[Pediatric procedural sedation: a new protocol implemented]. / Implémentation d'un nouveau protocole pour la sédation procédurale pédiatrique.

Pediatric procedural sedation is a difficult exercise aiming to find the balance between optimal quality of a medical imaging or act, and maximal reduction of risks for the patient. Harmlessness of chloral hydrate has been recently questioned, thus promoting the use of the dexmedetomidine for these kinds of procedures. In this context we decided to develop a new protocol at the CHUV. We tested different combinations of molecules until we found the best association and dosage. We present here the analysis of our patient cohort, attesting the efficiency, reliability, and safety of combined dexmedetomidine and midazolam given intranasal for pediatric MRI.

La sédation procédurale pédiatrique représente un défi pour garantir la qualité optimale d'un examen ou d'un acte médical tout en assurant la sécurité maximale du patient. Comme l'innocuité de l'hydrate de chloral semble être remise en question, la communauté médicale se dirige de plus en plus vers l'usage intranasal de la dexmédétomidine pour les sédations. Dans ce contexte, nous avons élaboré un nouveau protocole au CHUV, après avoir testé différentes combinaisons médicamenteuses dans le cadre d'examen d'imagerie (IRM). Sur la base de nos résultats, il semble que l'efficacité, la fiabilité et la sécurité de la combinaison de dexmédétomidine et de midazolam par voie intranasale soient très satisfaisantes.

Formation and control of disinfection by-products during the trichloroisocyanuric acid disinfection in swimming pool water.

The increasing demand for trichloroisocyanuric acid (TCCA) in swimming pool disinfection highlights the need to evaluate its applicability in terms of disinfection by-product (DBP) formation. Nevertheless, there is limited understanding of DBP formation and control during TCCA disinfection, particularly concerning the effects of various management parameters. This study aimed to fill this knowledge gap by comprehensively investigating DBP formation during TCCA chlorination, with a particular focus on assessing the contribution and interaction of influencing factors using Box-Behnken Design and response surface methodology. Results indicated that the concentrations of trichloroacetaldehyde, chloroform, dichloroacetic acid, trichloroacetic acid, and dichloroacetonitrile produced by TCCA disinfectant were 42.5%, 74.0%, 48.1%, 94.7% and 42.6% of those by the conventional sodium hypochlorite disinfectant, respectively. Temperature exhibited the most significant impact on chloroform formation (49%), while pH played a major role in trichloroacetaldehyde formation (44%). pH2 emerged as the primary contributor to dichloroacetic acid (90%) and trichloroacetic acid (93%) formation. The optimum water quality conditions were determined based on the minimum total DBPs (pH = 7.32, Temperature = 23.7 °C, [Cl-] = 437 mg/L). Chlorine dosage and contact time exhibited greater influence than precursor concentration on chloroform, dichloroacetonitrile, trichloroacetaldehyde, trichloroacetic acid, and total DBPs. Although the interaction between water quality parameters was weak, the interaction between disinfection operating parameters demonstrated substantial effects on DBP formation (8.56-19.06%). Furthermore, the DBP predictive models during TCCA disinfection were provided for the first time, which provides valuable insights for DBP control and early warning programs.

Efficacy and safety of chloral hydrate in auditory brainstem response test: A systematic review and single-arm meta-analysis.

OBJECTIVES: To evaluate the safety and efficacy of chloral hydrate in auditory brainstem response (ABR) tests. SETTING AND DESIGN: In this study, the authors systematically searched both English (Embase, PubMed, and Web of Science) and Chinese (Chinese National Knowledge Infrastructure, Wanfang Data, and VIP Chinese Science) databases. Two authors independently performed data extraction and quality assessment. The pooled sedation failure rate and the pooled incidence of adverse events were calculated via a random-effects model. Sensitivity and subgroup analyses were performed to explore the sources of heterogeneity, and the PRISMA guideline was followed. PARTICIPANTS: Patients with ABR tests receiving chloral hydrate sedation. MAIN OUTCOME MEASURES: The pooled sedation failure rate and the pooled incidence of adverse events. RESULTS: A total of 23 clinical studies were included in the final analysis. The pooled sedation failure rate of patients who received chloral hydrate sedation before ABR examination was 10.0% [95% confidence interval (CI) (6.7%, 15.0%), I2 = 95%, p < .01]. There were significant differences in the prevalence of sedation failure between sample sizes greater than 200 and those less than or equal to 200 (5.6% vs. 19.6%, p < .01) and between the studies that reported sleep deprivation and those that did not report sleep deprivation (7.1% vs. 18.9%, p < .01). The pooled incidence of adverse events was 10.32% [95% CI (5.83%, 14.82%), I2 = 98.1%, p < .01]. CONCLUSIONS: Chloral hydrate has a high rate of sedation failure, adverse events, and potential carcinogenicity. Therefore, replacing its use in ABR tests with safer and more effective sedatives is warranted.

Analyzing disinfection by-products yield and mechanisms in UV/Cl2 using response surface methodology and quantitative structure-activity relationship models.

The study aimed to investigate the formation of halogenated disinfection byproducts (DBPs) during applying UV/chlorine (UV/Cl2) and unravel the interactive impacts of critical operational parameters and the mechanisms behind DBPs formation. Response surface methodology and quantitative structure-activity relationship models were developed to evaluate the contribution of electrophilic, nucleophilic, and free radical reactions to the formation of DBPs in UV/Cl2. The study found that Cl2 and its interactions dominated the total DBPs and non-Br-DBPs formation, while Br- and the Cl2-Br- interaction played a decisive role in the Br-DBPs formation. The study also observed significant interactions of Br, Cl2, and pH on chloroform, bromodichloromethane, dichloroacetonitrile, 1,1-dichloro-2-propanone, trichloroactic acid, and chlorodibromoacetic acid formations, while no evident interaction on chloral hydrate, dibromochloromethane, trichloroacetone, dibromoacetic acid, and bromodichloroacetic acid formations. The electrophilic substitution of HOBr mainly controlled the formation of trihalomethanes, and the contribution of nucleophilic, electrophilic, and free radical (•OH, Cl•, Cl2•- and ClO•) reactions depended on the molar ratio of Cl2 to Br, and pH-determined hydrolysis rate constants of DBPs and the types of free radicals. Overall, the response surface methodology and quantitative structure-activity relationship models provided a reference for revealing DBPs formation mechanisms in other disinfection processes.

A Comparative Analysis of Prehospital Emergency Treatments: Midazolam Intramuscularly, Diazepam Enema, and Chloral Hydrate Enema for Pediatric Convulsions.

Objective: This study aimed to compare the effectiveness of prehospital emergency treatments using midazolam (MDL) intramuscularly, diazepam (DZP) enema, and chloral hydrate (CH) enema in managing pediatric convulsions. Methods: A comparative observational study was conducted, and a total of 140 children with acute convulsions treated with prehospital anti-convulsions at Qinhuangdao First Hospital's emergency department between June 2015 and May 2019 were included in this study. The children were categorized based on the prehospital anti-convulsion measures received: group M (n = 48) received MDL intramuscularly, group D (n = 46) received DZP enema, and group C (n = 46) received CH enema. The emergency effects of the three treatment groups were compared. Results: 1. Group M showed significantly shorter treatment preparation time and total rescue time compared to groups C and D (both P < .05); no significant difference was observed between groups C and D (both P > .05), including convulsion control time in the effective cases (45 in group M, 42 in group C, and 43 in group D) (all P > .05 Group M had effective rates of 93.75%, while group C and group D had rates of 91.3% and 93.48%, respectively (all P > .05); Group M had more controlled cases at 1 min, 3 min, 5 min, and 10 min than group C and group D (all P > .05). Group M had significantly fewer relapses, cases requiring intravenous maintenance treatment, and faster convulsion control after intravenous maintenance compared to groups C and D (P < .05), with no significant differences between groups C and D in time to recovery of consciousness and length of hospitalization (P > .05). 4. Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR), respiratory (R) frequency, and peripheral oxygen saturation (SpO2) showed no significant differences before and 10 minutes after medication in all three groups (P > .05); SBP and DBP levels fluctuated within the normal range, while HR decreased, R frequency decreased, and SpO2 increased significantly 10 minutes after medication compared to before treatment (P < .05). 5. No significant adverse effects were observed in the three patient groups. Conclusions: MDL intramuscular injection, DZP enema, and CH enema were effective prehospital treatments for pediatric acute convulsions. MDL intramuscular injection demonstrated advantages such as fast onset, reliable efficacy, ease of use, and high safety, making it more suitable for the prehospital treatment of pediatric convulsions.

Dynamic effects of miR-20a-5p on hippocampal ripple energy after status epilepticus in rats.

To determine the dynamic effects of miR-20a-5p on hippocampal ripple energy in rats after status epilepticus (SE). A lithium pilocarpine (LiCl-PILO)-induced rat model of status epilepticus (SE) was established, and the rats were divided into the normal control (Control, CTL), epileptic control (PILO), valproic acid (VPA + PILO), miR-20a-5p overexpression lentivirus vector (miR + PILO), sponges blocking lentivirus vector (Sponges + PILO), and scramble sequence negative control (Scramble + PILO) groups (n = 6). Electroencephalograms (EEGs) were used to analyze changes in hippocampal ripple energy before and after SE. Quantitative polymerase chain reaction (q-PCR) analysis showed that miR-20a-5p levels gradually increased after miR-20a-5p overexpression lentivirus vector injection into the lateral ventricle, and the miR-20a-5p levels were significantly higher than that in CTL group on days 7 and 36 (P < 0.001). The miR-20a-5p levels decreased significantly on days 7 and 36 after blocking by sponges lentivirus vector injected into the lateral ventricle (P < 0.001). After injection of PILO, the average ripple energy expression in each group gradually increased, and reached the peak before chloral hydrate injection (compared with 1 day before SE, P < 0.05). The ripple energy in the VPA + PILO and Sponges + PILO groups was significantly lower than that in the PILO group at 60 min and 70 min after PILO injection and before chloral hydrate injection (P < 0.05), and maintained lower until 2 h after chloral hydrate injection in VPA + PILO (P < 0.05). Compared with the VPA + PILO group, the mean ripple energy of the Sponges + PILO group had no difference at all time points (P ≥ 0.05). After SE, ripple distribution of space and energy is closely related to the occurrence of epilepsy. Inhibition of miR20a-5p expression can downregulate ripple oscillation energy during seizure.

Intravenous chloral hydrate anesthesia provides appropriate analgesia for surgical interventions in male Sprague-Dawley rats.

BACKGROUND: The use of chloral hydrate as a sole maintenance anesthetic agent in rodent research has been controversial due to statements made in reference literature conflicting with results of primary research studies regarding its analgesic efficacy, and because of its associated tissue damage when administered intraperitoneally. OBJECTIVE: Our aim was to assess the analgesic efficacy of chloral hydrate using an intravenous (i.v.) route of administration, in order to prevent the local tissue irritation or ileus that has been previously reported using intraperitoneal (i.p.) routes. METHODS: We measured tail withdrawal latencies to a nociceptive thermal stimulus (infrared beam) in Sprague-Dawley rats-first when awake (unanesthetized), and then subsequently during i.v. chloral hydrate anesthesia. During anesthesia we also measured ongoing heart and respiration rates. RESULTS: Withdrawal latencies during chloral hydrate anesthesia were significantly higher, and often maximal, indicating a robust analgesic effect. Importantly, both respiration and heart rate remained unchanged following exposure to the nociceptive stimulus, and were comparable to values observed under other anesthetics and during natural sleep. CONCLUSIONS: Together with previous studies, these results demonstrate that i.v. chloral hydrate provides excellent anesthetic depth and analgesic efficacy for surgical manipulations in rats.

Safety and efficacy of pediatric sedation protocol for diagnostic examination in a pediatric emergency room: A retrospective study.

Pediatric patients undergoing diagnostic tests in the pediatric emergency room are frequently sedated. Although efforts are made to prevent adverse events, no sedation protocol has specified the optimal regimen, dosage, and interval of medication to prevent adverse events. This study analyzed the safety and efficacy of sequential pediatric sedation protocols for pediatric patients undergoing diagnostic tests in the pediatric emergency room of a single tertiary medical center. The medical records of patients aged < 18 years who visited the pediatric emergency room of Seoul Asan Medical Center between January and December 2019 for diagnostic testing were retrospectively reviewed. Sedation protocols consisted of 50 mg/kg and 25 mg/kg chloral hydrate, 0.1 mg/kg and 0.1 mg/kg midazolam, and 1 mg/kg and 0.5 to 1 mg/kg ketamine, administered sequentially at intervals of 30, 20, 10, 10, and 10 minutes, respectively. Patients were assessed prior to sedation, and adverse events were investigated. Of the 289 included patients, 20 (6.9%) experienced adverse events, none serious, and nine (3.1%) failed to reach the depth of sedation required to complete the test. The regimen (P = .622) and dosage (P = .777) of the sedatives were unrelated to the occurrence of adverse events when sedation was performed according to protocol. The sedation protocol used in these patients, consisting of sequential administration of minimum dosages, achieved a sufficient depth of sedation with relatively few adverse events, indicating that this protocol can be used safely and effectively for painless sedation in pediatric patients undergoing diagnostic testing.

Trichloroethanol, an active metabolite of chloral hydrate, modulates tetrodotoxin-resistant Na+ channels in rat nociceptive neurons.

BACKGROUND: Chloral hydrate is a sedative-hypnotic drug widely used for relieving fear and anxiety in pediatric patients. However, mechanisms underlying the chloral hydrate-mediated analgesic action remain unexplored. Therefore, we investigated the effect of 2',2',2'-trichloroethanol (TCE), the active metabolite of chloral hydrate, on tetrodotoxin-resistant (TTX-R) Na+ channels expressed in nociceptive sensory neurons. METHODS: The TTX-R Na+ current (INa) was recorded from acutely isolated rat trigeminal ganglion neurons using the whole-cell patch-clamp technique. RESULTS: Trichloroethanol decreased the peak amplitude of transient TTX-R INa in a concentration-dependent manner and potently inhibited persistent components of transient TTX-R INa and slow voltage-ramp-induced INa at clinically relevant concentrations. Trichloroethanol exerted multiple effects on various properties of TTX-R Na+ channels; it (1) induced a hyperpolarizing shift on the steady-state fast inactivation relationship, (2) increased use-dependent inhibition, (3) accelerated the onset of inactivation, and (4) retarded the recovery of inactivated TTX-R Na+ channels. Under current-clamp conditions, TCE increased the threshold for the generation of action potentials, as well as decreased the number of action potentials elicited by depolarizing current stimuli. CONCLUSIONS: Our findings suggest that chloral hydrate, through its active metabolite TCE, inhibits TTX-R INa and modulates various properties of these channels, resulting in the decreased excitability of nociceptive neurons. These pharmacological characteristics provide novel insights into the analgesic efficacy exerted by chloral hydrate.

Nrf2 regulates the activation of THP-1 cells induced by chloral hydrate.

Trichloroethylene (TCE) triggers a severe hypersensitivity syndrome in the occupational population dependent on dendritic cells (DCs). Chloral hydrate (CH), the major oxidative metabolite of TCE, has been proved to be the culprit causative substance of TCE-induced hypersensitivity by human patch tests. Because redox imbalance is essential for chemical sensitizers-induced maturation of DCs, we predicted that CH would activate DCs by the nuclear factor E2-related factor 2 (Nrf2)-mediated antioxidant response. This study selected THP-1 cells as the in vitro DC model, and we evaluated the cell activation markers, intracellular oxidative stress, and Nrf2 pathway related genes expression in response to CH in THP-1 cells. CH displayed significant stimulation of THP-1 cells activation, including CD54 and CD86 expression, IL-8 release, and cell migration, and damaged the redox balance by triggering ROS generation, GSH consumption, and antioxidase activities modulation. The levels of Nrf2 and its downstream genes (HO-1 and NQO1) in mRNA and protein expressions were upregulated by CH, and CH also promoted the nuclear translocation of Nrf2. Subsequently, we investigated the effects of antioxidant on Nrf2-mediated cell defense in CH treated cells. Pretreatment with curcumin dramatically reduced cell activation and oxidative stress triggered by CH in THP-1 cells. We also confirmed the specific role of Nrf2 in CH-induced cell activation using NRF2-knockout cells. Deficiency of Nrf2 inhibited cell activation and downregulated HO-1 and NQO1 expression in CH-challenged cells. These findings suggest that Nrf2-dependent redox homeostasis plays a pivotal role in CH-induced activation of THP-1 cells, thereby providing new knowledge of the allergen as well as the molecular mechanism involving in TCE-induce hypersensitivity syndrome.

French survey of sedation practices for pediatric magnetic resonance and computed tomography imaging.

BACKGROUND: Pediatric magnetic resonance imaging (MRI) and computed tompgraphy (CT) require patient immobility and therefore often require sedation or general anesthesia of patients. Consensus on these procedures is lacking in France. OBJECTIVE: Thus, the aim of this study was to describe the current sedation practices for pediatric MRI and CT in France. MATERIAL AND METHODS: From January 2019 to December 2019, an online questionnaire was delivered by electronic mail to a representative radiologist in 60 pediatric radiology centers registered by the French-speaking pediatric and prenatal imaging society. Questions included protocols, drugs used, monitoring and side effects. RESULTS: Representatives of 40 of the 60 (67%) radiology centers responded to the survey. Among them, 31 performed sedation including 17 (55%) centers where radiologists performed sedation without anesthesiologists present during the procedure. The premedication drugs were hydroxyzine (n = 8, 80%) and melatonin (n = 2, 20%), Sedation drugs used for children ages 0 to 6 years old were pentobarbital (n = 9, 60%), midazolam (n = 2, 13%), chloral hydrate (n = 2, 13%), diazepam (n = 1, 6.5%) and chlorpromazine (n = 1, 6.5%). A written sedation protocol was available in 10/17 (59%) centers. In 6/17 (35%) centers, no monitoring was used during the procedures. Blood pressure monitoring and capnography were rarely used (< 10%) and post-sedation monitoring was heterogeneous. No life-threatening adverse effect was reported, but 6 centers reported at least one incident per year. CONCLUSION: For half of the responding radiology centers, radiologists performed sedation alone in agreement with the local anesthesiology team. Sedation procedures and monitoring were heterogenous among centers. Adjustment and harmonization of the practices according to the capacity of each center may be useful.

Nasal drip of dexmedetomidine for optimal sedation during PICC insertion in pediatric burn care.

BACKGROUND: For peripherally inserted central catheter (PICC) inserting, tranquil cooperation of children for an extended period is often required. Therefore, sedation is routinely induced clinically prior to PICC inserting. Chloral hydrate is a commonly used sedative for children. However, its clinical acceptance has remained low. And the sedation effect is non-satisfactory. Previous studies have confirmed the safety and effectiveness of intravenous/oral dosing or nasal dripping for sedation during the examinations of electrocardiography and computed tomography. Yet few studies have assessed the sedating efficacy of dexmedetomidine nasal drops for PICC inserting. METHODS: From a cohort of 40 hospitalized patients scheduled for PICC inserting, 15 children employing a novel sedative mode of dexmedetomidine nasal drops at a dose of 2 ug/kg were assigned into group A while group B included another 25 children sedated routinely via an enema of 10% chloral hydrate at a dose of 0.5 mL/kg. The Ramsay's scoring criteria were utilized for assessing the status of sedation. Two groups were observed with regards to success rate of sedation, onset time of sedation and occurrences of adverse reactions. RESULTS: Statistical inter-group differences existed in success rate and onset time of sedation. The success rate of group A was higher than that of group B (93.3% vs 64.0%, X2 = 4.302, P = .038 < 0.05). Group A had a faster onset of sedation than group B (14.86 ± 2.57 vs 19.06 ± 3.40 minutes, t = 3.781, P = .001 < 0.05). No inter-group difference of statistical significance existed in occurrence of adverse reactions (P = 1.000 > 0.05). Logistic regression analysis showed that the success rate of sedation in group A was higher than that in group B, and the difference was statistically significant (P = .036 < 0.05). CONCLUSIONS: For sedating burn children, nasal dripping of dexmedetomidine is both safe and effective during PICC inserting. Without any obvious adverse reaction, it may relieve sufferings and enhance acceptance.

The impact of anesthetic drugs on hemodynamic parameters and neurological outcomes following temporal middle cerebral artery occlusion in rats.

The induction of ischemic stroke in the experimental model requires general anesthesia. One of the factors that can be effective in the size of ischemic brain lesions and neurological outcomes is the type of anesthesia. So, the current study was designed to compare the impacts of the most important and widely used anesthetics including halothane, isoflurane, and chloral hydrate on the transient middle cerebral artery occlusion (MCAO) outcomes. Adult Male Sprague-Dawley rats were randomly divided into three groups as follows: (1) MCAO + halothane group, (2) MCAO + isoflurane group, and (3) MCAO + chloral hydrate group. After 24 h, the mortality rate, infarct size, tissue swelling, neurological function, hemodynamic, and arterial blood gas parameters were assessed. Our finding showed that 60 min MCAO rats anesthetized with chloral hydrate significantly increased mortality rate, infarct size, tissue swelling, and neurological deficits compared with halothane and isoflurane anesthetics after 24 h of MCAO. Also, chloral hydrate caused a significant decrease in mean arterial pressure and arterial pO2 compared to halothane and isoflurane anesthetics. On the basis of the current data, we concluded that chloral hydrate increased cerebral infarct volume and neurological outcomes and reduced hemodynamic and metabolic parameters compared with halothane and isoflurane-anesthetized rats temporal MCAO.

Two-center randomized controlled trial comparing oral chloral hydrate and intranasal combination of dexmedetomidine and ketamine for procedural sedation in children: study protocol.

BACKGROUND: Oral chloral hydrate is widely used in pediatric sedation. Intranasal dexmedetomidine has been increasingly used for pediatric sedation; however, its improvement is warranted. The combination of dexmedetomidine with ketamine can improve onset and hemodynamic stability while maintaining sedative efficacy. This study aims to determine the efficacy and safety of intranasal combination of dexmedetomidine and ketamine compared to oral chloral hydrate. METHODS: This is a prospective, parallel-arm, single-blinded, two-center, superiority randomized controlled trial with 1:1 allocation, designed to compare the effects of intranasal combination of dexmedetomidine and ketamine with those of oral chloral hydrate. We shall enroll 136 patients aged < 7 years old in this study. Prior to the procedure, we shall randomize each patient into the control group (oral chloral hydrate 50 mg/kg) or study group (intranasal dexmedetomidine 2 µg/kg and ketamine 3 mg/kg). The primary outcome will be the rate of achieving an adequate sedation level (6-point Pediatric Sedation State Scale 1, 2, or 3) within 15 min. In addition, we shall measure the sedation time, sedation failure rate, completion of procedure, adverse events, patient acceptance, and physician satisfaction. DISCUSSION: This study will provide evidence of the efficacy and safety of the intranasal combination of dexmedetomidine and ketamine in comparison with oral chloral hydrate. TRIAL REGISTRATION: ClinicalTrials.gov , NCT04820205. Registered on 19th March 2021.

Comparison of oral triclofos and intranasal midazolam and dexmedetomidine for sedation in children undergoing magnetic resonance imaging (MRI): an open-label, three-arm, randomized trial.

The purpose of this study was to compare the efficacy of oral triclofos (TRI), intranasal midazolam (INM), and intranasal dexmedetomidine (IND) in achieving successful sedation in children undergoing MRI. This open-label, three-arm, randomized trial was conducted in a tertiary care teaching hospital over 18-month period. Children scheduled for MRI were enrolled. Rate of successful/adequate sedation was assessed using the Paediatric Sedation State Scale (PSSS). The primary outcome was the efficacy (successful sedation or sedation rate) of the three drugs. One-hundred and ninety-five children were included for the MRI procedure. IND was found to be superior in terms of achieving successful sedation. INM had a shorter onset and duration of sedation compared to IND and TRI, but with an increased failure rate (88.3%). Keeping INM as the reference group, it was found that the odds of sedation increased 4.1 times on changing from INM to IND (p < 0.01), and 2.26 times on changing from INM to TRI (p < 0.01). Adverse events included nasal discomfort (18.3%) in INM group; and self-limited tachycardia (4.6%) and hypotension (10.8%) in the IND group. CONCLUSION: IND was more efficacious than INM or TRI for procedural sedation in children undergoing MRI without any significant adverse events. CLINICAL TRIAL REGISTRATION: CTRI/2019/01/017257; date registered: 25/01/2019. WHAT IS KNOWN: • Oral triclofos (TRI) and intranasal midazolam (INM) have been used for procedural sedation in children undergoing MRI with variable success; but the experience with intranasal dexmedetomidine (IND) is limited. WHAT IS NEW: • IND provides more effective sedation compared to INM or TRI for procedural sedation in children undergoing MRI, without any significant adverse events.

Screening of new adsorbents to remove algal organic matter from aqueous solutions: kinetic analyses and reduction of disinfection by-products formation.

The algal organic matter (AOM) is a problem in water treatment. Although the adsorption process is extensively applied to drinking water treatment, little information is known about the potential of new adsorbents to remove AOM. Herein, this work evaluated the removal of AOM and its main compounds (dissolved organic carbon (DOC), carbohydrate, and protein) by new adsorbents-mesoporous silica (SBA-16), graphene oxide material from citric acid (CA), and sugar (SU), and a composite of CA immobilized on sand (GSC). In general, the removal efficiencies followed the order of SBA-16 > CA > SU or GSC for DOC, carbohydrate, and protein. At environmental condition (5 mg DOC·L-1 and pH 8), high removals were reported for SBA-16 (88.8% DOC, 80.0% carbohydrate, and 99.6% protein) and CA (70.0% DOC, 66.7% carbohydrate, and 89.7% protein), while moderate removals were found for SU (60.5% DOC, 47.9% carbohydrate, and 66.5% protein) and GSC (67.4% DOC, 60.8% carbohydrate, and 57.4% protein). Based on these results, further analyses were done with SBA-16 and CA. Both adsorbents' efficiencies decayed with the pH increment of the test water. Disinfection by-products reductions found using SBA-16 - trihalomethanes (58.2 to 94.7%) and chloral hydrate (48.7 to 78.8%) - were higher than the ones using CA-trihalomethanes (45.2 to 82.4%) and chloral hydrate (40.1 to 70.8%). This study showed the potential of applying these adsorbents for AOM removal, and further investigations are suggested to increase the adsorption capacity of these adsorbents.

Identification of the Acid-Sensitive Site Critical for Chloral Hydrate (CH) Activation of the Proton-Activated Chloride Channel.

The transmembrane protein TMEM206 was recently identified as the molecular basis of the extracellular proton-activated Cl- channel (PAC), which plays an essential role in neuronal death in ischemia-reperfusion. The PAC channel is activated by extracellular acid, but the proton-sensitive mechanism remains unclear, although different acid-sensitive pockets have been suggested based on the cryo-EM structure of the human PAC (hPAC) channel. In the present study, we firstly identified two acidic amino acid residues that removed the pH-dependent activation of the hPAC channel by neutralization all the conservative negative charged residues located in the extracellular domain of the hPAC channel and some positively charged residues at the hotspot combined with two-electrode voltage-clamp (TEVC) recording in the Xenopus oocytes system. Double-mutant cycle analysis and double cysteine mutant of these two residues proved that these two residues cooperatively form a proton-sensitive site. In addition, we found that chloral hydrate activates the hPAC channel depending on the normal pH sensitivity of the hPAC channel. Furthermore, the PAC channel knock-out (KO) male mice (C57BL/6J) resist chloral hydrate-induced sedation and hypnosis. Our study provides a molecular basis for understanding the proton-dependent activation mechanism of the hPAC channel and a novel drug target of chloral hydrate.SIGNIFICANCE STATEMENT Proton-activated Cl- channel (PAC) channels are widely distributed in the nervous system and play a vital pathophysiological role in ischemia and endosomal acidification. The main discovery of this paper is that we identified the proton activation mechanism of the human proton-activated chloride channel (hPAC). Intriguingly, we also found that anesthetic chloral hydrate can activate the hPAC channel in a pH-dependent manner. We found that the chloral hydrate activates the hPAC channel and needs the integrity of the pH-sensitive site. In addition, the PAC channel knock-out (KO) mice are resistant to chloral hydrate-induced anesthesia. The study on PAC channels' pH activation mechanism enables us to better understand PAC's biophysical mechanism and provides a novel target of chloral hydrate.

Needle-free pharmacological sedation techniques in paediatric patients for imaging procedures: a systematic review and meta-analysis.

BACKGROUND: Sedation techniques and drugs are increasingly used in children undergoing imaging procedures. In this systematic review and meta-analysis, we present an overview of literature concerning sedation of children aged 0-8 yr for magnetic resonance imaging (MRI) procedures using needle-free pharmacological techniques. METHODS: Embase, MEDLINE, Web of Science, and Cochrane databases were systematically searched for studies on the use of needle-free pharmacological sedation techniques for MRI procedures in children aged 0-8 yr. Studies using i.v. or i.m. medication or advanced airway devices were excluded. We performed a meta-analysis on sedation success rate. Secondary outcomes were onset time, duration, recovery, and adverse events. RESULTS: Sixty-seven studies were included, with 22 380 participants. The pooled success rate for oral chloral hydrate was 94% (95% confidence interval [CI]: 0.91-0.96); for oral chloral hydrate and intranasal dexmedetomidine 95% (95% CI: 0.92-0.97); for rectal, oral, or intranasal midazolam 36% (95% CI: 0.14-0.65); for oral pentobarbital 99% (95% CI: 0.90-1.00); for rectal thiopental 92% (95% CI: 0.85-0.96); for oral melatonin 75% (95% CI: 0.54-0.89); for intranasal dexmedetomidine 62% (95% CI: 0.38-0.82); for intranasal dexmedetomidine and midazolam 94% (95% CI: 0.78-0.99); and for inhaled sevoflurane 98% (95% CI: 0.97-0.99). CONCLUSIONS: We found a large variation in medication, dosage, and route of administration for needle-free sedation. Success rates for sedation techniques varied between 36% and 98%.