Curious Case of Pediatric One-Lung Ventilation with Two Endotracheal Tubes: A Case Report.

ABSTRACT: One-lung ventilation is indicated during thoracic surgery for visualization and exposure of surgical site. It is achieved with bronchial blockers, double-lumen endobronchial tube, single-lumen endotracheal tubes and Univent tube for infants and children. Fibreoptic bronchoscope is required for placing and confirming the correct position of these tubes. We report a perioperative management of safe conduct of one lung ventilation for a 6-year child undergoing left lower lobe lobectomy through C-MAC video laryngoscope guided two single lumen tubes in limited resource settings where paediatric-sized fibreoptic bronchoscope is unavailable.

Repair of a chronic myometrial defect with successful pregnancy outcome.

OBJECTIVE: To surgically demonstrate preconceptional laparoscopic repair of a chronic myometrial defect with mesh reinforcement, resulting in a successful pregnancy outcome. DESIGN: Video case report. The Institutional Ethical Committee was consulted, and the requirement for approval was waived because the video describes a modified surgical technique. The patient included in this video gave consent for publication of the video and posting of the video online, including on social media, the journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus, and others), and other applicable sites. SETTING: A referral advanced gynecological endoscopy center. PATIENT: A 27-year-old woman (P0A1) was diagnosed with myomas during pregnancy, resulting in miscarriage at 22 weeks. Laparotomy and myomectomy were performed 2 months later, and three 8-cm myomas were removed. The endometrial cavity opened posteriorly during surgery, and retained products of conceptions were removed. Periconceptional imaging done after two years showed few intramural myomas and a deficient myometrium in the posterior fundal region. Laparoscopy revealed a defect in the posterior fundal aspect of the uterus with leakage of dye, which was converted to laparotomy and myomectomy with the repair of the myometrial defect. After 1 year, follow-up magnetic resonance imaging showed thinned-out posterior myometrium with a focal area of absent myometrium in the midline and endometrial prolapse. The patient was advised on surrogacy, but she wanted to repair the defect again and try for pregnancy, so she was referred to our center. With the background of a few case reports using mesh to reinforce myometrial repair (1, 2), we counseled the patient about the myometrial repair with the additional use of mesh as an off-label use. INTERVENTION: The risk of uterine rupture after myomectomy is rare (<1%) (3), but it is a severe complication. High-risk cases, like significant myometrial defects or previous ruptures, may require surgical correction. Native repair may not achieve optimal results in all cases. Alternative approaches, like the additional use of mesh or biological materials, have been reported (4). In this case, we demonstrate the use of dual mesh for scar repair. Synthetic mesh over the uterus is used in laparoscopic procedures like sacrohysteropexy and cerclage. We used Parietex (Covidien, New Haven, CT, USA) mesh, a composite macroporous polyester mesh usually used for ventral hernia repair. It has an outer hydrophilic, absorbable collagen barrier that reduces adhesion formation. Laparoscopically, after adhesiolysis, a significant defect was demonstrated on the posterior wall of the uterus (Fig. 1). A complete resection of the fibrotic tissue along the edges of the scar defect was done to expose healthy myometrium. Myometrium was repaired in two layers, excluding the endometrium, with a V-Loc (Covidien, Dublin, Ireland) No. 1-0 suture. Parietex mesh was sutured over the repaired posterior myometrium to reinforce it (Fig. 2). MAIN OUTCOME MEASURES: The postoperative myometrial thickness on imaging and pregnancy outcome. RESULTS: Postoperative ultrasound scan after 6 weeks demonstrated restoration of posterior wall myometrial thickness of 14 mm. The patient was conceived through in vitro fertilization techniques 4 months after surgery. Antenatal follow-up was uneventful except for suspicion of posterior placenta accreta. She underwent an elective cesarean section with uterine artery embolization at 34 weeks and delivered a healthy infant weighing 1,950 g. Placental removal was uneventful. On inspection, the posterior surface of the uterus was intact without dehiscence, meshing in situ with minimal adhesions (Fig. 3). CONCLUSION: Myometrial scar defects can cause potential obstetric complications. Native repair of scar defects may not achieve optimal results, as in our case. Mesh repair of myomectomy scar defects can be used as an alternative approach, as exemplified in this case. However, further studies are required to establish the safety and efficacy of this approach.

Gene Therapy for ß-Hemoglobinopathies: From Discovery to Clinical Trials.

Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the 20th and 21st centuries. Extensive characterization of the globin gene locus, accompanied by pioneering work on the utilization of viruses as human gene delivery tools in human hematopoietic stem and progenitor cells (HPSCs), has led to transformative and successful therapies via autologous hematopoietic stem-cell transplant with gene therapy (HSCT-GT). Due to the advanced understanding of the ß-globin gene cluster, the first diseases considered for autologous HSCT-GT were two prevalent ß-hemoglobinopathies: sickle cell disease and ß-thalassemia, both affecting functional ß-globin chains and leading to substantial morbidity. Both conditions are suitable for allogeneic HSCT; however, this therapy comes with serious risks and is most effective using an HLA-matched family donor (which is not available for most patients) to obtain optimal therapeutic and safe benefits. Transplants from unrelated or haplo-identical donors carry higher risks, although they are progressively improving. Conversely, HSCT-GT utilizes the patient's own HSPCs, broadening access to more patients. Several gene therapy clinical trials have been reported to have achieved significant disease improvement, and more are underway. Based on the safety and the therapeutic success of autologous HSCT-GT, the U.S. Food and Drug Administration (FDA) in 2022 approved an HSCT-GT for ß-thalassemia (Zynteglo™). This review illuminates the ß-globin gene research journey, adversities faced, and achievements reached; it highlights important molecular and genetic findings of the ß-globin locus, describes the predominant globin vectors, and concludes by describing promising results from clinical trials for both sickle cell disease and ß-thalassemia.

Vaginoscopic Management of OHVIRA (Obstructive Hemivagina and Ipsilateral Renal Agenesis).

OBJECTIVE: To describe the vaginoscopic management of longitudinal vaginal septum in the case of obstructive hemivagina and ipsilateral renal agenesis (OHVIRA) syndrome. DESIGN: Surgical video describing step-by-step management. SETTING: OHVIRA syndrome also known as Herlyn-Werner-Wunderlich syndrome is a triad of obstructed hemivagina, uterus didelphys, and ipsilateral renal anomaly [1] (Supplimentary Video 1). Patients usually present after menarche with progressive dysmenorrhea, lower abdominal pain, a paravaginal mass, foul mucopurulent discharge, and intermenstrual bleeding due to hemi hematocolpos [2]. Magnetic resonance imaging is the choice of investigation [3]. Surgical resection of the septum is the choice of treatment, which can be done vaginoscopically to reduce postoperative pain and promote enhanced recovery [4]. In this video, we will demonstrate a case of a 28-years old, nulliparous woman diagnosed with uterine didelphys having lower abdominal pain and persistent vaginal discharge. INTERVENTIONS: The video demonstrates the technique of vaginoscopic excision of the right hemi-vaginal septum that resulted in complete visualization of both cervices. Diagnostic laparoscopy confirmed uterine didelphys. The left cervix was visualized and the hysteroscope was negotiated into the cervical canal (Supplimentary Video 2). The left cavity was normal with left ostia. Intraoperative transrectal-ultrasound was done to localize the cystic collection in the right hemivagina. Needle aspiration of cystic collection was done over the bulging portion of the right hemivagina and mucoid material was aspirated. Longitudinal obstructive vaginal septum was incised using a collins knife and mucoid secretions were drained (Supplimentary Video 3). Hysteroscope inserted into opened right hemivagina, negotiated through the right cervix and right hemiuterus with right ostia was visualized. The residual septum was resected with a loop electrode and hemostasis was ensured. Cystoscopy done, left ureteric orifice with urine reflux visualized. Vaginal examination showed both cervices with near normal reconstructed vagina. CONCLUSION: The possibility of OHVIRA syndrome should be considered in all cases of uterine didelphys. Vaginoscopic management is a safe and effective method with a minimally invasive approach.

Targeting Gαi/s Proteins with Peptidyl Nucleotide Exchange Modulators.

Chemical probes that specifically modulate the activity of heterotrimeric G proteins provide excellent tools for investigating G protein-mediated cell signaling. Herein, we report a family of selective peptidyl Gαi/s modulators derived from peptide library screening and optimization. Conjugation to a cell-penetrating peptide rendered the peptides cell-permeable and biologically active in cell-based assays. The peptides exhibit potent guanine-nucleotide exchange modulator-like activity toward Gαi and Gαs. Molecular docking and dynamic simulations revealed the molecular basis of the protein-ligand interactions and their effects on GDP binding. This study demonstrates the feasibility of developing direct Gαi/s modulators and provides a novel chemical probe for investigating cell signaling through GPCRs/G proteins.

Reproductive Outcomes after Laparoscopic Myomectomy: Conventional versus Barbed Suture.

STUDY OBJECTIVE: To study the reproductive outcomes after laparoscopic myomectomy comparing conventional (nonbarbed) suture with barbed suture used for myometrial defect closure. DESIGN: Monocentric retrospective cohort study with prospective follow-up survey for reproductive outcomes conducted in April and May 2020. SETTING: Tertiary care center (center for advanced gynecologic laparoscopy and infertility). PATIENTS: Women who underwent laparoscopic myomectomy for uterine leiomyomas from January 2004 to December 2017. INTERVENTIONS: Laparoscopic myomectomy with closure of the myometrium using either conventional (nonbarbed suture) or barbed suture and follow-up survey regarding reproductive outcomes. MEASUREMENTS AND MAIN RESULTS: The outcomes measured included the rate of conception, pregnancy complications, mode of delivery, and perioperative complications for both kinds of suture materials used. Of the 399 women who underwent laparoscopic myomectomy, 343 satisfied the inclusion criteria and were followed up; 235 patients responded. A total of 120 patients were included in the nonbarbed group (group A), and 115 patients were included in the barbed group (group B). A total of 182 (group A: 97 vs group B: 85; p = .204) women had actively sought pregnancy postoperatively, of whom 93 (51.09%) in total and 51 (54.8%) in group A vs 42 (45.1%) in group B reported at least 1 pregnancy with no significant difference in the incidence rate ratios between the 2 groups. Of the recorded pregnancies84.9% (group A: 88.2% vs group B: 80.9%) live births, 6.4% (group A: 5.8% vs group B: 7.1%) had first-trimester miscarriages, 2.1% (group A: 1.9% vs group B: 2.3%) had an ectopic pregnancy, and 6 were ongoing pregnancies at the time of the study analysis, which were compared statistically between both study groups. Pregnancy-related complications were noted in 12 of the 93 pregnant women (12.9%), which were comparable in both groups. No case of uterine rupture was reported. CONCLUSION: Our study supports good reproductive outcomes in women after laparoscopic myomectomy with barbed sutures. Furthermore, the inclusion of nonbarbed sutures as a control group in our study reinforces that barbed sutures in myomectomy are as safe as, and an easier alternative to, conventional sutures without affecting pregnancy outcomes.

NMR-Based Structural Characterization of a Two-Disulfide-Bonded Analogue of the FXIIIa Inhibitor Tridegin: New Insights into Structure-Activity Relationships.

The saliva of blood-sucking leeches contains a plethora of anticoagulant substances. One of these compounds derived from Haementeria ghilianii, the 66mer three-disulfide-bonded peptide tridegin, specifically inhibits the blood coagulation factor FXIIIa. Tridegin represents a potential tool for antithrombotic and thrombolytic therapy. We recently synthesized two-disulfide-bonded tridegin variants, which retained their inhibitory potential. For further lead optimization, however, structure information is required. We thus analyzed the structure of a two-disulfide-bonded tridegin isomer by solution 2D NMR spectroscopy in a combinatory approach with subsequent MD simulations. The isomer was studied using two fragments, i.e., the disulfide-bonded N-terminal (Lys1-Cys37) and the flexible C-terminal part (Arg38-Glu66), which allowed for a simplified, label-free NMR-structure elucidation of the 66mer peptide. The structural information was subsequently used in molecular modeling and docking studies to provide insights into the structure-activity relationships. The present study will prospectively support the development of anticoagulant-therapy-relevant compounds targeting FXIIIa.

Deaths in dementia: a scoping review of prognostic variables.

OBJECTIVES: To identify the types of factors included in research examining mortality in patients with dementia, and to stratify the identified factors by care settings. DESIGN: We systematically searched PubMed, Embase, PsycINFO and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases, and identified grey literature from the Networked Digital Library of Theses and Dissertations, Open Grey and Grey Literature Report. Two authors independently screened for eligibility of studies. Independent reviewers extracted relevant study information. We conducted a narrative synthesis of the data. RESULTS: We identified 8254 articles, of which 94 met the inclusion criteria. More than half (n=53) were published between 2009 and 2018 with half from Europe. Studies were conducted across hospices/nursing homes (n=25), hospital (n=23), outpatient clinics (n=21), mixed settings (n=15) and in the community (n=10). Nearly 60% adopted a prospective cohort study design with 87% performing multivariable analysis. Overall, 239 variables were identified and classified into six themes-individual factors, health status, functional ability, cognition and mental health, treatments and health system factors. Although a general set of factors were common across all studies, when stratified by care settings, variations were seen in the specific variables included. CONCLUSION: Identifying prognostic variables relevant to the dementia population in each setting is key to facilitate appropriate care plans and to ensure timely access to palliative care options. Future research should also focus on ensuring the replicability of prognostic models and to generate a better understanding of the direct and interacting influence of the identified factors on mortality.

Distinct 3-disulfide-bonded isomers of tridegin differentially inhibit coagulation factor XIIIa: The influence of structural stability on bioactivity.

Tridegin is a 66mer cysteine-rich coagulation factor XIIIa (FXI-IIa) inhibitor from the giant amazon leech Haementeria ghilianii of yet unknown disulfide connectivity. This study covers the structural and functional characterization of five different 3-disulfide-bonded tridegin isomers. In addition to three previously identified isomers, one isomer containing the inhibitory cystine knot (ICK, knottin) motif, and one isomer with the leech antihemostatic protein (LAP) motif were synthesized in a regioselective manner. A fluorogenic enzyme activity assay revealed a positive correlation between the constriction of conformational flexibility in the N-terminal part of the peptide and the inhibitory potential towards FXI-IIa with clear differences between the isomers. This observation was supported by molecular dynamics (MD) simulations and subsequent molecular docking studies. The presented results provide detailed structure-activity relationship studies of different tridegin disulfide isomers towards FXI-IIa and reveal insights into the possibly existing native linkage compared to non-native disulfide tridegin species.

Creating New ß-Globin-Expressing Lentiviral Vectors by High-Resolution Mapping of Locus Control Region Enhancer Sequences.

Hematopoietic stem cell gene therapy is a promising approach for treating disorders of the hematopoietic system. Identifying combinations of cis-regulatory elements that do not impede packaging or transduction efficiency when included in lentiviral vectors has proven challenging. In this study, we deploy LV-MPRA (lentiviral vector-based, massively parallel reporter assay), an approach that simultaneously analyzes thousands of synthetic DNA fragments in parallel to identify sequence-intrinsic and lineage-specific enhancer function at near-base-pair resolution. We demonstrate the power of LV-MPRA in elucidating the boundaries of previously unknown intrinsic enhancer sequences of the human ß-globin locus control region. Our approach facilitated the rapid assembly of novel therapeutic ßAS3-globin lentiviral vectors harboring strong lineage-specific recombinant control elements capable of correcting a mouse model of sickle cell disease. LV-MPRA can be used to map any genomic locus for enhancer activity and facilitates the rapid development of therapeutic vectors for treating disorders of the hematopoietic system or other specific tissues and cell types.

Laparoscopic Cervical Encerclage in Pregnancy in 6 Steps.

STUDY OBJECTIVE: Cervical insufficiency occurs in 0.1% to 1 % of all pregnancies and is associated with a high risk of second-trimester abortion and/or preterm delivery [1]. Laparoscopic encerclage is highly recommended for a previous failed vaginal encerclage and is superior to the laparotomy approach in terms of low morbidity and faster recovery [2]. Laparoscopic encerclage in pregnancy is more challenging than that in the nonpregnant state. This is because of the enlarged uterine size, engorged uterine vessels, and infeasibility of using a uterine manipulator. The standardization and description of the technique are the main objectives of this video (Video 1). We have described the surgery in 6 steps that could make this procedure easier and safer. DESIGN: A step-by-step video demonstration of the technique. SETTING: Paul's Hospital, Centre for Advanced Endoscopy & Infertility Treatment, Kochi, India. A 29-year-old pregnant woman, gravida 3 abortions 2, at 13 weeks period of gestation, with a history of 2 second-trimester abortions owing to cervical insufficiency. The patient had a failed vaginal cervical encerclage at 18 weeks in the second pregnancy. INTERVENTIONS: This is a step-wise laparoscopic approach for successful cervical encerclage in pregnancy. In this video, we demonstrate our technique for laparoscopic cervical encerclage in a pregnant woman's uterus in 6 steps using a Mersilene tape (Ethicon US, LLC, Somerville, NJ) as follows: (1) Opening the uterovesical fold and dissecting the bladder, (2) opening the left broad ligament and creating a window, (3) opening the right broad ligament and creating a window, (4) placing the Mersilene tape on the left side medial to the uterine vessels at the cervicoisthmic junction, (5) placing the Mersilene tape on the right side medial to the uterine vessels at the cervicoisthmic junction, (6) tying the Mersilene tape anteriorly. CONCLUSION: The standardization of laparoscopic cervical encerclage in pregnancy using the above 6 steps could make this procedure easier and safer to perform. Moreover, the standardization of the surgical technique could shorten the learning curve.

Laparoscopy-assisted Neocervicovaginal Reconstruction in a Rare Case of Müllerian Anomaly: Cervicovaginal Aplasia with Unicornuate Uterus.

STUDY OBJECTIVE: To demonstrate a technique of laparoscopy-assisted neocervicovaginal reconstruction in a case of cervicovaginal aplasia. DESIGN: Step-by-step demonstration of the surgery in an instructional video. SETTING: Cervicovaginal aplasia is a rare congenital anomaly that occurs in 1 in 80 000 to 100 000 live births [1]. Occasionally, there can be other associated anomalies. Epigenetic modifications of homeobox and Wnt genes (wingless-type mouse mammary tumor virus integration site family) are hypothesized to cause defects in the development of the müllerian reproductive tract by interfering with cell migration during organogenesis [2]. Our patient was a 15-year-old girl who had a unicornuate uterus along with cervicovaginal aplasia (American Society for Reproductive Medicine class Ia, Ib, and IIc and European Society of Human Reproduction and Embryology class U4a, C4, and V4). The most common approach to treat this particular anomaly is hysterectomy, but there are many reports of neocervicovaginal reconstruction with good results [3]. INTERVENTIONS: Laparoscopic assessment showed a right unicornuate uterus with hematometra, right hematosalpinx, and a left noncavitary rudimentary horn with endometriosis. A vertical incision was made over the most prominent bulging part of the uterine fundus, and the hematometra was drained. Laparoscopic inspection of the uterine cavity showed an irregular cavity with thickened endometrium. The cervical canal could not be identified. The inspection of the external genitalia revealed complete vaginal aplasia. An inverted T incision was made over the vestibule and neovagina created by blunt digital dissection. The bladder was laparoscopically mobilized down. A Maryland dissector was inserted into the uterine cavity through the incision in the fundus and directed toward the neovagina. The myometrium was then punctured while simultaneously visualizing the neovagina to create a neocervix. A 16-F Foley's catheter was then pulled into the uterine cavity with the Maryland dissector from the vaginal end. The neocervix was enlarged around the catheter and then sutured to the vestibular epithelium with 6 interrupted 1-0 polyglactin sutures. The Foley's catheter was anchored to the myometrium laparoscopically, and the uterine incision was closed with interrupted 1-0 polyglactin sutures. The right hematosalpinx was then excised. The intravaginal plastic mold was removed after 4 days. The patient was advised to use the bulb of a plastic pipette to help maintain vaginal patency. She resumed her menses 3 weeks after the surgery. Follow-up at 8 months revealed a normal-sized uterus on transabdominal ultrasound and a vaginal length of 5.5 cm on speculum examination. She currently reports regular cyclic menstruation with mild dysmenorrhea and has not yet begun sexual activity. CONCLUSION: Cervicovaginal aplasia can be successfully treated by laparoscopy-assisted neocervicovaginal reconstruction as demonstrated in the video.

Coagulation Factor XIIIa Inhibitor Tridegin: On the Role of Disulfide Bonds for Folding, Stability, and Function.

Tridegin is a potent and specific 66mer peptide inhibitor of coagulation factor XIIIa with six cysteines involved in three disulfide bonds. Three of the 15 possible 3-disulfide-bonded isomers have been identified, which share a bridge between cysteines 19 and 25. We synthesized the three possible 2-disulfide-bonded analogues using a targeted protecting group strategy to investigate the impact of the C19-C25 bond on tridegin's folding, stability, and function. The FXIIIa inhibitory activity of the analogues was retained, which was shown by in vitro fluorogenic activity and whole blood clotting assays. Molecular dynamics simulations of wild-type tridegin and the analogues as well as molecular docking studies with FXIIIa were performed to elucidate the impact of the C19-C25 bond on conformational stability and binding mode. The strategy of selectively reducing disulfide bonds to facilitate large-scale synthesis, while retaining the functionality of disulfide-bonded peptides, has been demonstrated with our present study.

The molecular basis of transient heme-protein interactions: analysis, concept and implementation.

Deviant levels of available heme and related molecules can result from pathological situations such as impaired heme biosynthesis or increased hemolysis as a consequence of vascular trauma or bacterial infections. Heme-related biological processes are affected by these situations, and it is essential to fully understand the underlying mechanisms. While heme has long been known as an important prosthetic group of various proteins, its function as a regulatory and signaling molecule is poorly understood. Diseases such as porphyria are caused by impaired heme metabolism, and heme itself might be used as a drug in order to downregulate its own biosynthesis. In addition, heme-driven side effects and symptoms emerging from heme-related pathological conditions are not fully comprehended and thus impede adequate medical treatment. Several heme-regulated proteins have been identified in the past decades, however, the molecular basis of transient heme-protein interactions remains to be explored. Herein, we summarize the results of an in-depth analysis of heme binding to proteins, which revealed specific binding modes and affinities depending on the amino acid sequence. Evaluating the binding behavior of a plethora of heme-peptide complexes resulted in the implementation of a prediction tool (SeqD-HBM) for heme-binding motifs, which eventually led and will perspectively lead to the identification and verification of so far unknown heme-regulated proteins. This systematic approach resulted in a broader picture of the alternative functions of heme as a regulator of proteins. However, knowledge on heme regulation of proteins is still a bottomless barrel that leaves much scope for future research and development.

Effectiveness of tobacco cessation pharmacotherapy in the Veterans Health Administration.

INTRODUCTION: In 2003, the Veterans Health Administration (VHA) implemented a directive that cessation pharmacotherapy be made available to all who use tobacco and are interested in quitting. Despite the efficacy of cessation pharmacotherapy shown in clinical trials, the generalisability of the results in real-world settings has been challenged. Hence, the specific aim of this study was to determine the effectiveness of cessation pharmacotherapies in the VHA. METHODS: This retrospective cohort study used VHA's electronic medical record data to compare quit rates among those who use tobacco and who did vs. did not receive any type of cessation pharmacotherapy. Included were 589 862 Veterans identified as current tobacco users during fiscal year 2011 who had not received cessation pharmacotherapy in the prior 12 months. Following a 6-month period to assess treatment, quit rates among those who were treated versus untreated were compared during the 7-18 months (12 months) post-treatment follow-up period. The estimated treatment effect was calculated from a logistic regression model adjusting for inverse probability of treatment weights (IPTWs) and covariates. Marginal probabilities of quitting were also obtained among those treated versus untreated. RESULTS: Adjusting for IPTWs and covariates, the odds of quitting were 24% higher among those treated versus untreated (OR=1.24, 95% CI 1.23 to 1.25, p<0.001). The marginal probabilities of quitting were 16.7% for the untreated versus 19.8% for the treated based on the weighted model. CONCLUSION: The increased quit rates among Veterans treated support the effectiveness and continuation of the VHA tobacco cessation pharmacotherapy policy.

Insights into the Folding of Disulfide-Rich µ-Conotoxins.

The study of protein conformations using molecular dynamics (MD) simulations has been in place for decades. A major contribution to the structural stability and native conformation of a protein is made by the primary sequence and disulfide bonds formed during the folding process. Here, we investigated µ-conotoxins GIIIA, KIIIA, PIIIA, SIIIA, and SmIIIA as model peptides possessing three disulfide bonds. Their NMR structures were used for MD simulations in a novel approach studying the conformations between the folded and the unfolded states by systematically breaking the distinct disulfide bonds and monitoring the conformational stability of the peptides. As an outcome, the use of a combination of the existing knowledge and results from the simulations to classify the studied peptides within the extreme models of disulfide folding pathways, namely the bovine pancreatic trypsin inhibitor pathway and the hirudin pathway, is demonstrated. Recommendations for the design and synthesis of cysteine-rich peptides with a reduced number of disulfide bonds conclude the study.

Parasitic Myomas: An Unusual Risk after Morcellation.

A 24-year-old unmarried woman had undergone laparoscopic myomectomy for single degenerated myoma of size 15 cm. Uncontained morcellation of the myoma was done with an electromechanical morcellator. Two years later, she presented with abdominal pain, and laparoscopy revealed enlarged uterus (20 weeks) with multiple degenerated myomas. There were multiple parasitic myomas measuring 1-3 cm in the pelvis and anterior abdominal wall which were removed laparoscopically. Histopathology of all the myomas including parasitic myomas confirmed the diagnosis of leiomyoma. The formation of parasitic myomas was assumed to be due to the myomatous fragments which were left behind during morcellation at the time of initial myomectomy. Methods to prevent this complication are colpotomy, mini-laparotomy, or in-bag morcellation.

Thirteen Years of Experience with Opportunistic Bilateral Salpingectomy During TLH in Low-Risk Premenopausal Women.

BACKGROUND: Opportunistic bilateral salpingectomy (OBS), also called as prophylactic salpingectomy or risk-reducing salpingectomy is the concurrent removal of the fallopian tubes in premenopausal women. Though there are some studies comparing the intraoperative complications and effect of salpingectomy on ovarian reserve, limited data are available on long-term follow-up after OBS. PURPOSE OF THE STUDY: To evaluate the surgical outcome of routine bilateral salpingectomy during total laparoscopic hysterectomy (TLH) in terms of intraoperative and postoperative complications. We also evaluated the incidence and reoperation rate for adnexal pathology after TLH. METHODS: A retrospective study of 1470 patients undergoing total laparoscopic hysterectomy (TLH) with opportunistic bilateral salpingectomy (OBS) over 13 years was carried out at Paul's Hospital. RESULTS: The mean age of the subjects was 43.6 ± 4.2 years, mean body mass index was 27 ± 5.4 kg/m2, and median parity was 2 (range 0-7). 43% of women had at least one previous surgery. The most common indication for surgery was fibroid uterus (67%, n = 985). The total complication rate was 4.4% (n = 65). One specimen showed paratubal borderline serous malignancy. The follow-up period ranged from 6 months to 13 years during which 17 (1.1%) women had adnexal pathology, and eight women (1.1%) needed resurgery for it. No ovarian malignancies were reported on follow-up. CONCLUSIONS: OBS is a simple and short surgical step during TLH without increasing morbidity. OBS eliminates the risk of future diseases of tubal origin, and there might be a possible reduction in incidence and reoperation rate for future ovarian pathologies.