Motivating patients towards better recovery after burn: The development of a booklet to reframe perspectives.

INTRODUCTION: Posttraumatic growth after burn results from integrated changes in worldview. It incorporates acceptance, belief in the self, compassion, determination and planning, emotional management and family/friend support. METHOD: The booklet was developed in two phases. In the first phase burn survivors were invited to tell their stories pertaining to their burn recovery experiences. These stories were categorised into the above framework, and presented alongside supporting information from the burn clinical psychologist in an initial draft of the booklet. In the second phase of the study, a combination of one-to-one interviews and a focus group of burn survivors discussed, suggested improvements to the final booklet and evaluated for usefulness and acceptability. RESULTS: A booklet was developed with a blend of patient stories and professional advice to positively reframe, integrate changed perspectives and motivate patients towards better psychological recovery after burn. It was evaluated to be useful and acceptable to new burn patients. CONCLUSION: This booklet, designed to positively reframe perspectives for better psychosocial burn recovery, was developed with patients and evaluated by patients. It was found to be useful and acceptable to new burn patients.

The co-administration of live fowlpox and Newcastle disease vaccines by non-invasive routes to chickens reared by smallholders in Tanzania and Nepal.

The co-administration of commercial live fowlpox (FP) and Newcastle disease (ND) vaccines when given by non-invasive (needle-free) routes was demonstrated to be safe and to elicit immunity in two field studies, one in Tanzania the other in Nepal. Both studies were of a cluster-randomised controlled design in which birds were randomly assigned to one of five treatment groups: (i) administration with FP vaccine alone (feather follicle), (ii) administration with ND vaccine alone (eye-drop), (iii) concurrent administration of FP (feather follicle) and ND (eye-drop) vaccines, (iv) concurrent administration of FP (wing-web) and ND (eye-drop) vaccines, and (v) unvaccinated, acting as environmental sentinels. Data from a total of 1167 birds from seven villages in Hanang District of Tanzania together with 1037 birds from eleven villages in Dhading District of Nepal were collected over a period of 21 and 28 days, respectively. Immune responses to FP vaccination were evaluated by local take reactions, while those to ND vaccination were evaluated serologically by haemagglutination inhibition test. The two studies demonstrated that the concurrent vaccination of free-range, indigenous breeds of chicken with live FP and ND vaccines, both administered by non-invasive routes, was safe and induced immunity against FP and ND that were non-inferior to the administration of FP and ND vaccines alone. These findings are important to appropriately trained small-scale backyard poultry farmers as well as to paraprofessionals and community health workers helping to increase vaccine uptake and the control of both FP and ND in low- to middle-income countries.

Delivery of a Laparoscopic Bile Duct Exploration Service as a Primary Treatment Modality for Choledocholithiasis within the NHS Healthcare System.

INTRODUCTION: The aim of this paper was to report the experience of one-stage LC and LCBDE service within a medium sized acute NHS healthcare trust to demonstrate the feasibility of this treatment modality in terms of safety, quality and effectiveness inside the limitations of the UK's nationalised healthcare system. METHODS: All patients undergoing LCBDE at our institution from November 2013 - July 2021 were included in the study. Data were collected from a prospectively maintained institutional database and data points corroborated by electronic patient data on hospital systems. RESULTS: Three hundred and eleven patients underwent LCBDE. Median age was 68 (range 21-95). Most cases were performed as urgent/emergency (n = 206, 66% vs n = 105, 34% elective). Bile duct stones were diagnosed pre-operatively in 23% of cases (n = 73). Intra-operative diagnosis was made using laparoscopic ultrasound (n = 228, 73%), cholangiogram (n = 44, 14%) or combination of both (n = 31, 10%). Laparoscopic completion rate was 94%. 56% were via choledochotomy and 44% trans-cystic. Incidence of bile leak was 4.2% (n = 13) and the incidence of retained stone within 90 days was 3.9%. Median length of stay was 2 days post-operatively (range 0-62). The rate of mortality was 0.66%. CONCLUSION: The data from our study shows that LC and LCBDE is a safe, effective service that can be successfully delivered in the NHS. With the developing specialisation of benign biliary units, we believe that this approach to choledocholithiasis is reproducible and achievable nationally and should be considered first-line in the management of this condition.

Success of intraoperative imaging and management of suspected choledocholithiasis without pre-operative bile duct imaging - A case series.

BACKGROUND: Laparoscopic common bile duct exploration (LCBDE) is gaining popularity over endoscopic retrograde cholangiopancreatography (ERCP) for the management of common bile duct stones. However, its application has been almost exclusively following preoperative stone confirmation via magnetic retrograde cholangiopancreatography (MRCP), endoscopic ultrasound (EUS) or ERCP. We present our series of LCBDE following detection of common bile duct stones with intraoperative imaging (IOI) alone, in consecutive elective and emergency patients with suspected choledocholithiasis. MATERIALS AND METHODS: All patients with suspected but unconfirmed choledocholithiasis undergoing LC with intention to proceed to LCBDE between January 2015 and June 2017 were included. LCBDE was performed following the discovery of choledocholithiasis on IOI. RESULTS: 371 patients with suspected choledocholithiasis underwent LC with IOI. CBD stones or obstructing sludge was identified in 107 patients (29%), with sensitivity of 96.2% and specificity of 98.5%. 100 patients, median age 59, went on to have LCBDE as indicated by intraoperative imaging. 76% were performed as emergency cases and conversion to open rate was 2%. There were no mortalities. Bile leak and retained stones occurred in 4% and 3% respectively. 7/100 patients required re-intervention, with re-look laparoscopy (n = 4) and ERCP (n = 3). Median length of stay was 1.5 and 3 days for elective and emergency cases respectively, and 30 readmission rate was 8%. DISCUSSION AND CONCLUSION: Traditionally patients presenting with suspicion of choledocholithiasis undergo preoperative MRCP/EUS and/or ERCP prior to eventual LC. We propose an alternative, more streamlined, pathway of treatment without requiring preoperative cholangiography, applicable to both elective and emergency patients.

Brain-Derived Neurotrophic Factor Elevates Activating Transcription Factor 4 (ATF4) in Neurons and Promotes ATF4-Dependent Induction of Sesn2.

Activating transcription factor 4 (ATF4) plays important physiologic roles in the brain including regulation of learning and memory as well as neuronal survival and death. Yet, outside of translational regulation by the eIF2α-dependent stress response pathway, there is little information about how its levels are controlled in neurons. Here, we show that brain-derived neurotrophic factor (BDNF) promotes a rapid and sustained increase in neuronal ATF4 transcripts and protein levels. This increase is dependent on tropomyosin receptor kinase (TrkB) signaling, but independent of levels of phosphorylated eIF2α. The elevation in ATF4 protein occurs both in nuclei and processes. Transcriptome analysis revealed that ATF4 mediates BDNF-promoted induction of Sesn2 which encodes Sestrin2, a protector against oxidative and genotoxic stresses and a mTor complex 1 inhibitor. In contrast, BDNF-elevated ATF4 did not affect expression of a number of other known ATF4 targets including several with pro-apoptotic activity. The capacity of BDNF to elevate neuronal ATF4 may thus represent a means to maintain this transcription factor at levels that provide neuroprotection and optimal brain function without risk of triggering neurodegeneration.

A Single Centre Experience of Day Case Laparoscopic Cholecystectomy Outcomes by Body Mass Index Group.

AIM: The purpose of this study was to evaluate whether patients with a high BMI can undergo safe day case LC for cholecystitis compared to groups of patients with a lower BMI. SETTING: NHS District General Hospital, UK. METHODS: A retrospective review of 2391 patients who underwent an attempted day case LC between 1 January 2009 and 15 August 2015 was performed. Patients were divided into five groups depending on their BMI. Inclusion criteria were patients undergoing elective day case laparoscopic cholecystectomy with cholecystitis on histology. The endpoints were complication requiring readmission and postoperative length of stay (LOS). RESULTS: There were 2391 LCs performed in the time period of which 1646 were eligible for inclusion. These LCs were classified as 273 (16.9%), 608 (37.8%), 428 (26.6%), 208 (12.9%), and 91 (5.66%) patients in the groups with BMI values of 18.5-24.9, 25-29.9, 30-34.9, 35-39.9, and >40, respectively. Average BMI was 30.0 (±5.53, 19-51) with an average postoperative LOS of 0.86, and there was no difference between the BMI groups. Overall complication rate was 4.3%; there was no significance between BMI groups. CONCLUSIONS: Increased BMI was not associated with worse outcomes after day case LC.

Bioremediation of mercury: not properly exploited in contaminated soils!

Contamination of land and water caused by heavy metal mercury (Hg) poses a serious threat to biota worldwide. The seriousness of toxicity of this neurotoxin is characterized by its ability to augment in food chains and bind to thiol groups in living tissue. Therefore, different remediation approaches have been implemented to rehabilitate Hg-contaminated sites. Bioremediation is considered as cheaper and greener technology than the conventional physico-chemical means. Large-scale use of Hg-volatilizing bacteria are used to clean up Hg-contaminated waters, but there is no such approach to remediate Hg-contaminated soils. This review focuses on recent uses of Hg-resistant bacteria in bioremediation of mercury-contaminated sites, limitation and advantages of this approach, and identifies the gaps in existing research.

Bio-augmentation and nutrient amendment decrease concentration of mercury in contaminated soil.

Four mercury (Hg) contaminated soils with different pH (7.6, 8.5, 4.2 and 7.02) and total organic carbon contents (2.1, 2.2, 4 and 0.9%) were subjected to bioremediation utilizing a Hg volatilizing bacterial strain Sphingobium SA2 and nutrient amendment. In a field with ~280mg/kgHg, 60% of Hg was removed by bio-augmentation in 7days, and the removal was improved when nutrients were added. Whereas in artificially spiked soils, with ~100mg/kgHg, removal due to bio-augmentation was 33 to 48% in 14days. In the field contaminated soil, nutrient amendment alone without bio-augmentation removed 50% of Hg in 28days. Nutrient amendment also had an impact on Hg remediation in the spiked soils, but the best results were obtained when the strain and nutrients both were applied. The development of longer root lengths from lettuce and cucumber seeds grown in the remediated soils confirmed that the soil quality improved after bioremediation. This study clearly demonstrates the potential of Hg-reducing bacteria in remediation of Hg-contaminated soils. However, it is desirable to trap the volatilized Hg for enhanced bioremediation.

Implementation of next generation sequencing into pediatric hematology-oncology practice: moving beyond actionable alterations.

BACKGROUND: Molecular characterization has the potential to advance the management of pediatric cancer and high-risk hematologic disease. The clinical integration of genome sequencing into standard clinical practice has been limited and the potential utility of genome sequencing to identify clinically impactful information beyond targetable alterations has been underestimated. METHODS: The Precision in Pediatric Sequencing (PIPseq) Program at Columbia University Medical Center instituted prospective clinical next generation sequencing (NGS) for pediatric cancer and hematologic disorders at risk for treatment failure. We performed cancer whole exome sequencing (WES) of patient-matched tumor-normal samples and RNA sequencing (RNA-seq) of tumor to identify sequence variants, fusion transcripts, relative gene expression, and copy number variation (CNV). A directed cancer gene panel assay was used when sample adequacy was a concern. Constitutional WES of patients and parents was performed when a constitutionally encoded disease was suspected. Results were initially reviewed by a molecular pathologist and subsequently by a multi-disciplinary molecular tumor board. Clinical reports were issued to the ordering physician and posted to the patient's electronic medical record. RESULTS: NGS was performed on tumor and/or normal tissue from 101 high-risk pediatric patients. Potentially actionable alterations were identified in 38% of patients, of which only 16% subsequently received matched therapy. In an additional 38% of patients, the genomic data provided clinically relevant information of diagnostic, prognostic, or pharmacogenomic significance. RNA-seq was clinically impactful in 37/65 patients (57%) providing diagnostic and/or prognostic information for 17 patients (26%) and identified therapeutic targets in 15 patients (23%). Known or likely pathogenic germline alterations were discovered in 18/90 patients (20%) with 14% having germline alternations in cancer predisposition genes. American College of Medical Genetics (ACMG) secondary findings were identified in six patients. CONCLUSIONS: Our results demonstrate the feasibility of incorporating clinical NGS into pediatric hematology-oncology practice. Beyond the identification of actionable alterations, the ability to avoid ineffective/inappropriate therapies, make a definitive diagnosis, and identify pharmacogenomic modifiers is clinically impactful. Taking a more inclusive view of potential clinical utility, 66% of cases tested through our program had clinically impactful findings and samples interrogated with both WES and RNA-seq resulted in data that impacted clinical decisions in 75% of cases.

An assessment of forward and inverse GIA solutions for Antarctica.

In this work we assess the most recent estimates of glacial isostatic adjustment (GIA) for Antarctica, including those from both forward and inverse methods. The assessment is based on a comparison of the estimated uplift rates with a set of elastic-corrected GPS vertical velocities. These have been observed from an extensive GPS network and computed using data over the period 2009-2014. We find systematic underestimations of the observed uplift rates in both inverse and forward methods over specific regions of Antarctica characterized by low mantle viscosities and thin lithosphere, such as the northern Antarctic Peninsula and the Amundsen Sea Embayment, where its recent ice discharge history is likely to be playing a role in current GIA. Uplift estimates for regions where many GIA models have traditionally placed their uplift maxima, such as the margins of Filchner-Ronne and Ross ice shelves, are found to be overestimated. GIA estimates show large variability over the interior of East Antarctica which results in increased uncertainties on the ice-sheet mass balance derived from gravimetry methods.

A case study of an integrative genomic and experimental therapeutic approach for rare tumors: identification of vulnerabilities in a pediatric poorly differentiated carcinoma.

BACKGROUND: Precision medicine approaches are ideally suited for rare tumors where comprehensive characterization may have diagnostic, prognostic, and therapeutic value. We describe the clinical case and molecular characterization of an adolescent with metastatic poorly differentiated carcinoma (PDC). Given the rarity and poor prognosis associated with PDC in children, we utilized genomic analysis and preclinical models to validate oncogenic drivers and identify molecular vulnerabilities. METHODS: We utilized whole exome sequencing (WES) and transcriptome analysis to identify germline and somatic alterations in the patient's tumor. In silico and in vitro studies were used to determine the functional consequences of genomic alterations. Primary tumor was used to generate a patient-derived xenograft (PDX) model, which was used for in vivo assessment of predicted therapeutic options. RESULTS: WES revealed a novel germline frameshift variant (p.E1554fs) in APC, establishing a diagnosis of Gardner syndrome, along with a somatic nonsense (p.R790*) APC mutation in the tumor. Somatic mutations in TP53, MAX, BRAF, ROS1, and RPTOR were also identified and transcriptome and immunohistochemical analyses suggested hyperactivation of the Wnt/ß-catenin and AKT/mTOR pathways. In silico and biochemical assays demonstrated that the MAX p.R60Q and BRAF p.K483E mutations were activating mutations, whereas the ROS1 and RPTOR mutations were of lower utility for therapeutic targeting. Utilizing a patient-specific PDX model, we demonstrated in vivo activity of mTOR inhibition with temsirolimus and partial response to inhibition of MEK. CONCLUSIONS: This clinical case illustrates the depth of investigation necessary to fully characterize the functional significance of the breadth of alterations identified through genomic analysis.

A histone H3K9M mutation traps histone methyltransferase Clr4 to prevent heterochromatin spreading.

Histone lysine-to-methionine (K-to-M) mutations are associated with multiple cancers, and they function in a dominant fashion to block the methylation of corresponding lysines on wild type histones. However, their mechanisms of function are controversial. Here we show that in fission yeast, introducing the K9M mutation into one of the three histone H3 genes dominantly blocks H3K9 methylation on wild type H3 across the genome. In addition, H3K9M enhances the interaction of histone H3 tail with the H3K9 methyltransferase Clr4 in a SAM (S-adenosyl-methionine)-dependent manner, and Clr4 is trapped at nucleation sites to prevent its spreading and the formation of large heterochromatin domains. We further determined the crystal structure of an H3K9M peptide in complex with human H3K9 methyltransferase G9a and SAM, which reveales that the methionine side chain had enhanced van der Waals interactions with G9a. Therefore, our results provide a detailed mechanism by which H3K9M regulates H3K9 methylation.

Technique to manage persistent leak from a prepyloric ulcer where a distal gastrectomy is not appropriate.

Perforated peptic ulcer disease remains a relatively frequent emergency surgery presentation. Persistent leak is the most common indication for return to theatre. We present a technique to manage patients in whom a more substantial resection is not possible. A 45-year-old woman underwent initial laparoscopic primary closure of a non-malignant perforated gastric ulcer. This subsequently leaked on return to the UK and had a further graham patch formed via a laparotomy. Unfortunately, the patch repair leaked and at reoperation a wedge excision or distal gastrectomy was not possible given the friability of the tissues and instability of the patient, a transgastric drain and perigastric drain were therefore placed. This created a controlled fistula, which was managed eventually as an outpatient. Transgastric drains in the context of the persistent perforated gastric ulcer leak are a safe way to manage the unstable patient with poor tissues where more substantial surgeries such as a distal gastrectomy are not possible.

Isoform-level brain expression profiling of the spermidine/spermine N1-Acetyltransferase1 (SAT1) gene in major depression and suicide.

Low brain expression of the spermidine/spermine N-1 acetyltransferase (SAT1) gene, the rate-limiting enzyme involved in catabolism of polyamines that mediate the polyamine stress response (PSR), has been reported in depressed suicides. However, it is unknown whether this effect is associated with depression or with suicide and whether all or only specific isoforms expressed by SAT1, such as the primary 171 amino acid protein-encoding transcript (SSAT), or an alternative splice variant (SSATX) that is involved in SAT1 regulated unproductive splicing and transcription (RUST), are involved. We applied next generation sequencing (RNA-seq) to assess gene-level, isoform-level, and exon-level SAT1 expression differences between healthy controls (HC, N = 29), DSM-IV major depressive disorder suicides (MDD-S, N = 21) and MDD non-suicides (MDD, N = 9) in the dorsal lateral prefrontal cortex (Brodmann Area 9, BA9) of medication-free individuals postmortem. Using small RNA-seq, we also examined miRNA species putatively involved in SAT1 post-transcriptional regulation. A DSM-IV diagnosis was made by structured interview. Toxicology and history ruled out recent psychotropic medication. At the gene-level, we found low SAT1 expression in both MDD-S (vs. HC, p = 0.002) and MDD (vs. HC, p = 0.002). At the isoform-level, reductions in MDD-S (vs. HC) were most pronounced in four transcripts including SSAT and SSATX, while reductions in MDD (vs. HC) were pronounced in three transcripts, one of which was reduced in MDD relative to MDD-S (all p < 0.1 FDR corrected). We did not observe evidence for differential exon-usage (i.e. splicing) nor differences in miRNA expression. Results replicate the finding of low SAT1 brain expression in depressed suicides in an independent sample and implicate low SAT1 brain expression in MDD independent of suicide. Low expressions of both SSAT and SATX isoforms suggest that shared transcriptional mechanisms involved in RUST may account for low SAT1 brain expression in depressed suicides. Future studies are required to understand the functions and regulation of SAT1 isoforms, and how they relate to the pathogenesis of MDD and suicide.

Characterization of a novel fusion gene EML4-NTRK3 in a case of recurrent congenital fibrosarcoma.

We describe the clinical course of a recurrent case of congenital fibrosarcoma diagnosed in a 9-mo-old boy with a history of hemimelia. Following complete surgical resection of the primary tumor, the patient subsequently presented with bulky bilateral pulmonary metastases 6 mo following surgery. Molecular characterization of the tumor revealed the absence of the prototypical ETV6-NTRK3 translocation. However, tumor characterization incorporating cytogenetic, array comparative genomic hybridization, and RNA sequencing analyses, revealed a somatic t(2;15)(2p21;15q25) translocation resulting in the novel fusion of EML4 with NTRK3. Cloning and expression of EML4-NTRK3 in murine fibroblast NIH 3T3 cells revealed a potent tumorigenic phenotype as assessed in vitro and in vivo. These results demonstrate that multiple fusion partners targeting NTRK3 can contribute to the development of congenital fibrosarcoma.

Tls1 regulates splicing of shelterin components to control telomeric heterochromatin assembly and telomere length.

Heterochromatin preferentially forms at repetitive DNA elements through RNAi-mediated targeting of histone-modifying enzymes. It was proposed that splicing factors interact with the RNAi machinery or regulate the splicing of repeat transcripts to directly participate in heterochromatin assembly. Here, by screening the fission yeast deletion library, we comprehensively identified factors required for telomeric heterochromatin assembly, including a novel gene tls1+. Purification of Tls1 and mass spectrometry analysis of its interacting proteins show that Tls1 associates with the spliceosome subunit Brr2. RNA sequencing analysis shows that the splicing of a subset of mRNAs are affected in tls1Δ cells, including mRNAs of shelterin components rap1+ and poz1+. Importantly, replacing rap1+ and poz1+ with their cDNAs significantly alleviated heterochromatin defects of tls1Δ cells, suggesting that the missplicing of shelterin components is the cause of such defects, and that splicing factors regulate telomeric heterochromatin through the proper splicing of heterochromatin factors. In addition to its role in telomeric heterochromatin assembly, Tls1-mediated splicing of shelterin mRNAs also regulates telomere length. Given that its human homologue C9ORF78 also associates with the spliceosome and is overexpressed in multiple cancer cell lines, our results suggest that C9ORF78 overexpression might alter the proper splicing of genes during cancer progression.

Safety and efficacy of an aroA-deleted live vaccine against avian colibacillosis in a multicentre field trial in broilers in Morocco.

The safety and efficacy of an aroA-deleted live vaccine against avian colibacillosis (Poulvac(®) E. coli) was evaluated in broilers in a multicentre field trial. The trial sites consisted of 18 paired bird houses (randomly assigned to either the vaccination or the control treatment groups) located in 15 farms in three different regions of Morocco. A field dose of vaccine was administered on day of hatch by the spray route. Both clinical and performance parameters were compared between vaccinated and control groups, in which the experimental unit was defined as the individual bird house. No adverse reactions attributable to the vaccine were observed throughout the study. Non-inferiority of the vaccinated bird houses versus the control houses during a 2-week period post vaccination was statistically demonstrated for mortality and average daily weight gain. Vaccine efficacy was confirmed based on significant differences between vaccinated and unvaccinated groups measured for the full duration of the trial, including colibacillosis-like lesions observed at slaughter (1.7 versus 3.5%; P = 0.0054), total mortality (9.3 versus 10.3%; P = 0.0203), average daily weight gain (47.8 versus 46.2 g/day; P = 0.0006), average number of antibiotic treatment days (0.5 versus 2.0; P = 0.0008) and percentage of the birds that was marketed (90.0 versus 89.0%; P = 0.0309). In conclusion, the vaccine was demonstrated to be both safe and efficacious under field conditions.

The proper splicing of RNAi factors is critical for pericentric heterochromatin assembly in fission yeast.

Heterochromatin preferentially assembles at repetitive DNA elements, playing roles in transcriptional silencing, recombination suppression, and chromosome segregation. The RNAi machinery is required for heterochromatin assembly in a diverse range of organisms. In fission yeast, RNA splicing factors are also required for pericentric heterochromatin assembly, and a prevailing model is that splicing factors provide a platform for siRNA generation independently of their splicing activity. Here, by screening the fission yeast deletion library, we discovered four novel splicing factors that are required for pericentric heterochromatin assembly. Sequencing total cellular RNAs from the strongest of these mutants, cwf14Δ, showed intron retention in mRNAs of several RNAi factors. Moreover, introducing cDNA versions of RNAi factors significantly restored pericentric heterochromatin in splicing mutants. We also found that mutations of splicing factors resulted in defective telomeric heterochromatin assembly and mis-splicing the mRNA of shelterin component Tpz1, and that replacement of tpz1+ with its cDNA partially rescued heterochromatin defects at telomeres in splicing mutants. Thus, proper splicing of RNAi and shelterin factors contributes to heterochromatin assembly at pericentric regions and telomeres.

Prevalence of the Leptospira serovars bratislava, grippotyphosa, mozdok and pomona in French dogs.

Although most French dogs are correctly vaccinated against leptospirosis with inactivated strains of canicola and icterohaemorrhagiae, the disease is still very prevalent in France raising the question of whether the vaccines used require updating. The aim of the present study was to provide serological data regarding circulation of the Leptospira serovars: grippotyphosa, bratislava, pomona and mozdok, which are contained in vaccines available in other parts of the world and which could be rapidly adapted for France. Results indicated that the epidemiology was consistent with the circulation of Leptospira belonging to the serogroups Australis and Grippotyphosa and that the case to support the inclusion of either pomona or mozdok in a dog vaccine for France was weak.

Knockdown of osteopontin reduces the inflammatory response and subsequent size of postsurgical adhesions in a murine model.

Adhesions between organs after abdominal surgery remain a significant unresolved clinical problem, causing considerable postoperative morbidity. Osteopontin (OPN) is a cytokine up-regulated after cell injury and tissue repair. Our previous studies have shown that blocking OPN expression at sites of cutaneous wounding resulted in reduced granulation tissue and scarring. We hypothesize that it may be possible to similarly reduce inflammation-associated fibrosis that causes small-bowel adhesions after abdominal surgery. By using a mouse model, we deliver OPN antisense oligodeoxynucleotides via Pluronic gel to the surface of injured, juxtaposed small bowel and show a significant reduction of inflammatory cell influx to the developing adhesion and a dramatic reduction in the resulting adhesion size. A significant reduction in α-smooth muscle actin expression and collagen deposition within the mature adhesion is also demonstrated. We see no impact on mortality, and the healing of serosal injury to intact bowel appeared normal given the reduced inflammatory response. Our studies suggest that dampening OPN levels might be a potentially important target for anti-adhesion therapeutics.