Dynamic Behavior of Spatially Confined Sn Clusters and Its Application in Highly Efficient Sodium Storage with High Initial Coulombic Efficiency.

Advanced battery electrodes require a cautious design of microscale particles with built-in nanoscale features to exploit the advantages of both micro- and nano-particles relative to their performance attributes. Herein, the dynamic behavior of nanosized Sn clusters and their host pores in carbon nanofiber) during sodiation and desodiation is revealed using a state-of-the-art 3D electron microscopic reconstruction technique. For the first time, the anomalous expansion of Sn clusters after desodiation is observed owing to the aggregation of clusters/single atoms. Pore connectivity is retained despite the anomalous expansion, suggesting inhibition of solid electrolyte interface formation in the sub-2-nm pores. Taking advantage of the built-in nanoconfinement feature, the CNF film with nanometer-sized interconnected pores hosting Sn clusters (≈2 nm) enables high utilization (95% at a high rate of 1 A g-1) of Sn active sites while maintaining an improved initial Coulombic efficiency of 87%. The findings provide insights into electrochemical reactions in a confined space and a guiding principle in electrode design for battery applications.

A review of the functional activities of chia seed and the mechanisms of action related to molecular targets.

In recent years, as a functional potential pseudocereal, chia seed (Salvia hispanica L.) has been of great interest for its comprehensive nutritional profile and attractive qualities after ingestion. It is reported that a reasonable dietary supplementation of chia seed (CS) contributes to the prevention and treatment of acute and chronic diseases (inflammation, diabetes, hypertension, obesity, kidney stone, etc.). CS contains a variety of bioactive macromolecular substances, such as oil, protein and gum, which manifest distinguished health-promoting activities in both in vivo and in vitro research studies. This article provides a comprehensive compendium on the functional importance of CS, in the context of biological activities and mechanism of actions of CS. Specifically, CS and its components alleviate inflammation and regulate glucose and fatty acid metabolism by regulating key influencing factors in the adenosine 5'-monophosphate-activated protein kinase (AMPK), mitogen-activated protein kinases (MAPK), nuclear factor kappa B (NF-κB), peroxisome-activated receptor gamma (PPAR-γ) and transforming growth factor-beta (TGF-ß) pathways and the insulin receptor substrate (IRS)-mediated insulin signaling pathway. In the meantime, predictions of metabolic pathways of CS peptides based on the known tracks of newly researched active peptides were proposed, with the aim of emphasizing the enormous research space of CS peptides compared to other functional active peptides.

Comparison of postoperative analgesia in children following ropivacaine and lidocaine surgical field infiltration with epinephrine for cleft palate repair: A double-blinded, randomized controlled trial.

STUDY OBJECTIVE: The study aimed to evaluate the efficacy of ropivacaine in providing postoperative analgesia for children undergoing cleft palate repair. METHODS: A double-blinded, randomized controlled trial was conducted on sixty-four children scheduled for cleft palate repair. The patients received either local infiltration with 1% lidocaine or 0.2% ropivacaine before incision. The primary outcome was the postoperative average pain score, and secondary outcomes included pain scores at various time points, consumption of flurbiprofen and hydromorphone, effectiveness of nurse-controlled analgesia pump, and incidence of bradycardia, vomiting, and respiratory depression. MAIN RESULTS: The results showed that the postoperative average pain score was significantly lower in the ropivacaine group compared to the lidocaine group (1.27±0.28 vs. 1.75±0.29, P<0.001). Pain scores at multiple postoperative time points were also lower in the ropivac:aine group. Additionally, consumption of flurbiprofen and hydromorphone was lower, and ineffective compressions of the nurse-controlled analgesia pump were reduced in the ropivacaine group. The incidence of vomiting, bradycardia, and respiratory depression did not show significant differences between the two groups. CONCLUSION: Local infiltration with ropivacaine effectively provided postoperative analgesia for children undergoing cleft palate repair without major side effects. It was found to be superior to lidocaine in reducing the need for additional rescue analgesia.

Anaesthesia of a parturient with uncorrected pentalogy of Fallot undergoing caesarean section and postpartum sterilisation.

Pentalogy of Fallot is a rare congenital cyanotic heart disease; few patients with uncorrected disease survive to childbearing age. Cardiovascular changes during pregnancy and delivery can lead to haemodynamic instability, while anaesthesia can cause right-to-left shunting and worsen hypoxaemia.We present the learning points from the anaesthetic management of an obstetric patient with uncorrected pentalogy of Fallot. We describe the successful application of general anaesthesia, choice of transoesophageal echocardiography for real-time haemodynamic monitoring and management, and the comprehensive multidisciplinary care of this high cardiovascular risk obstetric patient perioperatively. We also review the literature and discuss the anaesthetic management of patients with pentalogy of Fallot going for caesarean section.

Modified nusinersen intrathecal injection method: inclusion of a septal needle-free closed infusion connector.

Objective: Nusinersen, an extremely expensive biologic drug (around 100,000 US$ per dose) that needs to be administered intrathecally, is approved for the treatment of 5q-spinal muscular atrophy (SMA). Because of the low muscle tone of the back muscles of pediatric SMA patients, especially type 1 SMA patients, the safe, effective, and fast execution of sheath injection is needed. Therefore, a modified intrathecal injection method was developed accordingly. This paper aims to describe the applicability and safety of this modified method. Methods: The modified intrathecal injection method (MIIM) mainly includes a septal needle-free closed infusion connector between the lumbar puncture needle and the syringe, besides the procedures of routine lumbar puncture. Its applicability and safety were evaluated through clinical observation. Results: A total of 92 children with SMA have successfully received nusinersen treatment at our hospital using the modified method since 2019 without obvious adverse events related to the modified injection method. Based on the clinical feedback of operators, the advantages of the modified method include successfully injecting the total dose of nusinersen with constant injection rate and a more stable fixation of the puncture needle, as well as making the operator more relaxed. However, compared with the routine method, the procedure of the modified method has additional steps. Conclusion: The modified intrathecal injection method is an effective and safe method to inject nusinersen when weighing the pros and cons, and it may also be used for administering intrathecal injections of other expensive medicines or for patients with other strict requirements for intrathecal injection.

Prophylactic Epidural Blood Patch or Prophylactic Epidural Infusion of Hydroxyethyl Starch in Preventing Post-Dural Puncture Headache - A Retrospective Study.

BACKGROUND: Post-dural puncture headache (PDPH) is particularly likely to happen in patients under obstetric care due to an unintentional dural puncture (UDP). There is as yet no ideal strategy for preventing UDP-induced PDPH. OBJECTIVES: The primary objective of this study was to assess whether a prophylactic epidural blood patch (EBP) or prophylactic epidural infusion of hydroxyethyl starch (HES) is effective in preventing PDPH for parturients with UDP compared with conservative treatments. STUDY DESIGN: Retrospective analysis from a single center's inpatient data. SETTING: Department of Anesthesiology at a single center. METHODS: A retrospective study was conducted of a single center's inpatient data from January 2017 through March 2020. The study included parturients with UDP during neuraxial anesthesia. The interventions of UDP included conservative treatment, prophylactic EBP, and prophylactic epidural infusion of HES. The incidence of PDPH, the use of intravenous aminophylline, therapeutic EBP, symptom onset, duration of headache, and duration of hospital stay were compared. RESULTS: A total of 85 patients were analyzed. The incidences of PDPH were 84%, 52.6% and 54.5% with conservative, prophylactic EBP, and prophylactic epidural HES treatments, respectively. Compared with the conservative treatment, prophylactic EBP and prophylactic epidural HES treatment significantly reduced the incidence of PDPH (P < 0.05). No significant difference was found between the prophylactic EBP and prophylactic epidural HES groups. Compared with the conservative treatment group, therapeutic EBP was significantly less used in the prophylactic EBP and prophylactic epidural HES groups (P < 0.05). Prophylactic EBP shortened the length of hospital stay of parturients with UDP (P < 0.05) while prophylactic epidural HES showed no statistical difference compared with conservative treatment. No severe complications, such as central nervous system and puncture site infection or nerve injury, were found in those patients. LIMITATIONS: Retrospective nature and single center data with a relatively small sample size. CONCLUSIONS: Prophylactic management with EBP and epidural infusion of HES has an effect in preventing the occurrence of PDPH; prophylactic EBP significantly shortened hospital stay length in parturients with UDP. KEY WORDS: Unintentional dural puncture, epidural blood patch, hydroxyethyl starch, post-dural puncture headache, parturient.

Intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during cesarean section: a prospective, double-blinded, randomized trial for ED50 determination using an up-down sequential allocation method.

BACKGROUND: Intrathecal dexmedetomidine, as an adjuvant to local anesthetics, has been reported to improve the quality of spinal anesthesia and reduce the required local anesthetic dose. However, the optimal dosage regimen for intrathecal dexmedetomidine combined with plain ropivacaine for cesarean section (CS) remains undetermined. The present study aimed to determine the median effective dose (ED50) of intrathecal dexmedetomidine as an adjuvant to plain ropivacaine for spinal anesthesia during CS. METHODS: Sixty parturients undergoing CS were randomly assigned to either group: plain ropivacaine 8 mg (Group Rop8) or plain ropivacaine 10 mg (Group Rop10). The initial dosage of intrathecal dexmedetomidine in each group was 5 µg. The effective dose was defined as a bilateral sensory block at the level of T6 or above to pinprick attained within 10 min after intrathecal injection, without the need for supplementary intraoperative epidural anesthesia. Effective or ineffective responses were determined, followed by a 1 µg increment or decrement in the dose of intrathecal dexmedetomidine for the next parturient using up-down sequential allocation. ED50 were calculated using probit regression. RESULTS: The ED50 of intrathecal dexmedetomidine with plain ropivacaine was 5.9 µg (95% confidence interval [CI], 4.9-7.4 µg) in Group Rop8 and 3.1 µg (95% CI, 0.1-4.8 µg) in Group Rop10 (P < 0.05). Hemodynamic stability, side effects, patient satisfaction and neonatal outcomes were comparable between the two groups. CONCLUSIONS: The present data suggested that the ED50 of intrathecal dexmedetomidine as an adjuvant to 8 mg and 10 mg plain ropivacaine in spinal anesthesia during cesarean section was approximately 6 µg and 3 µg, respectively. TRIAL REGISTRATION: Chinese Clinical Trial Registry, identifier: ChiCTR2200055928.

Multiple models for outbreak decision support in the face of uncertainty.

Policymakers must make management decisions despite incomplete knowledge and conflicting model projections. Little guidance exists for the rapid, representative, and unbiased collection of policy-relevant scientific input from independent modeling teams. Integrating approaches from decision analysis, expert judgment, and model aggregation, we convened multiple modeling teams to evaluate COVID-19 reopening strategies for a mid-sized United States county early in the pandemic. Projections from seventeen distinct models were inconsistent in magnitude but highly consistent in ranking interventions. The 6-mo-ahead aggregate projections were well in line with observed outbreaks in mid-sized US counties. The aggregate results showed that up to half the population could be infected with full workplace reopening, while workplace restrictions reduced median cumulative infections by 82%. Rankings of interventions were consistent across public health objectives, but there was a strong trade-off between public health outcomes and duration of workplace closures, and no win-win intermediate reopening strategies were identified. Between-model variation was high; the aggregate results thus provide valuable risk quantification for decision making. This approach can be applied to the evaluation of management interventions in any setting where models are used to inform decision making. This case study demonstrated the utility of our approach and was one of several multimodel efforts that laid the groundwork for the COVID-19 Scenario Modeling Hub, which has provided multiple rounds of real-time scenario projections for situational awareness and decision making to the Centers for Disease Control and Prevention since December 2020.

Outcomes after natural orifice extraction vs conventional specimen extraction surgery for colorectal cancer: A propensity score-matched analysis.

BACKGROUND: Natural orifice specimen extraction (NOSE) via the anus or vagina replaces conventional transabdominal specimen retrieval via the transabdominal route through a limited mid-line laparotomy or Pfannenstiel incision. Reducing the number of laparoscopic ports further decreases operative abdominal wall trauma. These techniques reduce the surgical wound size as well as the risk of incision-related morbidity. AIM: To compare short-term outcomes following 3-port NOSE surgery with a matched cohort of conventional non-NOSE colorectal cancer surgery. METHODS: Patients who underwent elective 3-port laparoscopic colorectal NOSE surgery between February to October 2021 were identified. Selection criteria for NOSE surgery was adapted from the 2019 International Consensus on Natural Orifice Specimen Extraction Surgery for colorectal cancer. Patients with clinical T4 or N2 tumors on staging computed tomography were also excluded. The propensity score-matched cohort was identified amongst patients who underwent conventional laparoscopic colorectal surgery from January 2019 to December 2020. Matching was performed in the ratio of 1:4 based on age, gender, type of resection, and p - tumor node metastasis staging. RESULTS: Over the eight-month study duration, 14 consecutive cases (nine female, five male) of elective 3-port laparoscopic surgery with NOSE were performed for colorectal cancer. Median age and body mass index were 70 (range 43-82) years and 24.1 (range 20.0-31.7) kg/m2 respectively. Six patients underwent transanal NOSE and eight had transvaginal NOSE. Median operative time, intraoperative blood loss and postoperative length of stay were 208 (range 165-365) min, 30 (range 10-150) mL and 3 (range 2-6) d respectively. Two (14%) suffered minor postoperative compilations not attributable to the NOSE procedure. Median follow-up duration was 12 (range 8-15) mo. No instances of mortality, local or distant disease recurrence were recorded in this cohort. Compared to the conventional surgery cohort of 56 patients, the 3-port NOSE cohort had significantly quicker mean return of bowel function (2.6 vs 1.2 d, P < 0.001), reduced postoperative pain and patient-controlled analgesia use, and decreased length of hospital stay (6.4 vs 3.4 d, P < 0.001). There were no statistical differences in surgical duration and perioperative complication rates between the NOSE and non-NOSE cohorts. CONCLUSION: 3-port laparoscopic colorectal surgery with NOSE is a feasible technique, augmenting the minimally invasive nature of surgery and producing good outcomes. Appropriate patient selection and expertise in conventional laparoscopy are required.

Effect of mindfulness meditation on depression during pregnancy: A meta-analysis.

Purpose: This study systematically evaluates the effect of mindfulness meditation on depression during pregnancy. We provide evidence-based suggestions for preventing and reducing depression during pregnancy by exploring the most effective intervention mode, cycle, and frequency of mindfulness meditation. Methods: Records were retrieved from PubMed, Web of Science, EBSCO, and Science Direct. A total of 1,612 randomized controlled trial studies on the effect of mindfulness meditation on pregnancy depression were collected. 10 studies with 658 subjects meeting the inclusion criteria were extracted and analyzed by Revman 5.3 to evaluate study qualities. Stata 12.0 was used for the meta-analysis. Results: Mindfulness meditation had a positive effect on depression during pregnancy [standardized difference of the mean (SMD) = -0.786, 95% confidence interval (-1.289, -0.283), P < 0.001]. Subgroup analysis showed that mindfulness-based cognitive therapy (MBCT) had the best intervention effect on depression during pregnancy (SMD = 2.795), the best intervention duration was below 4 weeks (SMD = 1.756), applied from the first to the third stage of pregnancy (SMD = 1.024), the frequency guided by experts was less than six times a week (SMD = 2.055) of <60 min each time (SMD = 1.068), and completing homework by themselves every day for 30 mins (SMD = 1.822) was most significant for the improvement of depression during pregnancy. We found high heterogeneity across studies [q = 97.003, DF = 10, I2 = 88.0% (P < 0.001), I2 > 75%]. This may be caused by variance in measurement tools, among which Beck Depression Inventory-II was a significant source of heterogeneity. Conclusion: Mindfulness meditation can improve the prevention, remission, and reduction of depression during pregnancy and can be used as an auxiliary measure for the clinical treatment of pregnancy depression.

Basal Planes Unlocking and Interlayer Engineering Endows Proton Doped-MoO2.8F0.2 with Fast and Stable Magnesium Storage.

Molybdenum trioxide has served as a promising cathode material of rechargeable magnesium batteries (RMBs), because of its rich valence states and high theoretical capacity; yet, it still suffers from sluggish (de)intercalation kinetics and inreversible structure change for highly polarized Mg2+ in the interlayer and intralayer of structure. Herein, F- substitutional and H+ interstitial doping is proposed for α-MoO3 materials (denoted HMoOF) by the intralayer/interlayer engineering strategy to boost the performance of RMBs. F- substitutional doping generates molybdenum vacancies along the Mo-O-□ or Mo-F-□ configurations (where □ represents the cationic vacancy) for unlocking the inactive basal plane of the layered crystal structure, and it further accelerates Mg2+ diffusion along the b-axis. Interstitial-doped H+ can expand interlayer spacing for reducing Mg2+ energy barrier along the ac plane and serve as a "pillar" to stabilize the interlayer structure. Moreover, anion and cation dual doping trigger shallow impurity levels (acceptors levels and donor levels), which helps to easily acquire the electrons from the valence band and donate the electrons to the conduction band. Consequently, the HMoOF electrode exhibits a high reversible capacity (241 mA h g-1 at 0.1 A g-1), an excellent rate capability (137.4 mAh g-1 at 2 A g-1), and a long cycling stability (capacity retention of 98% after 800 cycles at 1 A g-1) in RMBs. This work affords meaningful insights in layered materials for developing high-kinetics and long-life RMBs.

Finite Element Analysis and Near-Infrared Hyperspectral Reflectance Imaging for the Determination of Blueberry Bruise Grading.

Bruising of the subcutaneous tissues of blueberries is an important form of mechanical damage. Different levels of bruising have a significant effect on the post-harvest marketing of blueberries. To distinguish different grades of blueberry bruises and explore the effects of different factors, explicit dynamic simulation and near-infrared hyperspectral reflectance imaging were employed without harming the blueberries in this study. Based on the results of the compression experiment, an explicit dynamic simulation of blueberries was performed to measure the potential locations of bruises and preliminarily divide the bruise stages. A near-infrared hyperspectral reflectance imaging system was used to detect the actual blueberry bruises. According to the blueberry photos taken by the near-infrared hyperspectral reflectance imaging system, the actual bruise rates of blueberries were obtained by using the Environment for Visualizing Images software for training and classification. Bruise grades of blueberries were divided accordingly. Response surface methodology was used to determine the effects of ripeness, loading speed and loading location on the blueberry bruising rate. Under the optimized parameters, the actual damage rate of blueberries was 1.1%. The results provide an important theoretical basis for the accurate and rapid identification and classification of blueberry bruise damage.

Programmed Intermittent Epidural Bolus in Comparison with Continuous Epidural Infusion for Uterine Contraction Pain Relief After Cesarean Section: A Randomized, Double-Blind Clinical Trial.

Purpose: Programmed intermittent epidural bolus (PIEB) was reported to provide superior maintenance of labour analgesia with better pain relief and less motor block than continuous epidural infusion (CEI). Whether this is also evident for uterine contraction pain relief after cesarean section remains unknown. Patients and Methods: Parturients scheduled for cesarean section were recruited for the study. At the end of the surgery, after a similar epidural loading dose given, patients received either PIEB (6 mL·h-1) or CEI (6 mL·h-1) of 0.1% ropivacaine. The primary outcome was the uterine contraction pain assessed with visual analog scale (VAS-U) at the postoperative 36 h. Secondary outcomes included incision pain at the rest (VAS-R) and in the movement-evoked (VAS-P), and lower extremity motor block (defined as Bromage score > 0). The whole profile of VAS scores between groups was analyzed using linear mixed model. When significant differences were found, the pairwise comparison was done with the Mann Whitney U-test followed by Bonferroni correction. Results: One hundred and twenty parturients were studied (PIEB, 60; CEI, 60). VAS-U at the postoperative 36 h in the PIEB group was lower than in the CEI group (Bonferroni-adjusted P < 0.01). The linear mixed model indicated that VAS-U, VAS-R and VAS-P were lower in the PIEB group compared with the CEI group (all P < 0.01). Motor block was higher in the CEI group than in the PIEB group during the study period except 2 h (all P < 0.05). No differences of adverse events such as hypotension and urinary retention were observed between the two groups. Conclusion: Programmed intermittent epidural bolus provides more effective uterine contraction and incision pain relief and less motor block after cesarean section than continuous epidural infusion without an increased risk of urinary retention and blood pressure instability.

Anaesthetic management of a patient with complex, cyanotic congenitally corrected transposition of great arteries for electrophysiological study and thermoablation.

Congenitally corrected transposition of great arteries (ccTGA) is a rare congenital heart disease, and little literature is available that describes its anaesthetic management. We present the perioperative management of a patient with complex, cyanotic ccTGA who underwent electrophysiological study with catheter ablation under general anaesthesia. Good understanding of the patient's complex cardiac anatomy and physiology and multidisciplinary communication are vital to facilitate the successful care of the patient.

COVID-19 reopening strategies at the county level in the face of uncertainty: Multiple Models for Outbreak Decision Support.

Policymakers make decisions about COVID-19 management in the face of considerable uncertainty. We convened multiple modeling teams to evaluate reopening strategies for a mid-sized county in the United States, in a novel process designed to fully express scientific uncertainty while reducing linguistic uncertainty and cognitive biases. For the scenarios considered, the consensus from 17 distinct models was that a second outbreak will occur within 6 months of reopening, unless schools and non-essential workplaces remain closed. Up to half the population could be infected with full workplace reopening; non-essential business closures reduced median cumulative infections by 82%. Intermediate reopening interventions identified no win-win situations; there was a trade-off between public health outcomes and duration of workplace closures. Aggregate results captured twice the uncertainty of individual models, providing a more complete expression of risk for decision-making purposes.

Involvement of Orai1 in tunicamycin-induced endothelial dysfunction.

Endoplasmic reticulum (ER) stress is mediated by disturbance of Ca2+ homeostasis. The store-operated calcium (SOC) channel is the primary Ca2+ channel in non-excitable cells, but its participation in agent-induced ER stress is not clear. In this study, the effects of tunicamycin on Ca2+ influx in human umbilical vein endothelial cells (HUVECs) were observed with the fluorescent probe Fluo-4 AM. The effect of tunicamycin on the expression of the unfolded protein response (UPR)-related proteins BiP and CHOP was assayed by western blotting with or without inhibition of Orai1. Tunicamycin induced endothelial dysfunction by activating ER stress. Orai1 expression and the influx of extracellular Ca2+ in HUVECs were both upregulated during ER stress. The SOC channel inhibitor SKF96365 reversed tunicamycin-induced endothelial cell dysfunction by inhibiting ER stress. Regulation of tunicamycin-induced ER stress by Orai1 indicates that modification of Orai1 activity may have therapeutic value for conditions with ER stress-induced endothelial dysfunction.

The effects of novel α2-adrenoreceptor agonist dexmedetomidine on shivering in patients underwent caesarean section.

Objective: Meperidine used to control shivering during perioperative period has associated side effects. The present study compared the safety of selective α2-adrenoreceptor agonist dexmedetomidine and meperidine for anti-shivering in primiparas after caesarean delivery under combined spinal-epidural anesthesia (CSEA).Methods: 100 primiparas scheduled for caesarean delivery were randomly allocated to dexmedetomidine group (Group D, n=50) and meperidine positive control group (Group M, n=50). Primiparas experienced shivering that continued to cord clamping were treated with dexmedetomidine (0.5 µg/kg) or meperidine (0.5 mg/kg) after cord clamping. The primary outcome measures were incidence of nausea, vomiting, and respiratory depression. Secondary outcome measures were shivering score, vital signs including blood pressure, heart rate and O2 saturation, tympanic temperature, and sedation score.Results: Dexmedetomidine provided similar anti-shivering effects as meperidine in patients after caesarean delivery under CSEA, evidenced as all shivering primiparas responded to either dexmedetomidine or meperidine treatment within 15 min. However, incidence of nausea and vomiting were significantly lower after dexmedetomidine treatment, accompanied with more stable blood pressure. Dexmedetomidine also provided well regulation of tympanic temperature and good sedation.Conclusion: Selective α2-adrenoreceptor agonist dexmedetomidine has a better safety profile compared with meperidine for anti-shivering in primiparas undergoing caesarean delivery. Dexmedetomidine could be a better choice for anti-shivering in patients requiring caesarean section. The mechanism of anti-shivering for dexmedetomidine may relate to well regulation of temperature and good sedation.

A novel mutation in the STK11 gene causes heritable Peutz-Jeghers syndrome - a case report.

BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare disorder characterized by multiple gastrointestinal hamartomatous polyps and mucocutaneous pigmentation. STK11 has been identified as a causative gene for this disease. CASE PRESENTATION: Herein we report a Chinese Han kindred with PJS. Onset for the PJS signs in three of the patients was rarely as early as at birth. We identified a novel heterozygous mutation (c.440_441delGT, p.Arg147Leufs*15) in the gene STK11, causing a short frameshift followed by a deletion of 63% of the amino acids in the STK protein. This mutation co-segregated with the PJS phenotype, and was absent in two hundred of unrelated ethnicity-matched controls. The mutation led to expression decrease of unaffected STK11 protein in patients than in controls, as well in PJ polyps than in circulating leucocytes from the patients. Phosphorylation levels of the downstream kinase AMPKα altered according with the expression of STK11. These results indicated the possibility that haploinsufficiency and epigenetic reduction of STK11 contributed to the pathogenesis of the disease. CONCLUSION: This study identifies a novel mutation in the pathogenic gene STK11 leading to PJS.

Median Effective Dose of Intranasal Dexmedetomidine for Rescue Sedation in Pediatric Patients Undergoing Magnetic Resonance Imaging.

BACKGROUND: The median effective dose (ED50) of intranasal dexmedetomidine after failed chloral hydrate sedation has not been described for children. This study aims to determine the ED50 of intranasal dexmedetomidine for rescue sedation in children aged 1 to 36 months, who were inadequately sedated by chloral hydrate administration during magnetic resonance imaging (MRI). METHODS: This study was performed on 120 children, who were 1 to 36 months old and underwent MRI scanning. Intranasal dexmedetomidine was administered as a rescue sedative to children not adequately sedated after the initial oral dose of chloral hydrate (50 mg/kg). Children were stratified into four age groups. ED50 values were estimated from the up-and-down method of Dixon and Massey and probit regression. Other variables included induction time, time to wake up, vital signs, oxygen saturation, MRI scanning time, and recovery characteristics. RESULTS: ED50 of intranasal dexmedetomidine for rescue sedation was 0.4 µg/kg (95% CI, 0.34 to 0.50) in children aged 1 to 6 months, 0.5 µg/kg (95% CI, 0.48 to 0.56) in children aged 7 to 12 months, 0.9 µg/kg (95% CI, 0.83 to 0.89) in children aged 13 to 24 months, and 1.0 µg/kg (95% CI, 0.94 to 1.07) in children aged 25 to 36 months. There were no significant differences in sedation induction time or time to wake up between the different age groups. Additionally, no significant adverse hemodynamic or hypoxemic effects were noted. CONCLUSIONS: The authors determined the ED50 for rescue sedation using intranasal dexmedetomidine after failed chloral hydrate sedation in children. It was found that ED50 increases with advancing age during the first 3 yr of life.

TRPC3 channel confers cerebrovascular remodelling during hypertension via transactivation of EGF receptor signalling.

AIMS: Ionic perturbation in vascular smooth muscle cells contributes to cerebrovascular remodelling in the setting of hypertension, but the role of transient receptor potential (TRP) channel superfamily remains unknown. The present study was conducted to define the contribution of TRP channels to cerebrovascular remodelling. METHODS AND RESULTS: By integrating quantitative PCR, western blotting, patch clamping, and Ca(2+) imaging, we identified TRP channel, subfamily canonical, member 3 (TRPC3) as the channel subtype most considerably elevated in basilar arteries of two-kidney, two-clip stroke-prone hypertensive rats. Importantly, administration of pyrazole 3 (Pyr3), a TRPC3 channel blocker, attenuated cerebrovascular remodelling. During hypertension, epidermal growth factor receptor (EGFR) was transactivated, as evidenced by marked EGFR phosphorylation, increased pro-HB-EGF shedding, and elevated activity of ADAM17 (HB-EGF sheddase). ADAM17 activity was increased owing to enhanced activation rather than elevated expression. Remarkably, Pyr3 treatment suppressed EGFR transactivation in hypertension. In proliferating basilar artery smooth muscle cells or basilar arteries of hypertensive rats, co-immunoprecipitation assay revealed an interaction between TRPC3 and ADAM17 upon Ang II stimulation. CONCLUSION: Collectively, we demonstrated that enhanced EGFR transactivation, due to increased TRPC3 expression and functional coupling of TRPC3/ADAM17, resulted in cerebrovascular remodelling. Therefore, TRPC3-induced EGFR transactivation may be therapeutically exploited to prevent hypertension-induced cerebrovascular remodelling.