Centralization of Internet-based services in few key players has been a topic of study in recent years. One of such services, the Domain Name System (DNS), is one of the pillars of the Internet, which allows users to access websites on the Internet through easy-to-remember domain names rather than complex numeric IP addresses. In this DNS context, the reliance on a small number of large DNS providers can lead to (a) risks of data breaches and disruption of service in the event of failures and (b) concerns about the digital sovereignty of countries regarding DNS hosting. As several essential services are provided through Electronic-Government (E-Gov), it is highly important to be able to measure the digital sovereignty of a nation and the impacts that the lack of such feature can bring to its citizens. This work approaches the issue of DNS concentration on the Internet by presenting a solution to measure DNS hosting centralization and digital sovereignty in different countries, such as Brazil, India, China, Russia, and South Africa. With the data obtained through these measurements, relevant questions are answered, such as which are the top-10 DNS providers, if there is DNS centralization, and how dependent countries are on such providers to manage domains using their country code Top-Level Domains (ccTLD). Future opportunities could investigate the impacts on sovereignty under the lens of other layers of the Open Systems Interconnection (OSI) Network Sovereignty representation model presented in this work.

This study investigates the impact of various surface finishes on the low cycle fatigue (LCF) properties of laser powder bed fusion GRCop-42. The evaluated surfaces include as-built, machined, and chemically polished finishes (1 .0% and 2 .0%). LCF life of polished GRCop-42 was assessed at cryogenic (−195 ◦ C ), ambient, and elevated temperatures (200 ◦ C , 400 ◦ C , 600 ◦ C , and 800 ◦ C ) across three strain amplitudes. Results indicate that surface finish has minimal impact on LCF life. Stress across different strain levels showed minimal effect of surface finish on cyclic hardening/softening. Cryogenic temperatures led to cyclic hardening followed by stabilization, while ambient and 200 ◦ C temperatures showed initial hardening followed by softening. At 400 ◦ C and above, specimens displayed continuous cyclic softening. Fractography showed that surface finish impacts plastic deformation: as-printed and polished surfaces had brittle fractures, while machined specimens were ductile. Specimens at cryogenic and ambient temperatures exhibited brittle fractures, whereas those at elevated temperatures showed plastic deformation and microcracks.

A document by Xueqin Chen. Click on the document to view its contents.

It is common practice in PV system simulation to use the De Soto model, which describes how to use the 1-diode equivalent circuit model for modules. De Soto’s model scales the shunt with irradiance, making it disappear towards zero W/m 2. Also, the commercial software PVsyst uses a parameterization that reduces the shunt effect when the irradiance goes down. However, the Si solar cells that make up a module typically do not have an illumination dependent shunt. We therefore investigate the origin of the intensity dependent apparent shunt in modules. We show that this apparent shunt (derived from the slope of the quasi-linear region from I SC onwards) is a misinterpretation and has little to do with a shunt conductance. Instead, the module I- V curve slope of the quasi-linear region from I SC onwards stems from I SC mismatches between the cells. Such mismatch can occur from small illumination inhomogeneity or cell production variation. Abandoning the practice of using the I- V curve slope to determine the shunt value for equivalent circuit models of modules (and the corresponding shunt scaling in the De Soto model or PVsyst), contributes to physically more meaningful I- V curve parameterizations and possibly also more accurate PV system energy yield prediction.

Title: Oh Groin: What to do with thou?Author: Gautam [email protected] of Missouri School of Medicine, Division of Cardiovascular MedicineThe field (art?) of electrophysiology (EP) has progressed exponentially over the last 3 decades. The delivery of ablative energy through transvenous catheters has revolutionized our ability to treat cardiac arrhythmia. At the time that this text is being put on paper, there are 3 remaining challenges in our field, namely, durable ablation for atrial fibrillation, ablation of non-focal non-ischemic ventricular tachycardia, and last but not the least, management of the pesky inguinal access region. The oral history of electrophysiology trainees is riddled with the litany of post-operative complaints from both patients and nurses, prolonged repeated compressions and late-night vascular imaging. Those of our ilk who have been unfortunate enough to deal with pseudoaneurysms and arteriovenous fistulae can never forget the resultant prolonged patient agony and depression. Thankfully, these have decreased significantly with the advent of ultrasound-guided vascular access.The ideal modality of post-ablation venous hemostasis should have each of the following characteristics: simple, fast, 100% effective, allow rapid patient mobility, and above all, cheap. This combination, however, has been surprisingly elusive. As opposed to the multitude of arterial closure options for our interventional colleagues, the electrophysiology field for long relied upon the old and non-tested method of plain manual compression (MC). As most of us have experienced, MC is unreliable and messy especially in procedures on uninterrupted anticoagulation. The degree and efficiency of MC is almost completely operator dependent. Luckily, the femoral veins are easily compressible and usually quite forgiving in the majority of cases. However, as we started to recognize the advantage of both uninterrupted anticoagulation and deep sedation (preferably general anesthesia) in left atrial ablation procedures, particularly atrial fibrillation (AF), MC became even more unreliable in ensuring venous haemostasis.The Figure-of-Eight (Fo8) suture was a handy replacement for MC. The goal of Fo8 is simple: create a compression zone of subcutaneous fat to allow healing of the venous puncture track. Fo8 seems to work well for all venous access procedures, allowing haemostasis even for large venous sheaths such as cryoablation, left atrial appendage closure systems and leadless pacemaker delivery sheaths. The Fo8 was a particular godsend for electrophysiologists without the luxury of MC by willing trainees or reliable lab staff. We and others also showed that it resulted in shorter lab recovery time after AF ablation and was reliable in presence of systemic anticoagulation. However, there remained a few drawbacks. The ideal duration of suture compression remains unknown and is variable by practice, from 2 to 4 hours, sometimes longer for larger or multiple sheaths. The degree of venous compression is lesser compared with MC, as evidenced by persistent oozing in some patients after Fo8 removal necessitating prolonged compression or administration of subcutaneous Lidocaine with Epinephrine. The requirement for ‘suture cutting’ also meant that nursing staff were uncomfortable removing it. The last and greatest drawback was that Fo8 is irreversible, that is, the suture could not be reapplied when cut, for patients with persistent oozing.The above drawbacks led to the development of the stopcock (SC) technique. This was being used by some vascular surgeons, called the ‘Woggle technique’ for suture closure of hemodialysis access catheterization sites (1). Sam Aznaurov first described this technique on ‘X’ (then Twitter) for femoral venous haemostasis (2). I and others tried it on a few patients and were impressed by the ease and sophistication of the technique. We published the first detailed description of this technique in 2018 showing it to be equivalent to Fo8 in achieving access site haemostasis in AF ablation patients (3). The SC technique, which is essentially using a simple 3-way stopcock to lock a tightened 0-Ethibond or 0-silk suture, has 2 major advantages over Fo8. It is easier to teach and apply, can be removed by nursing personnel and can be reapplied (the stopcock can simply be locked again) if haemostasis is incomplete. The technique is also inexpensive, as the stopcocks can simply be cut from the side arm of the venous sheaths. We also further showed that Heparin reversal with Protamine was not required for haemostasis with SC.As expected, Fo8 and SC have been widely taken up in EP labs around the world. In other centers, MC remains king. Many centers in the US have graduated to specialized venous closure devices which afford faster ambulation but are considerably more expensive. The time is ripe for the SC system to be commercialized and a few of these are being tested now in the EP community.In the present use of JCE, Katapadi and colleagues present a single-center retrospective observational analysis of 102 patient who underwent venous hemostasis with the LockeT vascular compression device (4). They report complete hemostasis in 97.8% of vascular access without major complications, mean time to ambulation 3.93 ± 1.10 hrs. The LockeT device is a commercial apparatus which uses a screw with 90 degrees rotation to lock or unlock the suture, with a flat round endplate (base) to provide uniform compression. Theoretically, the flat base would avoid one prior complaint with SC, namely skin pressure/ ulceration. Truly speaking, operators have long developed methods to avoid skin ulceration, including shorter SC retention times, use of an intervening gauze roll, and gentler compression in non-obese individuals. In this relatively small study, the authors have shown 98% complete hemostasis (likely prolonged compression in 2 patients), a stable mean ambulation time of 4 hours and mean time to discharge 8 hours (which could potentially be shortened with increased operator experience). The study has the usual drawbacks of retrospective observational studies, as acknowledged by the authors, as well as the lack of any comparative analysis to SC technique. We also do not have information about the financial implications of adding to the technical costs of EP studies or appendage closure. In the current reimbursement climate, especially with steadily rising healthcare costs, this would be important information.The LockeT device and other similar commercial devices that duplicate SC would be potentially useful if a) they add negligible incremental cost to the EP procedure and b) if they lead to further shortening of bedrest and time to discharge which would offset the device expenditure. One might argue against their use for simple EP procedures without systemic anticoagulation where MC has historically been simple and effective. These methods would be expected to hold an advantage over invasive venous closure devices of not requiring multiple devices (one for each access site), thus being less expensive, especially if the patient could be discharged within 2 hours as practiced by some operators with the venous closure devices. We need more larger volume studies on these issues to convince the greater the EP community.We could thus be finally reaching closer to a solution of the waxing problem: what to do with the groin?References:Simons ME, Rajan DK, Clark TW. The Woggle technique for suture closure of hemodialysis access catheterization sites. Journal of vascular and interventional radiology: JVIR 2003;14:485-8.https://x.com/epTicTocDoc/status/917473407524134914Payne J, Aznaurov S, Gautam S. Three-way stopcock suture technique for hemostasis after ablation for atrial fibrillation. J Cardiovasc Electrophysiol. 2018;29(12):1724-1727.(Attach reference for the LockeT manuscript )

To the Editor,

Spotlight Commentary: Examining Safety Profiles of Topical Ocular MedicationLorena Karla Šklebar1,2, Robert Likić2,3, Sonja Jandroković1,21 Department of ophthalmology, University Hospital Centre Zagreb, Zagreb, Croatia2 University of Zagreb, School of medicine, Zagreb, Croatia3 Division for clinical pharmacology and therapeutics, Department of internal medicine, University Hospital Centre Zagreb, Zagreb, CroatiaKeywords: eye drops; systemic side effect; ocular side effect; safety profile; topical ocular medicationWord count: 1085Table count: 1Figure count: 0Topical medications are frequently used in treating a wide range of ocular diseases due to their efficiency in delivery directly to the afflicted area. However, localized administration cannot prevent side effects, both local and systemic, which can sometimes be overlooked or underestimated. The aim of this spotlight commentary is to provide a review of safety profiles of topical ocular medications, analysing their effect on the ocular structures as well as their systemic and environmental impacts. 1Although topical ocular medications are designed for localized treatment and are administered directly on the surface of the eye, there is a significant systemic absorption of these drugs through several pathways. The first of two major pathways is from the lacrimal sac through the nasolacrimal duct into the nasopharynx where drugs can be systemically absorbed through the nasal mucosa. This pathway can easily be circumvented by manually providing pressure to the medial canthus or by closing the eyes for 5 minutes after the instillation of each drop, which will cause compression on the nasolacrimal duct. The other major pathway for systemic absorption is through the conjunctiva and conjunctival blood vessels. Minor pathways of systemic drug delivery are through the pharynx, gastrointestinal tract, skin of the cheeks and the eyelids, aqueous humour, and inner ocular tissues. Special care must be taken when treating the paediatric patients who have a much higher risk of developing systemic side effects, due to inadequate dosage and increased systemic permeability of the drugs. 2Localised adverse effects of topical ocular medications commonly arise due to preservatives, which are used in eye drops and ointments in order to prolong their shelf life and guard against microbiological contamination. Benzalkonium chloride (BAC) is the most used preservative in ophthalmic medications. Clinical studies have extensively examined the toxic effects of BAC, revealing that its prolonged use causes time- and dose-dependent cytotoxicity on the ocular surface, leading to tear film instability and the development of ocular surface disease, dry eye, and Meibomian gland dysfunction 3,4. Therefore, the European Medicine Agency recommends avoiding preservatives in patients who have pre-existing ocular surface disease or who develop dry eye or ocular irritation over time. 3Among eye drops, the most commonly discussed side effects, both local (as stated in Table 1) and systemic, in certain groups of topical ocular medications, pertain to antiglaucoma eyedrops, such as β receptor blockers, α receptor agonists and pilocarpine. Due to their chronic usage, physicians must take special care in choosing the right therapy for their patients as well as monitor for potential adverse events. β receptor blockers have a major limitation in their usage due to their frequent systemic side effects, although they are a potent antiglaucoma medications. Targeting β1-receptor causes reduced cardiac contractility and heart rate, bradycardia, and a blood pressure decrease and β2-receptor targeting leads to exacerbated asthma and chronic obstructive pulmonary disease symptoms. Additionally, central nervous system symptoms such as headaches, depression, and confusion may occur. Betaxolol is a selective β1-receptor antagonist which therefore causes fewer side effects to the respiratory system. 5 When α2 adrenergic agonists are applied, systemic side effects such as dry mouth, dizziness, fatigue, and drowsiness may occur, particularly in patients predisposed to bradycardia.6Excessive use of pilocarpine can also have numerous adverse effects due to its parasympathomimetic action which includes excessive sweating, drooling, bronchospasm, vomiting, diarrhea, stomach-ache, bradycardia, a drop in blood pressure, hallucinations and depression.Special caution also must be taken when prescribing topical ocular or systemic steroid medication. Because of their potential to change the microstructure of the trabecular meshwork, they can induce a rise in intraocular pressure by decreasing aqueous humour outflow and potentially causing the development of steroid induced glaucoma. Prolonged use of topical corticosteroids can also induce cataract formation and increase susceptibility to infection. If used in eyes with epithelial defects, they can inhibit growth factors and delay wound healing.Another group of eye drops which can have substantial systemic effects are mydriatics, such as phenylephrine and atropine. Phenylephrine, a selective α1-receptor, is applied in the form of eye drops for dilating the pupils during ophthalmological examinations. Due to its sympathomimetic effect it can cause major cardiovascular side effects, especially when administered in patients with pre-existing hypertension conditions.7 Atropine is a muscarinic receptor antagonist often used in ophthalmology in the form of eye drops for its mydriatic and cycloplegic effect. When systemically absorbed, it can potentially cause side effects like mouth and eye dryness, flushed skin and face, fever, tachycardia, delirium or restlessness, urinary retention, and constipation. If used in higher doses or over a longer period, in severe cases, central anticholinergic syndrome may occur, which is characterized by confusion, agitation, and hallucinations.8 Mydriatics also affect inner ocular structures. Phenylephrine is linked with a decrease in choroidal thickness, while atropine eye drops are associated with an increase in choroidal thickness. This necessitates careful monitoring of patients on long-term topical therapies for any alterations in choroidal structure because of their potential effect on visual function.9Other eyedrops, such as antiallergics, can also be sometimes used in treating eye conditions. Topical H1-receptor blockers and mast cell stabilizers in the form of antiallergic eye drops infrequently cause systemic side effects following ocular use. When they do occur, these side effects are usually mild, presenting as dry mouth, nausea, headache, or drowsiness.7The environmental effect is another part of pharmaceutical safety profiles which cannot be disregarded. Inappropriate disposal of drugs, including eye medications, poses a significant risk to public health and environmental sustainability by contaminating water supplies and disrupting ecosystems.10 Other than the drug itself, its packaging can also cause substantial waste, as is the case with monodose eye drops. These eyedrops are stored in small single-use containers, in order to prevent microbial growth which can occur in standard eye drop bottles after opening. However, their disposal creates a lot of waste. 11 Pharmaceutical companies should provide education and raise awareness among healthcare providers and patients about how to properly manage pharmaceutical waste.In conclusion, although topical ocular medication is the foundation of ophthalmic treatment, before prescribing physicians must be aware of their safety profiles. Although they are generally considered safe, their potential adverse effects on ocular and systemic health highlights challenges in the management of ocular diseases. Healthcare practitioners should choose preservative-free formulations where possible, monitor for both local and systemic side effects, and act responsibly while taking into consideration the environmental implications of pharmaceutical use. These safety concerns should be further investigated in future studies with the goal of improving therapeutic outcomes for patients while minimizing risks.

In everyday conversation, bilingual individuals switch between languages not only in reaction to monolinguals with different language profiles but also voluntarily and naturally. However, whether and how various switching contexts dynamically modulate the domain-general control were still illusive. Using a cross-task paradigm which flanker task was interleaved with language switching task trial-by-trial, the present study manipulated forced, voluntary and natural switching contexts. A group of unbalanced Chinese-English bilinguals performed a flanker task in the three switching contexts. The results showed that the cross-domain interaction on the P3 effect revealed an atypical flanker effect in forced switching contexts only, and P3 amplitude of incongruent trials in forced switching contexts was smaller than both natural and voluntary switching contexts. Furthermore, the robust brain-brain and brain-behavior relationships between language control and domain-general control were significantly emerged in the forced switching context only. Altogether, our findings support the dynamic adaptation of language control to cognitive control and highlight the importance of switching contexts.

Aiming at the optimal scheduling problem of virtual power plant ( VPP ) with multiple uncertainties on the source-load side, this paper proposes a two-stage stochastic robust optimal scheduling method considering the uncertainty of the source-load side. This method combines the characteristics of robust optimization and stochastic optimization to model the source-load uncertainty differentiation. The Wasserstein generative adversarial network with gradient penalty ( WGAN-GP ) is used to generate electric and thermal load scenarios, and then K-medoids clustering is used to obtain several typical scenarios. The min-max-min two-stage stochastic robust optimization model is constructed, and the column constraint generation ( C & CG ) algorithm and dual theory are used to solve the problem, and the scheduling scheme with the lowest operating cost in the worst scenario is obtained.

This study presents a procedure based on constant amplitude (CA) fatigue data to predict the statistical fatigue lifetime of glass/orthopolyester composites subjected to repeated ordered and random two, three, and six sequences of block loadings. A numerical routine was developed to detect cycle-by-cycle the statistical strength degradation progression until failure, assuming that the strength at the end of a block cycle equals the strength at the start of the successive one and that the individual samples’ static strength, residual strength, and fatigue life share the same rank in their respective cumulative distribution function. Predictions conform to the statistically undetectable loading sequence effects and lightly overestimate the lifetimes of random and ordered high-to-low (1/100 cycles) repeated two-block loadings. The vanishing effect of the loading sequence when the block extents remain fixed, the block extent effects for a given three-block sequence, and the lifetimes of three-block loadings were fully predicted. The six-block sequence’s experimental lifetimes with different block loading orders and block extent fell within the predicted lifetimes’ cumulative distribution function. A reliable damage rule based on residual strength was proposed and compared to the Miner’s rule.

Monacolin K is a valuable secondary metabolite produced after a period of fermentation by Monascus purpureus; however, our current understanding of the regulatory mechanisms of its synthesis remains incomplete. This study conducted functional analysis on the key transcription factor, comp54181_c0, that is involved in the synthesis of monacolin K in Monascus. Mutant strains with either knockout or overexpression of comp54181_c0 were constructed using CRISPR/Cas9. A comparison between the knockout and overexpression strains revealed changes in fungal morphology and growth, with a significant increase in the production of Monascus pigments and monacolin K when comp54181_c0 was absent. Real-time fluorescence quantitative PCR analysis revealed that comp54181_c0 significantly influenced the transcription of key genes related to monacolin K biosynthesis in Monascus. In conclusion, our study elucidates the crucial role of comp54181_c0 in Monascus, enriches our understanding of fungal secondary metabolite development and regulation, and provides a foundation for the development and regulation of Monascus and monacolin K production.

Plants maintain iron (Fe) homeostasis under varying environmental conditions by balancing processes such as Fe uptake, transport, and storage. In Arabidopsis, POPEYE (PYE), a basic helix-loop-helix (bHLH) transcription factor (TF), has been shown to play a crucial role in regulating this balance. In recent years, the mechanisms regulating Fe uptake have been well established but the upstream transcriptional regulators of Fe transport and storage are still poorly understood. In this study, we report that ELONGATED HYPOCOTYL5 (HY5), a basic leucine zipper (bZIP) TF which has recently been shown to play a crucial role in Fe homeostasis, interacts with PYE. Molecular, genetic and biochemical approaches revealed that PYE and HY5 have overlapping as well as some distinct roles in regulation of Fe deficiency response. We found that HY5 and PYE both act as a repressor of Fe transport genes such as YSL3, FRD3 NPF5.9, YSL2, NAS4, and OPT3. HY5 was found to directly bind on the promoter of these genes and regulate intercellular Fe transport. Further analysis revealed that HY5 and PYE directly interact at the same region on PYE and NAS4 promoter. Overall, this study revealed that HY5 regulates Fe homeostasis by physically interacting with PYE as well as independently.

Squalene (C30H50) is an acyclic triterpenoid compound renowned for its myriad physiological functions, such as anticancer and antioxidative properties, rendering it invaluable in both the food and pharmaceutical sectors. Owing to the constraints on natural resources, microbial fermentation has emerged as a prominent trend. Schizochytrium sp. known to harbor the intact Mevalonate (MVA) pathway, possesses the inherent capability to biosynthesize squalene. However, there is a dearth of reported key genes in both the MVA pathway and the squalene synthesis pathway, along with the associated promoter elements for their modification. This study commenced by cloning and characterizing 13 endogenous promoters derived from transcriptome sequencing data. Subsequently, five promoters exhibiting varying expression intensities were chosen from the aforementioned pool to facilitate the overexpression of the squalene synthase gene SQS, pivotal in the MVA pathway. Ultimately, a transformed strain designated as SQS-3626, exhibiting squalene production 2.8 times greater than that of the wild-type strain, was identified. Lastly, the optimization of nitrogen source concentrations and trace element contents in the fermentation medium was conducted. Following 120 hours of fed-batch fermentation, the accumulated final squalene yield in the transformed strain SQS-3626 reached 2.2 g/L.

Delivering in or out of water, the OASI rates in the POOL cohort study are disturbingly highDear Dr Papageorghiou,We have read with interest the POOL study report by Sanders et al. published in your journal.1 We acknowledge that the results of this study are based on a large obstetric cohort of low-risk women.The mere conclusion of the authors is that birth in water is not associated with increased risks for mothers and babies. However, in doing so, they seem to have overlooked an important issue related to the event rate in their comparator group. Indeed, the reported obstetric anal sphincter injury (OASI) rates of 5.0% in nulliparous and 1.3% in multiparous women are remarkably, if not unacceptably high. Particularly, given the risk for serious, often untreatable complications strongly associated with such injury.The reported event rates in the pool study are an outlier when compared to the 1.6% reported in other studies.3 The reported rates in the POOL study are comparable to those reported by Gurol-Urganci et al.4 Nonetheless, 20% of the women in the Gurol-Urganci et al study had operative vaginal births, a strong risk factor for OASI. In contrast, the POOL study cohort were all low-risk spontaneous births.The POOL study describes women delivering in and out of water, but the authors do not comment if manual perineal protection was used or not in either of the groups. Applying interventions, like manual perineal protection at the time of water birth may be challenging and does not tend to be attempted in some healthcare settings.Manual perineal protection was earlier associated with a significant reduction in OASI risk in Norway and Denmark and the UK. Fodstad et al. describe that the OASI prevalence in Norway in all vaginal deliveries has reduced from 4.2% in 2004 to 1.6% in 2023, after introduction of a national program with manual perineal protection.3Gurol-Urganci et al. have also demonstrated a significant reduction OASI rates in a healthcare setting comparable to that of Saunders et al. Moreover, the RCOG and, more recently, the published report from the All-Party Parliamentary Group on Birth Trauma have recommended the roll out and implementation, underpinned by sufficient training, of the OASI care bundle to all hospital trusts to reduce risk of perineal injuries in childbirth.4 Hence, it would have been expected that a UK based study using perineal trauma as its primary outcome would address and discuss what interventions were undertaken to mitigate the risk of trauma.We believe that there is a high risk that the exceptionally high OASI rate in the comparator arm has introduced bias in this non-inferiority RCT. Sanders et al conclude that their “Study findings provide reassurance that birth in water, in the context of UK midwifery practice, is not associated with increased risks for mothers or their babies. However, given the 2015 Supreme Court Montgomery ruling stating that “clinicians should disclose risks of childbirth” one should question, why the risk of childbirth in the POOL study was so unacceptably high and still remained undiscussed?Jan Willem de Leeuw, Department of Obstetrics and Gynaecology, Ikazia Ziekenhuis Rotterdam, the NetherlandsKatariina Laine, Norwegian Research Centre for Women’s Health, Oslo University Hospital, Oslo, Norway, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, NorwayMargareta Manresa, Clinic Institute of Gynaecology, Obstetrics and Neonatology, Hospital Clinic of Barcelona, Barcelona, SpainSari Raisanen, Laurea University of Applied Sciences, Vantaa, FinlandVladimir Kalis, Department of Obstetrics and Gynaecology, Faculty of Medicine in Pilsen, Charles University, Center for Pelvic-floor Disorders, Pilsen, CzechiaZdenĕk Rušavý, Department of Obstetrics and Gynaecology, Faculty of Medicine in Pilsen, Charles UniversityRenaud de Tayrac, Obstetrics and Gynaecology Department, Nimes University Hospital, University of Montpellier, Nimes, France

A document by Shrijan Shrestha. Click on the document to view its contents.

Optimal Timing and Feasibility of Single-Port Laparoscopic Ovarian Cystectomy on Postpartum Day Two After Vaginal DeliveryA 25-year-old woman presented at 39 weeks and 5 days of gestation, delivering vaginally at 40 weeks and 3 days. Initially, a 5 cm ovarian cyst was detected via early pregnancy ultrasound, remaining asymptomatic. Subsequent monitoring revealed an increase in cyst size to approximately 15 cm. Two days post-delivery, she underwent transumbilical single-port laparoscopic surgery, with a 2.5 cm incision at the umbilicus allowing access for cyst removal. The surgery revealed a 15 cm cyst on the left ovary and an enlarged uterus. Approximately 1500 mL of clear fluid was aspirated via a lotus suture, with the cyst wall excised and the ovary sutured under direct visualization. Immediate pathology confirmed a serous cyst. The patient recovered well and was discharged 48 hours later. Representative surgical images are provided in Fig.1.During the puerperal period, the uterus enlarges and the adnexa ascend, facilitating their extraction through the single incision. The abdominal wall laxity eases single-port enlargement, aiding in suture placement and improving cosmetic outcomes [1].Managing ovarian cysts during pregnancy involves risks of adverse outcomes, such as miscarriage or preterm labor [2]. Enlarged uterus poses challenges, increasing risks of complications like ovarian torsion and rupture, necessitating emergency interventions if managed post-delivery [3]. For asymptomatic giant ovarian cysts carried to full term, timely postpartum single-port laparoscopic surgery may be beneficial, leveraging physiological changes to reduce risks and improve surgical outcomes. These findings highlight the importance of optimal timing for surgical intervention in cases of ovarian cysts during pregnancy.

Cancer is a complex and heterogeneous disease characterized by uncontrolled cell growth and proliferation. One hallmark of cancer cells is their ability to undergo metabolic reprogramming, which allows them to sustain their rapid growth and survival. This metabolic reprogramming creates an immunosuppressive microenvironment that facilitates tumour progression and evasion of the immune system. In this paper, we review the mechanisms underlying metabolic reprogramming in cancer cells and discuss how these metabolic alterations contribute to the establishment of an immunosuppressive microenvironment. We also explore potential therapeutic strategies targeting metabolic vulnerabilities in cancer cells to enhance immune-mediated anti-tumour responses.

1 INTRODUCTIONKawasaki Disease (KD) is a rare entity but one of the most common pediatric vasculitis. It predominantly affects the pediatric population, generally before the age of 5 years with coronary artery aneurysms being the most feared complication; however, due to the broader disease spectrum, patients can present with diverse clinical presentations [1]. Coronary aneurysms generally develop after two weeks of disease onset in about 25% of cases [2]. The standard treatment includes IV immunoglobulin and aspirin [3]. There are no specific laboratory markers and the diagnosis is mainly based on a set of clinical criteria, featuring prolonged fever, polymorphous rash, conjunctivitis, mucosal changes, lymphadenopathy, and extremity changes [4]. Systemic arterial aneurysm formation is a very rare entity, affecting 0.8% to 2% of the cases, approximately 3 months after disease onset [5].