Potassium-ion batteries (KIBs) represent a promising energy storage solution owing to the abundance of potassium resources. The efficacy of KIBs relies significantly on the electrochemical attributes of both their electrode materials and electrolyte. In the current investigation, we synthesized a layered compound K2[(VOHPO4)2(C2O4)]·2H2O via a heterogeneous nucleation approach and assessed its viability as a cathode material for KIBs. When integrated with a salt-concentrated electrolyte with oxidation stability over 6 V, the compounds exhibits a high discharge potential of 4.1 V (vs. K+/K) alongside a reversible capacity of 106.2 mAh g−1. Furthermore, there is no capacity decay after 500 cycles at 100 mA g−1. This study shows the promise of layered metal organic frameworks as high-potential materials for KIBs.

Background: Existing reviews of pre-eclampsia determinants have focused on clinical and genetic risk factors. Objective: To evaluate social determinants for pre-eclampsia prevention. Search strategy: Systematic searches were conducted on relevant electronic databases to 31 st July 2023. Selection criteria: Reviews and large cohort studies (≥1,000 participants), published within the last 10 years, reporting quantitative associations between social determinant exposures and pre-eclampsia outcomes. Data collection and analysis: Titles and abstracts and then relevant full-texts were reviewed by two reviewers, independently. Strength of association was evaluated as ‘definite’ (odds ratios [OR] or relative risk [RR] ≥3.00 or <0.33), ‘probable’ (OR or RR 1.50-2.99 or 0.33-0.67), ‘possible’ (OR or RR 1.10-1.49 or 0.68-0.89), or ‘unlikely’ (OR or RR 0.90 - 1.09). Quality of the evidence was high, moderate, low, or very-low, using GRADE. Main results: Twenty-six publications found 22 associations of pre-eclampsia with socioeconomic status, social support/exclusion, healthcare access, and occupational and physical environmental factors. One association (polygamy) was definite (low-quality evidence). Probable associations included: work stress and lack of antenatal care (high-quality evidence); prolonged occupational exposure to whole body vibrations or bending, elevated temperatures beyond seasonal norms, and UV-B radiation exposure (protective factor), all based on moderate-quality evidence; and Asian/Oceanian origins (protective, low-quality evidence). There were 11 possible associations, which did not include education. Conclusion: Our findings support recommendations to address climate change, strengthen occupational protection, and promote early ANC attendance. Social determinants may be indicative of upstream factors (e.g., obesity) that increase likelihood of clinical risk factors for pre-eclampsia incidence and severity.

Causal analysis paves the way for more interpretable assessment of complex systems and phenomena, such as human-in-the-loop components of energy systems. This paper will pursue novel approaches for causal analysis of prosumers' behavior. The knowledge of this causality is core for multiple smart grid applications including but not limited to the design of demand side management programs, retail electricity market design, development of effective distributed energy resources aggregation strategies, and net load forecasting. The complex nature of human interactions with energy relies on many factors and understanding behavior causality is a core, unsolved challenge. This paper presents a probabilistic algorithm for discovering causal relationships between the end users' consumption flexibility and its influencing factors. The obtained causal knowledge is then utilized to boost the precision of demand flexibility prediction. Two causal-oriented approaches are proposed to enhance the performance and interpretability of predictive models, incorporating causal information through causal regularization and data preprocessing. Simulation results demonstrate that the algorithm can effectively identify causal probabilities among different factors and unveil key characteristics of the prosumers' behavior. Additionally, these proposed causal-oriented approaches outperform the non-causal oriented predictive models in terms of both performance and interpretability, highlighting the advantages of incorporating causal information.

Failures in ice accretion on power transmission lines during winter and early spring will lead to serious power system issues. This paper innovatively incorporates weather and topographic factors often overlooked due to their non-quantifiable nature. Textual weather and topographic data are quantified and combined with meteorological factors, including temperature, humidity, wind speed, and wind direction, to construct feature vectors. A transmission line ice accretion prediction model is developed using the SVM algorithm and 5-fold cross-validation, employing predicted ice accretion probability as the model output. According to the comparison results of the model before and after feature optimization, the model’s performance improves after incorporating weather and terrain conditions. The precision, recall, accuracy, and AUC reach 94.85%, 80.63%, 88.05%, and 0.9729, respectively, higher than the former’s 85.71%, 78.75%, 82.70%, and 0.9341. Field investigations are also implemented to validate the algorithm, and the results achieved by the proposed algorithm significantly align with ground observation data. Therefore, it is of great significance to prevent the occurrence of power grid icing accidents by incorporating weather and terrain factors into the ice accretion prediction model.

Masquerade is a form of camouflage in which animals use their body size, shape, and coloration to resemble inanimate objects in their environment to deceive predators. However, there is a lack of experimental evidence to show that animals actively choose objects that match these body parameters. To explore how the Hainan four-eyed turtle, Sacalia insulensis, masquerades using suitable stones, we used indoor video surveillance technology to study the preferences of juvenile S. insulensis for stones of different sizes, shapes, and colors. The results indicated that under normal conditions, the turtles preferred larger oval or round brown stones. When disturbed (swinging the arm of a researcher back and forth above the experimental setup every hour to mimic a predator), the turtles showed a preference for brown stones that were closer to their size and oval in shape. These findings suggest that juvenile S. insulensis prefer stones that resemble their carapace size, shape, and color to masquerade when undisturbed, and that this preference is reinforced when they masquerade to reduce the risk of predation. To the best of our knowledge, this is the first study to provide evidence that vertebrates can recognize object shapes and selectively choose objects that resemble their own shape for masquerading to reduce predation risk.

As societies abandon fossil fuels in favor of renewable energy, electric cars and other low-carbon technologies, environmental pressures shift from atmospheric carbon loading to adverse impacts of material extraction and waste flows, new infrastructure development, land use change, and the provision of new types of goods and services. We call for interdisciplinary modeling to investigate this major change in environmental and social burdens and identify systemic demand-led mitigation strategies that explicitly consider planetary boundaries associated with the earth's material resources.

Microalgal biotechnology offers a promising platform for the sustainable production of diverse renewable bioactive compounds. The main difference from other microbial bioprocesses is the crucial role that light plays for cultures since it can be used as a source of environmental information to control metabolic processes. Therefore, we can use these criteria to design a bioprocess that aims to stimulate the accumulation of target molecules by controlling light exposure. We study the effect on biochemical and photobiological responses of Golenkinia brevispicula FAUBA-3 to the exposition of different spectral irradiances (high-fluence PAR of narrow yellow spectrum complemented with low intensity of monochromatic radiations of red, blue, and UV-A) under pre-stress and salinity stress conditions. High light coupled to salinity stress affected the photosynthetic activity and photoprotection mechanisms as shown by maximal quantum yield ( Fv/Fm) and non-photochemical quenching (NPQ max) reduction, respectively. High light treatments combined with the proper dose of UV-A radiation under salinity stress induced the highest carotenoid content (2.75 mg g DW -1) composed mainly of lutein and β-carotene, and the highest lipid accumulation (35.3 % DW) with the highest PUFA content (ALA (C18:3) and LA (C18:2)). Our study can guide the strategies for commercial indoor production of G. brevispicula for high-value metabolites.

Acetogenic Clostridia are obligate anaerobes that have emerged as promising microbes for the renewable production of biochemicals owing to their ability to efficiently metabolize sustainable single-carbon feedstocks. Additionally, Clostridia are increasingly recognized for their biosynthetic potential, with recent discoveries of diverse secondary metabolites ranging from antibiotics to pigments to modulators of the human gut microbiota. Lack of efficient methods for genomic integration and expression of large heterologous DNA constructs remains a major challenge in studying biosynthesis in Clostridia and using them for metabolic engineering applications. To overcome this problem, we harnessed chassis-independent recombinase-assisted genome engineering (CRAGE) to develop a workflow for facile integration of large gene clusters (>10 kB) into the human gut acetogen Eubacterium limosum. We then integrated a non-ribosomal peptide synthetase gene cluster from the gut anaerobe Clostridium leptum, which previously produced no detectable product in traditional heterologous hosts. Chromosomal expression in E. limosum without further optimization led to production of phevalin at 2.4 mg/L. These results further expand the molecular toolkit for a highly tractable member of the Clostridia, paving the way for sophisticated pathway engineering efforts, and highlighting the potential of E. limosum as a Clostridial chassis for exploration of anaerobic natural product biosynthesis.

Polymer crystal hydrates (PCHs) are crystalline solids that form between a polymer and water. To date, only four distinct PCHs have been discovered – one of polyoxa- cyclobutane (POCB) and water, and three different polymorphs of polyethyleneimine (PEI) and water. These PCHs were first reported decades ago andhave fascinating structures and peculiar properties that make them potentially useful for a wide range of applications including refrigeration, proton conduction membranes, and desalination. This perspective revisits what is known about these compounds, categorizes their sim- ilarities and differences with other known compounds, and offers a perspective into future efforts to discover new PCHs to address technological needs for society.

Industrial chemical processes require sulfur-resistant catalysts, which reduce catalyst replacement costs and simplify process operations. Herein, a high-entropy-stabilized strategy was put forward for sulfur-resistant catalysis. A high entropy (Zn0.2Mg0.2Cu0.2Mn0.2Co0.2Al2O4) showed stable performance in CO oxidation with SO2, while unitary oxide and binary spinel oxide were all deactivated. The mechanism study showed that the adsorption of SO2 onto Zn0.2Mg0.2Cu0.2Mn0.2Co0.2Al2O4 was challenging. Moreover, Zn0.2Mg0.2Cu0.2Mn0.2Co0.2Al2O4 has a high degree of disorder, with five metal elements co-temporarily living in one cell location as cations. Thermodynamic equilibrium allows the sacrificial cations to capture the trace SO2 anchor on the Zn0.2Mg0.2Cu0.2Mn0.2Co0.2Al2O4 surface in time to protect the catalytically active cation. This work reveals the significance of high-entropy structures in sulfur resistance and offers a novel design strategy for sulfur-resistant catalysts.

Two nano-precursors with capping agent were incorporated in stearyl alcohol-adipic acid combination phase change material in this study. The addition of nanomaterials made the eutectic reliable in the manner of its thermal properties like higher enthalpy, degradation point and more compatible with the metal encapsulation materials when compared with the pristane eutectic. The importance of nano-metal oxides in parent material was shown by the reduced time frame of the PCM’s thermal energy storing and releasing process for space heating applications. The specific heat capacity of both the aluminium and titanium oxide nanocomposites were greater than the eutectic which indicates that the material can retain more energy. The thermal conductivities of base material and nanocomposite PCMs were 0.2686, 0.2815 and 0.4395 W/mK at 40 °C and the highest percentage increment of nanocomposites was seen as 9.19 and 63.62 % at varied encircled temperatures. The crystal structure and chemical disintegration was evinced with the X-ray diffractometer results of the composites.

Background: Adult T-cell leukemia (ATL) is one of the most important hematological malignancies caused by the HTLV-I virus. The disease has a poor prognosis due to the low median survival of the patients. Aim: Given the need for effective therapeutic interventions, this study aimed to investigate the efficacy of Hyper-CVAD and As/IFN/AZT regimens and compare their performance. Methods and Results: This study is a randomized clinical trial conducted on individuals recently diagnosed with acute ATL. Individuals who tested positive in a HTLV-I serological test based on ELISA and/or PCR were randomly assigned to receive treatment with either Hyper-CVAD or As/IFN/AZT using block randomization. The drug regimens were administered for 60 days, and patients underwent follow-up assessments. Overall, 29 individuals were enrolled in the trial. No significant differences were found in gender distribution, LDH levels, and lymphocyte counts between the two groups (P-value>0.05). The treatment response rates for the Hyper-CVAD and As/IFN/AZT regimens were 46.67% and 35.71%, respectively, with no significant differences between the two groups (P-value >0.05). Survival analysis revealed a significant difference in survival between the two groups, favoring those under the Hyper-CVAD regimen (P-value<0.05). The predominant toxicities were hematological toxicities; one patient in the Hyper-CVAD group experienced Grade 3 toxicity, while three patients in the As/IFN/AZT group experienced Grade 3 toxicity. Conclusion: The results of this study suggest no significant differences in efficacy between the Hyper-CVAD and As/IFN/AZT regimens. Additionally, higher toxicity rates were observed in the As/IFN/AZT regimen. Further investigations into frontline treatments and the timing of the As/IFN/AZT regimen in future studies may provide valuable insights in this regard. Clinical Trial Registration: IRCT20210703051770N1.

In this study, a questionnaire was administered to 634 fathers of preschool children.The results indicated that: (1) father’s involvement and support, child-parent relationship, and preschool children’s social competence were all at the middle level, and there were significant differences across demographic variables such as educational background, average monthly income, residence, and the number of children raised; (2) father’s involvement and support was significant positive correlation with child-parent relationship (r=0.632, p<.001) and preschool children’s social competence (r=0.431, p<.001); while child-parent relationship was positively correlated with preschool children’s social competence (r=0.434, p<.001); (3) structural equation modeling revealed the results: father’s involvement and support significantly predicted child-parent relationship (β=0.737, p<.001) and preschool children’s social competence (β=0.354, p<.001), meanwhile child-parent relationship can significantly positively predict the social competence of preschool children (β=0.169, p<.001); (4) further Bootstrap test shown that child-parent relationship had a significant intermediary effect in the relationship between father’s involvement and support and preschool children’s social competence (95% CI=[0.050,0.387]). The findings suggest that fathers should be mobilized to participate in parenting and provide adequate father support for preschool children to enhance parent-child closeness, mitigate parent-child conflict, and enhance social adaptation and social interaction among children with low social competence.

Lithium salt as a common drug in the clinical treatment of bipolar disorder, its application range is very wide. Lithium ions have many physiological functions, such as improving hematopoietic function, regulating the nervous system, improving heart function, antiviral, immune regulation, and neuroprotective effects. Lithium also has numerous pharmacological effects. For example, it can be used as an emotional stabilizer and has anti-inflammatory effects in dermatology. It also has protective effects against various neurological diseases, leukopenia, hepatitis, pancreatic islet cells, etc. After oral absorption of lithium salt, it can regulate gastrointestinal epithelial ion transport, affect intestinal absorption and secretion, and repair mucosal damage to promote wound healing. In this review, we review in detail the current status of lithium on gastrointestinal physiology and pathology. Based on the multiple regulatory effects of lithium salts on the gastrointestinal tract, we expect to find new drug targets to better treat gastrointestinal diseases.

Room-temperature sodium-sulfur (RT-Na/S) batteries display attractive potential in large-scale energy-storage, but their practical application was still restricted by the serious dissolution of polysulfides. Herein, supported by the constructing of interface engineering, the metal sulfide-carbon nanocomposite can be prepared with considerable electrochemical properties. Utilizing the double-helix structure of carrageenan-metal hydrogels as precursors, in-situ metal sulfide (MxSy) nanostructure/3D carbon aerogels (3D CAs) can be successfully constructed. Importantly, with the assistance of the vulcanization process, 3D carbon architecture was maintained in the composites and act as a skeleton to optimize their structural stability. As the anode of RT-Na/S batteries, ZnS/S@C and NiS2/S@C delivered an excellent cycling stability and rate performance (179.8mAhg−1 at 20Ag−1 after 10000 cycling for ZnS/S@C, 220.3 mAhg−1 at 10Ag−1 after 3000 cycling for NiS2/S@C). The detailed investigation of mechanism revealed that the powerful adsorption for Na2S4 was originated from 3D metal sulfide-carbon structure. The well-designed architecture of sulfide-carbon composites servers as an electrocatalyst to alleviate the shuttle effect of polysulfides, resulting in the long-term electrochemical stability. Given this, the work is expected to provide promising insights for designing advanced anode materials for RT-Na/S batteries.

The increasing prominence of converter-based assets in power systems has raised concerns about grid stability, necessitating the development of advanced performance analysis tools for effective grid planning and operations. To address this issue, we propose an automated architecture based on MATLAB/Simulink, which enables a comprehensive examination of converter-dominated distribution grids. This architecture facilitates analysis across various scenarios, including voltage and frequency instabilities, using techniques such as time domain and small-signal analyses. Moreover, it allows the aggregation of grid models to conduct more detailed studies. The integration of the Common Information Model (CIM) import tool enhances collaboration and interoperability with grid operator data. Case studies were conducted on a 1500-node UK distribution system dataset featuring over 500 dynamic assets to demonstrate the effectiveness of the architecture in analyzing voltage and frequency stability, fault responses, and the impact of energy storage reserve (ESR) under different converter control modes, including legacy grid-following and advanced grid-forming strategies. Furthermore, we outline future enhancements aimed at capturing more intricate converter dynamics and highlight the educational value of the proposed framework, which promises to advance the field of power system dynamic analysis.

In 1968, the idea of Ultimate Frisbee was introduced by Joel Silver. In this short time, it has slowly risen to popularity, but not to the level of other, more established sports. As such, the depth of research that sports like basketball or football athletes can benefit from are far greater than that of ultimate frisbee players. This study aims to assist in remedying that, and answered a central question: What would the ideal short-to-mid range pass look like in Ultimate Frisbee? Throws were simulated and given a rating, a single quantitative measure of the quality of the throw. Since this area has not been investigated in too much depth, this study used broad ranges for initial values of speed, pitch, and spin speed. This work provides a methodology for the analysis of frisbee throws, setting a foundation for future studies, which may look into more specific parameters and complex factors.

The Green Revolution, which entails the use of pesticides, fertilisers, and other agrochemicals, has greatly increased worldwide food production in the last sixty years. Nevertheless, this heightened efficiency has resulted in adverse consequences, including environmental deterioration such as water and land pollution. Land degradation, resulting from both natural phenomena and human actions, has a significant impact on a considerable area of the Earth’s land and affects billions of individuals globally. The annual economic cost of land degradation exceeds $300 billion, resulting from a variety of causes such as insufficient land management and the pressures of population increase. Anthropogenic factors such as deforestation, intensified agriculture, and population growth worsen soil degradation, jeopardising essential ecosystem services and endangering food security. Simultaneously, the increasing release of greenhouse gases and the resulting climate change pose a significant threat to the long-term viability of agriculture. It is imperative to take immediate action to reduce their impact. Given the importance of soil health in sustainable agriculture and climate mitigation, conservation agriculture (CA) is seen as a possible option. Conservation agriculture approaches promote soil health, lower cultivation expenses, and decrease land degradation by minimising soil disturbance, boosting soil organic matter, and stimulating biological activity. Land Degradation Neutrality (LDN) initiatives, which are essential for achieving Sustainable Development Goal 15, provide a structure for achieving a balance between land restoration and degradation. These initiatives highlight the significance of implementing sustainable land management methods. This review compiles up-to-date research on conservation measures that promote Land Degradation Neutrality (LDN) and examines their implications for ecosystem services and policy interventions. The assessment emphasises the importance of sustainable land management and stresses the necessity of collective actions to tackle land degradation concerns and ensure agricultural sustainability in response to increasing environmental risks.

CASE REPORTTITLE: Persistent Hypotension in a Patient on Trifluoperazine Undergoing Staging laparotomy under Combined General and Epidural Anaesthesia: A case report.1. Nirupa Ramakumar, Assistant professor, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India, 2480162. Arnpriya Pal, Junior resident, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India, 2480163. Ruhi Vaid , Senior resident, Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India , 248016Correspondence to:Nirupa Ramakumar,Assistant Professor,Department of Anaesthesiology, Himalayan Institute of Medical Sciences, Dehradun, Uttarakhand, India,248016Email- niru27r@gmail.comABSTRACTRefractory hypotension after combined epidural and general anaesthesia in a patient on trifluoperazine is rare. It is acceptable to continue these drugs; however, the anesthesiologist must be aware of the risk of interaction with other drugs and subsequent hemodynamic pertubations. Early use of nor-adrenaline should be considered to counter refractory hypotension.INTRODUCTIONDoctors prescribe long-term anxiolytic therapy, including benzodiazepines, anti-depressants, and anti-psychotics, to many patients with anxiety disorders. Meta-analyses reveal that India’s prevalence of anxiety neurosis, which ranges between 0.9% and 28.3%, is comparable to global reports. 1 A few case reports report perioperative hypotension in patients on long-term tricyclic depressants (TCAs). 2-4 It is imperative for anesthesiologists to possess knowledge regarding the potential interactions between psychotropic medications and anaesthetic agents. We present a case of persistent hypotension occurring after low thoracic epidural blockade in a patient who was on long-term trifluoperazine (an anti-psychotic drug) for anxiety disorder. This case highlights the importance of vigilant perioperative management of patients on longstanding antipsychotics.CASE PRESENTATIONCase history and examinationA 40-year-old woman (150 cm, 52 kg,BMI 23 kg/m2) was planned for an elective staging laparotomy. The team detected an adnexal mass in the patient. She had a medical history of anxiety disorder for one year and was under regular benzodiazepine (chlordiazepoxide 10mg OD) and anti-psychotic drug (trifluoperazine 1 mg HS) treatment; hypertension was under control with amlodipine 5mg H and atenolol 25mg HS for one year. Her past surgical history included a caesarean section. The patient was independent in routine household chores and had a metabolic equivalent of task >= 4. Her general physical and systemic examinations were normal. Routine preoperative investigations, including a complete hemogram, liver function tests, renal function tests, chest x-rays, and thyroid function tests, were normal. Her electrocardiogram was suggestive of sinus tachycardia. We asked the patient to continue taking her anxiolytics and anti-hypertensive drugs.TreatmentGeneral anaesthesia with epidural anaesthesia was planned to provide good postoperative analgesia considering the nature of surgery. We placed an epidural catheter at the T9-T10 interspace and tested it using 3 ml of 2% lignocaine and adrenaline. A positive meniscus sign was utilised to ensure the correct placement of the catheter. The patient’s pre-induction blood pressure was 130/80 mmHg, and her heart rate was 100 bpm. After a few minutes, the patient complained of feeling dizzy. We made her lie down and took her blood pressure, which was 102/56 mm Hg. We used propofol 100 mg and fentanyl 100 ug for induction. Tracheal intubation was facilitated with atracurium 25 mg, and maintenance of anaesthesia was done using 1% sevoflurane and an O2:air (50:50) mixture. 15 minutes after induction of anaesthesia, bupivacaine (5%) in 6 ml was given through the epidural catheter. The blood pressure reduced to 70/40 mmHg, and the heart rate ranged between 80 and 90 bpm. We administered rapid colloid and crystalloid boluses, along with boluses of mephentramine, but the mean arterial pressure was still lower than 65 mmHg. The surgery then started. We gave hydrocortisone 100 mg intravenously to treat possible adrenal insufficiency or anaphylaxis, but the blood pressure remained low. Blood pressure normalised with 50–100 ug bolus doses of phenylephrine. We administered 3 mg of morphine mixed in 7 ml of normal saline via epidural for analgesia.The ECG showed no abnormalities. We performed an ultrasound to examine the inferior vena caval distensibility index to assess hydration status prior to extubation and found it to be normal. A focused cardiac ultrasound revealed a normal ejection fraction and no other abnormalities. After the patient resumed spontaneous breathing and generated adequate tidal volume, we extubated her.Outcome and follow-upPost-extubation, the patient again had persistent hypotension with a mean arterial pressure (MAP) below 65 mmHg. We started a nor-adrenaline infusion at a rate of 0.03 mcg/kg/min, tapered it to maintain a MAP >65 mmHg, and gradually stopped it after 24 hours. We restarted her anxiolytics and discharged her on post-operative period 5.DISCUSSIONWe encountered a case of persistent hypotension following an epidural injection of lignocaine and adrenaline in a patient who had been on a year-long anxiolytic therapy that continued until the day of surgery. She did not respond to fluid bolusus and mephentramine but did respond to a high dose of phenylephrine and a nor-adrenaline infusion. We considered multiple potential factors contributing to her persistently low blood pressure. Long-lasting subarachnoid blockage leading to severe hypotension didn’t seem likely because aspiration tests done through the epidural catheter came back negative. This meant that the catheter’s accidental displacement wasn’t likely to be the cause. The patient did not exhibit bradycardia at the onset of hypotension, despite the possibility of high thoracic blockade. We were unlikely to attribute the patient’s refractory hypotension to an inadequate cortisol response to stress. Additionally, administering hydrocortisone did not effectively treat her hypotension. Furthermore, there were no indications of drug-related anaphylaxis. The onset of hypotension was influenced by preoperative hypovolemia and acute sympathectomy caused by epidural anaesthesia. However, we hypothesise that the main cause of refractory hypotension was the lack of cardiovascular response to sympathomimetics, likely due to the prolonged use of trifluoperazine (an anti-psychotic drug) until the day before surgery.We classify trifluoperazine as a first-generation antipsychotic drug with typical properties. Some first-generation antipsychotic (AP) drugs work by blocking dopamine receptors, which stops dopaminergic neurotransmission. This can cause a number of adverse effects, with extrapyramidal symptoms being the most common. The inhibition of muscarinic receptors and histamine receptors results in the occurrence of cholinergic side effects and sedation. Moreover, the antagonism of α-1 adrenergic receptors plays a crucial role in the occurrence of orthostatic hypotension and reflex tachycardia. First-generation AP use has been associated with several ECG changes, mainly QT abnormalities.5 The hypotension that occurred did not show improvement with the standard doses of sympathomimetics and fluid replacement. The ECG showed no abnormalities, indicating that AP’s cardiotoxicity was unlikely to have played a role in her hypotension. The normal echocardiographic observations further substantiate the previously stated conclusion.Ramirez reported a case of refractory hypotension in a patient on a high dose of quetiapine undergoing endovascular abdominal aortic aneurysm repair. The blood pressure normalised after starting the nor-adrenaline infusion as it has higher alpha-1 action with less affinity for beta-2 receptors. 6 Tanzer et al. included a study in their systematic review where clozapine caused low blood pressure that was unfixable with intravenous fluids or vasopressors. This happened during surgery. 7Antipsychotic drugs’s resistance to sympathomimetic drugs can be due to strong inhibition of α1-adrenergic activity, which in turn leads to vasodilation and a reflexive sympathetic response. It is likely that the added vasodilation occurred in our patient as a consequence of the combined impact of general and epidural anaesthesia. Furthermore, the concurrent injection of adrenaline has documented an inverse response to profound hypotension.8AP-induced β-blockade, especially in cases of overdose, can lead to uncontrolled β2-agonism when adrenaline is given, which causes a lot of vasodilation and low blood pressure that can’t be fixed with IV fluids and vasopressors.The Society for Perioperative Assessment and Quality Improvement came out with a consensus statement to provide recommendations regarding the use of psychotropic medications to improve perioperative care. They came to the conclusion that, while these drugs are better to be continued to avoid the risk of relapse of the patient’s condition, modifications are required on a case-by-case basis for particular drugs.9 Its crucial to avoid antipsychotic medication in situations of worsening pre-existing low or unstable blood pressures. The study’s findings suggest that sulpiride, amisulpiride, ariprazole, and olazepine have the least significant effects on blood pressure.10CONCLUSIONOur case highlights that the anaesthesia provider must be cautious when administering epidural anaesthesia to patients on long-term, first-generation anti-psychotic drugs. Lignocaine and adrenaline given through the epidural can cause paradoxical hypotension in these patients. All patients with anxiety disorders may experience increased anxiety before any surgical procedure. It is acceptable to continue these drugs; however, the anesthesiologist must be aware of the risk of interaction with other drugs and subsequent hemodynamic pertubations. It is therefore essential to take a detailed medical history. One must weigh the risk-to-benefit ratio of stopping or continuing these drugs. Stopping APs for one day before surgery is unlikely to change the anxiety status, bereft of unwanted cardiovascular effects. Early usage of nor-adrenaline should be considered to counter refractory hypotension.AUTHOR CONTRIBUTION1. Nirupa Ramakumar: This author helped in design of the work, substantial contributions to the conceptions, the acquisition of data, drafting the work and revising it critically for important intellectual content. All the authors approved the final version to be published and are accountable for all aspects of the work in ensuring that questions related to accuracy and integrity of any part of the work are appropriately investigated and resolved.2. Arnpriya Pal: This author helped in drafting of work, analysis, interpretation of data for the work and revising it critically for intellectual content.3.Ruhi Vaid: This author helped in drafting of work, analysis, interpretation of data for the work and revising it critically for intellectual content.ACKNOWLEDGMENTSI would like to thank Mr Mandal, anaesthesua technician in charge for assisting us in management of our patient.CONFLICT OF INTERESTNoneCONSENT STATEMENTWritten informed consent was obtained from the patient for publication of this case report.REFERENCESKhambaty M, Parikh RM. Cultural aspects of anxiety disorders in India. Dialogues Clin Neurosci. 2017;19(2):117-126.Chang HC, Guo SL, Feng YP, Wong CS, Liao JH. Severe Refractory Intraoperative Hypotension in a Patient with Major Depression under Long-Term Antidepressant Treatment: A Case of Left Nephrectomy Surgery. Journal of Medical Sciences. 2018;38(4):192. doi:10.4103/jmedsci.jmedsci_23_18Takakura K, Nagaya M, Mori M, Koga H, Yoshitake S, Noguchi T. Refractory hypotension during combined general and epidural anaesthesia in a patient on tricyclic antidepressants. Anaesth Intensive Care . 2006;34(1):111-114. doi:10.1177/0310057X0603400108Malan TP, Nolan PE, Lichtenthal PR, et al. Severe, Refractory Hypotension during Anesthesia in a Patient on Chronic Clomipramine Therapy. Anesthesiology . 2001;95(1):264-266. doi:10.1097/00000542-200107000-00040Meltzer HY. Update on Typical and Atypical Antipsychotic Drugs. Annual Review of Medicine. 2013;64(Volume 64, 2013):393-406. doi:10.1146/annurev-med-050911-161504Espinós Ramírez C, Artigas Soler A, Gil Esteller P, García Medina N, Tangarife Benjumea J, Martínez García M. Refractory hypotension secondary to chronic treatment with high doses of quetiapine. Revista Española de Anestesiología y Reanimación (English Edition). 2023;70(5):305-307. doi:10.1016/j.redare.2023.05.001Tanzer TD, Brouard T, Pra SD, et al. Treatment strategies for clozapine-induced hypotension: a systematic review. Therapeutic Advances in Psychopharmacology. 2022;12:20451253221092931. doi:10.1177/2045125322109293.Alagappan A, Baruah R, Cockburn A, Sandilands EA. Paradoxical refractory hypotension following adrenaline administration in a patient taking clozapine. BMJ Case Rep. 2021;14(11):e243363. doi:10.1136/bcr-2021-243363.Oprea AD, Keshock MC, O’Glasser AY, et al. Preoperative Management of Medications for Psychiatric Diseases: Society for Perioperative Assessment and Quality Improvement Consensus Statement. Mayo Clinic Proceedings. 2022;97(2):397-416. doi:10.1016/j.mayocp.2021.11.011Proudman RGW, Pupo AS, Baker JG. The affinity and selectivity of α-adrenoceptor antagonists, antidepressants, and antipsychotics for the human α1A, α1B, and α1D-adrenoceptors. Pharmacology Research & Perspectives. 2020;8(4):e00602. doi:10.1002/prp2.602

Title PageTitle: Endobronchial metastasis of fibrosarcoma successfully managed via rigid bronchoscopy: A Case Report

A document by Mehdi Jafarpour. Click on the document to view its contents.

Photoperiod is a pivotal factor in affecting spermatogenesis in seasonal-breeding animals. Transposable elements, a class of DNA sequences that can replicate and translocate in the genome, have regulatory functions during spermatogenesis. However, whether it also functions in photoperiodic spermatogenesis in seasonal breeding animals is unknown. To explore this, we first annotated 5,501,822 transposons in the whole genome of Brandt’s voles (Lasiopodomys brandtii), and revealed that LINEs were the most abundant, comprising 16.61% of the genome. Following closely, SINEs accounted for 10.13%, LTRs for 7.54%, and DNA transposons for 0.70%. Insertion bias analysis revealed that 74.75% of transposons were outside coding genes. Subsequently, we exposed male Brandt’s voles to long-photoperiod (LP, 16 hours/day) and short-photoperiod (SP, 8 hours/day) from their embryonic stages, and obtained testes transcriptome at 4 and 10 weeks after birth. Differential expression and Pearson analysis indicated strongly positive correlations between the expression of differentially expressed retrotransposons and the adjacent genes. KO, KEGG and GSEA results showed that flagellar genes were key target genes regulated by retrotransposons. RT-qPCR results validated the accuracy of the transcriptome using randomly selected six genes (Dnah1, Axdnd1, Ccdc13, Dnah17, Dnah2, Dnali1) and five transposons (LTR/ERVL-MaLR_113132, LINE/L1_1811211, LINE/L1_69082, LINE/L1_662502, SINE/Alu_1213291). RT-PCR results showed that SINE/Alu_1213291 regulates the transcriptional expression of the Dnali1 gene. This study suggests that transposon play a crucial role in the photoperiodic spermatogenesis in Brandt’s voles, especially in the flagella assembly at the late spermiogenesis. Our findings first reveal the regulatory function of transposons in photoperiodic spermatogenesis, providing insights into the role of photoperiod in seasonal reproduction in wild animals.

Aim: To investigate if interventions to discontinue or down-titrate heart failure (HF)-pharmacotherapy are feasible and associated with risks in older people. Methods: A systematic review and meta-analysis were conducted according to PRISMA 2020 guidelines. Electronic databases were searched from inception to March 8th 2023. Randomised controlled trials (RCTs) and observational studies included people with HF, aged >50 years and who discontinued or down-titrated HF-pharmacotherapy. Outcomes were feasibility (whether discontinuation or down-titration of HF-pharmacotherapy was sustained at follow-up) and associated risks (mortality, hospitalisation, adverse drug withdrawal effects [ADWE]). Random-effects meta-analysis was performed when heterogeneity was not substantial (Higgins I2<70%). Sub-analysis by frailty status was conducted. Results: Six RCTs (536-participants) and 27 observational studies (810,499-participants) across six therapeutic classes were included, for 3-260 weeks follow-up. RCTs were conducted in patients presenting with stable HF. Down-titrating a renin-angiotensin system inhibitor (RASI) in patients with chronic kidney disease was 76% likely than continuation (Risk Ratio [RR] 1.76, 95%CI 1.14-2.73), with no difference in mortality (RR 0.64, 95%CI 0.30-1.64). Discontinuation of beta-blockers were feasible compared to continuation in preserved ejection fraction (RR 1.00, 95%CI 0.68-1.47). Participants were 25% likely to re-initiate discontinued diuretics (RR 0.75, 95%CI 0.66-0.86). Digoxin discontinuation was associated with 5.5-fold risk of hospitalisation compared to continuation. Worsening HF was the commonest ADWE. One observational study measured frailty but did not report outcomes by frailty status. Conclusions: The appropriateness and associated risks of down-titrating or discontinuing HF-pharmacotherapy in people aged >75 years is uncertain. Evaluation of outcomes by frailty status necessitates investigation.

Massive malignant phyllodes tumor accompanied by anemia and ulceration in the breast: A case reportAttention:Written informed consent was obtained from the patient to publish this report in accordance with the journal’s patient consent policy.[Abstract] Large malignant breast phyllodes tumors are uncommon in clinical settings. Here, we report such a case to provide a reference for clinical work. A 48-year-old woman discovered a lump in her right breast, which eventually grew to 25 cm by 10 cm and began to rapidly bleed and ulcerate within 3 months. The patient had visible signs of anemia and significant emaciation as a result of the tumor’s wasting effect and the protracted course of the disease. The patient underwent modified radical mastectomy on the right breast. The pathology results obtained after surgery revealed a malignant phyllodes tumor. No adjuvant therapy, such as chemotherapy or radiation, was administered. The patient had no symptoms of tumor recurrence and complications from the surgery after a follow-up of 9 months.[Keywords] Breast cancer; Malignant phyllodes tumor; Diagnosis; Complications; Pathology1.IntroductionPhyllodes tumors of the breast (PTB), formerly known as ”cystosarcoma phyllodes,” are relatively rare in clinical practice, and they account for 0.3%–1% of breast tumors[1]. According to the histological features, the World Health Organization currently divides PTB into three categories, namely benign, borderline (also known as low-grade malignant PTB), and malignant (also known as high-grade malignant PTB)[2]. PTB rarely affects men, and typically affects women between 40 and 50 years of age[3]. In most cases, the clinical signs are unilateral, typically exhibited as a painless mass, and there may be a history of quick growth.The high-risk factors and pathogenesis of PTB are currently unclear. There are hypotheses suggesting that PTB originates from fibroadenomas, but there is still a significant debate[4]. High estrogen status may also be an independent pathogenic factor for PTB[5]. This tumor is a fibroepithelial tumor that contains both stromal and epithelial components. Reduction of the epithelial component is associated with greater malignancy. The characteristics of phyllodes tumors are composed of proliferative stroma accompanied by elongated fissure-like gaps, with the surface of the gaps covered by epithelium. Chromosomal changes are associated with the malignant phenotype of PTB. In borderline and malignant PTB, chromosome 1q amplification is common, and as the degree of amplification increases, malignant behavior increases[6, 7].Phyllodial breast tumors are generally rare, however, their incidence rates have increased in recent years. The clinical manifestations of phyllodial tumors lack specific characteristics but include insidious onset, slow progression, a long medical history, and the main manifestation being rapid growth of painless masses in the affected breast. These characteristics make it difficult to determine the nature of phyllodial tumors without surgery. In the present study, we report a case of a giant malignant phyllodial tumor and emphasize the importance of ”detect, diagnose, and treat early” to avoid serious complications.Case presentation 2.1 Background of the caseA 48-year-old woman with a right breast tumor was admitted to the hospital on February 2, 2023. Six years ago, the patient discovered the tumor in her right breast by chance. The tumor was left untreated and showed no signs of redness, swelling, pain, or ulceration. Three months ago, following a COVID-19 infection, the right breast’s lump rapidly grew, accompanied by bleeding and ulceration but without purulent secretion.2.2 Physical examination and laboratory testsPhysical examination of the patient revealed pale nail beds on both hands, pale eyes, and an anemic face. The skin in the right breast’s lateral quadrant was pigmented, with surface ulceration and bleeding, and the right breast was noticeably bigger than the left one. The left breast showed no signs of skin redness, swelling, nipple depression, dimples, or orange peel sign. The right breast was noticeably enlarged, and the tumor measuring roughly 25 cm by 10 cm protruded from the skin (Figures 1 and 2). The left breast did not have any discernible bulk. There were no swollen lymph nodes palpable in the bilateral supraclavicular area or left armpit, but there was a lymph node measuring roughly 2 cm by 1 cm in the right armpit. Ultrasound examination revealed a mixed echogenic mass of approximately 20 cm by 5.2 cm in the right breast. Blood flow signals were present within the bulk, and the boundary was clearly defined despite the uneven shape. In addition, ultrasound indicated hyperplastic alterations in the left breast. The left axillary region did not appear to have any noticeable anomalous lymph nodes. The right armpit revealed many lymph nodes, and the largest one was 1.6 cm by 0.6 cm in size and had a thicker cortex compared with the normal cortex. Ultrasonography of the right breast tumor indicated that the lesion was BI-RADS4 class 4b (Figure 3). Positron emission tomography–computed tomography (PET-CT) was also performed, and the right breast mass could not be ruled out as a phyllodes tumor with malignant transformation due to (1) its heterogeneous metabolism and mixed density; (2) elevated metabolism of lymph nodes situated in the right axilla and behind the pectoralis major and minor muscles, possibly suggesting the presence of metastasis; (3) slight inflammation in the upper and lower lobes of both lungs; an inflammatory small nodule in the upper lobe of the right lung; localized emphysema in the upper lobe of the right lung; and anemia. Puncture pathology of the right breast fibroepithelial tumor did not show any conclusive indications of malignancy. Because fibroepithelial tumors are heterogeneous and biopsy tissue is limited, it is important to integrate clinical information and, if necessary, perform full lesion resection. Owing to the tumor’s massive size and ulceration, the patient’s blood routine test revealed mild anemia (hemoglobin, 75 g/L) and infection (white blood cell count, 13.68×109/L). Hemoglobin level reached 99 g/L following a 400 mL leukocyte-free suspended red blood cell transfusion and using cephalosporin drugs to treat inflammation.2.3 TreatmentPreoperative diagnosis was a right breast phyllodes tumor (high likelihood of malignancy), and right axillary lymph node metastasis was highly probable. A modified radical mastectomy of the right breast was carried out (Figure 4). About 40 mL of blood was lost during the successful procedure.General morphology of surgical specimens: There was a large lobulated mass in the breast tissue (22 cm × 21 cm × 7.5 cm), with a solid and tough cut surface. The total volume of the breast and axilla measured 24 cm × 23 cm × 8 cm; the area of the spindle skin measured 24 cm × 17 cm; and the diameter of the nipple was 1.8 cm. The breast did not contain any normal glands. The tumor was located 0.1 cm from the superficial fascia. Locally, the tumor affected the skin. A single adipose tissue mass of 8 cm × 7 cm × 2 cm was discovered, and 25 lymph nodes with a diameter of 0.3–2 cm were palpable inside the mass. Microscopic examination (Figure 5) showed a 22 cm × 21 cm × 7.5 cm malignant phyllodes tumor in the right breast. Low-grade fibrosarcoma, characterized by localized ossification, intrusion into the duct to generate papilloma-like morphology, and myofibroblastic differentiation, constituted the sarcoma component. The tumor lacked a distinct capsule, most of which exhibit expansion and progressive growth, local skin invasion, and formation of skin ulcers. The tumor cells showed a wide range of morphologies, including myxoid, sparse, dense, and collagenized cells, and presented mild to severe atypia. Mitotic figures were found in 1–7/10 HPFs. No tumor metastases were found in the axillary lymph nodes, and there was no tumor infiltration of the papillary or superficial fascia (0/25). The postoperative pathological(Figure 6) diagnosis was a malignant breast phyllodes tumor. Immunohistochemistry: -3: CK5/6(−), CKpan(−), SATB2(+), ER(−); -8: Ki-67 (+20%), β-catenin (membrane +), CKpan (−), CD34 (+), CD31 (blood vessels +); -11: Ki-67 (+10% to 20%), Desmin (−), Calponin (foci+), S-100 (−), β-catenin (membrane +).2.4 Outcome and follow-upAfter surgery, the patient made a full recovery. Half a month after the operation, hemoglobin level improved (92 g/L), and no adjuvant therapy, such as chemotherapy or radiation, was administered. At a follow-up 9 months after surgery, the patient has not experienced any associated problems or indications of tumor recurrence thus far.