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Article ; Online: The aryl hydrocarbon receptor (AHR) repressor limits expression of antimicrobial genes but not AHR-dependent genes in intestinal eosinophils.

Weighardt, Heike / Shapiro, Michael / Mayer, Michelle / Förster, Irmgard / Stockinger, Brigitta / Diny, Nicola Laura

2024

Abstract: Intestinal eosinophils express the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor that responds to dietary or environmental ligands. AHR regulates tissue adaptation, survival, adhesion, and immune ... ...

Abstract	Intestinal eosinophils express the aryl hydrocarbon receptor (AHR), an environmental sensor and ligand-activated transcription factor that responds to dietary or environmental ligands. AHR regulates tissue adaptation, survival, adhesion, and immune functions in intestinal eosinophils. The AHR repressor (AHRR) is itself induced by AHR and believed to limit AHR activity in a negative feedback loop. We analysed gene expression in intestinal eosinophils from WT and AHRR-KO mice and found that AHRR did not suppress most AHR-dependent genes. Instead, AHRR limited the expression of a distinct small set of genes involved in the innate immune response. These included S100 proteins, antimicrobial proteins and alpha-defensins. Using bone marrow-derived eosinophils we found that AHRR-KO eosinophils released more reactive oxygen species upon stimulation. This work shows that the paradigm of AHRR as a repressor of AHR transcriptional activity does not apply to intestinal eosinophils. Rather, AHRR limits the expression of innate immune response and antimicrobial genes, possibly to maintain an anti-inflammatory phenotype in eosinophils when exposed to microbial signals in the intestinal environment.
Language	English
Publishing date	2024-05-03
Publishing country	England
Document type	Journal Article
ZDB-ID	605722-6
ISSN	1938-3673 ; 0741-5400
ISSN (online)	1938-3673
ISSN	0741-5400
DOI	10.1093/jleuko/qiae105
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Article: Burden of Episodic Migraine, Chronic Migraine, and Medication Overuse Headache in Alberta.

McMullen, Suzanne / Graves, Erin / Ekwaru, Paul / Pham, Tram / Mayer, Michelle / Ladouceur, Marie-Pier / Hubert, Martine / Bougie, Joanna / Amoozegar, Farnaz

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

2023 , Page(s) 1–11

Abstract: Objective: To describe demographic and clinical characteristics, healthcare resource use, costs, and treatment patterns in three migraine cohorts.: Methods: This retrospective observational study using administrative data examined patients with ... ...

Abstract	Objective: To describe demographic and clinical characteristics, healthcare resource use, costs, and treatment patterns in three migraine cohorts. Methods: This retrospective observational study using administrative data examined patients with episodic migraine (EM), chronic migraine (CM) (without medication overuse headache [MOH]), and medication overuse headache in Alberta, Canada. Migraine patients were identified between 2012 and 2018 based on ≥ 1 diagnostic codes or triptan prescription. Patients with CM were defined using parameter estimates of a logistic regression model, and MOH was defined as patients with an average of ≥ 15 supply days covered of acute medications. EM was defined as patients without CM or MOH. Study outcomes were summarized using descriptive statistics. Results: Patients with EM (n = 144,574), CM (n = 27,283), and MOH (n = 11,485) were included. Higher rates of healthcare use and costs were observed for CM (mean [SD] all-cause cost: ($12,693 [40,664]) and MOH ($16,611.5 [$38,748]) versus episodic migraine ($4,251 [$40,637]). Across all cohorts, opioids were the most dispensed acute medication (range across cohorts: 31.7%-89.8%), while antidepressants and anticonvulsants were the most dispensed preventive medication. Preventative medication classes were used by a minority of patients in each cohort, except anticonvulsants, where 50% of medication overuse patients had a dispensation. Conclusions: Patients with CM and MOH have a greater burden of illness compared to patients with EM. The overutilization of acute medication, particularly opioids, and the underutilization of preventive medications highlight an unmet need to more effectively manage migraine.
Language	English
Publishing date	2023-10-05
Publishing country	England
Document type	Journal Article
ZDB-ID	197622-9
ISSN	0317-1671
ISSN	0317-1671
DOI	10.1017/cjn.2023.289
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Article ; Online: Management of bone loss in recurrent traumatic anterior shoulder instability: a survey of North American surgeons.

Bois, Aaron J / Mayer, Michelle J / Fening, Stephen D / Jones, Morgan H / Miniaci, Anthony

JSES international

2020 Volume 4, Issue 3, Page(s) 574–583

Abstract: Background: Management of bone loss in recurrent traumatic anterior shoulder instability remains a topic of debate and controversy in the orthopedic community. The purpose of this study was to survey members of 4 North American orthopedic surgeon ... ...

Abstract	Background: Management of bone loss in recurrent traumatic anterior shoulder instability remains a topic of debate and controversy in the orthopedic community. The purpose of this study was to survey members of 4 North American orthopedic surgeon associations to assess management trends for bone loss in recurrent anterior shoulder instability. Methods: An online survey was distributed to all members of the American Shoulder and Elbow Surgeons, American Orthopaedic Society for Sports Medicine, and Canadian Orthopaedic Association and to fellow members of the Arthroscopy Association of North America. The survey comprised 3 sections assessing the demographic characteristics of survey respondents, the influence of prognostic factors on surgical decision making, and the operative management of 12 clinical case scenarios of varying bone loss that may be encountered in clinical practice. Results: A total of 150 survey responses were returned. The age of the patient and quantity of bone loss were consistently considered important prognostic criteria. However, little consensus was reached for critical thresholds of bone loss and how this affected the timing (ie, primary or revision surgery) and type of bony augmentation procedure to be performed once a critical threshold was reached, especially in the context of critical humeral and bipolar bone loss. Conclusions: Consistent trends were found for the management of recurrent anterior shoulder instability in cases in which no bone loss existed and when isolated critical glenoid bone loss was present. However, inconsistencies were observed when isolated critical humeral bone loss and bipolar bone loss were present.
Language	English
Publishing date	2020-05-26
Publishing country	United States
Document type	Journal Article
ISSN	2666-6383
ISSN (online)	2666-6383
DOI	10.1016/j.jseint.2020.04.015
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Article ; Online: Cylicins are a structural component of the sperm calyx being indispensable for male fertility in mice and human.

Schneider, Simon / Kovacevic, Andjela / Mayer, Michelle / Dicke, Ann-Kristin / Arévalo, Lena / Koser, Sophie A / Hansen, Jan N / Young, Samuel / Brenker, Christoph / Kliesch, Sabine / Wachten, Dagmar / Kirfel, Gregor / Strünker, Timo / Tüttelmann, Frank / Schorle, Hubert

eLife

2023 Volume 12

Abstract: Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 ( ...

Abstract	Cylicins are testis-specific proteins, which are exclusively expressed during spermiogenesis. In mice and humans, two Cylicins, the gonosomal X-linked Cylicin 1 (
MeSH term(s)	Humans ; Male ; Animals ; Mice ; Sperm Motility/genetics ; Semen/metabolism ; Spermatozoa/metabolism ; Cytoskeletal Proteins/metabolism ; Infertility, Male/genetics ; Porifera ; Fertility/genetics
Chemical Substances	Cytoskeletal Proteins
Language	English
Publishing date	2023-11-28
Publishing country	England
Document type	Journal Article
ZDB-ID	2687154-3
ISSN	2050-084X ; 2050-084X
ISSN (online)	2050-084X
ISSN	2050-084X
DOI	10.7554/eLife.86100
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Article: Disparities in geographic access to pediatric subspecialty care.

Mayer, Michelle L

Maternal and child health journal

2008 Volume 12, Issue 5, Page(s) 624–632

Abstract: Purpose: To identify correlates of geographic access to pediatric medical subspecialists in the United States and identify characteristics of populations at risk for poor geographic access.: Methods: Geographic access was operationalized as distance ... ...

Abstract	Purpose: To identify correlates of geographic access to pediatric medical subspecialists in the United States and identify characteristics of populations at risk for poor geographic access. Methods: Geographic access was operationalized as distance to care. Using data from the American Board of Pediatrics and the Claritas' Pop-Facts Database, the straight-line distance between each zip code in the United States and the nearest subspecialist was calculated for each pediatric subspecialty using zip code centroids. Using 16 specialty-specific, random-effects multiple regression models, zip code characteristics associated with being farther from a subspecialty provider were identified. Results: Under-18 population, metropolitan status, and presence of a nearby teaching facility were associated with shorter distances to care across pediatric subspecialties. The proportion of the population below the federal poverty level was positively associated with greater distances to care. Zip codes in the Mountain and West North Central regions, likewise, were significantly farther from pediatric subspecialists, even when statistically controlling for other factors. Conclusions: Pediatric populations at risk for poor geographic access to pediatric subspecialty care include those who reside in zip codes with high concentrations of poverty, in rural and small metropolitan areas, and in the Mountain and West North Central regions. The extent to which these distances create barriers to receipt of care is not established.
MeSH term(s)	Health Services Accessibility/statistics & numerical data ; Healthcare Disparities/statistics & numerical data ; Humans ; Pediatrics/organization & administration ; Pediatrics/statistics & numerical data ; Poverty Areas ; Rural Population/statistics & numerical data ; United States ; Urban Population/statistics & numerical data
Language	English
Publishing date	2008-09
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, P.H.S.
ZDB-ID	1339905-6
ISSN	1092-7875
ISSN	1092-7875
DOI	10.1007/s10995-007-0275-3
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Article: Migraine Treatment and Healthcare Resource Utilization in Alberta, Canada.

Graves, Erin / Cowling, Tara / McMullen, Suzanne / Ekwaru, Paul / Pham, Tram / Mayer, Michelle / Ladouceur, Marie-Pier / Hubert, Martine / Bougie, Joanna / Amoozegar, Farnaz

The Canadian journal of neurological sciences. Le journal canadien des sciences neurologiques

2023 , Page(s) 1–11

Abstract: Background: Migraine poses a significant burden worldwide; however, there is limited evidence as to the burden in Canada. This study examined the treatment patterns, healthcare resource use (HRU), and costs among newly diagnosed or recurrent patients ... ...

Abstract	Background: Migraine poses a significant burden worldwide; however, there is limited evidence as to the burden in Canada. This study examined the treatment patterns, healthcare resource use (HRU), and costs among newly diagnosed or recurrent patients with migraine in Alberta, Canada, from the time of diagnosis or recurrence. Methods: This retrospective observational study utilized administrative health data from Alberta, Canada. Patients were included in the Total Migraine Cohort if they had: (1) ≥1 International Classification of Diseases diagnostic code for migraine; or (2) ≥1 prescription dispense(s) for triptans from April 1, 2012, to March 31, 2018, with no previous diagnosis or dispensation code from April 1, 2010, to April 1, 2012. Results: The mean age of the cohort (n = 199,931) was 40.0 years and 72.3% were women. The most common comorbidity was depression (19.7%). In each medication class examined, less than one-third of the cohort was prescribed triptans and fewer than one-fifth was prescribed a preventive. Among patients with ≥1 dispense, the mean rate of opioid prescriptions was 4.61 per patient-year, compared to 2.28 triptan prescriptions per patient-year. Migraine-related HRU accounted for 3%-10% of all use. Conclusion: Comorbidities and high all-cause HRU were observed among newly diagnosed or recurrent patients with migraine. There is an underutilization of acute and preventive medications in the management of migraine. The high rate of opioid use reinforces the suboptimal management of migraine in Alberta. Migraine management may improve by educating healthcare professionals to optimize treatment strategies.
Language	English
Publishing date	2023-10-16
Publishing country	England
Document type	Journal Article
ZDB-ID	197622-9
ISSN	0317-1671
ISSN	0317-1671
DOI	10.1017/cjn.2023.299
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Article ; Online: Evaluating Metformin as a Potential Chemosensitizing Agent when Combined with Docetaxel Chemotherapy in Castration-resistant Prostate Cancer Cells.

Mayer, Michelle J / Klotz, Laurence H / Venkateswaran, Vasundara

Anticancer research

2017 Volume 37, Issue 12, Page(s) 6601–6607

Abstract: Background/aim: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining ... ...

Abstract	Background/aim: Docetaxel, the first-line chemotherapy for metastatic castration-resistant prostate cancer (mCRPC), provides certain survival benefits, but is associated with significant toxicity. A novel therapeutic approach for mCRPC is combining docetaxel with a chemosensitizing agent. We hypothesized that metformin, a potential chemosensitizer, would improve docetaxel efficacy in CRPC cells. Materials and methods: MTS assays were used to determine the effect of metformin-docetaxel treatment on PC3 and DU145 cell viability. Wound-healing and ATP concentration assays were used to evaluate cell migration and intracellular ATP levels following metformin-docetaxel treatment. Western blotting was used for mechanistic evaluation. Results: Metformin-docetaxel treatment significantly reduced PC3 cell viability. Metformin-docetaxel treatment did not significantly affect cell migration or intracellular ATP levels. Western blotting revealed metformin-docetaxel treatment did not significantly change AMPK or P-AMPK expression patterns. Conclusion: Metformin may be an effective chemosensitizer for certain types of CRPC cells, but further investigation is needed.
MeSH term(s)	AMP-Activated Protein Kinases/metabolism ; Adenosine Triphosphate/metabolism ; Blotting, Western ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Survival/drug effects ; Drug Screening Assays, Antitumor ; Drug Synergism ; Humans ; Male ; Metformin/pharmacology ; Phosphorylation/drug effects ; Prostatic Neoplasms, Castration-Resistant/metabolism ; Prostatic Neoplasms, Castration-Resistant/pathology ; Taxoids/pharmacology
Chemical Substances	Taxoids ; docetaxel (15H5577CQD) ; Adenosine Triphosphate (8L70Q75FXE) ; Metformin (9100L32L2N) ; AMP-Activated Protein Kinases (EC 2.7.11.31)
Language	English
Publishing date	2017
Publishing country	Greece
Document type	Journal Article
ZDB-ID	604549-2
ISSN	1791-7530 ; 0250-7005
ISSN (online)	1791-7530
ISSN	0250-7005
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Article ; Online: On being a 'difficult' patient.

Mayer, Michelle L

Health affairs (Project Hope)

2008 Volume 27, Issue 5, Page(s) 1416–1421

MeSH term(s)	Attitude to Health ; Clinical Competence ; Female ; Humans ; Patient Participation ; Patient-Centered Care ; Physician-Patient Relations ; Power (Psychology) ; Scleroderma, Systemic/diagnosis ; Scleroderma, Systemic/therapy
Language	English
Publishing date	2008-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	632712-6
ISSN	1544-5208 ; 0278-2715
ISSN (online)	1544-5208
ISSN	0278-2715
DOI	10.1377/hlthaff.27.5.1416
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Article ; Online: Enzymatic debridement with bromelain and development of bacteremia in burn injuries: A retrospective cohort study.

Deplazes, Barla C / Hofmaenner, Daniel A / Scheier, Thomas C / Epprecht, Jana / Mayer, Michelle / Schweizer, Tiziano A / Buehler, Philipp K / Frey, Pascal M / Brugger, Silvio D

Burns : journal of the International Society for Burn Injuries

2023 Volume 50, Issue 2, Page(s) 405–412

Abstract: Background: Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain ... ...

Abstract	Background: Debridement is crucial for effective wound management in patients with severe burn injuries, and bromelain, a proteolytic enzyme from pineapple stems, has emerged as a promising alternative for surgery. However, potential links of bromelain use to fever and sepsis have raised some concerns. Given the uncertainty as to whether this was caused by infection or other inflammatory sources, we aimed to investigate if the use of topical bromelain was associated with bacteremia. Methods: This single-centre retrospective cohort study included critically ill adult patients with severe burn injuries hospitalised at the Burn Center of the University Hospital Zurich between January 2017 and December 2021. Data were collected from two in-hospital electronic medical records databases. Our primary outcome, the association between topical bromelain treatment and the development of bacteremia, was investigated using a competing risk regression model, taking into account the competing risk of death. As a secondary outcome, the relationship between bromelain treatment and overall ICU mortality was examined using a Cox proportional hazards model. Results: The study included 269 patients with a median age of 50 years and median burnt total body surface area of 19%. A first bacteremia occurred in 61 patients (23%) after a median time of 6 days. Bromelain treatment was given to 83 (31%) of patients, with 22 (27%) of these developing bacteremia. In the fully adjusted competing risk regression model, no evidence for an association between bromelain treatment and bacteremia was found (SHR 0.79, 95%CI 0.42-1.48, p = 0.47). During hospital stay, 40 (15%) of patients died. There was no significant difference in mortality between patients treated with bromelain and those who were not (HR 0.55, 95%CI 0.26-1.20, p = 0.14). Among the five multidrug-resistant (MDR) pathogens identified, three were found in patients with bromelain treatment. Conclusion: Our study did not confirm an association between topical bromelain and bacteremia in patients with severe burn injuries. This finding can inform evidence-based practices by addressing concerns about potential risks of bromelain use, contributing to the development of more effective and safe burn wound management strategies.
MeSH term(s)	Adult ; Humans ; Middle Aged ; Retrospective Studies ; Debridement ; Bromelains/therapeutic use ; Burns/complications ; Bacteremia/drug therapy
Chemical Substances	Bromelains (9001-00-7)
Language	English
Publishing date	2023-12-12
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	197308-3
ISSN	1879-1409 ; 0305-4179
ISSN (online)	1879-1409
ISSN	0305-4179
DOI	10.1016/j.burns.2023.12.005
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Article ; Online: The Effect of Metformin Use during Docetaxel Chemotherapy on Prostate Cancer Specific and Overall Survival of Diabetic Patients with Castration Resistant Prostate Cancer.

Mayer, Michelle J / Klotz, Laurence H / Venkateswaran, Vasundara

The Journal of urology

2016 Volume 197, Issue 4, Page(s) 1068–1075

Abstract: Purpose: Docetaxel is the first line chemotherapy currently used to treat patients with symptomatic metastatic castration resistant prostate cancer. Although it provides survival benefits, it is associated with significant side effects. Novel ... ...

Abstract	Purpose: Docetaxel is the first line chemotherapy currently used to treat patients with symptomatic metastatic castration resistant prostate cancer. Although it provides survival benefits, it is associated with significant side effects. Novel therapeutic options are needed for patients with metastatic castration resistant prostate cancer and an approach is combining docetaxel with chemosensitizing agents. Metformin has been shown to improve the survival of patients with breast, lung and endometrial cancer receiving chemotherapy, and enhance chemotherapeutic efficacy in breast cancer and colon cancer cells. However, to our knowledge the chemosensitizing effect of metformin in prostate cancer has not been explored. Therefore, the hypothesis for our study was that diabetic patients with metastatic castration resistant prostate cancer who were administered metformin during docetaxel chemotherapy would have improved prostate cancer specific and overall survival. Materials and methods: This retrospective cohort study used data from several Ontario administrative health care databases. Men older than 65 years diagnosed with metastatic castration resistant prostate cancer and treated with docetaxel were stratified into groups based on diabetes status and use of antidiabetic medications. We evaluated the effect of metformin use with docetaxel on prostate cancer specific survival and overall survival using Kaplan-Meier survival curves, the log rank test and multivariate Cox proportional HRs. Results: Survival curves showed that metformin use with docetaxel did not improve prostate cancer specific survival (p = 0.9562) or overall survival (p = 0.9927). HRs showed no significant effect of metformin use with docetaxel on prostate cancer specific survival (HR = 0.96, p = 0.66) or overall survival (HR = 0.94, p = 0.39). Conclusions: Metformin use during docetaxel chemotherapy did not significantly improve prostate cancer specific or overall survival in diabetic patients with metastatic castration resistant prostate cancer. This study indicates that metformin may not be an effective chemosensitizer for metastatic castration resistant prostate cancer.
MeSH term(s)	Aged ; Aged, 80 and over ; Antineoplastic Agents/therapeutic use ; Cohort Studies ; Diabetes Complications/drug therapy ; Diabetes Complications/mortality ; Diabetes Mellitus/drug therapy ; Docetaxel/therapeutic use ; Drug Therapy, Combination ; Humans ; Hypoglycemic Agents/therapeutic use ; Male ; Metformin/therapeutic use ; Middle Aged ; Prostatic Neoplasms, Castration-Resistant/drug therapy ; Prostatic Neoplasms, Castration-Resistant/mortality ; Retrospective Studies ; Survival Rate
Chemical Substances	Antineoplastic Agents ; Hypoglycemic Agents ; Docetaxel (15H5577CQD) ; Metformin (9100L32L2N)
Language	English
Publishing date	2016-10-28
Publishing country	United States
Document type	Journal Article
ZDB-ID	3176-8
ISSN	1527-3792 ; 0022-5347
ISSN (online)	1527-3792
ISSN	0022-5347
DOI	10.1016/j.juro.2016.10.069
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