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Article ; Online: Deeper dive into tissue-level events that incite and promote pelvic organ prolapse.

Alperin, Marianna

American journal of obstetrics and gynecology

2020 Volume 224, Issue 1, Page(s) 1–2

MeSH term(s)	Female ; Humans ; Ligaments ; Pelvic Organ Prolapse ; Phenotype ; Uterine Prolapse
Language	English
Publishing date	2020-12-29
Publishing country	United States
Document type	Editorial ; Comment
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2020.11.003
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Article ; Online: Regenerative Medicine in Urogynecology: Where We Are and Where We Want to Be.

Henderson, Tatyanna / Christman, Karen L / Alperin, Marianna

Urogynecology (Philadelphia, Pa.)

2024 Volume 30, Issue 5, Page(s) 519–527

Abstract: Abstract: Pelvic floor disorders (PFDs) constitute a major public health issue given their negative effect on quality of life for millions of women worldwide and the associated economic burden. As the prevalence of PFDs continues to increase, novel ... ...

Abstract	Abstract: Pelvic floor disorders (PFDs) constitute a major public health issue given their negative effect on quality of life for millions of women worldwide and the associated economic burden. As the prevalence of PFDs continues to increase, novel therapeutic approaches for the effective treatment of these disorders are urgently needed. Regenerative medicine techniques, including cellular therapies, extracellular vesicles, secretomes, platelet-rich plasma, laser therapy, and bioinductive acellular biomaterial scaffolds, are emerging as viable clinical options to counteract urinary and fecal incontinence, as well as pelvic organ prolapse. This brief expert review explores the current state-of-science regarding application of these therapies for the treatment of PFDs. Although regenerative approaches have not been widely deployed in clinical care to date, these innovative techniques show a promising safety profile and potential to positively affect the quality of life of patients with PFDs. Furthermore, investigations focused on regeneration of the main constituents of the pelvic floor and lower urinary tract improve our understanding of the underlying pathophysiology of PFDs. Regenerative medicine techniques have a high potential not only to revolutionize treatment of PFDs but also to prevent these complex conditions.
MeSH term(s)	Humans ; Regenerative Medicine/methods ; Female ; Pelvic Floor Disorders/therapy ; Quality of Life ; Gynecology/methods
Language	English
Publishing date	2024-04-08
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2771-1897
ISSN (online)	2771-1897
DOI	10.1097/SPV.0000000000001461
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Article ; Online: The Effect of Menopause on Vaginal Tissue Mechanics: A Brief Review.

Gimenez, Clara / Alperin, Marianna / De Vita, Raffaella

Journal of biomechanical engineering

2023 Volume 146, Issue 6

Abstract: Often called "the change of life," menopause affects every part of a woman's body. As the sex hormones decrease, the reproductive organs experience the most remarkable changes, with the vagina becoming thinner, drier, and less elastic. Despite the ... ...

Abstract	Often called "the change of life," menopause affects every part of a woman's body. As the sex hormones decrease, the reproductive organs experience the most remarkable changes, with the vagina becoming thinner, drier, and less elastic. Despite the important implications of these changes in genitourinary conditions, there are only a few experimental studies that focus on quantifying the effect of menopause on the mechanical properties of the vagina. These studies are mostly conducted using uniaxial tests on strips of vaginal tissues isolated from rats, rabbits, and sheep and, in only a few cases, from humans. The purpose of this article is to present a systematic review of experimental protocols, methods, and results that are currently published on how menopause alters the mechanical behavior of the vagina. This review will enable new investigators in the biomechanics field to identify important gaps and frame research questions that inform the design of new treatment options for menopausal symptoms.
MeSH term(s)	Humans ; Female ; Rats ; Rabbits ; Animals ; Sheep ; Menopause ; Vagina ; Pelvis ; Biomechanical Phenomena
Language	English
Publishing date	2023-08-05
Publishing country	United States
Document type	Systematic Review ; Journal Article
ZDB-ID	243094-0
ISSN	1528-8951 ; 0148-0731
ISSN (online)	1528-8951
ISSN	0148-0731
DOI	10.1115/1.4063101
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Article ; Online: The Future of Basic Science: Development of the Next Generation of Mechanistic Researchers in Female Pelvic Medicine.

Alperin, Marianna / Alarab, May / Botros-Brey, Sylvia / Drutz, Harold / King, Jenny / Shynlova, Oksana

International urogynecology journal

2024 Volume 35, Issue 4, Page(s) 775–779

Abstract: Introduction and hypothesis: The International Urogynecological Association (IUGA) brought together senior and junior members actively engaged in scholarly and educational activities for a consensus conference centered on developing a strategy for ... ...

Abstract	Introduction and hypothesis: The International Urogynecological Association (IUGA) brought together senior and junior members actively engaged in scholarly and educational activities for a consensus conference centered on developing a strategy for sustainable training of the next generation of mechanistic researchers in female pelvic medicine. Methods: Four a priori identified major foci were explored in a half-day virtual consensus conference. Participants included representatives from various countries and disciplines with diverse backgrounds-clinicians, physician-scientists, and basic scientists in the fields of urogynecology, biomechanical engineering, and molecular biology. Following a keynote address, each focus area was first tackled by a dedicated breakout group, led by the Chair(s) of the most relevant IUGA committees. The break-out sessions were followed by an iterative discussion among all attendees to identify mitigating strategies to address the shortage of mechanistic researchers in the field of female pelvic medicine. Results: The major focus areas included: research priorities for IUGA basic science scholar program; viable strategies for sustainable basic science mentorship; core competencies in basic science training; and the challenges of conducting complex mechanistic experiments in low-resource countries. Key gaps in knowledge and core competencies that should be incorporated into fellowship/graduate training were identified, and existing training modalities were discussed. Recommendations were made for pragmatic approaches to increasing the exposure of trainees to learning tools to enable sustainable training of the next generation of basic science researchers in female pelvic medicine worldwide. Conclusions: The attendees presented multiple perspectives to gain consensus regarding critical areas of need for training future generations of mechanistic researchers. Recommendations for a sustainable Basic Science Scholar Program were developed using IUGA as a platform. The overarching goal of such a program is to ensure a successful bench-to-bedside-and-back circuit in Urogynecology and Pelvic Reconstructive Surgery, ultimately improving lives of millions of women worldwide through scientifically rational effective preventative and therapeutic interventions.
MeSH term(s)	Humans ; Female ; Gynecology/education ; Gynecology/trends ; Biomedical Research/trends ; Urology/education ; Mentors ; Forecasting ; Research Personnel/education
Language	English
Publishing date	2024-03-25
Publishing country	England
Document type	Journal Article ; Consensus Development Conference
ZDB-ID	1050631-7
ISSN	1433-3023 ; 0937-3462
ISSN (online)	1433-3023
ISSN	0937-3462
DOI	10.1007/s00192-024-05766-8
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Article ; Online: Effect of nonsteroidal anti-inflammatory drugs on pelvic floor muscle regeneration in a preclinical birth injury rat model.

Kobayashi, Alyssa J / Sesillo, Francesca Boscolo / Do, Emmy / Alperin, Marianna

American journal of obstetrics and gynecology

2023 Volume 230, Issue 4, Page(s) 432.e1–432.e14

Abstract: Background: Pelvic floor muscle injury is a common consequence of vaginal childbirth. Nonsteroidal anti-inflammatory drugs are widely used postpartum analgesics. Multiple studies have reported negative effects of these drugs on limb muscle regeneration, ...

Abstract	Background: Pelvic floor muscle injury is a common consequence of vaginal childbirth. Nonsteroidal anti-inflammatory drugs are widely used postpartum analgesics. Multiple studies have reported negative effects of these drugs on limb muscle regeneration, but their impact on pelvic floor muscle recovery following birth injury has not been explored. Objective: Using a validated rat model, we assessed the effects of nonsteroidal anti-inflammatory drug on acute and longer-term pelvic floor muscle recovery following simulated birth injury. Study design: Three-month old Sprague Dawley rats were randomly assigned to the following groups: (1) controls, (2) simulated birth injury, (3) simulated birth injury+nonsteroidal anti-inflammatory drug, or (4) nonsteroidal anti-inflammatory drug. Simulated birth injury was induced using a well-established vaginal balloon distension protocol. Ibuprofen was administered in drinking water (0.2 mg/mL), which was consumed by the animals ad libitum. Animals were euthanized at 1, 3, 5, 7, 10, and 28 days after birth injury/ibuprofen administration. The pubocaudalis portion of the rat levator ani, which, like the human pubococcygeus, undergoes greater parturition-associated strains, was harvested (N=3-9/time point/group). The cross-sectional areas of regenerating (embryonic myosin heavy chain Results: The pubocaudalis fiber size was significantly smaller in the simulated birth injury+nonsteroidal anti-inflammatory drug compared with the simulated birth injury group at 28 days after injury (P<.0001). The median size of embryonic myosin heavy chain Conclusion: Nonsteroidal anti-inflammatory drugs negatively impacted pelvic floor muscle regeneration in a preclinical simulated birth injury model. This appears to be driven by the negative impact of these drugs on pelvic muscle stem cell function, resulting in delayed temporal progression of pelvic floor muscle regeneration following birth injury. These findings provide impetus to investigate the impact of postpartum nonsteroidal anti-inflammatory drug administration on muscle regeneration in women at high risk for pelvic floor muscle injury.
MeSH term(s)	Humans ; Rats ; Female ; Animals ; Infant ; Muscle, Skeletal/physiology ; Rats, Sprague-Dawley ; Myogenin ; Ibuprofen/therapeutic use ; Pelvic Floor/physiology ; Myosin Heavy Chains/genetics ; Anti-Inflammatory Agents, Non-Steroidal/therapeutic use ; Regeneration/physiology ; Collagen ; Birth Injuries ; Cytokines
Chemical Substances	Myogenin ; Ibuprofen (WK2XYI10QM) ; Myosin Heavy Chains (EC 3.6.4.1) ; Anti-Inflammatory Agents, Non-Steroidal ; Collagen (9007-34-5) ; Cytokines
Language	English
Publishing date	2023-12-06
Publishing country	United States
Document type	Journal Article
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2023.12.001
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Article ; Online: Collagen scaffold: a treatment for large mesh exposure following vaginal prolapse repair.

Alperin, Marianna

International urogynecology journal

2014 Volume 25, Issue 11, Page(s) 1597–1599

Abstract: Transvaginal repair with mesh of pelvic organ prolapse (POP) provides women with the durability of a synthetic graft using the less-invasive route of vaginal surgery. However, morbidities such as mesh exposures are common and challenging to manage. Small ...

Abstract	Transvaginal repair with mesh of pelvic organ prolapse (POP) provides women with the durability of a synthetic graft using the less-invasive route of vaginal surgery. However, morbidities such as mesh exposures are common and challenging to manage. Small intestinal submucosa (SIS) is a naturally occurring collagen matrix derived from porcine intestine. It contains growth factors and cytokines that promote healing of damaged tissue. This case report describes a large vaginal mesh exposure due to necrosis of the full thickness of the anterior vaginal wall. A remarkable and rapid regeneration of vaginal tissue over the exposed mesh was achieved with SIS placement after failure of treatment with vaginal estrogen for >6 months. Collagen scaffold is an effective, rapid, and minimally invasive treatment for large vaginal mesh exposures.
MeSH term(s)	Collagen/therapeutic use ; Female ; Humans ; Middle Aged ; Pelvic Organ Prolapse/surgery ; Postoperative Complications/etiology ; Postoperative Complications/therapy ; Surgical Mesh/adverse effects ; Tissue Scaffolds
Chemical Substances	surgisis ; Collagen (9007-34-5)
Language	English
Publishing date	2014-05-16
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	1050631-7
ISSN	1433-3023 ; 0937-3462
ISSN (online)	1433-3023
ISSN	0937-3462
DOI	10.1007/s00192-014-2427-5
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Article ; Online: In-plane and out-of-plane deformations of gilt utero-sacral ligaments.

Donaldson, Kandace / Thomas, Joseph / Zhu, Yizheng / Clark-Deener, Sherrie / Alperin, Marianna / De Vita, Raffaella

Journal of the mechanical behavior of biomedical materials

2022 Volume 131, Page(s) 105249

Abstract: The uterosacral ligaments (USLs) are supportive structures of the uterus and apical vagina. The mechanical function of these ligaments within the pelvic floor is crucial not only in normal physiological conditions but also in reconstructive surgeries for ...

Abstract	The uterosacral ligaments (USLs) are supportive structures of the uterus and apical vagina. The mechanical function of these ligaments within the pelvic floor is crucial not only in normal physiological conditions but also in reconstructive surgeries for pelvic organ prolapse. Discrepancies in their anatomical and histological description exist in the literature, but such discrepancies are likely due to large variations of these structures. This makes mechanical testing very challenging, requiring the development of advanced methods for characterizing their mechanical properties. This study proposes the use of planar biaxial testing, digital image correlation (DIC), and optical coherence tomography (OCT) to quantify the deformations of the USLs, both in-plane and out-of-plane. Using the gilts as an animal model, the USLs were found to deform significantly less in their main direction (MD) of in vivo loading than in the direction perpendicular to it (PD) at increasing equibiaxial stresses. Under constant equibiaxial loading, the USLs deform over time equally, at comparable rates in both the MD and PD. The thickness of the USLs decreases as the equibiaxial loading increases but, under constant equibiaxial loading, the thickness increases in some specimens and decreases in others. These findings could contribute to the design of new mesh materials that augment the support function of USLs as well as noninvasive diagnostic tools for evaluating the integrity of the USLs.
MeSH term(s)	Animals ; Female ; Ligaments/diagnostic imaging ; Ligaments/physiology ; Ligaments, Articular ; Pelvic Floor/physiology ; Pelvic Organ Prolapse/diagnostic imaging ; Sus scrofa ; Swine ; Uterus/pathology ; Vagina
Language	English
Publishing date	2022-04-25
Publishing country	Netherlands
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2378381-3
ISSN	1878-0180 ; 1751-6161
ISSN (online)	1878-0180
ISSN	1751-6161
DOI	10.1016/j.jmbbm.2022.105249
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Article ; Online: Impact of sex and aging on radiographic and functional parameters of the anal sphincter complex in patients with accidental bowel leakage.

Artsen, Amanda M / Dyer, Keisha Y / Routzong, Megan R / Zazueta-Damian, Gisselle / Weinstein, Milena M / Alperin, Marianna

Neurourology and urodynamics

2023 Volume 42, Issue 4, Page(s) 751–760

Abstract: Aims: Treatment outcomes for accidental bowel leakage (ABL) may be influenced by age-related sarcopenia. We sought to determine if thickness of the anal sphincter complex on endoanal ultrasound correlated with function in women and men with ABL and if ... ...

Abstract	Aims: Treatment outcomes for accidental bowel leakage (ABL) may be influenced by age-related sarcopenia. We sought to determine if thickness of the anal sphincter complex on endoanal ultrasound correlated with function in women and men with ABL and if women demonstrated age-related anal sphincter thinning. Methods: Consecutive patients with ABL presenting to our pelvic floor clinic from 2012 to 2017 were included. Clinical data were obtained from medical records. External anal sphincter (EAS), imaged by endoanal ultrasound at proximal, mid and distal locations, and IAS thickness were measured at 12, 3, 6, and 9 o'clock; puborectalis muscle (PRM) was measured at 4, 6, and 8 o'clock; and averaged. Anorectal manometry was conducted when clinically indicated. Data were compared using Mann-Whitney tests and linear regression. Results are reported as mean ± SD or median (IQR). Results: Women (n = 136) were younger than men (n = 26) (61 ± 13 vs. 67 ± 13 years, p = 0.02). More women than men had pelvic surgery and less had colorectal surgery, spinal disorders, or a history of smoking (p < 0.05). Eighty-two percentage of women had an anal sphincter defect versus 31% of men (p < 0.01). All anal sphincter complex components were thinner in women than men with lower squeeze and resting pressures (p < 0.03), even in nulliparous women. Mean resting pressure was lower in older 6.1 (4.6-7.8) versus younger women 8.3 (5.0-12.9) mmHg, p = 0.04. Conclusions: Women, even nulliparous, with ABL demonstrate thinner and weaker anal sphincters than men, Aging correlated with an increase in anal sphincter thickness, suggesting that age-related changes in the intrinsic components of the anal sphincter complex associated with ABL are complex and are not always well demonstrated on endoanal ultrasound.
MeSH term(s)	Male ; Humans ; Female ; Aged ; Anal Canal ; Manometry/methods ; Pressure ; Ultrasonography ; Aging
Language	English
Publishing date	2023-02-19
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	604904-7
ISSN	1520-6777 ; 0733-2467
ISSN (online)	1520-6777
ISSN	0733-2467
DOI	10.1002/nau.25151
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Article ; Online: The influence of orbital architecture on strabismus in craniosynostosis.

Lee, Tonya C / Walker, Evan / Ting, Michelle A / Bolar, Divya S / Koning, Jeffrey / Korn, Bobby S / Kikkawa, Don O / Granet, David / Robbins, Shira L / Alperin, Marianna / Engle, Elizabeth C / Liu, Catherine Y / Rudell, Jolene C

Journal of AAPOS : the official publication of the American Association for Pediatric Ophthalmology and Strabismus

2024 Volume 28, Issue 1, Page(s) 103812

Abstract: Purpose: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis.: Methods: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, ...

Abstract	Purpose: To better characterize the correlation of bony orbital dysmorphology with strabismus in craniosynostosis. Methods: The medical records of patients with craniosynostosis with and without strabismus seen at Rady Children's Hospital (San Diego, CA) from March 2020 to January 2022 were reviewed retrospectively in this masked, case-control study. Computed tomography scans of the orbits were analyzed to obtain dimensions of the orbital entrance and orbital cone. Primary outcome was correlation of strabismus with orbital measurements. Results: A total of 30 orbits from 15 patients with strabismus and 15 controls were included. Craniofacial disorders included in the study were nonsyndromic craniosynostosis (63%), Crouzon syndrome (13%), Apert syndrome (13%), and Pfeiffer syndrome (10%). Orbital index (height:width ratio) (P = 0.01) and medial orbital wall angle (P = 0.04) were found to differ significantly between the strabismus and control groups. Conclusions: In our small cohort, bony orbital dimensions, including the ratio of orbital height to width and bowing of the medial orbital wall, were associated with strabismus in craniosynostosis.
MeSH term(s)	Child ; Humans ; Case-Control Studies ; Retrospective Studies ; Craniosynostoses/complications ; Craniosynostoses/diagnostic imaging ; Acrocephalosyndactylia/complications ; Strabismus/etiology ; Strabismus/complications ; Orbit/diagnostic imaging
Language	English
Publishing date	2024-01-13
Publishing country	United States
Document type	Journal Article
ZDB-ID	1412476-2
ISSN	1528-3933 ; 1091-8531
ISSN (online)	1528-3933
ISSN	1091-8531
DOI	10.1016/j.jaapos.2023.10.006
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Article ; Online: Mechanisms governing protective pregnancy-induced adaptations of the pelvic floor muscles in the rat preclinical model.

Rieger, Mary M / Wong, Michelle / Burnett, Lindsey A / Sesillo, Francesca Boscolo / Baynes, Brittni B / Alperin, Marianna

American journal of obstetrics and gynecology

2021 Volume 226, Issue 5, Page(s) 708.e1–708.e13

Abstract: Background: The intrinsic properties of pelvic soft tissues in women who do and do not sustain birth injuries are likely divergent. However, little is known about this. Rat pelvic floor muscles undergo protective pregnancy-induced structural adaptations- ...

Abstract	Background: The intrinsic properties of pelvic soft tissues in women who do and do not sustain birth injuries are likely divergent. However, little is known about this. Rat pelvic floor muscles undergo protective pregnancy-induced structural adaptations-sarcomerogenesis and increase in intramuscular collagen content-that protect against birth injury. Objective: We aimed to test the following hypotheses: (1) the increased mechanical load of a gravid uterus drives antepartum adaptations; (2) load-induced changes are sufficient to protect pelvic muscles from birth injury. Study design: The independent effects of load uncoupled from the hormonal milieu of pregnancy were tested in 3- to 4-month-old Sprague-Dawley rats randomly divided into the following 4 groups, with N of 5 to 14 per group: (1) load Results: An acute increase in load resulted in significant pelvic floor muscle stretch, accompanied by an acute increase in sarcomere length compared with nonloaded control muscles (coccygeus: 2.69±0.03 vs 2.30±0.06 μm, respectively, P<.001; pubocaudalis: 2.71±0.04 vs 2.25±0.03 μm, respectively, P<.0001; and iliocaudalis: 2.80±0.06 vs 2.35±0.04 μm, respectively, P<.0001). After 21 days of sustained load, the sarcomeres returned to operational length in all pelvic muscles (P>.05). However, the myofibers remained significantly longer in the load Conclusion: Load induces plasticity of the intrinsic pelvic floor muscle components, which renders protection against mechanical birth injury. The protective effect, which varies between the individual muscles and strain magnitudes, is further augmented by the presence of pregnancy hormones. Maximizing the impact of mechanical load on the pelvic floor muscles during pregnancy, such as with specialized pelvic floor muscle stretching regimens, is a potentially actionable target for augmenting pregnancy-induced adaptations to decrease birth injury in women who may otherwise have incomplete antepartum muscle adaptations.
MeSH term(s)	Animals ; Birth Injuries ; Collagen ; Female ; Hormones ; Humans ; Pelvic Floor/physiology ; Pregnancy ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Hormones ; Collagen (9007-34-5)
Language	English
Publishing date	2021-11-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	80016-8
ISSN	1097-6868 ; 0002-9378
ISSN (online)	1097-6868
ISSN	0002-9378
DOI	10.1016/j.ajog.2021.11.1353
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