Effectiveness of mouth rinses against COVID-19: a systematic review and network meta-analysis.

OBJECTIVE: This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III). METHODS: Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3rd March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review. RESULTS: Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO. CONCLUSION: Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive.

Profiled polyethylene terephthalate filaments that incorporate collagen and calcium phosphate enhance ligamentisation and bone formation.

Polyethylene terephthalate (PET) artificial ligaments offer an unlimited source of ligaments without donor-site-related morbidity and with good mechanical properties for a rapid return to sporting activities. Developing PET artificial ligaments with excellent ligamentisation and ligament-bone healing is still a considerable challenge. This study aimed to investigate the effects of the profiled PET/collagen/calcium phosphate (PET/C/CaP) ligament upon cell growth, ligamentisation and ligament-bone healing in vitro and in vivo. Profiled PET/C/CaP filaments were made by melt-spinning process with 2 % CaP hybrid spinning and collagen coating. Rat mesenchymal stem cells (MSCs) were cultured on the profiled PET/C filaments for cytotoxicity, viability, scanning electron microscopy (SEM) and ligament-related gene expression analysis. MSCs' osteogenic capacity on the profiled PET/CaP filaments was identified by detecting osteogenic gene expression and alizarin red S staining. For in vivo verification, an animal study was performed to evaluate the effect of the profiled PET/C/CaP ligament in a rabbit knee medial collateral ligament reinforcement reconstruction model. The graft ligamentisation and bone formation were investigated by SEM, histology, microcomputed tomography and mechanical tests. The profiled PET/C filaments enhanced MSC proliferation and ligament-related gene expression. Furthermore, they enhanced osteogenic gene expression, alkaline phosphatase activity and mineralisation of MSCs. The in vivo study indicated that the profiled PET/C/CaP ligament enhanced ligamentous matrix remodelling and bone formation. Therefore, their use is an effective strategy for promoting MSCs' ligamentous and osteogenic potential in vitro and enhancing ligamentous matrix remodelling and bone formation in vivo.

Genetic Polymorphisms of 18 Autosomal STR loci in Changsha Han Population.

OBJECTIVES: To investigate the genetic polymorphisms of 18 autosomal short tandem repeats （STR） loci in Changsha Han population, and explore the population genetic relationships and evaluate its application value in forensic medicine. METHODS: The DNA of 2 004 unrelated individuals in Changsha Han population were amplified using Goldeneye®DNA ID System BASIC, and the PCR products were analyzed by electrophoresis using 3130xl genetic analyzer. The fragment sizes of alleles were analyzed subsequently by GeneMapper® ID v3.2. The frequency data and forensic genetic parameters ï¼»observed heterozygosity （Ho）, expected heterozygosity （He）, power of discrimination （DP） and polymorphic information content （PIC）］ of 18 STR loci were statistically analyzed. Total probability of discrimination （TDP）, probability of exclusion in trio cases （PEtrio） and probability of exclusion in duo cases （PEduo） were calculated by Cervus 3.0. Hardy-Weinberg equilibrium and linkage disequilibrium of the loci were detected by Arlequin v3.5. The results were compared with the available data of other populations from different races and regions. RESULTS: The power of discrimination （DP）, and the polymorphic information content （PIC） of each locus of Changsha Han population ranged from 0.783 6 to 0.987 9 and 0.549 4 to 0.914 5, respectively. The TDP, cumulative probability of exclusion in trio cases （CPEtrio） and cumulative probability of exclusion in duo cases （CPEduo） were 0.999 999 999 999 999 999 999 865 2, 0.999 999 979 and 0.999 988 325, respectively. According to the Nei's DA genetic distance, the genetic distance between Changsha Han and Hunan Han populations was the smallest （0.014 1）, while it was the largest （0.041 8） between Changsha Han and Xinjiang Kazakh populations. CONCLUSIONS: The 18 STR loci shows abundant genetic polymorphisms in Changsha Han population. The study of genetic diversity among different populations has an important meaning for the research of their origins, migrations and their relationships.

[Analysis of adverse reaction induced by articaine hydrochloride and epinephrine tartrate injection in 75 cases].

Objective: To investigate the causes and clinical manifestation of adverse reaction of articaine hydrochloride and epinephrine tartrate injection. Methods: A retrospective analysis was conducted on the adverse drug reactions (ADR) of local anesthetic articaine hydrochloride and epinephrine tartrate injection. Results: In 75 cases of adverse reactions, there were 40 cases of female and 35 cases of male. Adverse reactions occured more frequently at the age of 3-10 [33% (25/75)] and 1-10 min and one day after injection, respectively accounting for 20% (15/75), and two days, accounting for 15% (15/75), 10-21 days accounting for 8% (6/75). The main manifestations were injection site ulcers, followed by skin reactions such as pain, swelling, necrosis and pruritus at the injection site. Conclusions: The main adverse reactions of articaine hydrochloride and epinephrine tartrate injection are the injection site ulceration, followed by injection site pain, rash, pruritus and drowsiness, nausea and dizziness, palpitations, sweat and hypotension. Doctors should ask the medical history in detail and pay close attention to the patient's medication safety.

Microstructural visual pathway abnormalities in patients with primary glaucoma: 3 T diffusion kurtosis imaging study.

AIM: To evaluate microstructural visual pathway damage in patients with primary glaucoma (PG) by using 3 T diffusion kurtosis imaging (DKI). MATERIALS AND METHODS: The study was approved by the ethics committee, and all participants provided written informed consent. Ten patients with PG were examined. Twenty healthy individuals served as control subjects. DKI was performed with a GE Silent 3 T magnetic resonance imaging (MRI) unit. Mean diffusivity (MD), fractional anisotropy (FA), and mean kurtosis (MK) maps were automatically created. Mean MK, MD, and FA values were calculated for each part of the visual pathway. RESULTS: No abnormalities in the shape and signal intensity were observed along the entire visual pathway in patients and the control group on the conventional MRI. Higher MD, and lower MK and FA were observed in the optic nerves (ON), lateral geniculate nucleus (LGN), optic radiations (OR), and visual cortex (VCx) of PG patients, as compared with control subjects. A significantly higher MD was observed in the ON (p<0.01), and significantly lower FA was observed in OR (p<0.05). Additionally, significantly lower MK was observed in the ON, LGN, and VCx, except for OR (p<0.01). Changes of DKI parameters in the ON were the most distinct. CONCLUSION: Glaucoma is a complex neurological disease that affects the entire visual pathway. MK derived from DKI would be a better biomarkers than FA and MD in detecting microstructural damage.

The advantage of digital tomosynthesis for pulmonary nodule detection concerning influence of nodule location and size: a phantom study.

AIM: To investigate the advantage of digital tomosynthesis (DTS) over chest radiography (CXR) and dual-energy subtraction radiography (DES) for pulmonary nodule detection according to the location and size of solid simulated pulmonary nodules (SPNs). MATERIALS AND METHODS: Ninety-six SPNs of variable sizes were inserted into eight different regions of a lung phantom. These regions were further classified into two groups of danger and non-danger zones based on anatomical location influencing the detection of pulmonary nodules. The 96 cases with inserted SPNs and an additional nodule-free 96 control cases all underwent CXR, DES, and DTS examinations. Three observers independently reviewed all the images. The jackknife alternative free-response receiver operating characteristic was used to analyse diagnostic performance for each technique. RESULTS: DTS was superior to CXR and DES for detection of smaller SPNs, except in the retrodiaphragmatic and apical regions. DTS outperformed CXR and DES for detection of larger SPNs in the paramediastinal region. For 5- and 8-mm SPNs, DTS was superior to CXR and DES in the apical, paramediastinal and lateral pulmonary regions. In the retrodiaphragmatic region, the three techniques showed similar diagnostic performance regardless of the SPN size. DES was similar to DTS for detection of 8-mm SPN in the apical region. For 10- and 12-mm SPNs, CXR and DES showed similar diagnostic performance to DTS in the apical and lateral pulmonary regions; however, DTS was superior to CXR and DES in the paramediastinal region. CONCLUSIONS: DTS significantly improved the capability to detect synthetic pulmonary nodules compared with CXR and DES, for detection of smaller nodules in the apical, paramediastinal, and lateral pulmonary regions, and larger nodules located in the paramediastinal region in a thoracic phantom.

The taste response to ammonia in Drosophila.

Ammonia is both a building block and a breakdown product of amino acids and is found widely in the environment. The odor of ammonia is attractive to many insects, including insect vectors of disease. The olfactory response of Drosophila to ammonia has been studied in some detail, but the taste response has received remarkably little attention. Here, we show that ammonia is a taste cue for Drosophila. Nearly all sensilla of the major taste organ of the Drosophila head house a neuron that responds to neutral solutions of ammonia. Ammonia is toxic at high levels to many organisms, and we find that it has a negative valence in two paradigms of taste behavior, one operating over hours and the other over seconds. Physiological and behavioral responses to ammonia depend at least in part on Gr66a+ bitter-sensing taste neurons, which activate a circuit that deters feeding. The Amt transporter, a critical component of olfactory responses to ammonia, is widely expressed in taste neurons but is not required for taste responses. This work establishes ammonia as an ecologically important taste cue in Drosophila, and shows that it can activate circuits that promote opposite behavioral outcomes via different sensory systems.

First-in-human phase I study of the DNA-repair inhibitor DT01 in combination with radiotherapy in patients with skin metastases from melanoma.

BACKGROUND: DT01 is a DNA-repair inhibitor preventing recruitment of DNA-repair enzymes at damage sites. Safety, pharmacokinetics and preliminary efficacy through intratumoural and peritumoural injections of DT01 were evaluated in combination with radiotherapy in a first-in-human phase I trial in patients with unresectable skin metastases from melanoma. METHODS: Twenty-three patients were included and received radiotherapy (30 Gy in 10 sessions) on all selected tumour lesions, comprising of two lesions injected with DT01 three times a week during the 2 weeks of radiotherapy. DT01 dose levels of 16, 32, 48, 64 and 96 mg were used, in a 3+3 dose escalation design, with an expansion cohort at 96 mg. RESULTS: The median follow-up was 180 days. All patients were evaluable for safety and pharmacokinetics. No dose-limiting toxicity was observed and the maximum-tolerated dose was not reached. Most frequent adverse events were reversible grades 1 and 2 injection site reactions. Pharmacokinetic analyses demonstrated a systemic passage of DT01. Twenty-one patients were evaluable for efficacy on 76 lesions. Objective response was observed in 45 lesions (59%), including 23 complete responses (30%). CONCLUSIONS: Intratumoural and peritumoural DT01 in combination with radiotherapy is safe and pharmacokinetic analyses suggest a systemic passage of DT01.

Retrocaval Ureter in Children: A Report of Eight Cases.

OBJECTIVE: The aim of this study is to report on our last nine years' experience in the diagnosis and treatment of retrocaval ureter. METHODS: Eight patients with retrocaval ureter were reviewed. Intravenous urography and retrograde pyelography were used for confirming the diagnosis. All of the patients had undergone surgery, one case being done laparoscopically. The mean age of the patients was 9.2 years (range 2 to 13 years). RESULTS: Five patients were boys and three were girls. The clinical manifestations were right flank pain in three (37.5%), gross haematuria in one (12.5%) and urinary tract infection in one (12.5%). Three asymptomatic patients were diagnosed by routine physical examination. All of the patients had Type 2 and right-sided retrocaval ureter. Associated anomalies were seen in none of the patients. Retrocaval ureter is a rare anomaly in the paediatric age group. CONCLUSION: Laparoscopy is a promising method to repair the retrocaval ureter.

Development of a DNA microarray-based multiplex assay of avian influenza virus subtypes H5, H7, H9, N1, and N2.

Outbreaks of highly pathogenic avian influenza have caused considerable economic losses in the poultry industry and have also resulted in human deaths since 2004. Rapid subtyping of highly pathogenic avian influenza viruses(HPAIVs) in clinical specimens is a prerequisite of prompt control of disease and prevention of its spreading. In this study, we describe development of a DNA microarray-based detection and subtyping of HPAIVs in field samples. DNA copies of matrix (M) protein genes for the H5, H7, and H9 subtypes of hemagglutinin (HA) and the N1 and N2 subtypes of neuraminidase (NA) were prepared by RT-PCR and specific primers and then spotted onto aldehyde slides to form DNA microarrays. The HPAIV samples to be tested were subjected to total RNA isolation, RT-PCR with universal primers and Cy3 labeling, and the obtained double-stranded DNAs (targets) were finally hybridized with DNA microarrays (probes). A fluorescent spot on the microarray, detected by scanning indicated positive hybridization, i.e. the involved subtype. The assay was specific as various heterologous viruses or HPAIVs of other subtypes tested were negative. No cross-hybridization among different subtypes could be detected. The assay was more sensitive than RT-PCR and chicken embryo inoculation and could be also used for field samples. Summing up, the assay has proved useful for simultaneous detection and differentiation of main epidemic HPAIV subtypes.

Unique features of non-obstructive emphysema and pure airway obstruction.

SETTING: Emphysema without airway obstruction or airway obstruction without emphysema are often detected clinically, although they are commonly co-existent. We therefore tested the hypothesis that non-obstructive emphysema and pure airway obstruction have unique features. METHODS: A case-control observation study was undertaken retrospectively in a patient cohort at a single centre. Among 2662 subjects who underwent chest computed tomography and pulmonary function tests, we enrolled 90 patients with non-obstructive emphysema, 119 with pure airway obstruction, 81 with obstructive emphysema and 2031 subjects as normal controls. The features of the four groups were analysed and compared. RESULTS: Higher serum homocysteine (13.4 ± 7.4 vs. 11.6 ± 4.6 mol/l), higher rate of osteoporosis (15.8% vs. 4.5%), higher leukocyte count, higher male ratio, lower serum albumin and lower body mass index were observed in subjects with non-obstructive emphysema than in controls (P < 0.05). In multiple logistic regression analysis of groups without airway obstruction, osteoporosis, hyperhomocysteinaemia, hypoalbuminaemia and higher leukocyte count were independent factors associated with non-obstructive emphysema (P < 0.05). CONCLUSION: Hyperhomocysteinaemia, hypoalbuminaemia, osteoporosis and higher leukocyte count were independent predictors of non-obstructive emphysema.

Assessment of myocardial viability using multidetector computed tomography in patients with reperfused acute myocardial infarction.

AIM: To assess the prognostic value of 64-section multidetector computed tomography (MDCT) to predict follow-up myocardial dysfunction and functional recovery after reperfusion therapy in patients with acute myocardial infarction (MI) as defined by echocardiography. MATERIALS AND METHODS: After reperfusion therapy for acute MI, 71 patients underwent two-phase contrast-enhanced MDCT and follow-up echocardiography. MDCT findings were compared with echocardiographic findings using kappa statistics. The areas under the receiver operating characteristic curves (AUCs) and the odds ratios (ORs) of early perfusion defects (EPD), delayed enhancement (DE), and residual perfusion defects (RPD) for predicting follow-up myocardial dysfunction and functional recovery were calculated on a segmental basis. RESULTS: The presence of transmural EPD (EPD(TM)) or RPD showed good agreement (k = 0.611 and 0.658, respectively) with follow-up myocardial dysfunction, while subendocardial EPD (EPD(sub)) or subendocardial DE (DE(sub)) showed fair agreement with follow-up myocardial dysfunction (k = 0.235 and 0.234, respectively). The AUC of RPD (0.796) was superior (p < 0.001 and 0.031, respectively) to those of EPD(TM) (0.761) and DE(TM) (0.771). The presence of EPD(TM), DE(TM), and RPD were significant, independent positive predictors of follow-up myocardial dysfunction (OR = 6.4, 1.9, and 9.8, respectively). EPD(TM) was a significant, independent negative predictor of myocardial functional recovery (OR = 0.13). CONCLUSION: Abnormal myocardial attenuation on two-phase MDCT after reperfusion therapy may provide promising information regarding myocardial viability in patients with acute MI.

Unusual causes of carpal tunnel syndrome: space occupying lesions.

Space occupying lesions found at surgery caused or contributed to carpal tunnel syndrome in 23 of 779 patients operated for carpal tunnel syndrome from January 1999 to December 2008. The mean age of these 23 patients was 52.9 years, and in patients who had a local swelling or palpable mass, ultrasonography or magnetic resonance imaging (MRI) was done. All had open release of the transverse carpal ligament and lesions were removed. Histopathology showed tophaceous gout in 10 men, tenosynovitis in seven patients and tumors in eight. The tumors included ganglion cysts in two, lipoma in three and fibroma of the tendon sheath in one. The neurological symptoms subsided after surgery in all. In patients with gout, one had an infected wound and another had recurrence of symptoms 1 year after later. Carpal tunnel syndrome caused by a space occupying lesion is rare and more complicated than idiopathic carpal tunnel syndrome.

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems.

Introducing small DNA molecules (Dbait) impairs the repair of damaged chromosomes and provides a new method for enhancing the efficiency of radiotherapy in radio-resistant tumors. The radiosensitizing activity is dependent upon the efficient delivery of Dbait molecules into the tumor cells. Different strategies have been compared, to improve this key step. We developed a pipeline of assays to select the most efficient nanoparticles and administration protocols before preclinical assays: (i) molecular analyses of complexes formed with Dbait molecules, (ii) cellular tests for Dbait uptake and activity, (iii) live zebrafish embryo confocal microscopy monitoring for in vivo distribution and biological activity of the nanoparticles and (iv) tumor growth and survival measurement on mice with xenografted tumors. Two classes of nanoparticles were compared, polycationic polymers with linear or branched polyethylenimine (PEI) and covalently attached cholesterol (coDbait). The most efficient Dbait transfection was observed with linear PEI complexes, in vitro and in vivo. Doses of coDbait ten-fold higher than PEI/Dbait nanoparticles, and pretreatment with chloroquine, were required to obtain the same antitumoral effect on xenografted melanoma. However, with a 22-fold lower 'efficacy dose/toxicity dose' ratio as compared with Dbait/PEI, coDbait was selected for clinical trials.

Molecular therapy in support to radiotherapy.

Approximately half of all cancer patients are treated with radiation therapy. However, some tumor cells can escape the lethal effects of irradiation by hypoxia, deregulation of the cell cycle or apoptosis or by increasing their ability to repair the DNA damage induced, resulting in recurrence of disease. In order to overcome these resistance mechanisms, various strategies have been developed. Over the last decade, extensive progress in human genomics and genetic tools has been made. Several methods using DNA or RNA molecules have been developed to target angiogenesis or other cellular functions in order to restore sensitivity to irradiation. In this review, we focus on five classes of nucleic acid-based approaches, (i) gene transfer by recombinant plasmid or virus, (ii) immune-stimulating oligonucleotides, (iii) antisense oligonucleotides, (iv) siRNA and shRNA, and (v) siDNA (signal interfering DNA), which target specific proteins or pathways involved in radioresistance. We review the results of the preclinical studies and clinical trials conducted to date by combining nucleic acid-based molecular therapy and radiotherapy.

A direct method to calculate thermal conductivity and its application in solid HMX.

The calculation of thermal conductivity for complex material systems is a challenging problem in computational materials science. Its key point is to calculate heat flux. In this work, we derive a concise formula for this purpose based on the equation of motion and then use it to study the thermal conduction properties of octahydro-1,3,5,7-tetranitro-1,3,5,7-tetrazocine (HMX), which is a widely used plastic-bonded explosive (PBX). The results are in fair agreement with experiments and show a distinct thermal conduction anisotropy for HMX single crystals. Then we investigate some key issues of thermal conductivity, such as its temperature-dependence and composition-dependence. A series of interesting results are obtained.

Benign bronchogastric fistula as a late complication after transhiatal oesophagogastrectomy: evaluation with multidetector row CT.

The late development of a bronchogastric fistula is a rare complication of oesophagectomy, although the anatomical relationship between the tracheobronchial tree and the neo-oesophagus is close. Its early diagnosis can be difficult and may result in a poor prognosis owing to the development of recurrent pulmonary infection and malnutrition. Multidetector row CT (MDCT) can provide excellent three-dimensional and multiplanar reconstruction images; therefore, the potential benefit of MDCT in diagnosing bronchogastric fistula is early and accurate detection. We present our experience with a late onset bronchogastric fistula evaluated using MDCT. Evaluation of bronchogastric fistulae using MDCT could help to confirm the diagnosis of this condition, and increase our understanding of the anatomical relationship between the neo-oesophagus and the bronchus. Therefore, it could provide valuable information for establishing a treatment plan.

Effect of dynamic compression on in vitro chondrocyte metabolism.

BACKGROUND: Chondrocytes can detect and respond to the mechanical environment by altering their metabolism. This study was designed to explore the effects of dynamic compression on chondrocyte metabolism. METHODS: Chondrocytes were harvested from newborn Wistar rats. After 7 days of expansion, chondrocytes embedded in agarose discs underwent uniaxial unconfined dynamic compression loads at different amplitudes (5%, 10%, and 15%) and frequencies (0.5 Hz, 1.0 Hz, 2.0 Hz, and 3.0 Hz) with a duration of 24 hours. The delayed effects on the chondrocytes were studied at 1, 3, and 7 days after the experiment. RESULTS: The results showed that at 10% strain, higher-frequency compression pressure can enhance the proliferation of chondrocytes. The synthesis of glycosaminoglycan (GAG) increased at 10%-15% strain and a 1-Hz load. The synthesis of nitric oxide (NO) increased at the 0.5-Hz load; while decreasing at the 15% strain. With 10% strain, 1 Hz dynamic compression, the proliferation of chondrocytes and GAG synthesis increased and persisted for 7 days, and NO synthesis decreased at the third and seventh days of culture. CONCLUSIONS: This study showed that chondrocytes respond metabolically to compressive loading, which is expected to modulate the growth and the resultant biomechanical properties of these tissue-engineered constructs during culture.

Optimization of beta-carotene production by Rhodotorula glutinis using high hydrostatic pressure and response surface methodology.

Rhodotorula glutinis RG6 was treated by high hydrostatic pressure (HHP) of 300 MPa for 15 min for improving its ability of beta-carotene production. After the treatments of 5 repeated cycles, the mutant strain RG6p was obtained, beta-carotene production of which reached 10.01 mg/L, increased by 57.89% compared with 6.34 mg/L from parent strain RG6. To optimize the medium for beta-carotene fermentation by mutant RG6p, a response surface methodology (RSM) approach was used in conjunction with a factorial design and a central composite design, and the maximum yield of beta-carotene (13.43 mg/L), an increase of 34.17% compared to the control, was obtained at a pH 6.7 with an optimum medium (40 mL/250 mL) of yeast extract (4.23 g/L), glucose (12.11 g/L), inoculum (30 mL/L), tomato extract (2.5 mL/L), peanut oil (0.5 mL/L), and (NH(4))(2)SO(4) (5 g/L).

Targeted gene correction with 5' acridine-oligonucleotide conjugates.

Single-stranded oligonucleotides (SSOs) mediate gene repair of punctual chromosomal mutations at a low frequency. We hypothesized that enhancement of DNA binding affinity of SSOs by intercalating agents may increase the number of corrected cells. Several biochemical modifications of SSOs were tested for their capability to correct a chromosomally integrated and mutated GFP reporter gene in human 293 cells. SSOs of 25 nucleotide length conjugated with acridine at their 5' end increased the efficiency of gene correction up to 10-fold compared to nonmodified SSOs. Acridine and psoralen conjugates were both evaluated, and acridine-modified SSOs were the most effective. Conjugation with acridine at the 3' end of the SSO inhibited gene correction, whereas flanking the SSO by acridine on both sides provided an intermediate level of correction. These results suggest that increasing the stability of hybridization between SSO and its target without hampering a 3' extension improves gene targeting, in agreement with the "annealing-integration" model of DNA repair.