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Article ; Online: Understanding the perspective of women who use the Billings Ovulation Method®: a focus group study.

Ayala-Ramirez, Montserrat / Grewe, Mary E / Kaiser, Julie / Kennedy, Emily / Winn, Martha / Urrutia, Rachel Peragallo

2023 Volume 23, Issue 1, Page(s) 251

Abstract: Background: The Billings Ovulation Method®(the Billings Method) is a fertility awareness-based method (FABM) of family planning that relies on the observation of patterns of fertility and infertility based on vulvar sensations and appearance of ... ...

Abstract	Background: The Billings Ovulation Method®(the Billings Method) is a fertility awareness-based method (FABM) of family planning that relies on the observation of patterns of fertility and infertility based on vulvar sensations and appearance of discharges. This allows people to choose when to have intercourse, depending on whether they want to avoid or achieve pregnancy. Few studies have documented user experiences with FABMs. Methods: We conducted four virtual focus groups (FGs) in May and June 2021 with current adult women users of the Billings Method. We asked questions about users' reasons for selecting a FABM and the Billings Method, positive experiences and challenges learning and using the Billings Method, and suggestions for improving the user experience. We performed a content analysis of the transcribed FGs to explore key themes from the discussions. COREQ guidelines were followed. Results: Twenty women between the ages of 23 and 43 participated in the FGs. Reasons women described choosing a FABM included to follow religious beliefs, to avoid side effects of hormonal contraception, and/or to learn more about their bodies. Reasons for selecting the Billings Method included perceiving it as more precise and easier to understand than other FABMs, having a scientific basis, and being recommended by family and friends. Experiences related to learning and using the Billings Method were mainly positive. They included finding the method easy to use and learn, successfully using it to either postpone or achieve a pregnancy and increasing their awareness of their bodies. Challenges for participants included the inherent learning curve for identifying sensations at the vulva and the required periods of abstinence. Participants provided suggestions and recommendations for improving users' experience, including raising awareness of the Billings Method among healthcare providers. Conclusions: Users of the Billings Method expressed an overall positive experience when learning and using it for family planning and body awareness. Some challenges were identified that offer opportunities to improve how the Billings Method is taught and delivered. These findings can also enhance healthcare providers' interactions with FABM users, including those of the Billings Method.
MeSH term(s)	Adult ; Pregnancy ; Humans ; Female ; Young Adult ; Focus Groups ; Fertility ; Family Planning Services ; Infertility ; Ovulation
Language	English
Publishing date	2023-05-10
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2050444-5
ISSN	1472-6874 ; 1472-6874
ISSN (online)	1472-6874
ISSN	1472-6874
DOI	10.1186/s12905-023-02398-w
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Article ; Online: Interactions With Police in the Emergency Care of Children: Ethical and Legal Considerations.

Schultz, Megan L / Winn, Madeline / Derse, Arthur R / Kaczor, Frances / Levas, Michael N

Pediatric emergency care

2023 Volume 39, Issue 4, Page(s) 226–229

Abstract: Objectives: Emergency medicine providers may interface with law enforcement personnel (LEP) on behalf of their pediatric patients for a variety of reasons, from reporting child abuse to caring for children who are in police custody. Given the unique ... ...

Abstract	Objectives: Emergency medicine providers may interface with law enforcement personnel (LEP) on behalf of their pediatric patients for a variety of reasons, from reporting child abuse to caring for children who are in police custody. Given the unique nature of caring for minors who may not have legal or medical autonomy, interactions with LEP can raise ethical concerns for emergency providers, specifically with regard to legal representation, developmental immaturity, and the civil rights of children and their parents/guardians. Methods: We review 4 patient scenarios, based on real cases experienced by the authors, to demonstrate the legal and ethical issues that may arise when LEP are involved in the emergency care of a child. These scenarios discuss parental/guardian visitation for children in police custody in the emergency department (ED), the practice of making arrests on hospital grounds, and police interviews of children in the ED. Results: Using the ethical principles of autonomy, beneficence, and justice, we offer recommendations for emergency providers on how to advocate for their pediatric patients in LEP custody within the constraints and protections of the law. We also suggest best practices for hospital systems to develop policies surrounding LEP activity in the ED. Conclusions: These nuanced situations require careful advocacy for the child and a collaborative approach between medical providers and LEP to balance the child's well-being with public safety. We offer recommendations here, and we maintain that clear, widely adopted best practices for the care of minors in LEP custody are long overdue.
MeSH term(s)	Child ; Humans ; Police ; Minors ; Emergency Medical Services ; Emergency Service, Hospital ; Parents
Language	English
Publishing date	2023-01-21
Publishing country	United States
Document type	Review ; Journal Article
ZDB-ID	632588-9
ISSN	1535-1815 ; 0749-5161
ISSN (online)	1535-1815
ISSN	0749-5161
DOI	10.1097/PEC.0000000000002908
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Article ; Online: Metabolic obesity phenotypes and obesity-related cancer risk in the National Health and Nutrition Examination Survey.

Winn, Maci / Karra, Prasoona / Freisling, Heinz / Gunter, Marc J / Haaland, Benjamin / Litchman, Michelle L / Doherty, Jennifer A / Playdon, Mary C / Hardikar, Sheetal

Endocrinology, diabetes & metabolism

2023 Volume 6, Issue 4, Page(s) e433

Abstract: Introduction: Body mass index (BMI) fails to identify up to one-third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity-related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess ... ...

Abstract	Introduction: Body mass index (BMI) fails to identify up to one-third of normal weight individuals with metabolic dysfunction who may be at increased risk of obesity-related cancer (ORC). Metabolic obesity phenotypes, an alternate metric to assess metabolic dysfunction with or without obesity, were evaluated for association with ORC risk. Methods: National Health and Nutrition Examination Survey participants from 1999 to 2018 (N = 19,500) were categorized into phenotypes according to the metabolic syndrome (MetS) criteria and BMI: metabolically healthy normal weight (MHNW), metabolically unhealthy normal weight (MUNW), metabolically healthy overweight/obese (MHO) and metabolically unhealthy overweight/obese (MUO). Adjusted multivariable logistic regression models were used to evaluate associations with ORC. Results: With metabolic dysfunction defined as ≥1 MetS criteria, ORC cases (n = 528) had higher proportions of MUNW (28.2% vs. 17.4%) and MUO (62.6% vs. 60.9%) phenotypes than cancer-free individuals (n = 18,972). Compared with MHNW participants, MUNW participants had a 2.2-times higher ORC risk [OR (95%CI) = 2.21 (1.27-3.85)]. MHO and MUO participants demonstrated a 43% and 56% increased ORC risk, respectively, compared to MHNW, but these did not reach statistical significance [OR (95% CI) = 1.43 (0.46-4.42), 1.56 (0.91-2.67), respectively]. Hyperglycaemia, hypertension and central obesity were all independently associated with higher ORC risk compared to MHNW. Conclusions: MUNW participants have a higher risk of ORC than other abnormal phenotypes, compared with MHNW participants. Incorporating metabolic health measures in addition to assessing BMI may improve ORC risk stratification. Further research on the relationship between metabolic dysfunction and ORC is warranted.
MeSH term(s)	Humans ; Overweight ; Nutrition Surveys ; Obesity/complications ; Metabolic Syndrome/epidemiology ; Metabolic Syndrome/etiology ; Metabolic Syndrome/diagnosis ; Phenotype ; Neoplasms/epidemiology ; Neoplasms/etiology
Language	English
Publishing date	2023-06-05
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ISSN	2398-9238
ISSN (online)	2398-9238
DOI	10.1002/edm2.433
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Article: The midwife bond.

Winn, Meredith

Midwifery today with international midwife

2009 , Issue 89, Page(s) 16

MeSH term(s)	Adult ; Anecdotes as Topic ; Attitude to Health ; Female ; Friends ; Humans ; Infant, Newborn ; Interpersonal Relations ; Midwifery/methods ; Natural Childbirth/nursing ; Nurse's Role ; Nurse-Patient Relations ; Pregnancy
Language	English
Publishing date	2009
Publishing country	United States
Document type	Journal Article
ZDB-ID	1378192-3
ISSN	1551-8892 ; 1522-2888 ; 0891-7701
ISSN	1551-8892 ; 1522-2888 ; 0891-7701
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Article ; Online: Harnessing and engineering amide bond forming ligases for the synthesis of amides.

Winn, Michael / Richardson, Shona M / Campopiano, Dominic J / Micklefield, Jason

Current opinion in chemical biology

2020 Volume 55, Page(s) 77–85

Abstract: The amide functional group is ubiquitous in nature and one of the most important motifs in pharmaceuticals, agrochemicals, and other valuable products. While coupling amides and carboxylic acids is a trivial synthetic transformation, it often requires ... ...

Abstract	The amide functional group is ubiquitous in nature and one of the most important motifs in pharmaceuticals, agrochemicals, and other valuable products. While coupling amides and carboxylic acids is a trivial synthetic transformation, it often requires protective group manipulation, along with stoichiometric quantities of expensive and deleterious coupling reagents. Nature has evolved a range of enzymes to construct amide bonds, the vast majority of which utilize adenosine triphosphate to activate the carboxylic acid substrate for amine coupling. Despite the fact that these enzymes operate under mild conditions, as well as possessing chemoselectivity and regioselectivity that obviates the need for protecting groups, their synthetic potential has been largely unexplored. In this review, we discuss recent research into the discovery, characterization, and development of amide bond forming enzymes, with an emphasis on stand-alone ligase enzymes that can generate amides directly from simple carboxylic acid and amine substrates.
MeSH term(s)	Acyltransferases/metabolism ; Adenosine Triphosphate/metabolism ; Amide Synthases/chemistry ; Amide Synthases/metabolism ; Amides/chemistry ; Amines/chemistry ; Biocatalysis ; Carboxylic Acids/chemistry ; Coenzyme A/metabolism ; Peptide Synthases/metabolism ; Protein Conformation ; Substrate Specificity
Chemical Substances	Amides ; Amines ; Carboxylic Acids ; Adenosine Triphosphate (8L70Q75FXE) ; Acyltransferases (EC 2.3.-) ; Amide Synthases (EC 6.3.1.-) ; Peptide Synthases (EC 6.3.2.-) ; non-ribosomal peptide synthase (EC 6.3.2.-) ; Coenzyme A (SAA04E81UX)
Language	English
Publishing date	2020-02-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1439176-4
ISSN	1879-0402 ; 1367-5931
ISSN (online)	1879-0402
ISSN	1367-5931
DOI	10.1016/j.cbpa.2019.12.004
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Article ; Online: Small molecules enhance the potency of natural antimicrobial peptides.

Losasso, Valeria / Agarwal, Khushbu / Waskar, Morris / Majumdar, Amitabha / Crain, Jason / Winn, Martyn / Hoptroff, Michael

Biophysical journal

2021 Volume 121, Issue 3, Page(s) 491–501

Abstract: The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the ... ...

Abstract	The skin-associated microbiome plays an important role in general well-being and in a variety of treatable skin conditions. In this regard, endogenous antimicrobial peptides have both a direct and indirect role in determining the composition of the microbiota. We demonstrate here that certain small molecular species can amplify the antimicrobial potency of naturally occurring antimicrobial peptides. In this study, we have used niacinamide, a form of vitamin B3 naturally found in foods and widely used in cosmetic skincare products, and two of its structural analogs, to investigate their cooperativity with the human antimicrobial peptide LL37 on the bacterium Staphylococcus aureus. We observed a clear synergistic effect of niacinamide and, to some extent, N-methylnicotinamide, whereas isonicotinamide showed no significant cooperativity with LL37. Adaptively biased molecular dynamics simulations using simplified model membrane substrates and single peptides revealed that these molecules partition into the headgroup region of an anionic bilayer used to mimic the bacterial membrane. The simulated effects on the physical properties of the simulated model membrane are well correlated with experimental activity observed in real biological assays despite the simplicity of the model. In contrast, these molecules have little effect on zwitterionic bilayers that mimic a mammalian membrane. We conclude that niacinamide and N-methylnicotinamide can therefore potentiate the activity of host peptides by modulating the physical properties of the bacterial membrane, and to a lesser extent through direct interactions with the peptide. The level of cooperativity is strongly dependent on the detailed chemistry of the additive, suggesting an opportunity to fine-tune the behavior of host peptides.
MeSH term(s)	Animals ; Anti-Infective Agents/chemistry ; Anti-Infective Agents/pharmacology ; Antimicrobial Peptides ; Humans ; Lipid Bilayers/chemistry ; Mammals ; Niacinamide ; Peptides/chemistry
Chemical Substances	Anti-Infective Agents ; Antimicrobial Peptides ; Lipid Bilayers ; Peptides ; Niacinamide (25X51I8RD4)
Language	English
Publishing date	2021-12-24
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	218078-9
ISSN	1542-0086 ; 0006-3495
ISSN (online)	1542-0086
ISSN	0006-3495
DOI	10.1016/j.bpj.2021.12.029
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Article ; Online: Discovery, characterization and engineering of ligases for amide synthesis.

Winn, Michael / Rowlinson, Michael / Wang, Fanghua / Bering, Luis / Francis, Daniel / Levy, Colin / Micklefield, Jason

Nature

2021 Volume 593, Issue 7859, Page(s) 391–398

Abstract: Coronatine and related bacterial phytotoxins are mimics of the hormone jasmonyl-L-isoleucine (JA-Ile), which mediates physiologically important plant signalling ... ...

Abstract	Coronatine and related bacterial phytotoxins are mimics of the hormone jasmonyl-L-isoleucine (JA-Ile), which mediates physiologically important plant signalling pathways
MeSH term(s)	Amides/chemistry ; Amides/metabolism ; Amino Acids/biosynthesis ; Amino Acids/chemistry ; Azospirillum lipoferum/enzymology ; Azospirillum lipoferum/genetics ; Carboxylic Acids/metabolism ; Cyclopentanes/chemistry ; Escherichia coli/genetics ; Escherichia coli/metabolism ; Herbicides/chemistry ; Herbicides/metabolism ; Indenes/chemistry ; Isoleucine/analogs & derivatives ; Isoleucine/biosynthesis ; Isoleucine/chemistry ; Kinetics ; Ligases/chemistry ; Ligases/metabolism ; Models, Molecular ; Pectobacterium/enzymology ; Pectobacterium/genetics ; Pseudomonas syringae/enzymology ; Pseudomonas syringae/genetics
Chemical Substances	Amides ; Amino Acids ; Carboxylic Acids ; Cyclopentanes ; Herbicides ; Indenes ; jasmonoyl-isoleucine ; Isoleucine (04Y7590D77) ; coronatine (62251-96-1) ; Ligases (EC 6.-)
Language	English
Publishing date	2021-05-19
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/s41586-021-03447-w
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Article ; Online: De novo Biosynthesis of "Non-Natural" Thaxtomin Phytotoxins.

Winn, Michael / Francis, Daniel / Micklefield, Jason

Angewandte Chemie (International ed. in English)

2018 Volume 57, Issue 23, Page(s) 6830–6833

Abstract: Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable ... ...

Abstract	Thaxtomins are diketopiperazine phytotoxins produced by Streptomyces scabies and other actinobacterial plant pathogens that inhibit cellulose biosynthesis in plants. Due to their potent bioactivity and novel mode of action there has been considerable interest in developing thaxtomins as herbicides for crop protection. To address the need for more stable derivatives, we have developed a new approach for structural diversification of thaxtomins. Genes encoding the thaxtomin NRPS from S. scabies, along with genes encoding a promiscuous tryptophan synthase (TrpS) from Salmonella typhimurium, were assembled in a heterologous host Streptomyces albus. Upon feeding indole derivatives to the engineered S. albus strain, tryptophan intermediates with alternative substituents are biosynthesized and incorporated by the NRPS to deliver a series of thaxtomins with different functionalities in place of the nitro group. The approach described herein, demonstrates how genes from different pathways and different bacterial origins can be combined in a heterologous host to create a de novo biosynthetic pathway to "non-natural" product target compounds.
MeSH term(s)	Biosynthetic Pathways ; Gene Expression Regulation, Bacterial ; Genes, Bacterial ; Genetic Engineering ; Indoles/chemistry ; Indoles/metabolism ; Peptide Synthases/genetics ; Peptide Synthases/metabolism ; Piperazines/chemistry ; Piperazines/metabolism ; Plants/microbiology ; Salmonella typhimurium/enzymology ; Salmonella typhimurium/genetics ; Salmonella typhimurium/metabolism ; Streptomyces/chemistry ; Streptomyces/enzymology ; Streptomyces/genetics ; Streptomyces/metabolism ; Tryptophan Synthase/genetics ; Tryptophan Synthase/metabolism
Chemical Substances	Indoles ; Piperazines ; thaxtomine A (122380-18-1) ; thaxtomine B (122380-19-2) ; Tryptophan Synthase (EC 4.2.1.20) ; Peptide Synthases (EC 6.3.2.-) ; non-ribosomal peptide synthase (EC 6.3.2.-)
Language	English
Publishing date	2018-05-08
Publishing country	Germany
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2011836-3
ISSN	1521-3773 ; 1433-7851
ISSN (online)	1521-3773
ISSN	1433-7851
DOI	10.1002/anie.201801525
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Article ; Online: Recent advances in engineering nonribosomal peptide assembly lines.

Winn, M / Fyans, J K / Zhuo, Y / Micklefield, J

Natural product reports

2015 Volume 33, Issue 2, Page(s) 317–347

Abstract: Nonribosomal peptides are amongst the most widespread and structurally diverse secondary metabolites in nature with many possessing bioactivity that can be exploited for therapeutic applications. Due to the major challenges associated with total- and ... ...

Abstract	Nonribosomal peptides are amongst the most widespread and structurally diverse secondary metabolites in nature with many possessing bioactivity that can be exploited for therapeutic applications. Due to the major challenges associated with total- and semi-synthesis, bioengineering approaches have been developed to increase yields and generate modified peptides with improved physicochemical properties or altered bioactivity. Here we review the major advances that have been made over the last decade in engineering the biosynthesis of nonribosomal peptides. Structural diversity has been introduced by the modification of enzymes required for the supply of precursors or by heterologous expression of tailoring enzymes. The modularity of nonribosomal peptide synthetase (NRPS) assembly lines further supports module or domain swapping methodologies to achieve changes in the amino acid sequence of nonribosomal peptides. We also review the new synthetic biology technologies promising to speed up the process, enabling the creation and optimisation of many more assembly lines for heterologous expression, offering new opportunities for engineering the biosynthesis of novel nonribosomal peptides.
MeSH term(s)	Amino Acid Sequence ; Models, Molecular ; Molecular Structure ; Peptide Synthases/metabolism ; Peptides/chemistry
Chemical Substances	Peptides ; Peptide Synthases (EC 6.3.2.-) ; non-ribosomal peptide synthase (EC 6.3.2.-)
Language	English
Publishing date	2015-11-25
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2002546-4
ISSN	1460-4752 ; 0265-0568
ISSN (online)	1460-4752
ISSN	0265-0568
DOI	10.1039/c5np00099h
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Article ; Online: Aberrant CREB1 activation in prostate cancer disrupts normal prostate luminal cell differentiation.

Watson, M J / Berger, P L / Banerjee, K / Frank, S B / Tang, L / Ganguly, S S / Hostetter, G / Winn, M / Miranti, C K

Oncogene

2021 Volume 40, Issue 18, Page(s) 3260–3272

Abstract: The molecular mechanisms of luminal cell differentiation are not understood well enough to determine how differentiation goes awry during oncogenesis. Using RNA-Seq analysis, we discovered that CREB1 plays a central role in maintaining new luminal cell ... ...

Abstract	The molecular mechanisms of luminal cell differentiation are not understood well enough to determine how differentiation goes awry during oncogenesis. Using RNA-Seq analysis, we discovered that CREB1 plays a central role in maintaining new luminal cell survival and that oncogenesis dramatically changes the CREB1-induced transcriptome. CREB1 is active in luminal cells, but not basal cells. We identified ING4 and its E3 ligase, JFK, as CREB1 transcriptional targets in luminal cells. During luminal cell differentiation, transient induction of ING4 expression is followed by a peak in CREB1 activity, while JFK increases concomitantly with CREB1 activation. Transient expression of ING4 is required for luminal cell induction; however, failure to properly down-regulate ING4 leads to luminal cell death. Consequently, blocking CREB1 increased ING4 expression, suppressed JFK, and led to luminal cell death. Thus, CREB1 is responsible for the suppression of ING4 required for luminal cell survival and maintenance. Oncogenic transformation by suppressing PTEN resulted in constitutive activation of CREB1. However, the tumor cells could no longer fully differentiate into luminal cells, failed to express ING4, and displayed a unique CREB1 transcriptome. Blocking CREB1 in tumorigenic cells suppressed tumor growth in vivo, rescued ING4 expression, and restored luminal cell formation, but ultimately induced luminal cell death. IHC of primary prostate tumors demonstrated a strong correlation between loss of ING4 and loss of PTEN. This is the first study to define a molecular mechanism whereby oncogenic loss of PTEN, leading to aberrant CREB1 activation, suppresses ING4 expression causing disruption of luminal cell differentiation.
MeSH term(s)	Cell Cycle Proteins ; Cell Differentiation ; Humans ; Male ; PTEN Phosphohydrolase ; Prostate ; Prostatic Neoplasms
Chemical Substances	Cell Cycle Proteins ; PTEN Phosphohydrolase (EC 3.1.3.67) ; PTEN protein, human (EC 3.1.3.67)
Language	English
Publishing date	2021-04-12
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	639046-8
ISSN	1476-5594 ; 0950-9232
ISSN (online)	1476-5594
ISSN	0950-9232
DOI	10.1038/s41388-021-01772-y
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