Outcomes of elective and emergency surgical repair of incisional hernia: a comparative observational study.

PURPOSE: Incisional hernia (IH) is a common complication following abdominal surgery. Surgical repair of IH is associated with the alleviation of symptoms and improvement of quality of life. Operative intervention can pose a significant burden to the patient and healthcare facilities. This study aims to describe and compare outcomes of elective and emergency surgical repair of IH. METHODS: This study is a single-centre comparative retrospective study including patients who had repair of IH. Patients were divided into Group I (Emergency) and Group II (Elective), and a comparison was conducted between them. RESULTS: Two hundred sixty-two patients were identified with a mean age of 61.8 ± 14.2 years, of which 152 (58%) were females. The mean BMI was 31.6 ± 7.2 kg/m2. More than 58% had at least one comorbidity. 169 (64.5%) patients had an elective repair, and 93 (35.5%) had an emergency repair. Patients undergoing emergency repair were significantly older and had higher BMI, p = 0.031 and p = 0.002, respectively. The significant complication rate (Clavien-Dindo III and IV) was 9.54%. 30 and 90-day mortality rates were 2.3% (n = 6) and 2.68% (n = 7), respectively. In the emergency group, the overall complications, 30-day and 90-day mortality rates were significantly higher than in the elective group, p ≤ 0.001, 0.002 and 0.001, respectively. Overall, 42 (16.1%) developed wound complications, 25 (9.6%) experienced a recurrence, and 41 (15.71%) were readmitted within 90 days, without significant differences between the two groups. CONCLUSION: Patients who underwent emergency repair were significantly older and had a higher BMI than the elective cases. Emergency IH repair is associated with higher complication rates and mortality than elective repair.

Evolution of the ecological niche behind the largest disjunct freshwater fish distribution in the world.

Ecological processes that are behind distributions of species that inhabit isolated localities, complex disjunct distributions, remain poorly understood. Traditionally, vicariance and dispersion have been proposed as explanatory mechanisms that drive such distributions. However, to date, our understanding of the ecological processes driving evolution of ecological niches associated with disjunct distributions remains rudimentary. Here, we propose a framework to deconstruct drivers of such distribution using World's most widespread freshwater fish Galaxias maculatus as a model and integrating marine and freshwater environments where its life cycle may occur. Specifically, we assessed ecological and historical factors (Gondwanan vicariance, marine dispersion) and potential dispersion (niche-tracking) that explain its distribution in the Southern Hemisphere. Estimated distribution was consistent with previously reported distribution and mainly driven by temperature and topography in freshwater environments and by primary productivity and nitrate in marine environments. Niche dynamics of G. maculatus provided evidence of synergy between vicariance and marine dispersion as explanatory mechanisms of its disjunct distribution, suggesting that its ecological niche was conserved since approximately 30 Ma ago. This integrated assessment of ecological niche in marine and freshwater environments serves as a generic framework that may be applied to understand processes underpinning complex distributions of diadromous species.

Los procesos ecológicos que subyacen a las distribuciones de especies que habitan en localidades aisladas, distribuciones disjuntas complejas, siguen siendo poco conocidos. Tradicionalmente, se han propuesto la dispersión y la vicarianza como mecanismos explicativos de tales distribuciones. Sin embargo, hasta la fecha, nuestra comprensión de los procesos ecológicos que impulsan la evolución de los nichos ecológicos de distribuciones disjuntas sigue siendo rudimentaria. Aquí proponemos un marco para de­construir los factores que impulsan dicha distribución, utilizando como modelo el pez de agua dulce con distribución más extendida del mundo, Galaxias maculatus, e integrando los entornos marinos y dulceacuícolas en los que se desarrolla su ciclo vital. En concreto, evaluamos los factores ecológicos e históricos (vicarianza gondwánica, dispersión marina) que explican su distribución en el hemisferio sur. La distribución estimada coincide con la descrita anteriormente para la especie y está determinada principalmente por la temperatura y la topografía en ambientes dulceacuícolas, y la productividad primaria y el nitrato en ambientes marinos. La dinámica de nicho de G. maculatus aportó pruebas de la sinergia entre vicarianza y dispersión marina como mecanismos explicativos de su distribución disjunta, lo que sugiere que su nicho ecológico se conservó desde hace aproximadamente 30 Ma. Esta evaluación integrada del nicho ecológico en ambientes marinos y dulceacuícolas puede aplicarse para comprender los procesos que subyacen a las distribuciones complejas de especies diádromas.

"I realised it weren't about spending the money. It's about doing something together:" the role of money in a community empowerment initiative and the implications for health and wellbeing.

Community initiatives aiming to reduce health inequalities are increasingly common in health policy. Though diverse many such initiatives aim to support residents of disadvantaged places to exercise greater collective control over decisions/actions that affect their lives - which research suggests is an important determinant of health - and some seek to achieve this by giving residents control over a budget. Informed by theoretical work in which community capabilities for collective control are conceptualised as different forms of power, and applying a relational lens, this paper presents findings on the potential role of money as a mechanism to enhance these capabilities from an on-going evaluation of a major place-based initiative being implemented in 150 neighbourhoods across England:The Big Local (BL). The research involved semi-structured interviews with 116 diverse stakeholders, including residents and participant observation in a diverse sample of 10 BL areas. We took a thematic constant comparative approach to the analysis of data from across the sites. The findings suggest that the money enabled the development of capabilities for collective control in these communities primarily by enhancing connectivity amongst residents and with external stakeholders. However, residents had to engage in significant 'relational work' to achieve these benefits and tensions around the money could hinder communities' 'power to act'. Greater social connectivity has been shown to directly affect individual and population health by increasing social cohesion and reducing loneliness. Additionally, supporting enhanced collective control of residents in these disadvantaged communities has the potential to improve population health and reduce health inequalities.

The prognostic impact of consensus molecular subtypes (CMS) and its predictive effects for bevacizumab benefit in metastatic colorectal cancer: molecular analysis of the AGITG MAX clinical trial.

Background: The consensus molecular subtypes (CMS) is a transcriptome-based classification of colorectal cancer (CRC) initially described in early-stage cohorts, but the associations of CMS with treatment outcomes in the metastatic setting are yet to be established. This study aimed to evaluate the prognostic impact of CMS classification and its predictive effects for bevacizumab benefit in metastatic CRC by correlative analysis of the AGITG MAX trial. Patients and methods: The MAX trial previously reported improved progression-free survival (PFS) for the addition of bevacizumab (B) to chemotherapy [capecitabine (C)±mitomycin (M)]. Archival primary tumours from 237 patients (50% of trial population) underwent gene expression profiling and classification into CMS groups. CMS groups were correlated to PFS and overall survival (OS). The interaction of CMS with treatment was assessed by proportional hazards model. Results: The distribution of CMS in MAX were CMS1 18%, CMS2 47%, CMS3 12%, CMS4 23%. CMS1 was the predominant subtype in right-sided primary tumours, while CMS2 was the predominant subtype in left-sided. CMS was prognostic of OS (P = 0.008), with CMS2 associated with the best outcome and CMS1 the worst. CMS remained an independent prognostic factor in a multivariate analysis. There was a significant interaction between CMS and treatment (P-interaction = 0.03), for PFS, with hazard ratios (95% CI) for CB+CBM versus C arms in CMS1, 2, 3 and 4: 0.83 (0.43-1.62), 0.50 (0.33-0.76), 0.31 (0.13-0.75) and 1.24 (0.68-2.25), respectively. Conclusions: This exploratory study found that CMS stratified OS outcomes in metastatic CRC regardless of first-line treatment, with prognostic effects of CMS groups distinct from those previously reported in early-stage cohorts. In CMS associations with treatment, CMS2 and possibly CMS3 tumours may preferentially benefit from the addition of bevacizumab to first-line capecitabine-based chemotherapy, compared with other CMS groups. Validation of these findings in additional cohorts is warranted. Clinical trial number: This is a molecular sub-study of MAX clinical trial (NCT00294359).

Enhanced Platelet-Activating Factor Synthesis Facilitates Acute and Delayed Effects of Ethanol-Intoxicated Thermal Burn Injury.

Thermal burn injuries in patients who are alcohol-intoxicated result in greater morbidity and mortality. Murine models combining ethanol and localized thermal burn injury reproduce the systemic toxicity seen in human subjects, which consists of both acute systemic cytokine production with multiple organ dysfunction, as well as a delayed systemic immunosuppression. However, the exact mechanisms for these acute and delayed effects are unclear. These studies sought to define the role of the lipid mediator platelet-activating factor in the acute and delayed effects of intoxicated burn injury. Combining ethanol and thermal burn injury resulted in increased enzymatic platelet-activating factor generation in a keratinocyte cell line in vitro, human skin explants ex vivo, as well as in murine skin in vivo. Further, the acute increase in inflammatory cytokines, such as IL-6, and the systemic immunosuppressive effects of intoxicated thermal burn injury were suppressed in mice lacking platelet-activating factor receptors. Together, these studies provide a potential mechanism and treatment strategies for the augmented toxicity and immunosuppressive effects of thermal burn injury in the setting of acute ethanol exposure, which involves the pleotropic lipid mediator platelet-activating factor.

Brief interventions to prevent sexually transmitted infections suitable for in-service use: A systematic review.

BACKGROUND: Sexually transmitted infections (STIs) are more common in young people and men who have sex with men (MSM) and effective in-service interventions are needed. METHODS: A systematic review of randomized controlled trials (RCTs) of waiting-room-delivered, self-delivered and brief healthcare-provider-delivered interventions designed to reduce STIs, increase use of home-based STI testing, or reduce STI-risk behavior was conducted. Six databases were searched between January 2000 and October 2014. RESULTS: 17,916 articles were screened. 23 RCTs of interventions for young people met our inclusion criteria. Significant STI reductions were found in four RCTs of interventions using brief one-to-one counselling (2 RCTs), video (1 RCT) and a STI home-testing kit (1 RCT). Increase in STI test uptake was found in five studies using video (1 RCT), one-to-one counselling (1 RCT), home test kit (2 RCTs) and a web-based intervention (1 RCT). Reduction in STI-risk behavior was found in seven RCTs of interventions using digital online (web-based) and offline (computer software) (3 RCTs), printed materials (1 RCT) and video (3 RCTs). Ten RCTs of interventions for MSM met our inclusion criteria. Three tested for STI reductions but none found significant differences between intervention and control groups. Increased STI test uptake was found in two studies using brief one-to-one counselling (1 RCT) and an online web-based intervention (1 RCT). Reduction in STI-risk behavior was found in six studies using digital online (web-based) interventions (4 RCTs) and brief one-to-one counselling (2 RCTs). CONCLUSION: A small number of interventions which could be used, or adapted for use, in sexual health clinics were found to be effective in reducing STIs among young people and in promoting self-reported STI-risk behavior change in MSM.

West Nile Virus Activity in a Winter Roost of American Crows (Corvus brachyrhynchos): Is Bird-To-Bird Transmission Important in Persistence and Amplification?

Since its emergence in North America, West Nile virus (WNV) has had a large impact on equines, humans, and wild bird communities, yet gaps remain in our understanding of how the virus persists at temperate latitudes when winter temperatures preclude virus replication and host-seeking activity by mosquito vectors. Bird-to-bird transmission at large communal American Crow roosts could provide one mechanism for WNV persistence. Herein, we describe seasonal patterns of crow and Culex mosquito abundance, WNV infection rates, and the prevalence of WNV-positive fecal samples at a winter crow roost to test the hypothesis that bird-to-bird transmission allows WNV to persist at winter crow roosts. Samples were collected from large winter crow roosts in the Sacramento Valley of California from January 2013 until August 2014, encompassing two overwintering roost periods. West Nile virus RNA was detected in local crow carcasses in both summer [13/18 (72% WNV positive)] and winter [18/44 (41% WNV positive)] 2013-2014. Winter infections were unlikely to have arisen by recent bites from infected mosquitoes because Culex host-seeking activity was very low in winter and all Culex mosquitoes collected during winter months tested negative for WNV. Opportunities existed for fecal-oral transfer at the overwintering roost: most carcasses that tested positive for WNV had detectable viral RNA in both kidney and cloacal swabs, suggesting that infected crows were shedding virus in their feces, and >50% of crows at the roost were stained with feces by mid-winter. Moreover, 2.3% of fecal samples collected in late summer, when mosquitoes were active, tested positive for WNV RNA. Nevertheless, none of the 1,119 feces collected from three roosts over two winters contained detectable WNV RNA. This study provided evidence of WNV infection in overwintering American crows without mosquito vector activity, but did not elucidate a mechanism of WNV transmission during winter.

Correlation of extended RAS and PIK3CA gene mutation status with outcomes from the phase III AGITG MAX STUDY involving capecitabine alone or in combination with bevacizumab plus or minus mitomycin C in advanced colorectal cancer.

BACKGROUND: Mutations affecting RAS genes are now established predictive markers of nonresponse to anti-EGFR antibodies in advanced CRC. This analysis assessed the prognostic and predictive impact of extended RAS and PIK3CA gene mutation status in patients receiving capecitabine plus or minus bevacizumab (±mitomycin C) in the randomised phase III MAX study. METHODS: DNA was extracted from archival macrodissected formalin-fixed paraffin-embedded tumour tissue. Mutation status was determined using pyrosequencing, confirmed with Sanger sequencing (for equivocal RAS) and correlated with efficacy outcomes. Predictive analyses were undertaken using a test for interaction involving both C vs CB+CBM. RESULTS: Of the available 280 of the 471 (59.4%) patients, mutations in KRAS exons 2, 3 and 4 and NRAS 2, 3 and 4 were as follows: 32%, 2.9%, 2.2%, 1.4%, 0.7% and 0% (total RAS MT 39%). The PIK3CA MT rate was 7.5% exon 9 and 3.6% exon 20. Extended RAS gene mutation status (WT vs MT) had no prognostic impact for PFS (HR 0.91 (0.71-1.17)) or OS (HR 0.95 (0.71-1.25)). The RAS gene mutation status was not predictive of the effectiveness of bevacizumab for PFS (HR 0.56 (0.37-0.85) for RAS MT and HR 0.69 (0.5-0.97) for RAS WT; P for interaction 0.50). The PIK3CA mutation was neither predictive for bevacizumab effect nor prognostic. CONCLUSION: Of KRAS exon 2 WT patients, 10% had additional RAS mutations. Neither all RAS gene mutation status nor PIK3CA mutation status was prognostic for PFS or OS, or predictive of bevacizumab outcome in patients with advanced CRC.

Determination of trace labile copper in environmental waters by magnetic nanoparticle solid phase extraction and high-performance chelation ion chromatography.

Cobalt magnetic nanoparticles surface functionalised with iminodiacetic acid were evaluated as a nano-particulate solid phase extraction absorbent for copper ions (Cu(2+)) from environmental water samples. Using an external magnetic field, the collector nanoparticles could be separated from the aqueous phase, and adsorbed ions simply decomplexed using dilute HNO3. Effects of pH, buffer concentration, sample and sorbent volume, extraction equilibrium time, and interfering ion concentration on extraction efficiency were investigated. Optimal conditions were then applied to the extraction of Cu(2+) ions from natural water samples, prior to their quantitation using high-performance chelation ion chromatography. The limits of detection (LOD) of the combined extraction and chromatographic method were ~0.1 ng ml(-1), based upon a 100-fold preconcentration factor (chromatographic performance; LOD=9.2 ng ml(-1) Cu(2+)), analytical linear range from 20 to 5000 ng mL(-1), and relative standard deviations=4.9% (c=1000 ng ml(-1), n=7). Accuracy and precision of the combined approach was verified using a certified reference standard estuarine water sample (SLEW-2) and comparison of sample determinations with sector field inductively coupled plasma mass spectrometry. Recoveries from the addition of Cu(2+) to impacted estuarine and rain water samples were 103.5% and 108.5%, respectively. Coastal seawater samples, both with and without prior UV irradiation and dissolved organic matter removal were also investigated using the new methodology. The effect of DOM concentration on copper availability was demonstrated.

Epidemiology of Mycoplasma bovis in Pennsylvania veal calves.

The objective of the study was to estimate the prevalence and incidence of Mycoplasma bovis, a common cause of pneumonia, in veal calves. Using simple random sampling, 252 calves from 4 veal herds located in central Pennsylvania were selected and longitudinally followed for monthly collection of nasal swabs. Bronchial swabs and lung lesions were collected at the slaughterhouse. Nasal, bronchial, and lung lesion swabs were cultured for bacterial respiratory pathogens. Ninety lung lesions were identified, of which 41.1, 1.1, 1.1, 7.8, and 4.4% were culture positive for M. bovis alone, Pasteurella multocida alone, Mannheimia haemolytica alone, M. bovis and P. multocida co-infection, and M. bovis and M. haemolytica co-infection, respectively. The data indicate that potential interventions, such as therapeutics, vaccines, or management control measures, would be most effective before 50 d of age based upon the cumulative incidence of colonization.

Support for men newly diagnosed with prostate cancer.

This article discusses the findings of a multi-hospital satisfaction survey of men with newly diagnosed prostate cancer. The survey was designed to enable direct comparison with a previously published satisfaction survey conducted by the Prostate Cancer Charity. Results showed that the nurse specialist is a valuable resource for patients and has an important role in maintaining standards of care.

Everyday ethics and help-seeking in early rheumatoid arthritis.

BACKGROUND: Sociological understandings of chronic illness have revealed tensions and complexities around help-seeking. Although ethics underpins healthcare, its application in the area of chronic illness is limited. Here we apply an ethical framework to interview accounts and identify ethical challenges in the early rheumatoid arthritis (RA) experience. METHODS: In-depth interviews were conducted with eight participants who had been diagnosed with RA in the 12 months prior to recruitment. Applying the concepts of autonomous decision-making and procedural justice highlighted ethical concerns which arose throughout the help-seeking process. Analysis was based on the constant-comparison approach. RESULTS: Individuals described decision-making, illness actions and the medical encounter. The process was complicated by inadequate knowledge about symptoms, common-sense understandings about the GP appointment, difficulties concerning access to specialists, and patient-practitioner interactions. Autonomous decision-making and procedural justice were compromised. The accounts revealed contradictions between the policy ideals of active self-management, patient-centred care and shared decision-making, and the everyday experiences of individuals. CONCLUSIONS: For ethical healthcare there is a need for: public knowledge about early RA symptoms; more effective patient-practitioner communication; and increased support during the wait between primary and secondary care. Healthcare facilities and the government may consider different models to deliver services to people requiring rheumatology consults.

Objective radiological disease control with sandostatin monotherapy in metastatic neuroendocrine tumours.

Conventional cytotoxic chemotherapy is not usually effective in neuroendocrine tumours (NET). Somatostatin analogues (SSA) such as octreotide (Sandostatin; octreotide LAR and lanreotide) are typically used to treat symptoms caused by NET, but not as the primary treatment aiming for an objective response. Recently, results from the PROMID (Placebo-controlled prospective Randomized study on the antiproliferative efficacy of Octreotide LAR in patients with metastatic neuroendocrine MIDgut tumours) trial were published showing that octreotide LAR significantly lengthens the time to tumour progression compared with a placebo in patients with functionally active and inactive metastatic midgut NET. We report a retrospective descriptive analysis of six patients, treated at two Australian institutions, who obtained an objective radiological tumour response on long acting SSA. In this retrospective series of NET, radiological responses were observed using single agent SSA, which was administered mainly for symptom management. This could be due to an antiproliferative and/or antiangiogenic activity of this agent in NET. A response can occur beyond 12 months, which might explain why the response rate is under reported in NET trials. Further investigation in prospective trials is warranted and the possibility for late responses might have implications for trial design.

Sediment profile characterisation at contaminated and reference locations in the Windmill Islands, East Antarctica.

Sediment profiles for pH, Eh, 28 elements, water and organic content are presented here for human impacted and reference locations in the Windmill Islands, East Antarctica. Variations in element concentrations are observed with increasing depth, especially at Brown Bay where the impact of past human activities is most pronounced in the top 10 cm. Spatial differences were observed between sediment profiles at reference and impacted locations and were largely explained by Pb variability in the top 5 cm. Median element concentrations from surface, middle and bottom regions of the sediment profile were compared to composite sample medians (no depth stratigraphy) for 11 elements at O'Brien Bay (reference) and Brown Bay (impacted). Pronounced differences were observed for Brown Bay, particularly surface and middle sections, implying that composite samples dilute the near surface anthropogenic signal by mixing with deeper uncontaminated sediment.

A phase I study to determine the safety, tolerability and maximum tolerated dose of green-lipped mussel (Perna canaliculus) lipid extract, in patients with advanced prostate and breast cancer.

BACKGROUND: This was a phase I trial to determine the maximum tolerated dose (MTD) of a marine lipid extract from the New Zealand green-lipped mussel (Perna canaliculus), as an inhibitor of 5- and 12-lipo-oxygenase enzymes, in patients with advanced breast and prostate cancers. PATIENTS AND METHODS: This was an open-labelled, phase I, dose-escalation study. Proprietary form of green-lipped mussel lipid extract (GLMLE), 260-mg capsule, was administered on a twice-daily schedule, orally. Patients remained on study until disease progression or unacceptable toxicity. RESULTS: From December 1999 to May 2003, 17 patients were enrolled. Fifteen of them were male with advanced prostate cancer and two were female with advanced breast cancer. The median age of the patients was 74 years (range 56-85 years). Sixteen patients were assessable for adverse events and dose-limiting toxicity (DLT). Reason for withdrawal from the study included progressive disease (n = 12), death (n = 1) and DLT (n = 3). Two patients had evidence of grade 4 hepatic dysfunction. The MTD was not reached. There were no objective tumour responses noted. CONCLUSIONS: GLMLE appears to be a well-tolerated compound in this setting. There appears to be no objective benefit. However, grade 3/4 hepatic toxicity noted in two patients is of concern and should be considered while evaluating patients taking GLMLE or while designing studies with this agent.

Lead isotopic signatures in Antarctic marine sediment cores: a comparison between 1M HCl partial extraction and HF total digestion pre-treatments for discerning anthropogenic inputs.

Sensitive analytical techniques are typically required when dealing with samples from Antarctica as even low concentrations of contaminants can have detrimental environmental effects. Magnetic Sector ICP-MS is an ideal technique for environmental assessment as it offers high sensitivity, multi-element capability and the opportunity to determine isotope ratios. Here we consider the Pb isotope record of five marine sediment cores collected from three sites in the Windmill Islands area of East Antarctica: Brown Bay adjacent to the current Australian station Casey, Wilkes near the abandoned US/Australian Station and McGrady Cove lying midway between the two. Two sediment pre-treatment approaches were considered, namely partial extraction with 1M HCl and total dissolution involving HF. Lead isotope ratio measurements made following sediment partial extraction provided a more sensitive indication of Pb contamination than either Pb concentrations alone (irrespective of sample pre-treatment method) or isotope ratios made after HF digestion, offering greater opportunity for discrimination between impacted and natural/geogenic samples and sites. Over 90% of the easily extractable Pb from sediments near Casey was anthropogenic in origin, consisting of Pb from major Australian deposits. At Wilkes impact from discarded batteries with a unique isotopic signature was found to be a key source of Pb contamination to the marine environment with ~70-80% of Pb being anthropogenic in origin. The country and source of origin of these batteries remain unknown. Little evidence was found suggesting contamination at Wilkes by Pb originating from the major US source, Missouri. No definitive assessment could be made regarding Pb impact at McGrady Cove as the collected sediment core was of insufficient depth. Although Pb isotope ratio signatures may indicate anthropogenic input, spatial concentration gradients at nearby Brown Bay suggest contamination at McGrady Cove is unlikely. We recommend Pb isotopic analysis following 1M HCl partial extraction pre-treatment as a powerful and sensitive method for tracing Pb contamination in marine sediments.

Effects of prior oral contraceptive use and soy isoflavonoids on estrogen-metabolizing cytochrome P450 enzymes.

Estrogen exposure and metabolism may play an important role in the development of estrogen-sensitive cancers in postmenopausal women. In this study we investigated whether past oral contraceptive (OC) administration or current dietary isoflavonoids (IF) affected expression and/or activity of steroid hormone-metabolizing cytochrome P450 (CYP) enzymes using complementary primate and cell culture models. One-hundred-eighty-one female cynomolgus macaques were randomized to receive OC or nothing for 26 months premenopausally, then ovariectomized and randomized to one of three diets for 36 months: an IF-depleted soy protein isolate (Soy-) diet, a Soy diet with IF (Soy+), or a Soy- diet supplemented with conjugated equine estrogens (CEE). Prior OC-treatment significantly reduced CYP gene expression in the mammary gland (< or =60% of OC-). Dietary IFs had no effect on CYP expression, while CEE-treatment decreased CYP1A1 and increased CYP3A4 mRNA in a tissue-specific manner. For in vitro studies, we measured effects of the isoflavonoids genistein, daidzein and equol on CYP activity using intact V79 cells stably transfected to express CYP1A1, CYP1B1, or CYP3A4. All three IFs significantly altered CYP activity in a dose-dependent and isoform-specific manner (20-95% inhibition versus controls). These results suggest potential mechanisms for prior OC and dietary IF effects on cancer risk in estrogen-responsive tissues.