Rosai Dorfman Disease of Nose and Paranasal Sinuses: An Incidental Discovery.

Rosai Dorfman disease is a benign lymphoproliferative disorder. Isolated extranodal involvement is rarely encountered. The causation has not been attributed to any particular factor and the clinical progress of the disease is varied. Treatment options range from observation to medical therapy to surgical excision. Long term follow up is advocated. We report an elderly female with complaints of nasal obstruction who underwent ESS and was diagnosed with this disease on account of histopathology. Follow up period has been uneventful. The case report illustrated here is aimed at highlighting high index of suspicion as well as creating awareness regarding diagnosis and management of a rarely seen pathology.

Mechanisms of well iron clogging in groundwater heat pump systems: Insights from video imaging, hydrogeochemical analysis, and geochemical modeling.

Groundwater heat pump (GWHP) systems are increasingly popular as low-carbon and environmentally friendly technologies, but well clogging induced by iron remains a significant issue. This study investigated the clogging characteristics and biogeochemistry of three typical wells (pumping, injection, and observation wells) in an operating GWHP system using video imaging, sampling, and analysis of hydrogeochemical and microbial data. The results revealed that iron-induced well clogging is a complex process involving physical, chemical, and microbial factors. Pumping wells experience clogging due to water mixing with varying redox conditions, resulting in hematite-based iron oxide deposits. Injection wells exhibit higher clogging severity, with transformed oxidation and accumulation of reduced iron minerals at the solid-liquid interface, resulting in darker colored clogs with magnetite. Clogging in both extraction and injection wells is closely related to iron-rich aquifer sections, where severe clogging occurs. Shallow clogging due to iron oxide is limited and attributed to the oxidation of zero-valent iron in well casing material. Iron-oxidizing bacteria and iron-reducing bacteria were detected in the consolidated deposits of clogged wells, indicating their involvement in the clogging formation process. Moreover, a strong correlation was observed between the presence of nitrate-reducing bacteria in the water phase and the severity of clogging, suggesting a possible link between iron oxidation and nitrate reduction in the system. Geochemical modeling results further supported the observed clogging severity in GWHP systems and confirmed varying clogging mechanisms in different wells and depths. These findings contribute to the understanding of clogging in GWHP operations, aiding in robust water utilization and energy-saving efforts, and supporting global carbon reduction initiatives.

Safety and efficacy of histotripsy delivery through overlying gas-filled small bowel in an ex vivo swine model.

PURPOSE: To evaluate the safety and efficacy of performing histotripsy through overlying gas-filled bowel in an ex vivo swine model. METHODS: An ex vivo model was created to simulate histotripsy treatment of solid organs through gas-filled bowel. Spherical 2.5 cm histotripsy treatments were performed in agar phantoms for each of five treatment groups: 1) control with no overlying bowel (n = 6), 2) bowel 0 cm above phantom (n = 6), 3) bowel 1 cm above phantom (n = 6), 4) bowel 2 cm above phantom (n = 6), and 5) bowel 0 cm above the phantom with increased treatment amplitude (n = 6). Bowel was inspected for gross and microscopic damage, and treatment zones were measured. A ray-tracing simulation estimated the percentage of therapeutic beam path blockage by bowel in each scenario. RESULTS: All histotripsy treatments through partial blockage were successful (24/24). No visible or microscopic damage was observed to intervening bowel. Partial blockage resulted in a small increase in treatment volume compared to controls (p = 0.002 and p = 0.036 for groups with bowel 0 cm above the phantom, p > 0.3 for bowel 1 cm and 2 cm above the phantom). Gas-filled bowel was estimated to have blocked 49.6%, 35.0%, and 27.3% of the therapeutic beam at 0, 1, and 2 cm, respectively. CONCLUSION: Histotripsy has the potential to be applied through partial gas blockage of the therapeutic beam path, as shown by this ex vivo small bowel model. Further work in an in vivo survival model appears indicated.

Peppermint essential oil enhances the vase life of Dendrobium orchids.

To extend the vase life of cut flowers, there is now a trend of using plant essential oils in place of synthetic chemicals, as they are fully biodegradable, more eco-friendly, and safer. The objective of this study was to examine the possible application and postharvest quality effects of three plant essential oils namely, ginger (Zingiber officinale Roscoe), peppermint (Mentha piperita L.), and citronella (Cymbopogon nardus Rendle), as natural vase solution for cut Dendrobium flowers. Peppermint essential oil showed promise as a holding solution for extending the vase life of Dendrobium orchids. To confirm vase life extension, emulsions containing peppermint essential oil at concentrations of 50 and 100 µg mL-1 combined with 4 % glucose to formulate holding solutions applied to Dendrobium orchids. Vase life, some biochemical changes, electrolyte leakage, total microbial count in the holding solution, and physical condition via scanning electron microscopy (SEM) were evaluated over a period of 25 days. The three major compounds in peppermint essential oil were identified as menthol (33.24 %), 1-menthone (18.91 %) and menthofuran (14.85 %). The essential oil was applied in emulsion form as a holding solution. Treatment with 4 % glucose and either 50 or 100 µg mL-1 peppermint essential oil prolonged the vase life of Dendrobium orchids to up to 28 days. Scanning electron microscopy on Day 7 showed that the xylem vessels of treated orchids remained clear, suggesting reduced microbial plugging at the stalk end. Similarly, on Day 20, a reduced microbial cell count was observed for treated orchids (<1 log CFU mL-1) in comparison with controls (7.20 ± 0.04 log CFU mL-1). Finally, the essential oil improved flower quality by helping preserve petal membrane stability and petal anthocyanin content. Our results suggest the application of peppermint essential oil as a novel alternative to chemicals used in holding solutions for extending the vase life of Dendrobium orchids.

Decoding ferroptosis: Revealing the hidden assassin behind cardiovascular diseases.

The discovery of regulatory cell death processes has driven innovation in cardiovascular disease (CVD) therapeutic strategies. Over the past decade, ferroptosis, an iron-dependent form of regulated cell death driven by excessive lipid peroxidation, has been shown to drive the development of multiple CVDs. This review provides insights into the evolution of the concept of ferroptosis, the similarities and differences with traditional modes of programmed cell death (e.g., apoptosis, autophagy, and necrosis), as well as the core regulatory mechanisms of ferroptosis (including cystine/glutamate transporter blockade, imbalance of iron metabolism, and lipid peroxidation). In addition, it provides not only a detailed review of the role of ferroptosis and its therapeutic potential in widely studied CVDs such as coronary atherosclerotic heart disease, myocardial infarction, myocardial ischemia/reperfusion injury, heart failure, cardiomyopathy, and aortic aneurysm but also an overview of the phenomenon and therapeutic perspectives of ferroptosis in lesser-addressed CVDs such as cardiac valvulopathy, pulmonary hypertension, and sickle cell disease. This article aims to integrate this knowledge to provide a comprehensive view of ferroptosis in a wide range of CVDs and to drive innovation and progress in therapeutic strategies in this field.

Nanoparticle-Mediated Immunotherapy in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is an aggressive subtype with the worst prognosis and highest recurrence rates. The treatment choices are limited due to the scarcity of endocrine and HER2 targets, except for chemotherapy. However, the side effects of chemotherapy restrict its long-term usage. Immunotherapy shows potential as a promising therapeutic strategy, such as inducing immunogenic cell death, immune checkpoint therapy, and immune adjuvant therapy. Nanotechnology offers unique advantages in the field of immunotherapy, such as improved delivery and targeted release of immunotherapeutic agents and enhanced bioavailability of immunomodulators. As well as the potential for combination therapy synergistically enhanced by nanocarriers. Nanoparticles-based combined application of multiple immunotherapies is designed to take the tactics of enhancing immunogenicity and reversing immunosuppression. Moreover, the increasing abundance of biomedical materials holds more promise for the development of this field. This review summarizes the advances in the field of nanoparticle-mediated immunotherapy in terms of both immune strategies for treatment and the development of biomaterials and presents challenges and hopes for the future.

A Study on the Effect of Lidocaine-Assisted Non-Coring Needle Placement Using Painless Encircling Puncture in Children with Totally Implantable Venous Access Device.

Purpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD). Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test. Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23±6.17 VS 7.89±2.38). The difference between the two groups had statistical significance (P < 0.05). Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.

Endolymphatic duct blockage surgery vs. intratympanic steroids for treatment of refractory Ménière's disease.

PURPOSE: To compare the effectiveness of the Endolymphatic duct blockage (EDB) and intratympanic methylprednisolone(ITMP) injection to control refractory Ménière's disease(MD) symptoms and evaluate their impact on hearing level. STUDY DESIGN: Retrospective study in a tertiary care center. METHODS: 36 received ITMP injection and 52 EDB. Mean outcome measures at 24 months included vertigo control, tinnitus, aural fullness and hearing level: pure-tone average (PTA), bone conduction average(BCA) and speech discrimination score(SDS). RESULTS: At 24 months postoperatively, 90.4% of the EDB group had complete control of vertigo and 43.4% of the ITMP group (p = 0.001). There was no significant difference in tinnitus or aural fullness control (p = 0.34 and p 0.21 respectively). In each group, the drop in tinnitus and aural fullness frequency at 24 months were significant for EDB (p = 0.03; p < 0.001 respectively) and for ITMP group in tinnitus (p = 0.03) but not aural fullness (p = 0.063). At 24 months, PTA, BCA and SDS were significantly worst in the ITMP group when compared to preoperative levels (p = 0.038, p = 0.027, p = 0.016). PTA in the EDB group was stable with no difference compared to ITMP group (p = 0.48). BCA and SDS in the EDB group were stable and better than the ITMP group (p = 0.032; p = 0.036). In each group, vestibular paresis was not significantly different before (p = 0.06) and after treatment (p = 0.68). CONCLUSION: EDB is more effective than the ITMP for controlling the vertigo symptoms of Ménière's disease and in preserving hearing function. It is a novel surgical technique with promising results for a complete treatment of Ménière's disease. ITMP decreases the frequency and the severity of the symptoms but only control vertigo in 27.8% of cases.

Antiproliferative and Pro-Apoptotic Activity and Tubulin Dynamics Modulation of 1H-Benzimidazol-2-yl Hydrazones in Human Breast Cancer Cell Line MDA-MB-231.

(1) Background: The aim of the work is the evaluation of in vitro antiproliferative and pro-apoptotic activity of four benzimidazole derivatives containing colchicine-like and catechol-like moieties with methyl group substitution in the benzimidazole ring against highly invasive breast cancer cell line MDA-MB-231 and their related impairment of tubulin dynamics. (2) Methods: The antiproliferative activity was assessed with the MTT assay. Alterations in tubulin polymerization were evaluated with an in vitro tubulin polymerization assay and a docking analysis. (3) Results: All derivatives showed time-dependent cytotoxicity with IC50 varying from 40 to 60 µM after 48 h and between 13 and 20 µM after 72 h. Immunofluorescent and DAPI staining revealed the pro-apoptotic potential of benzimidazole derivatives and their effect on tubulin dynamics in living cells. Compound 5d prevented tubulin aggregation and blocked mitosis, highlighting the importance of the methyl group and the colchicine-like fragment. (4) Conclusions: The benzimidazole derivatives demonstrated moderate cytotoxicity towards MDA-MB-231 by retarding the initial phase of tubulin polymerization. The derivative 5d containing a colchicine-like moiety and methyl group substitution in the benzimidazole ring showed potential as an antiproliferative agent and microtubule destabilizer by facilitating faster microtubule aggregation and disrupting cellular and nuclear integrity.

A dataset of blockade, vandalism, and harassment activities for the cause of climate change mitigation.

Environmental activism is crucial for raising public awareness and support toward addressing the climate crisis. However, using climate change mitigation as the cause for blockade, vandalism, and harassment activities might be counterproductive and risk causing negative repercussions and declining public support. The paper describes a dataset of metadata of 89 blockade, vandalism, and harassment events happening 13 countries in recent years. The dataset comprises three main categories: 1) Events, 2) Activists, and 3) Consequences. For researchers interested in environmental activism, climate change, and sustainability, the dataset is helpful in studying the effectiveness and appropriateness of strategies to raise public awareness and support. For researchers in the field of security studies and green criminology, the dataset offers resources to study features and impacts of blockade, vandalism, and harassment events. The Bayesian Mindsponge Framework (BMF) analytics was employed to validate the dataset. Consequently, the estimated result aligns with the Mindsponge Theory's theoretical reasoning.

Sixth order compact multi-phase block-AGE iteration methods for computing 2D Helmholtz equation.

We discuss sixth order accurate 9-point compact 2- and 3-phase block alternating group explicit (block-AGE) iteration methods for computing 2D Helmholtz equation. We use Dirichlet boundary conditions and no fictitious points are involved outside the solution region for computation. The proposed 2- and 3-phase block-AGE methods require only two and three sweeps for computation and the error analysis of the suggested approximation is analyzed. We have compared the 2- and 3-phase block-AGE iteration methods with the corresponding block successive over relaxation (block-SOR) method in three experiments, in regard to number of iterations required for convergence and cpu time, where the importance of the role performed by optimal relaxation parameters of the proposed block-AGE iteration methods become evident in stipulating the convergence and precision of the calculated results. In all cases we use the tridiagonal solver and obtain the optimal relaxation parameters through computation.

Hormone Receptor-Positive/HER2-Positive Breast Cancer: Hormone Therapy and Anti-HER2 Treatment: An Update on Treatment Strategies.

Hormone receptor (HR)-positive/HER2-positive breast cancer represents a distinct subtype expressing estrogen and progesterone receptors with an overexpression of HER2. Approximately 14% of female breast cancer cases are HER2-positive, with the majority being HR-positive. These tumors show a cross-talk between the hormonal and HER2 pathways; the interaction has implications for the treatment options for the disease. In this review, we analyze the biology of HR-positive/HER2-positive breast cancer and summarize the evidence concerning the standard of care options both in neoadjuvant/adjuvant settings and in advanced disease. Additionally, we focus on new trials and drugs for HR-positive/HER2-positive breast cancer and the new entity: HER2-low breast cancer.

Chief Complaint: Nasal Congestion.

Nasal obstruction is the subjective perception and objective state of insufficient airflow through the nose. Nasal congestion, conversely, describes a state of not just inadequate airflow or obstructive phenomena but also pressure- and mucus-related states to the patient. Nasal receptors belonging to the transient receptor potential (TRP) protein family mediate the sense of nasal patency via the trigeminal nerve. The transient receptor potential melastatin-8 (TRPM8) responds to temperatures around 8°C to 22°C, and is stimulated by menthol and other cooling agents. The radiant effects of airflow create heat loss to activate these receptors and humans perceive this as nasal patency rather than the direct detection of airflow. The thermovascular state of the mucosa, in conditions such as rhinitis, influence TRPM8 activation. Nasal endoscopy can show signs of rhinitis and should be considered an essential part of the workup of nasal congestion. Efforts to relieve nasal congestion need to manage the mucosal state and surgery needs to ensures that the nasal cavity mucosa is exposed to the cooling effects of airflow rather than simply creating a passage to the nasopharynx.

Elucidating the impact of sanitary waste on the formation of fat, oil and grease deposits in sewer systems.

The accumulation of fat, oil and grease (FOG) deposits in sanitary sewer systems is a significant cause of sewer overflows, mainly due to their tendency to adhere to pipe walls. The aim of this study is to (i) develop laboratory-prepared FOG deposits using a mixture of iron (Fe) and aluminium (Al) metal ions, fatty acids, saccharides and cooked oils, in addition to various sanitary waste materials such as paper towels, wipes and pads and (ii) examine the characteristics of these FOG deposits. The goals of this study were to (i) gain a deeper understanding of the impact of sanitary waste on the formation of FOG deposits and (ii) discuss the detailed physiochemical properties of these FOG deposits. The findings revealed that FOG deposits can vary in nature, appearing as either a smooth, paste-like substance or a coarse, semi-solid material, depending on the types of waste present in the sewer. Analysis of the fatty acid profile indicated that the FOG deposits with wipes have the highest viscosity (3.2 × 104 Pa s) and larger composition of smaller chain saturated fatty acids (caprylic acid 0.64%, undecanoic acid 5.61%, lauric acid 4.65%, myristic acid 3.21% and palmitic 8.38%). In contrast, FOG deposits with Fe and Al metal impurities have higher heat resistance and thermal stability (melting point of 125 °C) and have larger composition of long chain fatty acids. Furthermore, FTIR analysis confirmed that these FOG deposits are composed of metallic salts of fatty acids, aligning with samples from sewer lines. Our results suggest that FOG deposit formation involves the aggregation of excess calcium, which compresses free fatty acid micelles, and a saponification reaction between the calcium aggregates and free fatty acids. This research illuminates the complex processes behind FOG deposit formation and their varied characteristics, providing valuable insights into potential strategies for preventing FOG-related sewer blockages.

Large Vestibular Aqueduct-Associated Symptoms: Endolymphatic Duct Blockage as a Surgical Treatment.

OBJECTIVE: This study aimed to evaluate the effectiveness of endolymphatic duct blockage (EDB) on dizziness control in patients with a large vestibular aqueduct (LVA) and to evaluate its effect on hearing. STUDY DESIGN: This is a prospective nonrandomized study. SETTING: Five adults and one child with dizziness and five children with progressive hearing loss were referred to our tertiary centers. METHODS: The dizziness handicap inventory (DHI) and DHI-PC (dizziness handicap inventory-patient caregiver) questionnaires were used before and after surgery. All patients underwent a preoperative temporal bone HRCT scan and pure tone audiometry one day before surgery, then four and twelve months after surgery and at the last follow-up. The mean follow-up time was 5.6 years. Student's t-test was used to compare DHI/-PC results. RESULTS: The DHI scores were 44, 24, 84, 59 and 56 before surgery, respectively, for Patients 1 to 5. The DHI scores at four months was significantly different, i.e., 4, 6, 0, 7 and 18 (p = 0.001). No differences were found between 4 and 12 months. Patient 6 (child) had Trisomy 21; their DHI-PC score dropped from 38 (preoperative score) to 8 (postoperative score), showing no activity limitations; clinical evaluation showed the complete resolution of symptoms. We found no significant differences between hearing loss before the surgery and at 1 and 12 months post operation for four adult patients. Our fifth adult patient's hearing changed from severe to profound SNHL. For 5 out of 6 pediatric patients, preoperative PTA and mean ABG were 63 dB and 20 dB, respectively; postoperatively, they improved to 42 dB and 16 dB, respectively. The hearing loss level for the sixth pediatric patient dropped from moderate (PTA = 42 dB) to severe (PTA = 85 dB) due to an opening of the endolymphatic sac and a sudden leak of the endolymph. CONCLUSIONS: EDB, using two titanium clips, seems to be helpful for controlling vestibular symptoms and for stabilizing hearing or even to improve hearing in 82% of cases. Nevertheless, there is a risk of hearing worsening.

The interactive force between fat, oil, and grease (FOG) deposits and the effect of food waste disposers on kitchen drainage systems.

Food waste disposers (FWDs) streamline kitchen waste management and facilitate waste classification, whether they would increase the potential of blockage in kitchen drainage system is still unknown. This study conducted a theoretical analysis of the interactive forces between fat, oil, and grease (FOG) deposits and their aggregation on pipe walls. The study involved grading food waste particles processed by FWDs using sieving and weighing techniques to determine the mean weight diameter (MWD) of various aggregations. A full-scale experimental system, implemented in a 60-m high test tower, simulated blockages in horizontal pipes of high-rise buildings. The effect of pipeline materials and particle sizes on blockage were examined by measuring the adhesion of deposits on horizontal pipes. Energy dispersive spectrometer (EDS) analysis suggested that liquid bridge force is a primary factor in aggregate formation. Hand-cut particles formed aggregates with the highest MWD value. Particle size analysis revealed that sizes ranging from 2.36 to 4.75 mm, 1.18-2.36 mm, and 0.60-1.18 mm constituted over 80 % of particles ground by FWDs, with an average size of 2.16 mm. Results of full-scale experiment indicate particle diameters, friction coefficients and lipophilic coefficient significantly affected the propensity of these aggregates to adhere to pipes. Notably, particles processed by FWDs tended to cause blockages more frequently than hand-cut particles. These findings elucidate the deposition mechanism of FOG deposits and offer strategies to reduce blockages in kitchen drainage systems, such as reducing current grinding particle size by 18 % to 1.77 mm or selecting pipes like cast iron and high-density polyethylene.

Experimental study of rainwater grate blocking and submergence of outfall on drainage network capacity.

Accurately evaluating the performance of urban underground drainage network and its influencing factors is a challenging problem, as this process is affected by many complex factors. In this study, based on an overland flow experiment considering drainage process of pipe network, a series of physical model experiments were conducted to investigate the influences of different surface slopes, rainwater grate blockage and the submergence of outfall on the performance of the drainage pipe network system. The hydrographs of surface runoff and pipe network flow were recorded in collection tanks by precise digital pressure sensors to provide comprehensive information about the characteristics of drainage performance in the pipe network. Through a series of experimental data collection and analysis, the following conclusions are drawn from this study: (1) The longitudinal slope of the road decreases the pipe drainage capacity by 1.68%-8.94%, and this reduction effect is more significant with the increase of slope. (2) The blockage of rainwater grate at different locations has different impacts on the road drainage system, the downstream rainwater grate blockage has the most obvious impact on the performance of the drainage system, which reduces the drainage capacity by 22.59%-25.38%. (3) Different submergence degrees of rainwater outlet have different impacts on the drainage system. Under different slopes, the drainage capacity of the pipe network decreases by 1.88%-23.46% with the increase of the submergence degree of the outfall. These experimental results are helpful in understanding the working conditions of urban road drainage system and the influencing factors of the system's drainage capacity, and also provide measured data for verification of relevant numerical models and coefficient calibration.

FASN-mediated fatty acid biosynthesis remodels immune environment in Clonorchis sinensis infection-related intrahepatic cholangiocarcinoma.

BACKGROUND & AIMS: Intrahepatic cholangiocarcinoma (iCCA) is the second most common primary liver cancer and is highly lethal. Clonorchis sinensis (C. sinensis) infection is an important risk factor for iCCA. Here we investigated the clinical impact and underlying molecular characteristics of C. sinensis infection-related iCCA. METHODS: We performed single-cell RNA sequencing, whole-exome sequencing, RNA sequencing, metabolomics and spatial transcriptomics in 251 patients with iCCA from three medical centers. Alterations in metabolism and the immune microenvironment of C. sinensis-related iCCAs were validated through an in vitro co-culture system and in a mouse model of iCCA. RESULTS: We revealed that C. sinensis infection was significantly associated with iCCA patients' overall survival and response to immunotherapy. Fatty acid biosynthesis and the expression of fatty acid synthase (FASN), a key enzyme catalyzing long-chain fatty acid synthesis, were significantly enriched in C. sinensis-related iCCAs. iCCA cell lines treated with excretory/secretory products of C. sinensis displayed elevated FASN and free fatty acids. The metabolic alteration of tumor cells was closely correlated with the enrichment of tumor-associated macrophage (TAM)-like macrophages and the impaired function of T cells, which led to formation of an immunosuppressive microenvironment and tumor progression. Spatial transcriptomics analysis revealed that malignant cells were in closer juxtaposition with TAM-like macrophages in C. sinensis-related iCCAs than non-C. sinensis-related iCCAs. Importantly, treatment with a FASN inhibitor significantly reversed the immunosuppressive microenvironment and enhanced anti-PD-1 efficacy in iCCA mouse models treated with excretory/secretory products from C. sinensis. CONCLUSIONS: We provide novel insights into metabolic alterations and the immune microenvironment in C. sinensis infection-related iCCAs. We also demonstrate that the combination of a FASN inhibitor with immunotherapy could be a promising strategy for the treatment of C. sinensis-related iCCAs. IMPACT AND IMPLICATIONS: Clonorchis sinensis (C. sinensis)-infected patients with intrahepatic cholangiocarcinoma (iCCA) have a worse prognosis and response to immunotherapy than non-C. sinensis-infected patients with iCCA. The underlying molecular characteristics of C. sinensis infection-related iCCAs remain unclear. Herein, we demonstrate that upregulation of FASN (fatty acid synthase) and free fatty acids in C. sinensis-related iCCAs leads to formation of an immunosuppressive microenvironment and tumor progression. Thus, administration of FASN inhibitors could significantly reverse the immunosuppressive microenvironment and further enhance the efficacy of anti-PD-1 against C. sinensis-related iCCAs.

Anesthetic Challenges Associated With Posterior Reversible Encephalopathy Syndrome in a Pregnant Woman Scheduled for a Caesarean Section.

Recently, there has been a rise in reports of posterior reversible encephalopathy syndrome (PRES), which is an uncommon neurologic illness. The precise cause of PRES syndrome is yet unknown, but there are certain illnesses that have been associated with it. Furthermore, because of advances in imaging methods and growing awareness, the connection between PRES and pre-eclampsia/eclampsia is becoming increasingly recognised. Pre-eclampsia/eclampsia by itself poses distinct perioperative difficulties; in addition, PRES makes anesthesia administration more difficult. Regretfully, there is a lack of knowledge regarding the anesthetic treatment provided to the extremely sick and medically complex patients, and it is uncertain whether the chosen anesthetic might exacerbate neurologic problems. Here, we discuss the implications for the anesthetic management of PRES presentations.

[Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria]. / Beyond NICE: Aktualisierte systematische Übersicht zur Evidenzlage der Pubertätsblockade und Hormongabe bei Minderjährigen mit Geschlechtsdysphorie.

Beyond NICE: Updated Systematic Review on the Current Evidence of Using Puberty Blocking Pharmacological Agents and Cross-Sex-Hormones in Minors with Gender Dysphoria Abstract: Objective: The suppression of physiological puberty using puberty-blocking pharmacological agents (PB) and prescribing cross-sex hormones (CSH) to minors with gender dysphoria (GD) is a current matter of discussion, and in some cases, PB and CSH are used in clinical practice for this particular population. Two systematic reviews (one on PB, one on CSH treatment) by the British National Institute for Clinical Excellence (NICE) from 2020 indicated no clear clinical benefit of such treatments regarding critical outcome variables. In particular, these two systematic NICE reviews on the use of PB and CSH in minors with GD detected no clear improvements of GD symptoms. Moreover, the overall scientific quality of the available evidence, as discussed within the above-mentioned two NICE reviews, was classified as "very low certainty" regarding modified GRADE criteria. Method: The present systematic review presents an updated literature search on this particular topic (use of PB and CSH in minors with GD) following NICE principles and PICO criteria for all relevant new original research studies published since the release of the two above-mentioned NICE reviews (updated literature search period was July 2020-August 2023). Results: The newly conducted literature search revealed no newly published original studies targeting NICE-defined critical and important outcomes and the related use of PB in minors with GD following PICO criteria. For CSH treatment, we found two new studies that met PICO criteria, but these particular two studies had low participant numbers, yielded no significant additional clear evidence for specific and clearly beneficial effects of CSH in minors with GD, and could be classified as "low certainty" tfollowing modified GRADE criteria. Conclusions: The currently available studies on the use of PB and CSH in minors with GD have significant conceptual and methodological flaws. The available evidence on the use of PB and CSH in minors with GD is very limited and based on only a few studies with small numbers, and these studies have problematic methodology and quality. There also is a lack of adequate and meaningful long-term studies. Current evidence doesn't suggest that GD symptoms and mental health significantly improve when PB or CSH are used in minors with GD. Psychotherapeutic interventions to address and reduce the experienced burden can become relevant in children and adolescents with GD. If the decision to use PB and/or CSH is made on an individual case-by-case basis and after a complete and thorough mental health assessment, potential treatment of possibly co-occurring mental health problems as well as after a thoroughly conducted and carefully executed individual risk-benefit evaluation, doing so as part of clinical studies or research projects, as currently done in England, can be of value in terms of generation of new research data. The electronic supplement (ESM) 1 is an adapted and abreviated English version of this work.