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.

Abstracts of Scottish Vision Group 2023 Meeting.

Scottish Vision Group has become a yearly event for vision scientists based in Scotland since its inception in 2001. Each year, the conference is hosted at a different location and organised by a different team. The 2023 SVG meeting was hosted in the city of Dundee by Abertay University. Delegates travelled from the United Kingdom, Europe and beyond. The meeting started with a roundtable panel discussion sponsored by Meta Reality Labs. The roundtable, titled The Past, Present and Future of Visual Search, was organised and presented by Árni Kristjánsson (Iceland), Ioan Smart (Abertay) and Ian Thornton (Malta). The MDPI Keynote lecture was introduced by Professor Andrew Parker (Oxford University and Otto-von-Guericke University in Magdeburg, Germany) and presented by Prof. Timothy Ledgeway (Nottingham) on sensory eye dominance and plasticity in adult binocular vision. The remaining two days of the conference hosted a wide range of talks on topics ranging from insect navigation to visual illusions, facial recognition and binocular coding. The Saturday evening saw a special event where delegates explored the sensory properties of a range of single-malt whiskies. Here, we present a selection of abstracts for the various talks and posters.

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.

Analysis of neuropathological comorbid conditions in elderly patients with mild cognitive impairment in a tertiary care center in South India.

Introduction: Mild cognitive impairment (MCI) is a transitional stage in the continuum of cognitive decline. Multiple risk factors may be involved apart from neuropathological states such as Alzheimer's disease, Parkinson's disease, and vascular dementia. There is scant data in the literature pertaining to our study population in Kerala, South India that provide associations between suggested risk factors and MCI. Most of the elderly present to family and primary care physicians with complaints of some form of memory impairment. Objectives: To find out the significant neuropathological comorbid conditions present in elderly patients with MCI. To assess for other risk factors in the same population- including laboratory parameters, comorbidities, and psychosocial parameters. Methods: This retrospective record-based study included a sample of 93 patients with MCI as quantified by the Mini-Mental Status Examination (MMSE). These subjects were compared with controls (n = 97) without MCI, with respect to neuropathological diagnoses, laboratory parameters and psychosocial parameters. Results: The findings of our study were that female gender, higher depression scores, a greater number of medications taken, benzodiazepine use, higher alkaline phosphatase levels, positive fall history, loss of a spouse, and lower levels of education were associated with MCI. MCI is negatively associated with positive alcohol history. The most commonly seen proven neuropathological diagnosis was Parkinson's disease. Conclusion: The risk factors that were found in our study should be highlighted in the elderly and preventive measures should be taken to prevent the downward progression through the cognitive continuum. Prospective studies looking into mild cognitive impairment with better screening tools and proper assessment of neuropathological comorbid conditions can further elucidate the findings related to this study.

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.

Safety and efficacy of a feed additive consisting of 3-nitrooxypropanol (Bovaer® 10) for ruminants for milk production and reproduction (DSM Nutritional Products Ltd).

Following a request from the European Commission, EFSA was asked to deliver a scientific opinion on the safety and efficacy of Bovaer® 10 as a zootechnical additive for ruminants for milk production and reproduction. Systemic exposure or site of contact toxicity for the active substance 3-nitrooxypropanol (3-NOP), for which genotoxicity has not been fully clarified, in the target species, is unlikely based on ADME data available. Consequently, the FEEDAP Panel concluded that Bovaer® 10 was safe for dairy cows at the maximum recommended level. However, as a margin of safety could not be established, the FEEDAP Panel could not conclude on the safety of the additive for other animal species/categories. The FEEDAP Panel considered that the consumer was exposed to 3-nitrooxypropionic acid (NOPA), which is one of the 3-NOP metabolites. NOPA was not genotoxic based on the studies provided. The FEEDAP Panel concluded that the use of Bovaer® 10 in animal nutrition under the conditions of use proposed was of no concern for consumer safety and for the environment. The FEEDAP Panel concluded that the active substance 3-NOP may be harmful if inhaled. It is irritant (but not corrosive) to skin, irritant to the eyes but it is not a skin sensitiser. As the genotoxicity of 3-NOP is not completely elucidated, the exposure through inhalation of the additive may represent an additional risk for the user. The Panel concluded that the additive has a potential to be efficacious in dairy cows to reduce enteric methane production under the proposed conditions of use. This conclusion was extrapolated to all other ruminants for milk production and reproduction.

'The Violet Killer'-Successful Treatment of an Infant with Chromobacterium violaceum Sepsis.

Chromobacterium violaceum, a facultative anaerobic proteobacterium, is isolated from water and soil in tropical areas and has been implicated in infections like septicemia, visceral abscesses, skin and soft tissue infections, meningitis and diarrhea. Chromobacterium violaceum sepsis, a rarely reported phenomenon has a very high mortality rate. Here, we report a unique case of Chromobacterium sepsis in an infant. A 48-day-old baby boy was referred to our institution with h/o fever, loose stools and reduced activity. He was intubated and referred to us in septic shock. Radiological investigations revealed multiple abscesses in the liver, spleen and kidneys. The infant was successfully treated with trimethoprim-sulfamethoxazole and ciprofloxacin.

Strategies towards Targeting Gαi/s Proteins: Scanning of Protein-Protein Interaction Sites To Overcome Inaccessibility.

Heterotrimeric G proteins are classified into four subfamilies and play a key role in signal transduction. They transmit extracellular signals to intracellular effectors subsequent to the activation of G protein-coupled receptors (GPCRs), which are targeted by over 30 % of FDA-approved drugs. However, addressing G proteins as drug targets represents a compelling alternative, for example, when G proteins act independently of the corresponding GPCRs, or in cases of complex multifunctional diseases, when a large number of different GPCRs are involved. In contrast to Gαq, efforts to target Gαi/s by suitable chemical compounds has not been successful so far. Here, a comprehensive analysis was conducted examining the most important interface regions of Gαi/s with its upstream and downstream interaction partners. By assigning the existing compounds and the performed approaches to the respective interfaces, the druggability of the individual interfaces was ranked to provide perspectives for selective targeting of Gαi/s in the future.

Revisiting the interaction of heme with hemopexin.

In hemolytic disorders, erythrocyte lysis results in massive release of hemoglobin and, subsequently, toxic heme. Hemopexin is the major protective factor against heme toxicity in human blood and currently considered for therapeutic use. It has been widely accepted that hemopexin binds heme with extraordinarily high affinity of <1 pM in a 1:1 ratio. However, several lines of evidence point to a higher stoichiometry and lower affinity than determined 50 years ago. Here, we re-analyzed these data. SPR and UV/Vis spectroscopy were used to monitor the interaction of heme with the human protein. The heme-binding sites of hemopexin were characterized using hemopexin-derived peptide models and competitive displacement assays. We obtained a KD value of 0.32 ± 0.04 nM and the ratio for the interaction was determined to be 1:1 at low heme concentrations and at least 2:1 (heme:hemopexin) at high concentrations. We were able to identify two yet unknown potential heme-binding sites on hemopexin. Furthermore, molecular modelling with a newly created homology model of human hemopexin suggested a possible recruiting mechanism by which heme could consecutively bind several histidine residues on its way into the binding pocket. Our findings have direct implications for the potential administration of hemopexin in hemolytic disorders.

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.

Molecular Insights and Functional Consequences of the Interaction of Heme with Activated Protein C.

Aims: In hemolysis, which is accompanied by increased levels of labile redox-active heme and is often associated with hemostatic abnormalities, a decreased activity of activated protein C (APC) is routinely detected. APC is a versatile enzyme that exerts its anticoagulant function through inactivation of clotting factors Va and VIIIa. APC has not been demonstrated to be affected by heme as described for other clotting factors and, thus, is a subject of investigation. Results: We report the interaction of heme with APC and its impact on the protein function by employing spectroscopic and physiologically relevant methods. Binding of heme to APC results in inhibition of its amidolytic and anticoagulant activity, increase of the peroxidase-like activity of heme, and protection of human umbilical vein endothelial cells from heme-induced hyperpermeability. To define the sites that are responsible for heme binding, we mapped the surface of APC for potential heme-binding motifs. T285GWGYHSSR293 and W387IHGHIRDK395, both located on the basic exosite, turned out as potential heme-binding sites. Molecular docking employing a homology model of full-length APC indicated Tyr289 and His391 as the Fe(III)-coordinating amino acids. Innovation: The results strongly suggest that hemolysis-derived heme may directly influence the protein C pathway through binding to APC, conceivably explaining the decreased activity of APC under hemolytic conditions. Further, these results extend our understanding of heme as a multifaceted effector molecule within coagulation and may allow for an improved understanding of disease development in hemostasis under hemolytic conditions. Conclusion: Our study identifies APC as a heme-binding protein and provides insights into the functional consequences.

Chronic Q Fever Endocarditis in an Omani Child: The First Pediatric Case Report from Oman.

Q fever endocarditis is the most common presentation of chronic infection of Coxiella burnetii, but it rarely occurs in the pediatric age group. We report the first case of Q fever endocarditis in an Omani child. The affected 11-year-old female lives in the Al Batinah governorate in the north of Oman and was known to have congenital heart disease. She presented with features of chronic blood culture-negative endocarditis. The C. burnetii infection was confirmed with the indirect immunofluorescence assay. The patient responded well to a combination of doxycycline and hydroxychloroquine therapy.

Safety and efficacy of 'dry grape extract 60-20' when used as feed flavouring for dogs.

The feed additive 'dry grape extract 60-20' is a mixture of two extracts, one from the seed and the other from the skin of Vitis vinifera subsp. vinifera. It is intended to be used as a sensory additive (functional group: flavouring compound) in dogs. The additive 'dry grape extract 60-20' is specified to contain ■■■■■ The applicant proposes a maximum use level of 100 mg 'dry grape extract 60-20'/kg of complete feedingstuffs for dogs without a withdrawal period. The FEEDAP Panel was aware of case reports indicating acute toxicity for some dogs consuming grapes or raisins at exposure levels relevant to the use of 'dry grape extract 60-20'. The FEEDAP Panel considered that rare idiosyncratic effects could be possibly responsible for the reported cases of fatality in dogs due to acute renal failure following exposure to different types of grapes. The FEEDAP Panel considered that the additive is poorly characterised. Based on the data available, the FEEDAP Panel was not able to conclude on the safety of 'dry grape extract 60-20' when used as a feed additive for dogs. In the absence of studies to assess the safety for the user, the FEEDAP Panel could not conclude on the safety for the user when handling the additives. Since grape seed extract is used in food as flavouring, and its function in feed is essentially the same as that in food no further demonstration of efficacy was necessary.

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.