Rapid Onset Research Articles

Preparation and evaluation of Diclofenac & Aceclofenac pain relieving gel

It is phenyl acetic acid derivative developed as anti-inflammatory agent. It has analgesic anti-inflammatory antipyretic like actions like other NSAIDS. . It is recommended in long term treatment of rheumatoid arthritis, osteoarthritis and enclosing spondylitis. It is also useful acute miscue skeletal disorder post operative pain and dysmenorrhoea Diclofenac sodium gel were developed in seven different formulations) by employing different grades of polymers such as Hpmck4m and Crbopol940. There the various Diclofenac gels are available in market. But the propose gel is formulated with two key ingredients oleoresin, and l linseed oil contribute to anti-inflammatory effect. The formulations were evaluated for various physical parameters, pH spredability, drug release excludability studies drug released mechanisms. Formulation showed maximum drug release of 8 hours and maximum drug. Finally the gel formulations found to be economical and may overcome the draw backs associated with the drug during its absorption. The purpose of the study is to prepare the combination of diclofenac and aceclofenac pain relieving gel. This gel combined form of gel is multifunctional and getting rapid onset of action. And that is to get instant relieve from pain as comparison of plain aceclofenac tablet and plain Diclofenac gel. This formulation is also beneficial for diabetic patient to get cure fast of skin injury and buildup of skin irritation and growth or new epidermis layer of skin in the body.

Remimazolam for anesthesia and sedation in cardiac surgery and for cardiac patients undergoing non-cardiac surgery: a systematic-narrative hybrid review.

Remimazolam, an ultra-short-acting benzodiazepine recognized and approved as an anesthetic and sedative in multiple countries, offers a distinctive pharmacokinetic profile, boasting advantages such as rapid onset, short action duration, and rapid recovery. These attributes may contribute to enhanced hemodynamic stability and a diminished risk of respiratory depression compared to other sedatives. We conducted the first comprehensive systematically structured narrative review to evaluate the role and potential application of remimazolam in cardiac surgery. Twenty-one studies published from 2021 to 2023 delved into remimazolam's application in open cardiac surgery, cardiac catheterization or electrophysiology laboratories, and high-risk cardiovascular patients undergoing non-cardiac surgery. Overall, remimazolam usage was apparently linked to potentially superior hemodynamic stability compared to other hypnotic drugs. However, findings regarding the reduction in postoperative delirium incidence with remimazolam and the doses of remimazolam for anesthesia induction and maintenance were inconsistent across the studies. Though remimazolam has demonstrated potential safety, efficacy, and ease-of-use for both anesthesia induction and maintenance in cardiac surgery patients and high-risk cardiovascular patients undergoing non-cardiac surgery, further research is imperative to delve into specific patient subgroups (e.g., the elderly or emergent procedures) so as to ascertain optimal dose ranges to suit diverse clinical scenarios.

Skillful seasonal prediction of the 2022–23 mega soil drought over the Yangtze River basin by combining dynamical climate prediction and copula analysis

An unprecedented soil moisture drought broke out over the Yangtze River basin (YRB) in the summer of 2022 and lasted until the spring of 2023, caused great economic losses and serious environmental issues. With the rapid onset and long-lasting duration, the mega soil drought challenges the current seasonal prediction capacity. Whether the state-of-the-art climate models provide skillful predictions of the onset, persistence and recovery of the 2022–23 mega soil drought needs to be assessed. Identified by the drought area percentage, here we show that the mega soil drought over the YRB started from July, 2022, reached the peak in August, and diminished in April, 2023. Combined with real-time predictions of monthly precipitation released by three climate models participating in the North American multi-model ensemble (NMME) project, we predict the monthly evolution of the 2022–23 soil drought through a joint distribution between precipitation and soil moisture established by the copula method. The results indicate that the NMME/copula prediction well reproduced the spatiotemporal evolution of the mega soil drought at 1 month lead. Using the climatological prediction that relies on the information of initial soil moisture conditions as the reference forecast, the Brier skill score (BSS) values for NMME multi-model ensemble are 0.26, 0.23 and 0.2 for the forecast lead times increased from 1 to 3 months during the entire soil drought period. Specifically, the BSS is 0.14 at 2 months lead during drought onset stage, and 0.26 at 3 months lead during persistence stage, while it is close to zero at all leads during the recovery stage. Our study implies that climate models have great potential in probabilistic seasonal prediction of the onset and persistency of mega soil drought through combining with the copula method.

Balanoposthitis in type 2 diabetes mellitus within a brief duration: A case report

AbstractThis case report documents the rapid onset of balanoposthitis in a 58‐year‐old male patient diagnosed with type 2 diabetes mellitus just 2 weeks prior. The patient presented with acute penile pain, swelling, and purulent discharge, necessitating circumcision due to balanoposthitis and phimosis. The diagnosis of type 2 diabetes mellitus 14 days prior highlights the potential for rapid development of balanoposthitis despite practicing proper hygiene. This underscores the importance of healthcare practitioners proactively examining the penile area in newly diagnosed diabetic patients to prevent balanoposthitis and, conversely, screening patients with balanoposthitis for type 2 diabetes mellitus.

Formulation and evaluation of mouth-dissolving films of memantine

This present research aims to formulate and evaluate mouth dissolving films using Memantine as model drug to improve bioavailability and facilitate rapid onset of action to relieve vomiting and nausea. The thicknesses of the films were in the range of 0.234 mm to 0.271mm. The weights of the films were found to be in the range of ±10%. The folding endurance of the films was found to be in the range of 38± 1 to 57 ± 2. The surface pHs of all the films were neutral, as there was no color change in the litmus paper. All the films were found to be 98 to 102. The disintegration time of the prepared films ranged from 21sec to 32sec. Acceptable mechanical properties were obtained in batch F-9, and the in vitro disintegration time was below 27 sec. It has been determined that formulations F-9 were found to be satisfactory batches and were optimized for the desirable properties.

CHRONIC INFECTION AND SEVERE MITRAL REGURGITATION: A TRICKY CASE REPORT

Abstract Background Techniques of mitral valve repair has improved in the last decades. Percutaneous approach is now a reliable and safe therapy in those patients with high surgical risk. Of note, the presence of implanted prothesis may increase the risk of endocarditis, especially in those patients experiencing recurrent infection. Case Summary We describe a case of a 75–year–old with medical history of chronic lymphedema. It was characterized by periodical episode (yearly) of cellulitis, with a rapid onset of fever (38.5–39° C), lasting for a few days after paracetamol therapy. Patients had severe mitral valve regurgitation due to prolapse of the posterior leaflet (P2). In December 2022, he had percutaneous edge–to–edge mitral valve. Three months later the patient was admitted to the emergency department of our hospital due to fever without any specific symptoms. The patient was well compensated, normal blood pressure, heart rate and oxygen saturation. He had emocolture which revealed the presence of Staphilococcus lugdunensis. Transesophageal echocardiogram confirmed the presence endocarditis, showing a huge (10x12 mm) vegetation at the level of mitral device (Fig 1 and 2). Patients was then referred to cardiac surgery for urgent mitral valve replacement with mitral bioprothesis (Fig 3). He was treated with ev antibiotic for six weeks after cardiac surgery. Additionally, chronic treatment with amoxicillin 500 mg/day was also prescribed at discharge. After six months follow–up, patients had no signs of endocarditis. Conclusion The management and treatment of chronic infection is of paramount importance to reduce the risk of prothesis infection procedure in patients needing a prothesis implantation. The last European Society of Cardiology guidelines on endocarditis do not provide any recommendation regarding a long–term treatment of patients with high risk of infection (i.e. due to chronic infection) and with an implanted cardiac device/prothesis. We believe this represents an important unmeet need.

Water in nigella oil microemulsion for enhanced oral bioavailability of linagliptin.

Linagliptin is hydrophilic antidiabetic with poor oral bioavailability due to poor permeability and pre-systemic metabolism. The objective was to assess w/o microemulsion for enhanced oral bioavailability of linagliptin. Nigella oil was used as oily phase based on its reported antidiabetic effect. Isopropyl myristate (IPM) or capryol were combined with nigella oil to impart intestinal membrane permeabilizing abilities. Pseudoternary phase diagrams were constructed utilizing nigella oil in presence and absence of isopropyl myristate or capryol as oily phase using Tween 60 as surfactant. W/O microemulsion formulations were selected from the constructed phase diagrams and linagliptin was loaded in the internal aqueous phase at a concentration of 0.5mg/ml. The prepared formulations were physically evaluated and linagliptin in vitro release was monitored. Eventually, the in vivo hypoglycemic effect was assessed using diabetic rats. The developed microemulsions were of w/o type and exhibited Newtonian flow behavior with nigella/capryol microemulsion recording the lowest viscosity. The recorded droplet size values were 104.9, 121.2 and 86.4nm for nigella, nigella/IPM and nigella/capryol microemulsions, respectively. All microemulsion formulations showed slower drug release rate compared with aqueous suspension with nigella/capryol microemulsion showing the highest release rate compared to other microemulsions. Release data from microemulsion best fitted to Higuchi model. In vivo oral hypoglycemic activity measurement reflected a more intensified hypoglycemic effect with rapid onset after oral ingestion of microemulsion compared to linagliptin dispersion. Nigella oil/IPM-based microemulsion was ranked as the most effective. The investigation highlighted the feasibility of w/o microemulsion for enhanced oral bioavailability of hydrophilic drugs like linagliptin.

Rapid onset Cushing's syndrome induced by the ACTH-producing pancreatic neuroendocrine tumor: a therapeutic challenge.

Rapid onset Cushing's syndrome induced by the ACTH-producing pancreatic neuroendocrine tumor: a therapeutic challenge.

Remembering for resilience: nature-based tourism, COVID-19, and green transitions

The COVID-19 pandemic had transformative effects on the tourism sector at an unparalleled scale. With the rapid onset of unprecedented travel restrictions, tourists were abruptly confined to experiences in their regional surroundings that led to new and refreshed relationships with local destinations. This paper draws on qualitative interviews with small tourism businesses in two distinct but proximate nature-based destinations in Ontario, Canada and considers how they responded to the COVID-19 pandemic. Findings are positioned within Holling's Adaptive Cycle to consider implications for ongoing resiliency planning for disturbances relating to climate change. Over a 2-year period (2020–2022), SMEs revealed that after an initially turbulent period they quickly adapted to the absence of international long-haul visitors by embracing a surge in domestic demand for nature-based, outdoor experiences. The paper contributes to the literature on tourism SMEs by connecting experiences of COVID-19 to resiliency planning for future predictable disturbances. Two critical lessons for enhancing destination resiliency are identified: engagement of regional tourism demand, and destination level leadership, through investment in infrastructure and partnerships, can both be harnessed to support SMEs and their communities in transitioning toward a more sustainable, resilient and climate-friendly tourism future. Given the growing demand for tourism businesses to transition away from environmentally harmful practices and a longstanding dependency on economic growth, these resources can help destinations enhance preparedness for future changes to tourism flows driven by decarbonization scenarios and increased climatic impacts.

Rapidly progressing ascites in a pregnancy with a massive fibroid: A case report and review of pseudo-Meigs syndrome.

Meigs syndrome is a classic triad of ascites, pleural effusions, and an ovarian fibroma with resolution following excision. Pseudo-Meigs syndrome presents similarly but is caused by a pelvic mass other than an ovarian fibroma, such as a fibroid. We present a case report of a 33-year-old gravida 2 para 0-0-1-0 woman with a massive, pedunculated fibroid who developed rapid onset of ascites and edema beginning at 5 weeks of gestation. Malignant, cardiac, renal, hepatic, and rheumatologic causes were ruled out. Her symptoms resolved following myomectomy and delivery via cesarean. Pseudo-Meigs syndrome was suspected. Pseudo-Meigs syndrome is a diagnosis of exclusion and requires surgical management for resolution. Pregnancy may be an inciting factor. Myomectomy may be done safely at the time of cesarean.

Aptameric hirudins as selective and reversible EXosite-ACTive site (EXACT) inhibitors

Potent and selective inhibition of the structurally homologous proteases of coagulation poses challenges for drug development. Hematophagous organisms frequently accomplish this by fashioning peptide inhibitors combining exosite and active site binding motifs. Inspired by this biological strategy, we create several EXACT inhibitors targeting thrombin and factor Xa de novo by linking EXosite-binding aptamers with small molecule ACTive site inhibitors. The aptamer component within the EXACT inhibitor (1) synergizes with and enhances the potency of small-molecule active site inhibitors by many hundred-fold (2) can redirect an active site inhibitor’s selectivity towards a different protease, and (3) enable efficient reversal of inhibition by an antidote that disrupts bivalent binding. One EXACT inhibitor, HD22-7A-DAB, demonstrates extraordinary anticoagulation activity, exhibiting great potential as a potent, rapid onset anticoagulant to support cardiovascular surgeries. Using this generalizable molecular engineering strategy, selective, potent, and rapidly reversible EXACT inhibitors can be created against many enzymes through simple oligonucleotide conjugation for numerous research and therapeutic applications.

The Effect of Educational Intervention on Inhaler Technique of Patients in Asian Countries: A Systematic Review

Background: Inhalation therapy is the main line of treatment for the management of various respiratory diseases due to localized delivery and rapid onset of action. Incorrect inhaler technique is very common and subsequently leads to poor disease management. Pharmacist can have a positive impact on patient’s education about proper inhaler technique that can lead to a significant improvement of asthma and COPD management. Objective: The objective of this study was to determine the effectiveness of pharmacist education program on inhaler technique of asthmatic and COPD patients in South Asian countries. The outcome regarding inhalation technique was reviewed and summarized. Methodology: The outcome regarding inhalation technique was reviewed and summarized. For this systematic review, basic electronic academic databases (Scopus, Science Direct, ProQuest, Web of Science and PubMed) were used for the search, along with a manual search on Google Scholar. This systematic review was conducted by following the “Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)” guidelines. Moreover, utilizing the framework of the PECO-S (Population Exposure Comparison Outcome Study design), various observational studies were recruited for this review. The ZEE tool was utilized to minimize the risk of bias among extracted cross-sectional studies. Inclusion criteria included studies on inhaler using patients of all ages from South Asian countries along with the influence of educational intervention outcomes. Results: Out of 2191 studies, 24 studies meeting the inclusion criteria were included in the current review. All of the included studies were about pharmacist intervention on inhaler technique in South Asian countries. Conclusion: The systematic literature review summarizes the impact of educational intervention provided to inhaler using patients from South Asian countries. It was assessed that patient education and counselling produced improvement in inhalation technique of various devices especially metered dose inhalers. The primary outcome of most the studies was the improvement in inhaler technique assessment and enhanced quality of life. Therefore, inhaler technique education to patients should be made compulsory by the Health-care authorities to enhance compliance and effectiveness of inhalational therapy by avoiding irrational use of inhalers.

Additional Results from Two Randomized, Placebo-Controlled Trials of Stiripentol in Dravet Syndrome Highlight a Rapid Antiseizure Efficacy with Longer Seizure-Free Periods.

The efficacy of stiripentol in Dravet syndrome children was evidenced in two randomized, double-blind, placebo-controlled, phase 3 studies, namely STICLO France (October 1996-August 1998) and STICLO Italy (April 1999-October 2000), but data were not fully exploited at the time. This post-hoc analysis used additional information, notably collected during the open-label extension (OLE) month, or reported by caregivers in individual diaries, to evaluate new outcomes. Overall, 64 patients were included (31 in the placebo group, 33 in the stiripentol group) of whom 34 (53.1%) were female. Patients' mean and median (25%; 75%) age were 9.2years (range 3.0-20.7years) and 8.7years (6.0; 12.1) respectively. At the end of the double-blind treatment period, 72% of the patients in the stiripentol group had a≥50% decrease in generalized tonic-clonic seizure (GTCS) frequency, versus 7% in the placebo group (P<0.001), 56% had a profound (≥75%) decrease versus 3% in the placebo group (P<0.001), and 38% were free of GTCS, but none in the placebo group (P<0.001). The onset of stiripentol efficacy was rapid, significant from the fourth day of treatment onwards. The median longest period of consecutive days with no GTCS was 32days in the stiripentol group compared to 8.5days in the placebo group (P<0.001). Further to the switch to the third month OLE, an 80.2% decrease in seizure frequency from baseline was observed in patients previously receiving placebo, while no change in efficacy was observed in those already on stiripentol. Adverse events were more frequent in the stiripentol group, with significantly more episodes of somnolence, anorexia, and weight decrease than in the placebo group. Altogether these new analyses of the STICLO data reinforce the evidence for a remarkable efficacy of stiripentol in Dravet syndrome, with a demonstrated rapid onset of action and sustained response, as also evidenced in further post-randomized trials.

Rapid and sustained antidepressant effects of intravenous ketamine in treatment-resistant major depressive disorder and suicidal ideation: a randomized clinical trial

BackgroundMajor depressive disorder (MDD) is the most disabling and burdensome mental disorder, negatively affecting an individual’s quality of life and daily functioning. the current study was conducted with the aim of investigating the clinical effects of intravenous ketamine on symptoms of MDD and suicidal ideation.MethodsThe current randomized clinical trial was carried out on 64 patients diagnosed with treatment-resistant major depressive disorder between April and August 2022. The participants were randomly assigned to two groups: the intervention group received a dose of 0.5 mg/kg of ketamine, while the control group received normal saline. The Montgomery-Asberg Depression Scale and Beck’s Suicidal Ideation Scale were utilized to assess depression and suicidal ideation, respectively.ResultsOne hour after the administration of ketamine treatment, there was a notable and significant improvement in both depression symptoms (35.16 ± 8.13 vs. 14.90 ± 10.09) and suicidal ideation (6.74 ± 6.67 vs. 0.42 ± 1.52). Moreover, there were statistically significant differences in depression scores between the two groups at one hour, four hours, one day, three days, one week, one month, and two months after the administration of ketamine (p-value < 0.001). However, ketamine recipients frequently experienced side effects such as increased heart rate, headache, dizziness, and dissociative syndrome symptoms.ConclusionThe observed rapid onset of action and sustained effect demonstrate the potential of ketamine to provide relief from depressive symptoms in a shorter timeframe compared to traditional treatment approaches. These findings contribute to the growing body of evidence supporting the use of ketamine as a valuable therapeutic option for patients with treatment-resistant depression.IRCT registrationIRCT registration number: IRCT20210806052096N1; IRCT URL: https://www.irct.ir/trial/62243; Ethical code: IR.ZUMS.REC.1400.150; Registration date: 2022-04-09.

Ketamine subcutaneous continuous infusion for depressive symptoms at home: A case report beyond pain use.

Ketamine has been widely used in refractory pain as an opioid adjuvant. Evidence suggests that ketamine can also have an essential role in easing depressive symptoms. Its rapid onset of action makes it a valuable choice in palliative care. We present a case of a 70-year-old man with stage IV renal carcinoma and bone metastasis. The main symptoms included neuropathic pain, depression, and a persistent and severe desire for death. We started continuous subcutaneous infusion with morphine 30 mg and ketamine 100 mg/day. The dose of ketamine was incremented to the maximum of 250 mg/day. During the 28-day treatment, we observed an overall improvement in neuropathic pain, depressive symptoms, and other end-of-life psychological aspects of distress. Only minor psychological side effects were identified, which were controlled by using midazolam in the continuous subcutaneous infusion. Some studies have already demonstrated the benefits of ketamine use in alleviating depression, using parental infusion or oral formulas, which are administered in hospice care. Our report enhances the benefit of the subcutaneous route for palliative patients cared for at home.

Rapid-onset, short-duration induction of colorectal contractions in anesthetized, adult, male rats.

Rapid-onset, short-duration induction of colorectal contractions in anesthetized, adult, male rats.

Evaluation of humoral and cellular immune responses against Vibrio cholerae using oral immunization by multi-epitope-phage-based vaccine

IntroductionCholera is a severe gastrointestinal disease that manifests with rapid onset of diarrhea, vomiting, and high mortality rates. Due to its widespread occurrence in impoverished communities with poor water sanitation, there is an urgent demand for a cost-effective and highly efficient vaccine. Multi-epitope vaccines containing dominant immunological epitopes and adjuvant compounds have demonstrated potential in boosting the immune response. Material and methodsB and T epitopes of OMPU, OMPW, TCPA, CTXA, and CTXB proteins were predicted using bioinformatics methods. Subsequently, highly antigenic multi-epitopes that are non-allergenic and non-toxic were synthesized. These multi-epitopes were then cloned into the pCOMB phagemid. A plasmid M13KO7ΔpIII containing all helper phage proteins except pIII was created to produce the recombinant phage. Female Balb/c mice were divided into three groups and immunized accordingly. The mice received the helper phage, recombinant phage or PBS via gavage feeding thrice within two weeks. Serum samples were collected before and after immunization for the ELISA test as well as evaluating immune system induction through ELISpot testing of spleen lymphocytes. ResultsThe titer of the recombinant phage was determined to be 1011 PFU/ml. The presence of the recombinant phage was confirmed through differences in optical density between sample and control groups in the ELISA phage technique, as well as by observing transduction activity, which demonstrated successful production of a recombinant phage displaying the Vibrio multi-epitope on M13 phage pIII. ELISA results revealed significant differences in phage antibodies before and after inoculation, particularly notable in the negative control mice. Mice treated with multi-epitope phages exhibited antibodies against Vibrio cholerae lysate. Additionally, ELISpot results indicated activation of cellular immunity in mice receiving both Vibrio and helper phage. ConclusionThis study emphasizes the potential of multi-epitope on phage to enhance both cellular and humoral immunity in mice, demonstrating how phages can be used as adjuvants to stimulate mucosal immunity and act as promising candidates for oral vaccination.

Analyzing DNA barcoding and identifying toxins caused by neurotoxic mushroom poisoning using liquid chromatography tandem mass spectrometry

Background: Neurotoxic mushroom poisoning often exhibits rapid symptom onset, typically attributed to compounds such as Ibotenic acid, which affect the central nervous system. This study addresses a new case of mushroom-related food poisoning in southern Thailand. Objective: The objectives are to determine the presence of ibotenic acid in cases of mushroom-related food poisoning utilizing liquid chromatography-tandem mass spectrometry (LC-MS/MS) and to identify toxic Amanita species implicated in these cases. Materials and methods: Remnant mushroom samples obtained from three clinically reported cases were used. Nucleotide similarity was compared against the rRNA/ ITS databases using NCBI BLAST search. Phylogenetic analyses were conducted using maximum likelihood (ML) and FastTree approaches. LC-MS/MS was employed to separate of Ibotenic acid, determine its molecular weight and perform precursor ion fragmentation. Results: Analysis of the rRNA/ITS databases revealed a high nucleotide similarity between suspected mushroom samples and Amanita digitosa. Detailed phylogenetic analysis confirmed that mushroom samples from the three poisoning cases clustered with A. digitosa. LC-MS/MS analysis showed the presence of ibotenic acid, with precursor ion (m/z 159) and product ion (m/z 113.1) as the major toxic substances. Clinically, patients poisoned by ibotenic acid-containing mushrooms exhibited a short latent period with symptoms of nausea, vomiting, vertigo, delirium, confusion, and fatigue. Conclusion: The genus Amanita comprises both edible and inedible species that produce several lethal toxins. The report of ibotenic acid in A. digitosa is a novel finding, valuable for food safety monitoring and healthcare decision-maker. This is especially notable due to the accuracy and rapidity of the analytical process.

Clinical analysis and literature review of two paediatric cases of anti-IgLON5 antibody-related encephalitis.

Anti-IgLON5 antibody-related encephalitis is a rare autoimmune disorder of the central nervous system, predominantly occurring in middle-aged elderly individuals, with paediatric cases being exceptionally rare. This study aims to enhance the understanding of paediatric anti-IgLON5 antibody-related encephalitis by summarising its clinical and therapeutic characteristics. A retrospective analysis was conducted on two paediatric patients diagnosed with anti-IgLON5 antibody-related encephalitis at Hunan Children's Hospital from August 2022 to November 2023. This involved reviewing their medical records and follow-up data, in addition to a literature review. The study involved two patients, one male and one female, aged between 2.5 and 9.6 years, both presenting with an acute/subacute course of illness. Clinically, both exhibited movement disorders (including dystonia, involuntary movements, and ataxia), cognitive impairments, sleep disturbances, and psychiatric symptoms. Patient 1 experienced epileptic seizures, while Patient 2 exhibited brainstem symptoms and abnormal eye movements. Neither patient showed autonomic dysfunction. Patient 1 had normal cerebrospinal fluid (CSF) and Brain MRI findings, whereas Patient 2 showed moderate leukocytosis and mild protein elevation in the CSF, and Brain MRI revealed symmetrical lesions in the basal ganglia and cerebellum. Oligoclonal bands in the CSF were positive in both cases. Both patients tested negative for HLA-DQB*05:01 and HLA-DRB*10:01. They received both first-line and second-line immunotherapies, with Patient 2 showing a poor response to treatment. Paediatric cases of anti-IgLON5 antibody-related encephalitis similarly present sleep disturbances as a core symptom, alongside various forms of movement disorders. Immunotherapy is partially effective. Compared to adult patients, these paediatric cases tend to exhibit more pronounced psychiatric symptoms, a more rapid onset, and more evident inflammatory changes in the CSF. The condition appears to have a limited association with HLA-DQB*05:01 and HLA-DRB*10:01 polymorphisms.

Hydrology and oxygen addition drive nutrients, metals, and methylmercury cycling in a hypereutrophic water supply reservoir

Impaired water quality in Mediterranean climate reservoirs is mainly associated with eutrophication and internal nutrient loading. To improve water quality in hypereutrophic Hodges Reservoir, California, United States, a hypolimnetic oxygenation system (HOS), using pure oxygen gas, was implemented in 2020. This study encompasses 3 years of pre-oxygenation data (2017–2019) and 2 years of post-oxygenation data (2020–2021) to understand the cycling of nutrients, metals, and mercury in the reservoir. During the wet year of 2017, mildly reduced conditions lasted until mid-summer in the enlarged reservoir. Nutrients and metals were seen in the hypolimnion including ammonia (~2 mg-N/L), manganese (~0.5 mg/L), phosphate (~0.5 mg-P/L), and sulfide (~10 mg/L). Production of methylmercury (MeHg), an important bioaccumulative toxin, was favored from April to June with a hypolimnetic accumulation rate of around 200 ng/m2·d. In contrast, the dry year of 2018 exhibited higher hypolimnetic concentrations of ammonia (~4 mg-N/L), manganese (~1 mg/L), phosphate (&amp;gt;0.5 mg-P/L), and sulfide (&amp;gt;15 mg/L). The rapid onset of highly reduced conditions in 2018 corresponded with low MeHg hypolimnetic accumulation (~50 ng/m2·d). It seems that mildly reduced conditions were associated with higher MeHg accumulation, while sulfidic, reduced conditions impaired inorganic mercury bioavailability for MeHg production and/or promoted microbial demethylation. Sulfide also appeared to act as a sink for iron via FeS precipitation, and potentially for manganese via MnS precipitation or manganese coprecipitation with FeS. Mass flux estimates for 2017–2019 indicate that much of the nutrients that accumulated in the hypolimnion moved via turbulent diffusion into the epilimnion at loading rates far exceeding thresholds predicting eutrophic conditions. After oxygenation in 2020–2021, the reservoir water column was highly oxidized but showed a lack of thermal stratification, suggesting reservoir operations in combination with HOS implementation inadvertently mixed the water column in this relatively shallow reservoir. Post-oxygenation, concentrations of ammonia, phosphate, manganese, and mercury in bottom waters all decreased, likely in response to oxidized conditions. Oxygenated bottom waters exhibited elevated nitrate, a byproduct of ammonia nitrification, and iron, a byproduct of FeS oxidation, indicating a lake-wide response to oxygenation.