and reducing sugar yield. The reducing sugars obtained from dyed or discolored waste textiles by cellulase hydrolysis demonstrated no inhibitory effect on ethanol fermentation activity of Zymomonas mobilis employed in SSF. SSF with a high waste textile loading (75 g L-1) could still be operable due to the fast liquefaction of the pretreated substrate via enzymatic hydrolysis. Approximately 50 g L-1 ethanol was achieved within 24 h. In addition to 100% cotton textiles, the 40/60 polyester/cotton (T/C) blend waste textile could also be pretreated under the same condition to achieve the comparable ethanol production yield (~0.4 g EtOH g-1 glucose) from its cotton fraction in SSF.

Ideal EROI (energy return on investment) deepens the understanding of energy systems

This article presents a new EROI (energy return on investment) factor named the ideal EROI, or EROIide, that provides the theoretical upper boundary of the EROI of a given system. The EROIide is the ratio between the inputs within the EROIstnd boundaries and the theoretical maximum output from a given system; i.e, all losses are omitted and the maximum theoretical energy output of the system is used. EROIide resembles the concept of the idealised Carnot heat engine. Although the EROI of a given system can never be equal to EROIide, the EROIide can be used to estimate the potential for improvement; e.g., if the difference between the EROIide and EROIstnd is small then little improvement can be expected from further research funding. Calculations using EROIide can add a valuable depth to the overall results of an EROI study, benefitting policy makers involved in energy policy planning. Three application examples of EROIide are provided, one for a hydroelectric power plant, one for a geothermal power plant and one example for a hypothetical wind farm. The calculations show that the hydro power plant could improve approximately 3 fold, whereas the geothermal plant had a potential of 27 fold improvement over its lifetime.

Getting Things Backwards to Prevent Primer Dimers

This Commentary highlights the article by Satterfield that describes a new class of primer technology-cooperative primers, which prevent primer-dimer amplification.

Recent Progress in Colloidal Quantum Dot Solar Cells: Novel Strategies in Synthesis and Device Structure

Colloidal quantum dot (CQD) solar cells have attracted great attention due to their cost-effectiveness and solution- processability, as well as their size-dependent optical and electrical properties. The power conversion efficiency of CQD solar cells has rapidly increased up to ~8.6%, which corresponds to the 3 - 4 fold improvement during the last 3 - 4 years. Up to now, there have been many pioneering results in CQD solar cells. Here, we review the recent progress of CQD solar cells including CQD synthesis strategy and device structure engineering.

Effect of Vermi-compost and Inorganic Fertilizers on Growth, Yield and Quality of Sprouting Broccoli (Brassica oleraceaL. var.italicaPlenck)

The response of vermi-compost and inorganic fertilizers on growth, yield and quality of sprouting broccoli was studied during 2011–13 at UBKV, Pundibari, West Bengal, India. The treatments comprised of five levels of vermi-compost (0, 2.5, 5, 7.5 and 10 t ha−1) and four levels of inorganic fertilizers (0, 50, 75 and 100% of recommended dose) were evaluated in two factor factorial RBD with three replications. The result revealed that successive increase in vermi-compost level significantly increased the growth and yield attributes and application of highest level of vermi-compost (10 t ha−1) registered 38% and 43% improvement of central head weight and total head yield respectively over control, whereas application of 100% recommended fertilizers enhanced the head weight and total head yield by 32% and 35% respectively over control. The nutrient schedule comprising of higher level of vermi-compost (10 t ha−1) and 100% of recommended inorganic fertilizers emerged as potential nutrient source and resulted in many fold improvement in the form of vigorous growth, early head initiation, advanced head maturity and higher yield as well as superior quality of head as compared other nutrient combination.

Multiple habit-induced nail problems including diffuse brownish chromonychia.

Dear Editor: Chromonychia is the discoloration of the nail plate or subungual soft tissue with various causes1. Exogenous causes such as occupational agents, trauma or infection may provoke nail color change, and rarely, overproduction or storage of endogenous pigments is also responsible for chromonychia1,2. External dye stains the nail plate along the proximal fold, whereas endogenous pigmentation follows the shape of the lunula2. Melanonychia is a specific type of chromonychia with brown or black pigmentation1. Several reports have indicated that nail associated habits induce longitudinal melanonychia3,4,5, but none mentioned diffuse brownish chromonychia. Herein, we report a case of brownish chromonychia occurred with other nail deformities because of nail irritating habits. This study is approved by Catholic Medical Center (IRB No. SC13RISI0039). A 15-year-old girl presented with diffuse dark brown discoloration of the fingernails for several months. The patient had no remarkable medical or family history. The physical examination revealed brownish chromonychia, periungual erythema and swelling, cuticle loss and nail pitting on the left 3rd, 4th, and 5th fingernails (Fig. 1A). Onychoschizia and onycholysis with irregular grooves on the left thumbnail were also detected (Fig. 1C). Moreover, her right 4th fingernail had a longitudinal depression on its medial side (Fig. 2A). She said that she had been poking under the proximal nail folds of the left 3rd, 4th, and 5th fingers with the lead of a mechanical pencil. She had been sucking and biting the left thumbnail and had a peculiar pencil grip that was supported by the right 4th fingernail (Fig. 2B). Fig. 1 (A) Brown chromonychia on the left 3rd, 4th, and 5th fingernails. (B) After 4 months of treatment. (C) Onychoschizia and onycholysis with irregular grooves on the left thumbnail. (D) Left thumbnail fully recovered after 4 months of treatment. Fig. 2 (A) A longitudinal groove on the right 4th fingernail. (B) Probably the effect of a peculiar pencil grip. Because the patient's nail trauma history and development of melanonychia presented sequentially, we considered a strong association between them and delayed nail matrix biopsy. We educated her on discontinuing all habits and applying diflucortolone valerate 0.3% ointment to the periungual area of the affected fingernails regularly. In 4 months of follow-up, the fingernails gradually restored their natural shapes and colors (Fig. 1B, D). Because of the diffuse brownish pigmentation along the proximal nail fold and obvious improvement after stopping habit, we presumed that the lead had stained the nail plate. Repetitive mechanical stimulation on the nail matrix such as picking, chewing, breaking or rubbing would fluctuate the nail formation and make nail thickness irregular1,3. These habitual behaviors are easily seen in children, as 60% of children and 45% of teenagers are indulged in onychophagia1. In our case, we observed diffuse brownish chromonychia with other forms of nail deformities caused soley by her habits. Observing multiple nail problems in different fingers of a patient simultaneously is notable, because habit induced nail problem usually occurs as one type at a time. Fortunately, she managed to stop all habits so that the disfigurements improved. Occasionally, children with onychophagia may need psychiatric consultation for the obsessive-compulsive features and treatment with a selective serotonin reuptake inhibitor1. Thorough history taking and physical examination would be enough for diagnosis in children with nail irritating behaviors, avoiding unnecessary invasive examination including nail matrix biopsy4,5.

Crystalline-Oriented Beta-Sialon:Eu2+ Deposits Fabricated by Electrophoretic Deposition (EPD) within Strong Magnetic Field

Electrophoretic deposition (EPD) assisted with a horizontally-setup strong magnetic field (12 T) was utilized to fabricate the deposits of the β-sialon:Eu2+ phosphor. The direction of the magnetic field was perpendicular to that of the electric field. The deposits were fabricated by aligning the β-sialon:Eu2+ particles along the higher magnetic-susceptibility c-crystal axis (a, b-crystal plane), therefore making the oriented deposits consist of the phosphor particles present dominant appearances of the side faces (a, b-plane). Particularly, longer depositing time gave rise to higher orientation degree. Photoluminescence (PL) intensities of the deposits oriented along a, b-plane were significantly improved by comparing with those of the randomly-oriented samples; especially, the 12.4%-fold improvement of the PL intensity was obtained at 150 s depositing time. This fabrication technique of the oriented phosphor deposit may be potentially used to prepare the flat LEDs, with more brightness, instead of conventional methods.

Cooperative Primers: 2.5 Million–Fold Improvement in the Reduction of Nonspecific Amplification

The increasing need to multiplex nucleic acid reactions presses test designers to the limits of amplification specificity in PCR. Although more than a dozen hot starts have been developed for PCR to reduce primer-dimer formation, none can stop the propagation of primer-dimers once formed. Even a small number of primer-dimers can result in false-negatives and/or false-positives. Herein, we demonstrate a new class of primer technology that greatly reduces primer-dimer propagation, showing successful amplification of 60 template copies with no signal dampening in a background of 150,000,000 primer-dimers. In contrast, normal primers, with or without a hot start, experienced signal dampening with as few as 60 primer-dimers and false-negatives with only 600 primer-dimers. This represents more than a 2.5 million-fold improvement in reduction of nonspecific amplification. We also show how a probe can be incorporated into the cooperative primer, with 2.5 times more signal than conventional fluorescent probes.

Recyclable Decoration of Amine-Functionalized Magnetic Nanoparticles with Ni2+ for Determination of Histidine by Photochemical Vapor Generation Atomic Spectrometry

It is critically important to accurately determine histidine since it is an indicator for many diseases when at an abnormal level. Here, an inexpensive and simple method using an amine-functionalized magnetic nanoparticle-based Ni(2+)-histidine affinity pair system was developed for highly sensitive and selective detection of histidine in human urine by photochemical vapor generation atomic spectrometry. Ni(2+) was first bound to the amine groups of the amine-functionalized magnetic nanoparticles and then liberated to solution via the highly specific interaction between the histidine and Ni(2+) in the presence of histidine. The liberated histidine-Ni(2+) complex was exposed to UV irradiation in the presence of formic acid to form gaseous nickel tetracarbonyl, which was separated from the sample matrix and determined by atomic absorption/fluorescence spectrometry. Compared to other methods, this approach promises high sensitivity, simplicity in design, and convenient operation. The need for organic solvents, enzymatic reactions, separation processes, chemical modification, expensive instrumentations, and sophisticated and complicated pretreatment is minimized with this strategy. A limit of detection of 1 nM was obtained and provided tens-to-hundreds of fold improvements over that achieved with conventional methods. The protocol was evaluated by analysis of several urine samples with good recoveries and showed great potential for practical application.

Optimized platform medium and feed for rCHO cell lines using the CHEF1® expression system

Optimized platform medium and feed for rCHO cell lines using the CHEF1® expression system

Preparation and characterization of cyclodextrin inclusion complex of naringenin and critical comparison with phospholipid complexation for improving solubility and dissolution

Naringenin, a flavonoid specific to citrus fruits shows a variety of therapeutic effects like anti-inflamma- tory, anticarcinogenic, and antitumour effects. But it is associated with some limitations like poor water solubility, poor dissolution, lower half-life, and rapid clearance from the body. With the aim of improving amorphous nature, water solubility, and dissolution profile of naringenin and its complexes were prepared with b-cyclodextrin in three different molar ratios (1:1, 1:2, and 1:3) by solvent evap- oration method. These complexes were characterized for solubility, drug content, chemical interaction (using FTIR), phase transition behavior (using DSC), crystallinity (using XRPD), surface morphology (using SEM), and in vitro dissolution study. The results were also critically compared with the results obtained from naringenin-phospholipid complexes (from author's previous study). The prepared complexes showed high drug content (ranging from 69.53 to 84.38 %) and about two fold improvement in water solubility (from 41.81 to 76.31 l gm L -1 in the complex with 1:3 ratio). SEM of the complexes showed irregular and rough surface morphology. FTIR, DSC, and XRPD data confirmed the formation of the complex. Unlike the free naringenin which showed a total of only 48.78 % drug release at the end of 60 min, the complex showed 98.0-100 % in dissolution study. Thus it was concluded that the b-cyclodextrin of naringenin may be of potential use for improving bioavailability of poorly soluble phytoconstituents/herbal drugs. On critical comparison with the phospholipid complex of naringenin both the techniques were found almost equally effective in improving the solubility and the dissolution performance of naringenin in the complex form.

Pseudo-Sanger sequencing: massively parallel production of long and near error-free reads using NGS technology

BackgroundUsually, next generation sequencing (NGS) technology has the property of ultra-high throughput but the read length is remarkably short compared to conventional Sanger sequencing. Paired-end NGS could computationally extend the read length but with a lot of practical inconvenience because of the inherent gaps. Now that Illumina paired-end sequencing has the ability of read both ends from 600 bp or even 800 bp DNA fragments, how to fill in the gaps between paired ends to produce accurate long reads is intriguing but challenging.ResultsWe have developed a new technology, referred to as pseudo-Sanger (PS) sequencing. It tries to fill in the gaps between paired ends and could generate near error-free sequences equivalent to the conventional Sanger reads in length but with the high throughput of the Next Generation Sequencing. The major novelty of PS method lies on that the gap filling is based on local assembly of paired-end reads which have overlaps with at either end. Thus, we are able to fill in the gaps in repetitive genomic region correctly. The PS sequencing starts with short reads from NGS platforms, using a series of paired-end libraries of stepwise decreasing insert sizes. A computational method is introduced to transform these special paired-end reads into long and near error-free PS sequences, which correspond in length to those with the largest insert sizes. The PS construction has 3 advantages over untransformed reads: gap filling, error correction and heterozygote tolerance. Among the many applications of the PS construction is de novo genome assembly, which we tested in this study. Assembly of PS reads from a non-isogenic strain of Drosophila melanogaster yields an N50 contig of 190 kb, a 5 fold improvement over the existing de novo assembly methods and a 3 fold advantage over the assembly of long reads from 454 sequencing.ConclusionsOur method generated near error-free long reads from NGS paired-end sequencing. We demonstrated that de novo assembly could benefit a lot from these Sanger-like reads. Besides, the characteristic of the long reads could be applied to such applications as structural variations detection and metagenomics.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2164-14-711) contains supplementary material, which is available to authorized users.

Efficiency Improvement of 630 nm AlGaInP Light-Emitting Diodes based on AlGaAs Bottom Window

Metal organic chemical vapor deposition (MOCVD) based aluminum gallium arsenide (AlGaAs) used as the bottom window (BW), which was inserted between the light-emitting diode (LED) structure and the absorbing substrate, has been proposed to improve the extraction efficiency of 630 nm AlGaInP LEDs. In an AlGaInP LED with this AlGaAs BW, enhanced light extraction efficiency was observed, as some of the light emitted from the active region to the absorbing substrate could pass out of the LED through the BW. In addition, it was found that a output power of 8 mW was obtained from an AlGaInP LED with both a BW and a distribution Bragg reflector (DBR), a nearly two fold improvement of over 4.2 mW that was obtained from a conventional one at an injection current of 80 mA.

Subperiosteal Midface-Lift

The subperiosteal midface-lift has benefited from significant technological advances in medicine. The endoscope now allows extensive subperiosteal undermining of facial soft tissue through minimal access incisions. Improved understanding of facial anatomy and the facial aging process now allow repositioning and remodeling of the soft tissue envelope with excellent aesthetic results. The subperiosteal midface-lift by a temporal approach is a procedure designed to rejuvenate the middle third of the face. After subperiosteal detachment, the soft tissues of the cheek, jowls, lateral canthus, and inferior orbital rim can be lifted to reestablish their youthful relationship with the underlying skeleton. It is a technique that produces satisfactory cosmetic results in most cases, causing malar augmentation, nasolabial fold improvement, and mild jowl improvement. We describe our preferred technique in detail and discuss its indications, complications, advantages, and limitations.