Impact of different mating and surgical protocols on the establishment of a mouse model for fetal scarless skin healing.
The mouse fetal intrauterine wound healing model is crucial and commonly used for investigating mechanisms and evaluating potential therapies for scarless skin regeneration compared to fibrotic healing. However, traditional intrauterine surgery remains technically challenging and understudied, which is associated with high maternal mortality and pregnancy loss, prompting us to refine the surgical protocol. Here, we report how the choice of surgical and mating procedure impact outcomes obtained. Pregnant mice underwent fetal surgery at embryonic days 15.5, 16.5 (E15.5, E16.5, scarless) and 18.5 (e18.5, fibrotic). Two surgical protocols were used: traditional method involved purse-string sutures, microsurgical scissors, amniotic fluid supplementation, and suture closure (Traditional); and our modified method omitting purse-string sutures, replacing scissors with needle puncture for uterine and fetal incisions, eliminating amniotic fluid supplementation, and employing skin staples for abdominal closure (Modified). The modified protocol significantly increased the likelihood of successful pregnancy, reduced operative time, decreased abortion rates, and enabled earlier modeling compared to the traditional method. At 48h, 7days, and 9days post-surgery, E15.5 wounds healed scarlessly, displaying regenerated hair follicles and organized collagen. Conversely, E18.5 wounds formed typical fibrotic scars, characterized by dense, disorganized collagen without hair follicles. The optimized surgical protocol presented here provides a simplified, reliable fetal mouse model with improved pregnancy success, reduced fetal loss, earlier implementation, and consistent phenotypic outcomes. This refined model enhances experimental efficiency, reproducibility, and animal welfare, having a major impact on mechanistic studies and therapeutic exploration for scarless skin regeneration.
174
- 10.1016/0022-3468(71)90373-3
- Oct 1, 1971
- Journal of Pediatric Surgery
63
- 10.1097/01.prs.0000219340.47232.eb
- Jun 1, 2006
- Plastic and Reconstructive Surgery
185
- 10.1016/s0002-9440(10)64555-5
- Aug 1, 2000
- The American Journal of Pathology
97
- 10.1097/00006534-200201000-00026
- Jan 1, 2002
- Plastic and Reconstructive Surgery
12
- 10.1111/j.1469-7580.2011.01366.x
- Mar 24, 2011
- Journal of Anatomy
3
- 10.1007/978-1-0716-0845-6_2
- Aug 18, 2020
450
- 10.1016/j.bjps.2008.03.020
- Jul 9, 2008
- Journal of Plastic, Reconstructive & Aesthetic Surgery
70
- 10.1097/00006534-199211000-00003
- Nov 1, 1992
- Plastic and Reconstructive Surgery
24
- 10.3791/52297
- Jan 16, 2015
- Journal of Visualized Experiments
367
- 10.1016/s0022-3468(05)80165-4
- Jan 1, 1990
- Journal of Pediatric Surgery
- Research Article
4
- 10.1007/s11250-018-1749-6
- Nov 10, 2018
- Tropical Animal Health and Production
High reproductive performance is an element factor for profitability in dairy herds; although, pregnancy loss of non-infectious nature during early and mid-to-late embryonic period is increasing in dairy cattle. Based on that, the present study aimed to determine the incidence of pregnancy loss before and after 60days of insemination, and to identify some non-infectious causes that could enhance it. The herd was composed by 600 crossbred dairy cows and those with a corpus luteum (CL) were treated with prostaglandinF2α, then inseminated, on the other hand, those without a CL were submitted to a timed artificial insemination protocol (TAI). Pregnancy losses rates were analyzed by logistic regression by SAS, and differences were considered significant when P < 0.05. The overall pregnancy loss and mid-to-late pregnancy loss were not affected by animal category (P > 0.05); although, early pregnancy loss was higher in cows than in heifers (11.90 vs. 3.39%). The early pregnancy loss was higher in those cows that calved on spring/summer when compared to those calved on fall/winter (9.22% vs. 16.11%), moreover, those inseminated during spring/summer tended to have higher early pregnancy loss when compared to those inseminated on fall/winter (13.35% vs. 8.57%). In conclusion, when some of non-infectious causes were evaluated, it was observed that cows that calved on spring/summer had higher pregnancy loss. At this point, strategies should be developing to minimize pregnancy loss in dairy herds, as it could be considered an important reproductive problem.
- Research Article
37
- 10.1111/j.1365-4632.2007.03253.x
- Jul 1, 2007
- International Journal of Dermatology
The purse string suture can be used to provide primary closure for small skin defects or as a partial closure for larger round wounds. The size of the defect is reduced secondary to the tension placed on the suture, which uniformly advances the skin from the entire periphery of the wound. We reviewed retrospectively the features of 98 consecutive patients for whom a total of 100 cuticular purse string sutures were used to partially close their postoperative surgical defects. The location and types of the tumors removed were also summarized. Postoperative wounds were created following Mohs' micrographic excision of nonmelanoma skin cancer (basal cell carcinoma, 44; squamous cell carcinoma, 25), wide local excision of melanoma (29), or conservative excision of benign cutaneous neoplasms (two). The incidence of purse string suture for partial closure of each tumor was 4.1% for basal cell carcinoma, 7.3% for squamous cell carcinoma, and 46.3% for melanoma. The tumors were equally distributed on the trunk, head and neck, and extremities; however, purse string closures for basal cell carcinomas were more frequent on the trunk, head, and neck, relative to squamous cell carcinomas and melanomas, which were more common on the extremities. Concurrent medical problems and/or the use of an agent with anticoagulant or antiplatelet effects were noted in more than 50% of patients. Absorbable material of thicker diameter was most frequently used for the suture, and the postoperative wound area decreased by 6-90% (mean, 60%) following purse string partial closure. The suture was usually removed after 3-4 weeks. Postoperative complications occurred in six patients: allergic contact dermatitis in two, wound infection in two, exuberant granulation tissue in one, and hypertrophic scar in one. All of the wounds healed completely with either a round or linear scar. The cuticular purse string suture is a rapid and simple procedure that provides complete or partial closure of round skin defects and excellent long-term cosmetic and functional results. This closure provides uniform tension to the wound, enhances hemostasis at the tissue edge, and significantly decreases the size of the defect. Partial wound closure with the purse string suture may be advantageous following the local excision of melanoma, either as definitive surgical wound management or as a temporary partial wound closure prior to subsequent complete repair of the surgical defect. The purse string suture is also useful following nonmelanoma skin cancer removal in patients who insist on maintaining an active lifestyle in the immediate postoperative period, who are receiving one or more systemic anticoagulant and/or antiplatelet agents, and who have large surgical wounds that would require either a skin graft or a local cutaneous flap in order to close the postoperative defect.
- Abstract
1
- 10.1016/j.fertnstert.2004.07.523
- Sep 1, 2004
- Fertility and Sterility
Estradiol production during controlled ovarian hyperstimulation correlates with the risk of pregnancy loss in pregnancies achieved after IVF-ET
- Research Article
46
- 10.1097/00006534-199801000-00003
- Jan 1, 1998
- Plastic and Reconstructive Surgery
Fetal mammals heal skin wounds through the second trimester of development without evidence of scar. We have investigated the role of bone morphogenetic protein 2 (BMP-2), which is a member of the TGF-beta superfamily, in normal skin development and fetal wound healing. We first used RNA in situ hybridization to demonstrate that BMP-2 was expressed at low levels in the developing hair follicles and in the epidermis of normal human fetal skin. We then created an in vivo model to test how exogenous BMP-2 would affect fetal skin development and wound healing. Fifty micrograms of BMP-2 was implanted into the subcutis of five 70-day-old fetal lambs through a full-thickness linear incision. The BMP-2 was placed beneath the right half of the wound, whereas the left half served as an untreated control. In two of the five animals 1 microgram of TGF-beta was placed into the same position in addition to the 50 micrograms of BMP-2. Twenty days later (90 days gestation, term = 140 days) all the fetal wounds were examined for evidence of cellular hyperproliferation and scar formation. BMP-2 induced massive dermal and epidermal growth when compared with controls. This finding was characterized by marked epidermal thickening and keratinization, a dramatic increase in the number of hair follicles, and more than 50 percent thickening of the dermis. The dermal thickening was the result of both increased cellularity and deposition of large irregular collagen bundles. Wounds treated with both BMP-2 and TGF-beta healed also with an adult-like pattern of scar formation. Surprisingly, the wounds with BMP-2 alone healed with an equal pattern of scar, indicating that there was not an additive effect of combining BMP-2 and TGF-beta. We conclude that BMP-2 is a pleomorphic growth factor that induces cellular growth, maturation, and fibroplasia in both the dermis and epidermis. Further analysis of this growth factor in both fetal and adult wound healing may lead to important discoveries regarding the control of scar formation and fibrosis in many adult tissues.
- Research Article
48
- 10.1093/jas/sky015
- Jan 30, 2018
- Journal of Animal Science
Pregnancy loss is a major contributing factor to reproductive inefficiency in both the beef and dairy industries. Sires can have a significant influence on the amount of pregnancy loss; however, this relationship is still poorly investigated. The primary objective of this study was to identify sires associated with high or low incidence of pregnancy loss (between d 30 and 100 of gestation) and investigate their effect on concentration of circulating pregnancy-associated glycoproteins (PAGs). Postpartum multiparous Nelore cows were inseminated artificially at a fixed time (FTAI, d 0) after synchronization of ovulation. A total of 736 cows were assigned randomly to be inseminated with semen from either of 6 Angus sires, whereas a separate subset of 492 cows were inseminated randomly with semen from either of 3 Nelore (n = 235) or either of 2 Angus sires (n = 257). Estrus expression was evaluated on d 0 using Estrotect Heat Detector patches. Blood samples were collected on d 30 of gestation for quantification of PAGs and pregnancy diagnosis was performed by ultrasound on d 30 and 100 after FTAI. Cows diagnosed pregnant at the first examination but not pregnant at the second were defined to have pregnancy loss. Overall pregnancy rate at d 30 was 54% (660/1,228) and pregnancy loss was 6.21% (41/660). Cows receiving semen from Nelore sires had greater (P < 0.001) pregnancy rate, greater (P = 0.014) pregnancy loss, and lesser (P = 0.002) PAG concentrations at d 30 of gestation compared with cows receiving Angus semen. Circulating PAG concentrations were lower (P = 0.008) in cows that had pregnancy loss (9.76 ± 0.25 vs. 7.41 ± 1.02 ng/mL). Angus sires were retrospectively classified according to percentage of pregnancy loss as either high pregnancy loss (mean of 7.25% or 67% of total) or low pregnancy loss (mean of 3.93% or 33% of total). Cows receiving semen from high pregnancy loss sires had 1.9 times greater (P = 0.123) rate of pregnancy loss and had lower (P = 0.059) PAG concentrations at d 30 of gestation compared with cows mated to low pregnancy loss sires. In summary, PAG concentrations reflected probability of pregnancy maintenance and were influenced by both sire and sire breed used at FTAI. Variation in the incidence of pregnancy loss was detected among sires that could not be predicted with standard semen fertility evaluations. Exploring the relationship of sire and PAG production might be promising to improve sire selection with regard to pregnancy loss.
- Research Article
54
- 10.3168/jds.2012-6260
- Sep 18, 2013
- Journal of Dairy Science
Timed artificial insemination programs during the summer in lactating dairy cows: Comparison of the 5-d Cosynch protocol with an estrogen/progesterone-based protocol
- Research Article
- 10.1071/rdv32n2ab9
- Dec 2, 2019
- Reproduction, Fertility and Development
The objective of this study was to evaluate the pregnancy loss (PL) between Day 30 (P30) and Day 80 (P80) of pregnancy in lactating Holstein recipients that received an invivo- (flush) or invitro-produced (IVF) embryo. The recipient cows were located at Maddox Dairy in Riverdale, CA, USA, a Holstein herd that milks 3500 cows with a 305-day mature-equivalent milk production of 12 800 kg. First-lactation cows were enrolled in a Presynch-Ovsynch oestrus-synchronization program and scheduled to be artificially bred for the first time at 80 days after calving or to receive an embryo 7 or 8 days after the expected heat (recipients). The data from 590 pregnancies (1045 embryo transfers) from embryos transferred between January 2018 and March 2019 was analysed. Only grade 1 embryos (from morula to hatched blastocyst stage) produced invivo or invitro from Holstein donor heifers, lactating or dry cows, were transferred fresh (invivo or invitro) or frozen-thawed (invivo), and pregnancy rates are shown in Table 1. The ruminant trophoblast produces pregnancy-associated glycoproteins (PAG) that can be detected by enzyme-linked immunoassay (ELISA) in the blood of pregnant cattle as early as 28 days after insemination. Various dairy herds in the USA have been using this test to supplement or replace the use of transrectal ultrasonography for early pregnancy diagnosis. Blood was sampled on P30 after expected heat day (23 days after embryo transfer) from the recipient cows and sent to IDEXX for the PAG Bovine Pregnancy Test, which was reconfirmed on P80 of pregnancy by transrectal ultrasonography. Pregnancy loss was considered to have occurred when a cow was pregnant on P30 but not pregnant on P80. The variable PL was analysed by binary logistic regression in the MINITAB program, and the model included effects of donor status (heifer vs. milk vs. dry) and embryo type. The total PL was 12.2% (72/590) and the details are shown in Table 1. No effect of donor status (P=0.80) was detected. However, there was effect of embryo type (P=0.004). The IVF embryos had a PL of 18.0% compared with 9.5% for the invivo-produced embryos. Further research should be performed to study heifer embryos PL, because currently more embryos are being produced from very young donor cows and sires due to intensive use of genomic testing. In conclusion, there is a higher PL in lactating dairy recipients receiving IVF fresh embryos compared with fresh or frozen invivo-produced embryos. Table 1.Embryo transfer (ET) pregnancy rates (PR, P30) in first-lactation Holstein cows (top) and pregnancy loss (PL) from Day 30 (P30) to 80 (P80) in first-lactation recipient Holstein cows (bottom) Item Heifer donor Lactating donor Dry donor Total ET P30 PR% ET P30 PR% ET P30 PR% ET P30 PR% Invivo - fresh 6 3 50.0 43 25 58.1 329 206 62.6 378 234 61.9 Invivo - frozen 75 38 50.7 221 129 58.4 296 167 56.4 IVF - fresh 123 61 49.6 91 42 46.2 157 86 54.8 371 189 50.9 Total 129 64 49.6 209 105 50.2 707 421 59.5 1045 590 56.5 P30 P80 PL% P30 P80 PL% P30 P80 PL% P30 P80 PL% Invivo - fresh 3 3 0.0 25 24 4.0 206 186 9.7 234 213 9.0 Invivo - frozen 38 35 7.9 129 115 10.9 167 150 10.2 IVF - fresh 61 48 21.3 42 35 16.7 86 72 16.3 189 155 18.0 Total 64 51 20.3 105 94 10.5 421 373 11.4 590 518 12.2
- Research Article
7
- 10.1097/qad.0000000000002799
- Dec 17, 2020
- AIDS
With ever-expanding antiretroviral therapy (ART) access among pregnant women in sub-Saharan Africa, it is more than ever important to address the gap in knowledge around ART effectiveness, as measured by HIV viral load, and pregnancy loss. A population-based cohort study. The study sample consisted of 3431 pregnancies from 2835 women living with HIV aged 16-35 years old. All women participated in a population-based cohort conducted between 2004 and 2018 in rural KwaZulu-Natal, South Africa. Viral load data were collected at prior surveys and an HIV care registry. The closest available viral load to the date that each pregnancy ended was used and classified as either a pre- or postconception viral load. Logistic regression was used to investigate the association between high viral load (log10 viral load >4.0 copies/ml) and pregnancy loss, defined as either a miscarriage or stillbirth. Pregnancy loss occurred at a rate of 1.3 (95% confidence interval: 1.0-1.8) per 100 pregnancies. There were 1451 pregnancies (42.3%) with postconception viral load measurements. The median time between the viral load measurement and the pregnancy end date was 11.7 (interquartile range: 5.0-25.4) months. We found a higher likelihood of pregnancy loss in women who had high viral loads prior to the outcome of their pregnancy (adjusted odds ratio: 2.38, 95% confidence interval: 1.10-5.18). Given the significant relationship between high viral load and pregnancy loss, our study lends further credence to ensuring effective ART through enrolment and retention of pregnant women living with HIV in ART programs, treatment adherence interventions, and viral load monitoring during pregnancy.
- Research Article
4
- 10.1016/j.ijcard.2017.06.077
- Jun 23, 2017
- International Journal of Cardiology
How safe are NOACs compared with phenprocoumon after pulmonary vein isolation with the cryoballoon technique using purse-string suture closure?
- Research Article
10
- 10.1186/s12893-021-01446-2
- Dec 1, 2021
- BMC Surgery
BackgroundThe American Society of Surgery and American Society for Surgical Infections issued guidelines for surgical site infections (SSIs) in December 2016. These guidelines recommend a purse-string suture (PSS) for stoma closure as it facilitates granulation and enables open wound drainage. This study investigated the effect of using negative pressure wound therapy (NPWT) along with standard PSS and aimed to determine the optimal period of NPWT use.MethodsThe patients were divided into three groups as follows: Group A, postoperative wound management alone with gauze exchange as the representative of conventional PSS; Group B, the performed management was similar to that of Group A plus NPWT for 1 week; and Group C, the performed management was similar to that of Group A plus NPWT for 2 weeks. Regarding objective measures, the wound reduction rate was the primary outcome, and the incidence of SSIs, length of hospital stay, and wound healing duration were the secondary outcomes.ResultsIn total, 30 patients (male: 18, female: 12) were enrolled. The average age was 63 (range: 43–84) years. The wound reduction rate was significantly higher in Group B than in Group A on postoperative days (PODs) 7 (66.1 vs. 48.4%, p = 0.049) and 10 (78.6 vs. 58.2%, p = 0.011), whereas no significant difference was observed on POD 14. Compared with Group A, Group C (POD 7: 65.9%, POD 10: 69.2%) showed an increase in the wound reduction rate on POD 7, although the difference was not significant (p = 0.075). SSIs were observed in Groups B (n = 2) and C (n = 2) (20%) but not in Group A (0%).ConclusionsThe most effective duration of NPWT use for ileostomy closure with PSS in terms of the maximum wound reduction rate was from PODs 3 to 10. However, NPWT did not shorten the wound healing duration. NPWT may reduce the wound size but should be used with precautions for SSIs. The small sample size (30 cases), the use of only one type of NPWT system, and the fact that wound assessment was subjective and not blinded were the limitations of this study. Further studies are needed to confirm our findings.Trial registration: UMIN Clinical Trials Registry; UMIN000032174 (10/04/2018).
- Research Article
20
- 10.1016/j.ygyno.2014.06.012
- Jun 18, 2014
- Gynecologic Oncology
A phase II trial of a surgical protocol to decrease the incidence of wound complications in obese gynecologic oncology patients
- Research Article
1
- 10.1111/1471-0528.17864
- Jun 10, 2024
- BJOG : an international journal of obstetrics and gynaecology
To determine the prevalence of maternal morbidity and death from pregnancy loss before 28 weeks in referral-level hospitals in Nigeria. Secondary analysis of a nationwide cross-sectional study. Fifty-four referral-level hospitals. Women admitted for complications arising from pregnancy loss before 28 weeks between 1 September 2019 to 31 August 2020. Frequency and type of pregnancy loss were calculated using the extracted data. Multilevel logistic regression was used to determine sociodemographic and clinical factors associated with early pregnancy loss. Factors contributing to death were also analysed. Prevalence and outcome of pregnancy loss at <28 weeks; sociodemographic and clinical predictors of morbidity after early pregnancy loss; contributory factors to death. Of the 4798 women who had pregnancy loss at <28 weeks of pregnancy, spontaneous abortion accounted for 49.2%, followed by missed abortion (26.9%) and ectopic pregnancy (15%). Seven hundred women (14.6%) had a complication following pregnancy loss and 99 women died (2.1%). Most complications (26%) and deaths (7%) occurred after induced abortion. Haemorrhage was the most frequent complication in all types of pregnancy loss with 11.5% in molar pregnancy and 6.9% following induced abortion. Predictors of complication or death were low maternal education, husband who was not gainfully employed, grand-multipara, pre-existing chronic medical condition and referral from another facility or informal setting. Pregnancy loss before 28 weeks is a significant contributor to high maternal morbidity and mortality in Nigeria. Socio-economic factors and delays in referral to higher levels of care contribute significantly to poor outcomes for women.
- Research Article
41
- 10.3168/jds.2019-16251
- May 15, 2019
- Journal of Dairy Science
Effects of intrauterine infusion of seminal plasma at artificial insemination on fertility of lactating Holstein cows
- Research Article
47
- 10.1016/j.fertnstert.2016.11.029
- Jan 9, 2017
- Fertility and Sterility
Luteal start vaginal micronized progesterone improves pregnancy success in women with recurrent pregnancy loss
- Research Article
3
- 10.1186/s13104-017-2412-4
- Feb 8, 2017
- BMC Research Notes
BackgroundColorectal cancer is common in humans where treatment involves surgical removal of the cancerous part of the intestines. In the anastomosis procedure a purse-string suture may be time consuming to perform. The aim was to replace the purse-string suture, to develop and test a self-locking loop for temporary sealing of the lumen in colon anastomosis.MethodsA new device, a flexible band with a locking mechanism was constructed, the I-Tie®. Small protrusions, designed for increased friction between device and tissue, were added to one side of the flexible band in order to enhance the grip at closure of the loop around tissue. The device was initially tested in vitro on pig intestines. In an in vivo study, the short-term implant was tested in a new suture-free method, CREX, and with traditional circular staplers for colonic anastomosis. Ten female pigs of approximately 50 kg were used in the in vivo test. The self-locking device was used for closure of the lumen around anvils in CREX (n = 5), and around anvil in traditional circular stapler anastomosis (n = 5). Two self-locking devices were used in each animal.ResultsThe self-locking device could close the lumen of colon around the anvil and trocar. Subjectively, the device achieved a tight closure of the colon and did not interfere with the anastomosis techniques.ConclusionsThe technology was perceived as potentially timesaving and easy to use. We conclude the device may be an alternative to the traditional purse-string suture for temporary closure of the colon lumen in colon anastomosis.
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