Study protocol for improving mental health during pregnancy: a randomized controlled low-intensity m-health intervention by midwives at primary care centers.

BACKGROUND: Pregnancy-related anxiety and depression has received considerable attention worldwide. Mental health problems in pregnant women already since early weeks of gestation may have important consequences to the fetus. The necessity for more effective health care pathways, including some early interventions that reduce the overall burden of the childbearing situation appears a key factor for a successful birth and care of the baby. The few studies focalized in interventions, are focused on delivery and postpartum, without taking into account the whole maternity process. Current literature recommends the use of interventions based on new technologies for the treatment of mood disorders, already during the prenatal period. There have been scarce well-designed intervention studies that test technological low-intensity interventions by midwives to address pregnant women's mental health, diminishing anxiety and depression during pregnancy. METHODS/DESIGN: Adult pregnant women (weeks 12-14 of gestation) will be recruited and screened from different primary care centers in Catalonia, Spain. Women who pass the initial mental screening will be randomly allocated to the relaxation virtual reality intervention or control group. The intervention aims to improve mental state of pregnant women during pregnancy, work through breathing, mindfulness and muscle relaxation techniques. Women in the control group will receive standard care offered by the public funded maternity services in Catalonia. The primary outcome measures will include the Edinburg Postnatal Depression (EPDS), State Trait Anxiety Inventory (STAI), Symptom Checklist-90 (SCL-90), and the Cambridge Worry Scale (CWS) instruments. Secondary outcome measures will include the Temperament and Character Inventory-Revised (TCI-R) and the Whooley and Generalized Anxiety Disorder-2 (GAD-2) questions. Routinary pregnancy monitoring measures will be also evaluated. DISCUSSION: This study aims to test the efficacy of a low-intensity, midwife-led e-health intervention based on new technologies to work on women's anxiety and depression during pregnancy. We hypothesize that low-intensity mental health intervention during pregnancy, using an e-health (virtual reality) as a support tool, will be effective in reducing of anxiety, depressive symptoms, and improving satisfaction with pregnancy follow-up. TRIAL REGISTRATION: Clinical Trials ID NCT05756205.

Vaginal packing after vaginal hysterectomy: systematic review and recommendations.

INTRODUCTION AND HYPOTHESIS: Vaginal packing is often used after vaginal hysterectomy to reduce the risk of haemorrhagic and infectious complications, but the procedure may impair spontaneous bladder emptying and necessitate permanent bladder catheterization, which itself increases the risk of urinary infection, patient bother, delayed discharge, and increased costs. This systematic review was aimed at assessing the complications and outcomes associated with vaginal packing after vaginal hysterectomy. METHODS: We conducted a systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) Statement, using the Population, Interventions, Comparators, Outcomes, and Study design (PICOS) framework to define eligibility. Following data synthesis and subgroup analyses, we assessed the certainty of evidence according to GRADE guidance and formulated a clinical recommendation. RESULTS: The review included four clinical trials (involving 337 participants). These provided no clear evidence that vaginal packing led to clinically meaningful reductions in adverse effects, such as vaginal bleeding, hematoma formation, or postoperative vaginal cuff infection. Overall, the intervention produced no clear benefit regarding the predefined outcomes. CONCLUSIONS: Routine vaginal packing after vaginal hysterectomy had no clear benefit on outcomes. We therefore advise against this procedure.

Comparison of a human acellular dermal matrix and a polypropylene mesh for pelvic floor reconstruction: a randomized trial study in a rabbit model.

Non-absorbable polypropylene (PP) meshes have been widely used in surgical reconstruction of the pelvic floor disorders. However, they are associated with serious complications. Human acellular dermal matrices (hADM) have demonstrated safety and efficacy in reconstructive medicine, but their suitability and efficacy at vaginal level is not known. This study compares the biological performance of PP mesh and a newly developed hADM. 20 rabbits were randomized to receive the hADM graft or the PP mesh. Grafts were surgically implanted in the abdominal wall and vagina. After 180 days, grafts were explanted and evaluated. The vaginal mesh extrusion rate was higher in the PP group (33% vs. 0%, p = 0.015). Full integration of the vaginal grafts was more frequent in the hADM group, where 35% of the grafts were difficult to recognize. In the PP group, the vaginal mesh was identified in 100% of the animals (p = 0.014). In PP group, the infiltrates had a focal distribution and were mostly located in the internal part of the epithelium, while in the hADM group, the infiltrates had a diffuse distribution. Additionally, the hADM group also presented more B-lymphocytes and less T-lymphocytes. Biomechanical analysis showed that hADM had lower resistance to stress. Moreover, PP mesh stiffness and elasticity were higher. Then, hADM is associated with fewer clinical complications, as well as better tissue integration. However, it shows greater incorporation into the surrounding native tissue, especially in the vaginal location, undergoing a reduction in its biomechanical properties 6 months after implantation.

What do female university students know about pelvic floor disorders? A cross-sectional survey.

INTRODUCTION AND HYPOTHESIS: Pelvic floor dysfunction (PFD) is common in women but few seek medical attention. Poor recognition of the condition as pathological and unawareness of treatments may account for low consultation rates. METHODS: This cross-sectional study was based on an online survey that was responded to in February and March 2020 by 768 female university students. Knowledge of PFD was assessed using the Prolapse and Incontinence Knowledge Questionnaire (PIKQ). Descriptive and inferential analyses were performed using IBM-SPSS (V26.0). RESULTS: Respondents had poor knowledge of PFD and especially of pelvic organ prolapse. Health science students (n = 531; 69.1%) obtained significantly higher scores (p < 0.001) than other students (n = 237; 30.9%). Those who had received information on how to perform pelvic floor muscle training were more likely to score higher than those who had not received previous information. CONCLUSIONS: While health science students have better knowledge of PFD than other students, university students in general are little aware of PFD. Most students considered the issue of PFD to be important and wanted more information. Our findings may be useful in planning strategies to raise women's awareness of PFD and its prevention and treatment.

Rabbit as an animal model for the study of biological grafts in pelvic floor dysfunctions.

The aims of this study were to evaluate the feasibility of the New Zealand White (NZW) rabbit for studying implanted biomaterials in pelvic reconstructive surgery; and to compare the occurrence of graft-related complications of a commercial polypropylene (PP) mesh and new developed human dermal matrix implanted at vaginal and abdominal level. 20 white female NZW rabbits were randomized into two groups, experimental group (human acellular dermal matrices-hADM-graft) and control group (commercial PP graft). In each animal, grafts were surgically implanted subcutaneously in the abdominal wall and in the vaginal submucosa layer for 180 days. The graft segments were then removed and the surgical and clinical results were analyzed. The main surgical challenges during graft implantation were: (a) an adequate vaginal exposure while maintaining the integrity of the vaginal mucosa layer; (b) to keep aseptic conditions; (c) to locate and dissect the breast vein abdominal surgery; and (d) to withdraw blood samples from the ear artery. The most abnormal findings during the explant surgery were found in the PP group (33% of vaginal mesh extrusion) in comparison with the hADM group (0% of vaginal graft extrusion), p = 0.015. Interestingly, macroscopic observation showed that the integration of the vaginal grafts was more common in the hADM group (40%) than in the PP group, in which the vaginal mesh was identified in 100% of the animals (p = 0.014). The NZW rabbit is a good model for assessing materials to be used as grafts for pelvic reconstructive surgery and vaginal surgery. Animals are easily managed during the procedures, including surgical intervention and vaginal mucosa approach. Additionally, hADM is associated with fewer clinical complications, as well as better macroscopic tissue integration, compared to PP mesh.

Use of an Intrauterine Foley Probe for Ultrasound-Assisted Hysteroscopic Resection of Complete Uterine Septum.

STUDY OBJECTIVE: To demonstrate our technique for hysteroscopic resection of the complete uterine septum. DESIGN: Step-by-step description and demonstration of the procedure using pictures and video (educational video). The video was approved by our hospital's Ethical Committee. SETTING: Uterine malformations represent a rare, yet usually asymptomatic condition that can be associated with poor obstetric outcomes. The European Society for Gynaecological Endoscopy(ESGE)/European Society of Human Reproduction and Embryology (ESHRE)classification is widely accepted for the description of female genital tract anomalies. Treatment of the uterine septum should be considered if fertility is desired, with hysteroscopic resection the gold standard procedure. INTERVENTION: A patient with a U2bC2V1 malformation according to the ESGE/ESHRE classification was treated with hysteroscopy. The procedure was performed in the operating room under general anesthesia using a 9-mm hysteroscope with a bipolar cutting loop. Surgery began with resection of the vaginal septum with monopolar electrosurgery until the cervix was visualized. A Foley probe was placed in 1 uterine hemicavity, and then hysteroscopy on the other hemicavity was performed. Transrectal ultrasound guidance was used to identify the limits of the septum and thereby enhance the safety of the procedure. Resection of the septum started in the upper part until the Foley probe was seen, then continued downward until internal cervical orifice was reached. In the hysteroscopic follow-up after 3 months, we visualized a small residual septum that was resected to fully restore the uterine cavity and improve the patient's obstetric outcomes. The procedure was completed without complications, and a second-look hysteroscopy showed a normal uterine cavity. CONCLUSION: The combination of real-time ultrasound guidance and placement of an intrauterine balloon through the cervix may increase safety during the procedure by providing clear visualization of the uterine cavity and septum border during resection.

Adherence to pelvic floor muscle training with or without vaginal spheres in women with urinary incontinence: a secondary analysis from a randomized trial.

INTRODUCTION AND HYPOTHESIS: Pelvic floor muscle training (PFMT) is widely recommended as first-line therapy for women with urinary incontinence. However, adherence to PFMT decreases over time, and information regarding barriers to PFMT is scarce. The primary aim of our study was to investigate whether a vaginal spheres device helped improve adherence to PFMT. The secondary aim was to assess determinants of adherence and the association with treatment outcome. METHODS: This was a secondary analysis of a randomized trial with a 6-month follow-up in women with urinary incontinence (UI) in whom we evaluated adherence to PFMT, performed either with (spheres group) or without (control group) vaginal spheres. The Morisky-Green Questionnaire (MGQ) was used to assess adherence, defined as the extent to which participants corresponded to the agreed recommendations; participants were classified as adherent or nonadherent according to their responses. Efficacy of PFMT was assessed using the International Consultation on Incontinence Questionnaire Short Form scale (ICIQ-SF). RESULTS: Seventy women were enrolled and data from 65 (35 treated and 30 controls) were suitable for analysis. There were no significant differences in adherence to treatment between groups at the end of follow-up (33.3 % in controls and 42.9 % in spheres). The largest group of nonadherent women in both arms were those who mainly forgot to do the exercises. ICIQ-SF results between adherent and nonadherent women did not differ significantly [mean 0.55, 95 % confidence interval (CI) 1.13-2.25]. No significant difference was observed between women who attained greater and lesser improvement in UI after treatment (4.5 %; 95 % CI -11.7 to 20.6). CONCLUSIONS: In patients with UI, vaginal spheres as an adjunct to PFMT did not increase adherence to pelvic muscle exercises. Lack of persistence appeared to be due to forgetfulness and did not seem to be influenced by the efficacy of PFMT.

Mode of vaginal delivery: a modifiable intrapartum risk factor for obstetric anal sphincter injury.

The aim of this study was to analyze the comparative risks of this anal sphincter injury in relation to the type of intervention in vaginal delivery. We performed an observational, retrospective study of all vaginal deliveries attended at a tertiary university hospital between January 2006 and December 2009. We analyzed the incidence of obstetric anal sphincter injury for each mode of vaginal delivery: spontaneous delivery, vacuum, Thierry spatulas, and forceps. We determined the proportional incidence between methods taking spontaneous delivery as the reference. Ninety-seven of 4526 (2.14%) women included in the study presented obstetric anal sphincter injury. Instrumental deliveries showed a significantly higher risk of anal sphincter injury (2.7 to 4.9%) than spontaneous deliveries (1.1%). The highest incidence was for Thierry spatulas (OR 4.804), followed by forceps (OR 4.089) and vacuum extraction (OR 2.509). The type of intervention in a vaginal delivery is a modifiable intrapartum risk factor for obstetric anal sphincter injury. Tearing can occur in any type of delivery but proportions vary significantly. All healthcare professionals attending childbirth should be aware of the risk for each type of intervention and consider these together with the obstetric factors in each case.

Effect of vaginal spheres and pelvic floor muscle training in women with urinary incontinence: a randomized, controlled trial.

AIMS: To compare the efficacy and safety of Kegel exercises performed with or without, vaginal spheres as treatment for women with urinary incontinence. METHODS: Multicentre parallel-group, open, randomized controlled trial. Women were allocated to either a pelvic floor muscle-training program consisting of Kegel exercises performed twice daily, 5 days/week at home, over 6 months with vaginal spheres, or to the same program without spheres. The primary endpoint was women's report of urinary incontinence at 6 months using the International Consultation on Incontinence Questionnaire-Short Form (ICIQ-UI-SF). Secondary outcome measures were the 1 hr pad-test, King's Health Questionnaire (KHQ) and a five-point Likert scale for subjective evaluation. Adherence was measured with the Morisky-Green test. RESULTS: Thirty-seven women were randomized to the spheres group and 33 to the control group. The primary endpoint was evaluated in 65 women (35 in the spheres group vs. 30 controls). ICIQ-UI-SF results improved significantly at 1-month follow-up in the spheres group (P < 0.01) and at 6 months in the controls. The 1 hr pad-test improved in the spheres group but not in the control group. No significant differences were found in the KHQ results or in the subjective evaluation of efficacy and safety. Adherence was higher in the spheres group but differences were not significant. Mild transient side effects were reported in four patients in the spheres group and one in the control group. CONCLUSIONS: Both treatments improved urinary incontinence but women who performed the exercises with vaginal spheres showed an earlier improvement. Vaginal spheres were well tolerated and safe.

A regression model approach to enable cell morphology correction in high-throughput flow cytometry.

Cells exposed to stimuli exhibit a wide range of responses ensuring phenotypic variability across the population. Such single cell behavior is often examined by flow cytometry; however, gating procedures typically employed to select a small subpopulation of cells with similar morphological characteristics make it difficult, even impossible, to quantitatively compare cells across a large variety of experimental conditions because these conditions can lead to profound morphological variations. To overcome these limitations, we developed a regression approach to correct for variability in fluorescence intensity due to differences in cell size and granularity without discarding any of the cells, which gating ipso facto does. This approach enables quantitative studies of cellular heterogeneity and transcriptional noise in high-throughput experiments involving thousands of samples. We used this approach to analyze a library of yeast knockout strains and reveal genes required for the population to establish a bimodal response to oleic acid induction. We identify a group of epigenetic regulators and nucleoporins that, by maintaining an 'unresponsive population,' may provide the population with the advantage of diversified bet hedging.

Role of the histone variant H2A.Z/Htz1p in TBP recruitment, chromatin dynamics, and regulated expression of oleate-responsive genes.

The histone variant H2A.Z (Htz1p) has been implicated in transcriptional regulation in numerous organisms, including Saccharomyces cerevisiae. Genome-wide transcriptome profiling and chromatin immunoprecipitation studies identified a role for Htz1p in the rapid and robust activation of many oleate-responsive genes encoding peroxisomal proteins, in particular POT1, POX1, FOX2, and CTA1. The Swr1p-, Gcn5p-, and Chz1p-dependent association of Htz1p with these promoters in their repressed states appears to establish an epigenetic marker for the rapid and strong expression of these highly inducible promoters. Isw2p also plays a role in establishing the nucleosome state of these promoters and associates stably in the absence of Htz1p. An analysis of the nucleosome dynamics and Htz1p association with these promoters suggests a complex mechanism in which Htz1p-containing nucleosomes at fatty acid-responsive promoters are disassembled upon initial exposure to oleic acid leading to the loss of Htz1p from the promoter. These nucleosomes reassemble at later stages of gene expression. While these new nucleosomes do not incorporate Htz1p, the initial presence of Htz1p appears to mark the promoter for sustained gene expression and the recruitment of TATA-binding protein.

Galectin-1 is a novel functional receptor for tissue plasminogen activator in pancreatic cancer.

BACKGROUND & AIMS: Tissue plasminogen activator (tPA) exerts many different functions in addition to its role in fibrinolysis. In pancreatic ductal adenocarcinoma (PDA), tPA is overexpressed and plays an important role in proliferation, invasion, and angiogenesis. tPA interaction with cell membrane receptors has been related to increased proteolytic activity and to signal transduction through nonenzymatic mechanisms. The aim was to analyze the role of galectin-1 (Gal-1), an endogenous lectin that also is overexpressed in PDA, as a new functional receptor for tPA. METHODS: Gal-1/tPA interaction was analyzed using surface plasmon resonance and pull-down assays. Pancreatic cells and tumors were used to study Gal-1 expression and localization by Western blot and immunostaining. Down-regulation of Gal-1 by small interference RNA was used to analyze the involvement of Gal-1/tPA interaction in extracellular signal-regulated kinase 1/2 activation, cell proliferation, and invasion in pancreatic and fibroblastic cells. RESULTS: Gal-1/tPA interaction is direct, specific, and of high affinity. Gal-1 moderately increases the catalytic activity of tPA. High Gal-1 levels were detected in PDA cells in culture, where it concentrates at the migration front, and in tissues, where it is expressed in epithelial cells and in the stroma. Down-regulation of Gal-1 abolished the effects of tPA on extracellular signal-regulated kinase 1/2 activation, cell proliferation, and invasion, both in pancreatic and in tumor-derived fibroblasts. CONCLUSIONS: These findings support a new molecular mechanism by which Gal-1 interaction with tPA contributes to PDA progression involving both transformed epithelial cells and tumor fibroblasts.

Control of transcriptional variability by overlapping feed-forward regulatory motifs.

In yeast, beta-oxidation of fatty acids (FAs) takes place in the peroxisome, an organelle whose size and number are controlled in response to environmental cues. The expression of genes required for peroxisome assembly and function is controlled by a transcriptional regulatory network that is induced by FAs such as oleate. The core FA-responsive transcriptional network consists of carbon source-sensing transcription factors that regulate key target genes through an overlapping feed-forward network motif (OFFNM). However, a systems-level understanding of the function of this network architecture in regulating dynamic FA-induced gene expression is lacking. The specific role of the OFFNM in regulating the dynamic and cell-population transcriptional response to oleate was investigated using a kinetic model comprised of four core transcription factor genes (ADR1, OAF1, PIP2, and OAF3) and two reporter genes (CTA1 and POT1) that are indicative of peroxisome induction. Simulations of the model suggest that 1), the intrinsic Adr1p-driven feed-forward loop reduces the steady-state expression variability of target genes; 2), the parallel Oaf3p-driven inhibitory feed-forward loop modulates the dynamic response of target genes to a transiently varying oleate concentration; and 3), heterodimerization of Oaf1p and Pip2p does not appear to have a noise-reducing function in the context of oleate-dependent expression of target genes. The OFFNM is highly overrepresented in the yeast regulome, suggesting that the specific functions described for the OFFNM, or other properties of this motif, provide a selective advantage.

Distancias anatómicas de la pelvis en relación con las técnicas quirúrgicas a través del foramen obturador / Anatomical distances among pelvic structures related to surgical techniques through the obturator foramen

Objetivo: Describir las distancias entre las principales estructuras óseas, vasculares, neurológicas y viscerales que son relevantes para guiar el paso de las agujas insertoras en las técnicas quirúrgicas a través del foramen obturador. Material y métodos: Se diseccionaron 6 hemipelvis femeninas de cadáver embalsamado, procedentes de donantes de cuerpo voluntarias del Departament de Ciències Morfològiques de la Universitat Autònoma de Barcelona (UAB). En la disección se hizo especial hincapié en la delimitación del agujero obturador y la localización de estructuras osteomusculoaponeuróticas y neurovasculares adyacentes. Resultados: Se midieron distintas distancias. Son especialmente relevantes las distancias en relación con la rama isquiopubiana, la espina ciática y el arco tendinoso del músculo elevador del ano, ya que constituyen las principales referencias para la cirugía. Conclusiones: Un buen conocimiento de la anatomía trae luz al paso a ciegas de los tunelizadores que utilizan el foramen obturador para acceder a la pelvis. Ello debe permitir una cirugía más segura y una mejor comprensión de los riesgos potenciales, cómo evitarlos y cómo tratar las complicaciones perioperatorias

Objective: To describe distances between the major bony, vascular, neurologic and visceral structures of importance when guiding trocar needles through the obturator foramen. Material and methods: Six embalmed female hemipelvises from voluntary donors were dissected at the Department of Anatomy of the Universitat Autònoma de Barcelona (UAB) School of Medicine. Special attention was paid to the obturator foramen and its neighboring bony, aponeurotic and muscular structures, and neurovascular bundles. Results: Several distances were collected. Distances in relation to the ischiopubic ramus, the ischial spine and the arcus tendineus of levator ani seemed to be particularly important, as they are the main landmarks for surgery. Conclusion: A good knowledge of anatomy illuminates the passage of trocar needles inserted through the obturator foramen as a route to enter the pelvic space. This knowledge improves safety, understanding of potential risks and how to avoid them, as well as the management of perioperative complications

Tissue plasminogen activator induces pancreatic cancer cell proliferation by a non-catalytic mechanism that requires extracellular signal-regulated kinase 1/2 activation through epidermal growth factor receptor and annexin A2.

Tissue plasminogen activator (tPA) is overexpressed in pancreatic ductal carcinoma and is involved in tumor progression. This effect is probably mediated through the activation of angiogenesis, cell invasion, and cell proliferation. Previous studies support the notion that the effects of tPA on cell invasion require its proteolytic activity. Here, we report the molecular mechanism responsible for the proliferative effects of tPA on pancreatic tumor cells. tPA activates the extracellular signal-regulated kinase 1/2 signaling pathway in a manner that is independent of its catalytic activity. We also show that at least two membrane receptors, epidermal growth factor receptor and annexin A2, which are overexpressed in pancreatic cancer, are involved in the transduction of tPA signaling in pancreatic tumors. This observation suggests the establishment of an amplification loop in tumor cell proliferation. Double immunofluorescence experiments showed co-localization of tPA/epidermal growth factor receptor and tPA/annexin A2 in pancreas cancer cells. These results add novel insights into the non-catalytic functions of tPA in cancer and the molecular mechanisms behind the effects of this protease on cell proliferation, including a role for epidermal growth factor receptor.

A proteomic approach to the identification of new tPA receptors in pancreatic cancer cells.

We have developed a strategy to identify putative tissue-type plasminogen activator (tPA)receptors present in pancreatic cancer cells by affinity capture with tPA-Sepharose followed by 2-DE and MALDI-MS PMF. Proteins pulled down from either total lysates or raft membrane fractions were characterized and compared with those from a total lysate of an endothelial cell line (HUVEC) to identify pancreas-restricted tPA receptors. A total of 31 proteins were found by this approach, including annexin A2, already described as a tPA receptor in pancreas and endothelial cells, other proteins acting as tPA receptors (i.e., enolase, cytokeratins 8 and 18) in other tissues, and additional proteins not previously identified as candidate tPA receptors. Confirmation of the results was performed for some of these proteins using immunoblotting. These studies are the basis for further functional analyses on the role of these proteins in the biological effects of tPA.

New insights into the tPA-annexin A2 interaction. Is annexin A2 CYS8 the sole requirement for this association?

Annexin A2 has been described as an important receptor for tissue-type plasminogen activator in endothelium and other cell types. Interaction between tissue-type plasminogen activator and its cellular receptor is critical for many of the functions of this protease. The annexin A2 motif that mediates tissue plasminogen activator interaction has been assigned to the hexapeptide LCKLSL in the amino-terminal domain of the protein, and it has been proposed that Cys(8) of this sequence is essential for tPA binding. In an attempt to identify other amino acids critical for tPA-annexin A2 interaction, we have analyzed a set of peptides containing several modifications of the original hexapeptide, including glycine scans, alanine scans, d-amino acid scans, conservative mutations, cysteine blocking, and enantiomer and retroenantiomer sequences. Using a non-radioactive competitive binding assay, we have found that all cysteine-containing peptides, independently of their sequence, compete the interaction between tPA and annexin A2. Cysteine-containing peptides also inhibit tPA binding to the surface of cultured human umbilical vein endothelial cells (HUVEC). Mass spectrometry demonstrates that the peptides bind through a disulfide bond to a cysteine residue of annexin A2, the same mechanism that has been suggested for the inhibition mediated by homocysteine. These data call for a revision of the role of the LCKLSL sequence as the sole annexin A2 structural region required to bind tPA and indicate that further studies are necessary to better define the annexin A2-tPA interaction.