Sexual rehabilitation recommendations for prostate cancer survivors and their partners from a biopsychosocial Prostate Cancer Supportive Care Program.

PURPOSE: This study aimed to highlight the biopsychosocial recommendations provided to prostate cancer survivors and their partners during sexual rehabilitation. METHODS: Retrospective analysis of a prospectively maintained patient database was conducted for visits between 2013 and 2019. The sexual health rehabilitation action plan (SHRAP) is a standardized 29-item list of biopsychosocial recommendations. The frequency of biopsychosocial recommendations provided to patients via their SHRAPs was assessed. RESULTS: Among 913 patients, across 2671 appointments, nearly 74% of patients underwent radical prostatectomy. Other treatments included combination therapy (surgery, radiation, and/or androgen deprivation therapy (ADT)) (13%), radiation (external beam radiation or brachytherapy) (5%), and active surveillance (2%). Each patient had a median of 2 (SD 2.06) appointments and received a mean of 10.0 (SD 3.9) recommendations at each visit. Educational recommendations (penile rehabilitation, orgasmic guidelines, and climacturia management) were provided in 84% of visits followed by psychosexual recommendations (pleasure-focused, dedicated time, simmering, sexual aids, and sensate focus) in 71% of all appointments. The top recommendations (total n, frequency of recommendation) were penile rehabilitation (2253, 84%), pleasure-focus (1887, 71%), phosphodiesterase inhibitors (1655, 62%), clinical counselor (1603, 60%), vacuum erectile device (1418, 53%) and intracavernosal injections (1383, 52%). CONCLUSIONS: Biopsychosocial programs are evolving to be a key part of prostate cancer survivorship. This study's insight suggests that prostate cancer survivors require education around their sexual consequences and psychosexual counseling alongside proven biomedical strategies for erectile dysfunction. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivorship programs should integrate educational and psychosocial strategies alongside biological strategies for prostate cancer survivors and their partners.

Effect of a computerized brain exercise program on cognitive performance in older adults.

OBJECTIVES: Research indicates an association between stimulating mental activities and better memory performance as people age, but studies on computerized mental stimulation programs are limited. We explored whether computerized brain training exercises improved cognitive performance in older adults. METHODS: In local retirement communities, a convenience sample was randomized into an intervention group (N = 36), who used a computer program 5 days a week for 20-25 minutes each day, or a wait-list control group (N = 33). All were older adults without dementia (mean age: 81.8 years; SD: 6.1; 67% female). Neuropsychological testing was completed at baseline (Time 1), 2 months (Time 2), and 6 months (Time 3). Three cognitive domains (Immediate Memory, Delayed Memory, Language) were compared in the two groups as a function of time using mixed models. RESULTS: The intervention group used the computerized program (Brain Fitness, Dakim Inc., Santa Monica, CA) for an average of 43 (SD: 4.4) sessions by Time 2 and 81 (SD: 37.5) sessions by Time 3. Mixed models examining cognitive domains as function of time revealed significant group differences in Delayed Memory (F(2,72) = 4.7, p = 0.01) but not Immediate Memory and Language; no significant improvements were noted for the control group. Among all participants, anyone playing at least 40 sessions over the 6 months improved in all three domains (Immediate Memory, Delayed Memory, and Language). CONCLUSION: Participating in a computerized brain exercise program over 6 months improves cognitive abilities in older adults. These results extend literature indicating the benefit of training exercises, whether in a classroom format or via a computerized self-paced program.

Methods to increase equity, diversity, and inclusion in Canadian urology programs.

INTRODUCTION: Women and ethnic minorities are underrepresented at all levels of training and practice in urology residency programs. Equity, diversity, and inclusion (EDI) is a growing field of interest in medical research and business literature, especially regarding recruitment. The objective of this review was to evaluate evidence-based strategies to increase EDI to improve urology residency recruitment. METHODS: A review was conducted using Ovid Medline to identify publications reporting strategies to increase women and underrepresented minorities (URM ) in healthcare fields. An evaluation of business models was incorporated. Identified strategies were sorted and ranked based on how many papers reported an increased proportion of women or URM in their program following implementation. RESULTS: We assessed 234 publications from 1972-2022. Eleven underwent full review. Six additional pieces of business literature were reviewed and incorporated. The following methods were most often identified to increase diversity: mentorship and holistic application review (six publications), as well as funded internship programs and diverse selection committees (four publications). Diversity statements and application blinding were highlighted by multiple business sources but were each only reviewed in one medical publication. CONCLUSIONS: Recommendations identified include mentorship, holistic application review by diverse selection committees with bias training, and development of funded internship programs. Standardized questions and rubrics were also well-studied. Business strategies, such as publishing diversity statements and application blinding, are less studied in medical education literature. This study is unique in its inclusion of both medical and business literature and highlights concrete strategies for urology residency programs to increase EDI during recruitment.

De novo urethral stricture disease in renal transplant recipients.

INTRODUCTION: With routine catheterization and low urine output pre-transplant, renal transplant recipients (RTRs) may be at risk of urethral stricture disease post-transplant. The objective of this study was to characterize new urethral stricture disease in males following renal transplant. METHODS: A retrospective chart review was carried out on all male RTRs at Vancouver General Hospital who developed urethral strictures from October 2009-2019. Descriptive analyses were conducted on patient characteristics. Comparative analyses against non-stricture RTRs were carried out. RESULTS: Of 636 RTRs, 18 (2.8%) developed a postoperative urethral stricture. Median time from transplant to stricture discovery was 56 days (range 8-618 days). One-third of stricture patients had prior risk factors for stricture formation. Post-transplant, 77.8% presented symptomatically, with 61.1% requiring intervention. Overall graft survival rate was 88.9% among the RTR stricture group; 16.7% experienced acute rejection and 22.2% had delayed graft function (DGF). There was no significant association between developing postoperative urethral stricture and urinary tract infection (Chi-squared [X2]=0.04, p=0.84; odds ratio [OR ] 0.81, 95% confidence interval [CI] 0.1-6.21), DGF (X2=0.14, p=0.70; OR 0.8, CI 0.26-2.48), or acute rejection (X2=2.02, p=0.14; OR 2.55, CI 0.71-9.12). CONCLUSIONS: De novo post-transplant urethral stricture rates appear to occur at a higher rate than the general population and contribute to patient morbidity. Stricture disease should be considered post-transplantation in patients with voiding dysfunction, even if they don't have prior risk factors. Multicenter studies should be considered to elucidate any relationship between urethral stricture and graft survival.

3D bioprinting for organ and organoid models and disease modeling.

INTRODUCTION: 3D printing, a versatile additive manufacturing technique, has diverse applications ranging from transportation, rapid prototyping, clean energy, and medical devices. AREAS COVERED: The authors focus on how 3D printing technology can enhance the drug discovery process through automating tissue production that enables high-throughput screening of potential drug candidates. They also discuss how the 3D bioprinting process works and what considerations to address when using this technology to generate cell laden constructs for drug screening as well as the outputs from such assays necessary for determining the efficacy of potential drug candidates. They focus on how bioprinting how has been used to generate cardiac, neural, and testis tissue models, focusing on bio-printed 3D organoids. EXPERT OPINION: The next generation of 3D bioprinted organ model holds great promises for the field of medicine. In terms of drug discovery, the incorporation of smart cell culture systems and biosensors into 3D bioprinted models could provide highly detailed and functional organ models for drug screening. By addressing current challenges of vascularization, electrophysiological control, and scalability, researchers can obtain more reliable and accurate data for drug development, reducing the risk of drug failures during clinical trials.

Integration of hospital with congregate care homes in response to the COVID-19 pandemic.

Background: The coronavirus disease 2019 (COVID-19) pandemic has highlighted the need to improve the safety of the environments where we care for older adults in Canada. After providing assistance during the first wave, many Ontario hospitals formally partnered with local congregate care homes in a "hub and spoke" model during second pandemic wave onward. The objective of this article is to describe the implementation and longitudinal outcomes of residents in one hub and spoke model composed of a hospital partnered with 18 congregate care homes including four long-term care and 14 retirement or other congregate care homes. Intervention: Homes were provided continuous seven-day per week access to hospital support, including infection prevention and control (IPAC), testing, vaccine delivery and clinical support as needed. Any COVID-19 exposure or transmission triggered a same-day meeting to implement initial control measures. A minimum of weekly on-site visits occurred for long-term care homes and biweekly for other congregate care homes, with up to daily on-site presence during outbreaks. Outcomes: Case detection among residents increased following implementation in context of increased testing, then decreased post-immunization until the Omicron wave when it peaked. After adjusting for the correlation within homes, COVID-related mortality decreased following implementation (OR=0.51, 95% CI, 0.30-0.88; p=0.01). In secondary analysis, homes without pre-existing IPAC programs had higher baseline COVID-related mortality rate (OR=19.19, 95% CI, 4.66-79.02; p<0.001) and saw a larger overall decrease during implementation (3.76% to 0.37%-0.98%) as compared to homes with pre-existing IPAC programs (0.21% to 0.57%-0.90%). Conclusion: The outcomes for older adults residing in congregate care homes improved steadily throughout the COVID-19 pandemic. While this finding is multifactorial, integration with a local hospital partner supported key interventions known to protect residents.

Under-recognized factors affecting penile implant satisfaction in patients.

INTRODUCTION: Surgical management via penile prosthesis is an option for patients who have failed medical management. There is a paucity of literature surrounding factors contributing to patient satisfaction after implant surgery. The objective of this study was to characterize patients' and surgeons' attitudes toward factors affecting satisfaction with this procedure. METHODS: Two patient cohorts were identified and contacted via email: a medical management of erectile dysfunction (ED) cohort and a penile implant patient cohort. A third cohort, Canadian urologists who perform penile implant surgeries, was also contacted. The surveys consisted of 5-7 questions, including a rating question regarding the importance of various penile implant factors. RESULTS: Forty-six ED patients, 45 post-implant patients, and 12 urologists completed the survey. The mean overall satisfaction on a 10-point scale was 6.49 (standard deviation [SD] 2.92). Most (67%) urologists selected patient satisfaction as one of their least favorite aspects of penile implant surgery. Compared to postimplant patients, ED patients reported greater importance in the areas of appearance (p=0.035), soft glans (p=0.040), and concealment of implant (p=0.007). Urologists ranked natural feel (p=0.019) and generating a discrete erection (p=0.022) as less important than patients. CONCLUSIONS: This is the first study that examines which specific variables of penile implant surgery are associated with satisfaction while comparing surgeons' understanding of what patients desire from this surgery. This study identifies several factors deemed important by patients but under-recognized by urologists. This knowledge can aid urologists in optimizing preoperative counselling and improving patient satisfaction.

What difference might retractions make? An estimate of the potential epistemic cost of retractions on meta-analyses.

The extent to which a retraction might require revising previous scientific estimates and beliefs - which we define as the epistemic cost - is unknown. We collected a sample of 229 meta-analyses published between 2013 and 2016 that had cited a retracted study, assessed whether this study was included in the meta-analytic estimate and, if so, re-calculated the summary effect size without it. The majority (68% of N = 229) of retractions had occurred at least one year prior to the publication of the citing meta-analysis. In 53% of these avoidable citations, the retracted study was cited as a candidate for inclusion, and only in 34% of these meta-analyses (13% of total) the study was explicitly excluded because it had been retracted. Meta-analyses that included retracted studies were published in journals with significantly lower impact factor. Summary estimates without the retracted study were lower than the original if the retraction was due to issues with data or results and higher otherwise, but the effect was small. We conclude that meta-analyses have a problematically high probability of citing retracted articles and of including them in their pooled summaries, but the overall epistemic cost is contained.

Predictors of urosepsis in struvite stone patients after percutaneous nephrolithotomy.

PURPOSE: This study aims to identify clinical factors that may predispose struvite stone patients to urosepsis following percutaneous nephrolithotomy (PCNL). MATERIALS AND METHODS: A retrospective review was conducted on patients who received PCNL for struvite stones. The Systemic Inflammatory Response Syndrome (SIRS) criteria and quick-Sepsis Related Organ Failure Assessment (q-SOFA) criteria were used to identify patients who were at an increased risk for urosepsis. Statistical analysis was performed using Fisher's exactness test, Wilcoxon rank test, and logistic regression. RESULTS: Chart review identified 99 struvite stone patients treated with PCNL. Post-operatively, 40 patients were SIRS positive (≥2 criteria) and/or q-SOFA positive (score ≥2). Using SIRS as an approximation for urosepsis, longer operative times (p<0.001), higher pre-operative white blood cell counts (p=0.01), greater total stone surface area (p<0.0001), and pre-operative stenting (OR, 5.75; p=0.01) were identified as independent risk factors for urosepsis. Multivariate analysis demonstrated pre-operative stenting (OR, 1.46; p=0.01) to be a risk factor. With q-SOFA, univariable analysis found that antibiotic use within 3 months prior to a PCNL (OR, 4.44; p=0.04), medical comorbidities (OR, 4.80; p=0.02), longer operative times (p<0.001), lengthier post-operative hospitalization (p<0.01), and greater total stone surface area (p<0.0001) were risk factors for urosepsis. Multivariate analysis revealed that bladder outlet obstruction (OR, 2.74; p<0.003) and pre-operative stenting (OR, 1.27; p=0.01) significantly increased odds of being q-SOFA positive. CONCLUSIONS: Several risk factors for urosepsis following PCNL for struvite stones have been identified. These risk factors should be taken into consideration in peri-operative care to mitigate the risks of urosepsis.

Clinic Utilization and Characteristics of Patients Accessing a Prostate Cancer Supportive Care Program's Sexual Rehabilitation Clinic.

Prostate cancer (PC) treatment leads to impairment of sexual function. The Prostate Cancer Supportive Care (PCSC) Program's Sexual Rehabilitation clinic (SRC) assists patients and their partners with sexual recovery using a biopsychosocial approach to rehabilitation. This study characterizes patients seen in the SRC between July 2013-1 July 2019. Data was retrospectively abstracted from clinic records. In total, 965 patients were seen over 3391 appointments during the study period. Median age (standard deviation (SD)) was 66 years (SD = 7.1), 82.0% were partnered, yet 81.7% attended appointments alone. 88.0% were treated with surgery, 5.1% with brachytherapy, 3.7% with external beam radiation (EBRT), 1.8% with combined brachytherapy and EBRT, and 1.4% with androgen deprivation therapy. In total, 708 patients (73.4%) attended ≥1 follow-up appointment. Median time (SD) between end of prostate cancer treatment to first SRC appointment was 270 days (range 0-7766). The mean (SD) self-reported overall sexual satisfaction (extracted from International Index of Erectile Function-5 (IIEF-5)) significantly increased both with erectile aids (1.69 (SD = 1.52) to 2.26 (SD = 1.66), p < 0.001, n = 148) and without erectile aids (1.71 (SD = 1.44) to 2.35 (SD = 1.57), p < 0.001, n = 235). This study provides guidance for further investigation to refine treatment, wait-times, support, and/or resource offerings in this type of program.

Multicenter comparison of two norovirus ORF2-based genotyping protocols.

Point source norovirus outbreaks can be difficult to track due to high background levels of the virus in the environment and the limited strain variation in some genotyping regions. However, rapid and accurate source identification can limit the spread of a foodborne outbreak and reduce the number of cases. Harmonization of genotyping assays is critical for enabling the rapid exchange of sequence data nationally and internationally. Several regions of the genome have been proposed for this purpose, but no consensus has been reached. In the present study, two standardized genotyping protocols (region C and region D) were evaluated by nine laboratories in Canada and the United States, using a coded panel of 96 fecal specimens representing 22 different norovirus genotypes. Overall, region C typing had a success rate of 78% compared to 52% for region D; however, region D provides greater nucleotide sequence diversity for identifying new GII.4 variant strains. Significant differences in the genotyping success rate were observed among the nine participating laboratories (10% to 100%) and among the different genotypes (6% to 100%). For several genogroup II strains, reduced region D amplification correlated directly with mismatches between primer sequences and the template. Based on overall performance, we recommend the region C protocol for routine genotyping of noroviruses, while the region D protocol may be useful for identifying new GII.4 variants. Standardized genotyping protocols will enable rapid exchange of outbreak and sequence data through electronic norovirus surveillance networks.

Outbreak of Escherichia coli O157:H7 Infections Linked to Aged Raw Milk Gouda Cheese, Canada, 2013.

Between 12 July and 29 September 2013, 29 individuals in five Canadian provinces became ill following infection with the same strain of Escherichia coli O157:H7 as defined by molecular typing results. Five case patients were hospitalized, and one died. Twenty-six case patients (90%) reported eating Gouda cheese originating from a dairy plant in British Columbia. All of the 22 case patients with sufficient product details available reported consuming Gouda cheese made with raw milk; this cheese had been produced between March and July 2013 and was aged for a minimum of 60 days. The outbreak strain was isolated from the implicated Gouda cheese, including one core sample obtained from an intact cheese wheel 83 days after production. The findings indicate that raw milk was the primary source of the E. coli O157:H7, which persisted through production and the minimum 60-day aging period. This outbreak is the third caused by E. coli O157:H7 traced to Gouda cheese made with raw milk in North America. These findings provide further evidence that a 60-day ripening period cannot ensure die-off of pathogens that might be present in raw milk Gouda cheese after production and have triggered an evaluation of processing conditions, physicochemical parameters, and options to mitigate the risk of E. coli O157:H7 infection associated with raw milk Gouda cheese produced in Canada.

Multiple clusters of norovirus among shellfish consumers linked to symptomatic oyster harvesters.

We describe the investigation of a norovirus outbreak associated with raw oyster consumption affecting 36 people in British Columbia, Canada, in 2010. Several genotypes were found in oysters, including an exact sequence match to clinical samples in regions B and C of the norovirus genome (genogroup I genotype 4). Traceback implicated a single remotely located harvest site probably contaminated by ill shellfish workers during harvesting activities. This outbreak resulted in three recalls, one public advisory, and closure of the harvest site.

Investigation of the concurrent emergence of Salmonella enteritidis in humans and poultry in British Columbia, Canada, 2008-2010.

An increase in the rate of human infections with Salmonella enteritidis (SE) occurred between 2007 and 2010 in British Columbia (BC). During the same time period, an increase in SE from poultry-sourced isolates and increased clinical severity in poultry were also observed in BC. This article describes a multi-sectoral collaboration during a 3-year investigation, and the actions taken by public health and animal health professionals. Human cases were interviewed, clusters were investigated, and a case-control study was conducted. Environmental investigations were conducted in food service establishments (FSE). Suspect foods were tested. Laboratory data from poultry-sourced isolates were analysed. Five hundred and eighty-four human cases of SE with the same pulsed-field gel electrophoresis pattern were identified between May 2008 and August 2010. Seventy-three percentage of cases reported consumption of eggs. The odds of egg consumption were 2.4 times higher for cases than controls. Implicated FSE were found to use ungraded eggs, which had been distributed illegally. Investigation suggested that there were multiple suppliers of these eggs. Collaboration between public health and animal health professionals led to data sharing, improved understanding of SE, engagement with the poultry industry and public communication. Multi-disciplinary, multi-sectoral and multi-pronged investigations are recommended to identify the likely source of illness in large, protracted foodborne outbreaks caused by commonly consumed foods.

Analytical performance of norovirus real-time RT-PCR detection protocols in Canadian laboratories.

BACKGROUND: Noroviruses (NoVs) are the leading cause of infectious gastroenteritis worldwide. Real-time reverse transcription PCR (real-time RT-PCR) is the preferred method of NoV detection for the majority of testing laboratories. Although the accepted target region for molecular detection assays is the conserved ORF1/ORF2 junction, multiple variations have been published with differences in primers, probes, reagents, multiplexing, etc. OBJECTIVES: We assessed the detection limit for GII.4 NoV real-time RT-PCR assays as well as the ability to detect the non-GII.4 NoV genotypes in each participating laboratory. STUDY DESIGN: A panel of 25 RNA samples was circulated to 18 testing laboratories for comparison of their real-time RT-PCR procedures for NoV detection. RESULTS: Multiple protocols with slight differences in reagents or conditions successfully detected 10 genome equivalents or fewer of NoV per reaction. Multiplex procedures were significantly associated (p=0.04) with false negative results, particularly for a GI.2 strain. Sensitive detection was associated with false positive results (p=0.03). CONCLUSIONS: Overall, the data indicate that comparable results are produced under slightly different assay conditions.

A carboxy-terminal affinity tag for the purification and mass spectrometric characterization of integral membrane proteins.

G-protein-coupled receptors (GPCRs) and other structurally and functionally related membrane proteins represent particularly attractive targets for drug discovery. Integral membrane proteins are often difficult to purify from native contexts, and lack of sufficient quantities hampers subsequent structural and functional proteomic studies. We describe here an optimized enrichment strategy involving a membrane protein-compatible 1D4 affinity tag that is derived from the carboxy-terminal nine amino residues of bovine rhodopsin, and its corresponding tag-specific, high-affinity monoclonal antibody. When two GPCRs as well as two related ATP binding cassette (ABC) transporters are expressed in their functional forms in human cell lines, we have shown that a single detergent and wash condition can be employed for the purification of all said membrane proteins. Subsequent in-gel digestion with trypsin and mass spectrometric peptide analysis resulted in high sequence coverage for the ABC transporters ABCA1-1D4 and ABCA4-1D4. In contrast, digestion by various enzymatic combinations was necessary to obtain the best sequence coverage for affinity-enriched GPCRs CXCR4-1D4 and CCR5-1D4 as compared against other entries in an annotated spectrum library. Furthermore, specific enzyme combinations were necessary to produce suitable peptides for deducing N-glycosylation sites on CXCR4. Our results demonstrate that the 1D4-tag enrichment strategy is a versatile tool for the characterization of integral membrane proteins that can be employed for functional proteomic studies.

RS1, a discoidin domain-containing retinal cell adhesion protein associated with X-linked retinoschisis, exists as a novel disulfide-linked octamer.

RS1, also known as retinoschisin, is an extracellular protein that plays a crucial role in the cellular organization of the retina. Mutations in RS1 are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. RS1 is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Each subunit consists of a 157-amino acid discoidin domain flanked by two small segments of 39 and 5 amino acids. To begin to understand how the structure of RS1 relates to its role in retinal cell adhesion and X-linked retinoschisis, we have determined the subunit organization and disulfide bonding pattern of RS1 by SDS gel electrophoresis, velocity sedimentation, and mass spectrometry. Our results indicate that RS1 exists as a novel octamer in which the eight subunits are joined together by Cys(59)-Cys(223) intermolecular disulfide bonds. Subunits within the octamer are further organized into dimers mediated by Cys(40)-Cys(40) bonds. These cysteines lie just outside the discoidin domain indicating that these flanking segments primarily function in the octamerization of RS1. Within the discoidin domain, two cysteine pairs (Cys(63)-Cys(219) and Cys(110)-Cys(142)) form intramolecular disulfide bonds that are important in protein folding, and one cysteine (Cys(83)) exists in its reduced state. Because mutations that disrupt subunit assembly cause X-linked retinoschisis, the assembly of RS1 into a disulfide-linked homo-octamer appears to be critical for its function as a retinal cell adhesion protein.

Matrix metalloproteinase processing of monocyte chemoattractant proteins generates CC chemokine receptor antagonists with anti-inflammatory properties in vivo.

Monocyte chemoattractant protein (MCP)-3 is inactivated upon cleavage by the matrix metalloproteinase (MMP) gelatinase A (MMP-2). We investigated the susceptibility to proteolytic processing of the 4 human MCPs by 8 recombinant MMPs to determine whether MCP-3 is an isolated example or represents a general susceptibility of chemokines to proteolytic inactivation by these important inflammatory proteases. In addition to MMP-2, MCP-3 is efficiently cleaved by membrane type 1 (MT1)-MMP, the cellular activator of MMP-2, and by collagenase-1 and collagenase-3 (MMP-1, MMP-13) and stromelysin-1 (MMP-3). Specificity was shown by absence of cleavage by matrilysin (MMP-7) and the leukocytic MMPs neutrophil collagenase (MMP-8) and gelatinase B (MMP-9). The closely related chemokines MCP-1, MCP-2, and MCP-4 were not cleaved by MMP-2 or MT1-MMP, but were cleaved by MMP-1 and MMP-3 with varying efficiency. MCPs were typically cleaved between residues 4 and 5, but MCP-4 was further processed at Val7-Pro8. Synthetic MCP analogs corresponding to the MMP-cleaved forms bound CC chemokine receptor (CCR)-2 and CCR-3, but lacked chemoattractant activity in pre-B cells transfected with CCR-2 and CCR-3 or in THP-1 monocytic cells, a transformed leukemic cell line. Moreover, the truncated products of MCP-2 and MCP-4, like MCP-3, were potent antagonists of their cognate CC chemokine receptors in transwell cell migration assays in vitro. When they were injected 24 hours after the initiation of carrageenan-induced inflammation in rat paws, their in vivo antagonist activities were revealed by a greater than 66% reduction in inflammatory edema progression after 12 hours. We propose that MMPs have an important role in modulating inflammatory and immune responses by processing chemokines in wound healing and in disease.