-
Nature Reviews. Genetics Jul 2023Primary cilia, antenna-like sensory organelles protruding from the surface of most vertebrate cell types, are essential for regulating signalling pathways during... (Review)
Review
Primary cilia, antenna-like sensory organelles protruding from the surface of most vertebrate cell types, are essential for regulating signalling pathways during development and adult homeostasis. Mutations in genes affecting cilia cause an overlapping spectrum of >30 human diseases and syndromes, the ciliopathies. Given the immense structural and functional diversity of the mammalian cilia repertoire, there is a growing disconnect between patient genotype and associated phenotypes, with variable severity and expressivity characteristic of the ciliopathies as a group. Recent technological developments are rapidly advancing our understanding of the complex mechanisms that control biogenesis and function of primary cilia across a range of cell types and are starting to tackle this diversity. Here, we examine the structural and functional diversity of primary cilia, their dynamic regulation in different cellular and developmental contexts and their disruption in disease.
Topics: Adult; Animals; Humans; Cilia; Signal Transduction; Ciliopathies; Mammals
PubMed: 37072495
DOI: 10.1038/s41576-023-00587-9 -
Proceedings of the National Academy of... Sep 2023Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that...
Stem cells in organoids self-organize into tissue patterns with unknown mechanisms. Here, we use skin organoids to analyze this process. Cell behavior videos show that the morphological transformation from multiple spheroidal units with morphogenesis competence (CMU) to planar skin is characterized by two abrupt cell motility-increasing events before calming down. The self-organizing processes are controlled by a morphogenetic module composed of molecular sensors, modulators, and executers. Increasing dermal stiffness provides the initial driving force (driver) which activates Yap1 (sensor) in epidermal cysts. Notch signaling (modulator 1) in epidermal cyst tunes the threshold of Yap1 activation. Activated Yap1 induces Wnts and MMPs (epidermal executers) in basal cells to facilitate cellular flows, allowing epidermal cells to protrude out from the CMU. Dermal cell-expressed Rock (dermal executer) generates a stiff force bridge between two CMU and accelerates tissue mixing via activating Laminin and β1-integrin. Thus, this self-organizing coalescence process is controlled by a mechano-chemical circuit. Beyond skin, self-organization in organoids may use similar mechano-chemical circuit structures.
Topics: Skin; Epidermis; Personality; Organoids; Emotions; Adaptor Proteins, Signal Transducing
PubMed: 37643215
DOI: 10.1073/pnas.2221982120 -
JAMA Aug 2023In many countries, sacrospinous hysteropexy is the most commonly practiced uterus-preserving technique in women undergoing a first operation for pelvic organ prolapse.... (Comparative Study)
Comparative Study Randomized Controlled Trial
IMPORTANCE
In many countries, sacrospinous hysteropexy is the most commonly practiced uterus-preserving technique in women undergoing a first operation for pelvic organ prolapse. However, there are no direct comparisons of outcomes after sacrospinous hysteropexy vs an older technique, the Manchester procedure.
OBJECTIVE
To compare success of sacrospinous hysteropexy vs the Manchester procedure for the surgical treatment of uterine descent.
DESIGN, SETTING, AND PARTICIPANTS
Multicenter, noninferiority randomized clinical trial conducted in 26 hospitals in the Netherlands among 434 adult patients undergoing a first surgical treatment for uterine descent that did not protrude beyond the hymen.
INTERVENTIONS
Participants were randomly assigned to undergo sacrospinous hysteropexy (n = 217) or Manchester procedure (n = 217).
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite outcome of success, defined as absence of pelvic organ prolapse beyond the hymen in any compartment evaluated by a standardized vaginal support quantification system, absence of bothersome bulge symptoms, and absence of prolapse retreatment (pessary or surgery) within 2 years after the operation. The predefined noninferiority margin was 9%. Secondary outcomes were anatomical and patient-reported outcomes, perioperative parameters, and surgery-related complications.
RESULTS
Among 393 participants included in the as-randomized analysis (mean age, 61.7 years [SD, 9.1 years]), 151 of 196 (77.0%) in the sacrospinous hysteropexy group and 172 of 197 (87.3%) in the Manchester procedure group achieved the composite outcome of success. Sacrospinous hysteropexy did not meet the noninferiority criterion of -9% for the lower limit of the CI (risk difference, -10.3%; 95% CI, -17.8% to -2.8%; P = .63 for noninferiority). At 2-year follow-up, perioperative outcomes and patient-reported outcomes did not differ between the 2 groups.
CONCLUSIONS
Based on the composite outcome of surgical success 2 years after primary uterus-sparing pelvic organ prolapse surgery for uterine descent, these results support a finding that sacrospinous hysteropexy is inferior to the Manchester procedure.
TRIAL REGISTRATION
TrialRegister.nl Identifier: NTR 6978.
Topics: Female; Humans; Middle Aged; Gynecologic Surgical Procedures; Pelvic Organ Prolapse; Treatment Outcome; Uterine Prolapse; Uterus; Aged
PubMed: 37581670
DOI: 10.1001/jama.2023.13140