The effects of combined spinal-epidural analgesia and epidural anesthesia on maternal intrapartum temperature: a randomized controlled trial.

BACKGROUND: Labor epidural analgesia has been suggested to be associated with intrapartum fever. We designed this study to investigate the effects of epidural analgesia and combined spinal-epidural analgesia on maternal intrapartum temperature. METHODS: Four hundred healthy nullipara patients were randomly assigned to receive either epidural analgesia (EA group) or combined spinal-epidural analgesia (CSEA group). Maternal temperature was measured hourly after analgesia administration. The primary outcome was the incidence of maternal fever, and the secondary outcomes were the duration of analgesia, analgesia to full cervical dilation and analgesia to delivery. Neonatal outcomes and other basic labor events were also recorded. RESULTS: Maternal temperature gradually increased with time in both analgesia groups during labor. However, the CSEA group had a lower incidence of maternal fever, and a lower mean maternal temperature at 5 h, 6 h, and 9 h after analgesia. In addtion, the CSEA group also had a shorter time of analgesia duration, analgesia to full cervical dilation, analgesia to delivery, and less dose of epidural local anesthetic than the EA group. CONCLUSION: Our findings suggest that combined spinal-epidural analgesia is associated with a lower risk of intrapartum fever than epidural analgesia. TRIAL REGISTRATION: ChiCTR1900026606 . Registered on 16/10/2019.

Protein complex interactor analysis and differential activity of KDM3 subfamily members towards H3K9 methylation.

Histone modifications play an important role in chromatin organization and gene regulation, and their interpretation is referred to as epigenetic control. The methylation levels of several lysine residues in histone tails are tightly controlled, and JmjC domain-containing proteins are one class of broadly expressed enzymes catalyzing methyl group removal. However, several JmjC proteins remain uncharacterized, gaps persist in understanding substrate recognition, and the integration of JmjC proteins into signaling pathways is just emerging. The KDM3 subfamily is an evolutionarily conserved group of histone demethylase proteins, thought to share lysine substrate specificity. Here we use a systematic approach to compare KDM3 subfamily members. We show that full-length KDM3A and KDM3B are H3K9me1/2 histone demethylases whereas we fail to observe histone demethylase activity for JMJD1C using immunocytochemical and biochemical approaches. Structure-function analyses revealed the importance of a single amino acid in KDM3A implicated in the catalytic activity towards H3K9me1/2 that is not conserved in JMJD1C. Moreover, we use quantitative proteomic analyses to identify subsets of the interactomes of the 3 proteins. Specific interactor candidates were identified for each of the three KDM3 subfamily members. Importantly, we find that SCAI, a known transcriptional repressor, interacts specifically with KDM3B. Taken together, we identify substantial differences in the biology of KDM3 histone demethylases, namely enzymatic activity and protein-protein interactions. Such comparative approaches pave the way to a better understanding of histone demethylase specificity and protein function at a systems level and are instrumental in identifying the more subtle differences between closely related proteins.

Application of affinity selection-mass spectrometry assays to purification and affinity-based screening of the chemokine receptor CXCR4.

Affinity selection-mass spectrometry (AS-MS) is a sensitive technology for identifying small molecules that bind to target proteins, and assays enabled by AS-MS can be used to delineate relative binding affinities of ligands for proteins. 'Indirect' AS-MS assays employ size-exclusion techniques to separate target-ligand complexes from unbound ligands, and target-associated ligands are then specifically detected by liquid chromatography mass spectrometry. We report how indirect AS-MS binding assays with known reference control compounds were used as guideposts for development of an optimized purification method for CXCR4, a G-protein coupled chemokine receptor, for which we sought novel antagonists. The CXCR4 purification method that was developed was amenable to scale-up and enabled the screening of purified recombinant human CXCR4 against a large combinatorial library of small molecules by high throughput indirect AS-MS. The screen resulted in the discovery of new ligands that competed off binding of reference compounds to CXCR4 in AS-MS binding assays and that antagonized SDF1α-triggered responses and CXCR4-mediated HIV1 viral uptake in cell-based assays. This report provides a methodological paradigm whereby indirect AS-MS-based ligand binding assays may be used to guide optimal integral membrane protein purification methods that enable downstream affinity selection-based applications such as high throughput AS-MS screens.

Resting state basal ganglia network in idiopathic generalized epilepsy.

The basal ganglia, a brain structure related to motor control, is implicated in the modulation of epileptic discharges generalization in patients with idiopathic generalized epilepsy (IGE). Using group independent component analysis (ICA) on resting-state fMRI data, this study identified a resting state functional network that predominantly consisted of the basal ganglia in both healthy controls and patients with IGE. In order to gain a better understanding of the basal ganglia network(BGN) in IGE patients, we compared the BGN functional connectivity of controls with that of epilepsy patients, either with interictal epileptic discharges (with-discharge period, WDP) or without epileptic discharge (nondischarge period, NDP) while scanning. Compared with controls, functional connectivity of BGN in IGE patients demonstrated significantly more integration within BGN except cerebellum and supplementary motor area (SMA) during both periods. Compared with the NDP group, the increased functional connectivity was found in bilateral caudate nucleus and the putamen, and decreases were observed in the bilateral cerebellum and SMA in WDP group. In accord with the proposal that the basal ganglia modulates epileptic discharge activity, the results showed that the modulation enhanced the integration in BGN of patients, and modulation during WDP was stronger than that during NDP. Furthermore, reduction of functional connectivity in cerebellum and SMA, the abnormality might be further aggravated during WDP, was consistent with the behavioral manifestations with disturbed motor function in IGE. These resting-state fMRI findings in the current study provided evidence confirming the role of the BGN as an important modulator in IGE.

Resting-state fMRI study of treatment-naïve temporal lobe epilepsy patients with depressive symptoms.

BACKGROUND: Patients with temporal lobe epilepsy are at high risk for comorbid depression, and it is hypothesized that these two diseases are share common pathogenic pathways. We aimed to characterize regional brain activation in treatment-naïve temporal lobe epilepsy patients with depressive symptoms and compare the results to epilepsy patients without depressive symptoms and to healthy controls. SUBJECTS AND METHODS: We recruited 23 treatment-naïve patients (including anti-epilepsy drugs (AEDs) and antidepressants) and 17 matched healthy controls for this study. The patients were further divided into two groups: patients with depressive symptoms and patients without; the patients then used a self-rating depression scale (SDS) to assess their depression. All participants underwent resting functional magnetic resonance imaging (fMRI) scans using the Trio Tim magnetic resonance (MR) image system (3.0 T). The data were processed and analyzed using REST and SPSS11.5 software. RESULTS: The patients with depressive symptoms showed significantly higher activity in the bilateral thalamus, insula and caudate and right anterior cingulate compared with the two other groups (p<0.05, corrected). Brain network connectivity analysis revealed that connectivity decreased in the prefrontal-limbic system and increased within the limbic system and angular gyrus in patients with depressive symptoms (p<0.05, corrected). CONCLUSION: The epilepsy patients with depressive symptoms showed regional brain activity alterations and disruption of the mood regulation network at the onset of seizures. The present study offers further insight into the underlying neuropathophysiology of epilepsy with depressive symptoms.

Historical and current records of aquarium cetaceans in China.

The number of cetaceans housed in aquariums in China is increasing. Detailed information on the historical and current population status has not been reported, despite its importance for successful breeding and population management. Questionnaires were conducted between December 2006 and May 2009, and the information was used to construct studbooks. Our survey showed that 10 species had been introduced to aquariums since 1978, including 26 (with 15 in the current population) finless porpoises (Neophocaena phocaenoides), 5 (5) false killer whales (Pseudorca crassidens), 94 (80) common bottlenose dolphins (Tursiops truncatus), 48 (30) Indo-Pacific bottlenose dolphins (Tursiops aduncus), 36 (32) beluga whales (Delphinapterus leucas), 10 (10) pantropical spotted dolphins (Stenella attenuata), 8 (8) Risso's dolphins (Grampus griseus), 2 (2) short-finned pilot whales (Globicephala macrorhynchus), 2 (2) Pacific white-sided dolphins (Lagenorhynchus obliquidens), and 5 (0) baiji dolphins (Lipotes vexillifer). The number of cetaceans has increased markedly in the past 32 years, especially since 1995. Currently, 184 individuals are under human care throughout China, a number larger than any other country with an International Species Information System membership. In addition, the Annual Survival Rates of bottlenose dolphins (0.959) and beluga whales (0.968) were found higher than those reported previously (0.93-0.951 and 0.94-0.954, respectively).

[Efficacy of radiofrequency hyperthermia combined with chemotherapy in treatment of malignant pericardial effusion caused by lung cancer].

BACKGROUND AND OBJECTIVE: Malignant pericardial effusion is one of the serious complications of lung cancer and lack effective treatment methods. The aim of this study is to evaluate the efficacy and safety of radiofrequency hyperthermia combined with chemotherapy for patients with malignant pericardial effusion caused by lung cancer. METHODS: Fifty-five patients with malignant pericardial effusion caused by lung cancer were divided into hyperthermia combined with chemotherapy group (combined therapy group) and chemotherapy group. The combined therapy group was treated with radiofrequency hyperthermia after the pericardiocentesis and intracavitary injection (cisplatin 20 mg and dexamethasone 5 mg), when patients' general state of health improved, systemic chemotherapy was performed. The chemotherapy group was treated only with intracavitary injection and systemic chemotherapy. Intracavitary chemotherapy was performed for 1-6 times (average 3 times). Hyperthermia was performed twice per week with an average of 6 times following intracavitary and systemic chemotherapy. The temperature of intracavitary was 40.5 °C-41.5 °C for 60 min during the hyperthermia periods. Systemic chemotherapy consists of cisplatin (75 mg/m²) and vinorelbine (50 mg/m²). RESULTS: The complete remission rate (CR) of malignant pericardial effusion was 54.3% and the response rate (RR) was 91.4% in the combined therapy group, while the rates of CR and RR of chemotherapy group were 25.0% and 70.0%, and the differences of CR and RR between the two groups were significant (P<0.05). After treatment, the quality of life improved significantly in both groups, but the combined therapy group had a higher KPS score than in the chemotherapy group (P<0.05). The adverse events associated with the chemotherapy included gastrointestinal toxicity and myelosuppression, and there were no significant differences between the two groups. The main side effects associated with radiofrequency hyperthermia included local skin ache (8.6%) and induration of subcutaneous fat (5.7%). CONCLUSIONS: Radiofrequency hyperthermia combined with chemotherapy is effective in treatment of malignant pericardial effusion and can significantly improve the quality of life of patients without increasing the toxicity of chemotherapy, and side effects could be tolerable.

Localization of pilomotor seizure demonstrated by electroencephalography /functional magnetic resonance imaging.

We report the first case of a pilomotor seizure detected by electroencephalography /functional magnetic resonance imaging (EEG/fMRI). An adult woman presented with history of bouts of gooseflesh feeling and poilomotor activity in the left leg following viral encephalitis. 24-hour video-EEG and simultaneous EEG during fMRI revealed ictal discharges in the right parietal and temporal lobes. Associated blood oxygen level- dependent (BOLD) activations were found mainly in the right parietal region. The result represents a different generator of pilomotor seizure compared to prior reports. We suggests that the feeling of gooseflesh could be the core ictal symptom and a direct pathway from the sensory cortex to the lower autonomic system may exist bypassing the classic cerebral autonomic center.

An epidemiological survey of stroke in Lhasa, Tibet, China.

BACKGROUND AND PURPOSE: There have not been any new epidemiological studies related to stroke in Tibet for 20 years. This study aimed to collect stroke data from The City Staff Medical Insurance Registry in Lhasa, Tibet, to describe the incidence, clinical subtypes, and associated risk factors of stroke. METHODS: We used retrospective, population-based descriptive analysis of all urban and rural workers in the City Staff Medical Insurance Registry who were admitted to designated hospitals from October 2006 to October 2008. Stroke was defined by the International Classification of Disease (ICD)-10 coded from hospital records. RESULTS: Workers (81,298) were listed in the City Staff Medical Insurance Registry. Stroke patients (165) were included in the study, with 133 being first-ever patients. The age-standardized incidence rate was 88.725/100,000 per year (95% CI, 72.228-105.221), and mortality rate was 25.941/100,000 per year (95% CI, 16.416-35.466). The case fatality rate was 21.82%. Seventeen of the 133 patients (12.8%) were < 45 years of age. Stroke incidence rate was higher in ethnic Han patients than ethnic Tibetan patients. The most common subtype was cerebral infarction, and the most important risk factor was hypertension. CONCLUSIONS: Since the last study 20 years ago in Lhasa, stroke remains the primary fatal disease for the elderly, and its occurrence at younger ages is higher in Lhasa than in other areas of China. However, the annual incidence rate and mortality rate have decreased. The annual incidence rate is at a similar level to that in other parts of China. The primary subtype of stroke in Lhasa is cerebral ischemia.

[Different expression of GluR5 and GluR6 in rat astrocyte induced with coriaria lactone and ATPA].

OBJECTIVE: To investigate the different expression of GluR5 and GluR6 in rat astrocyte induced with Coriaria Lactone (CL) and ATPA and to discuss the possible mechanism of the inducing epileptic model. METHODS: Astrocyte of neonate rats was treated with CL and ATPA respectively and the astrocyte treated with normal saline as control. The mRNA and protein levels of GluR5 and GluR6 were detected by RT-PCR and western blotting. RESULTS: Compared with the control, the expression of GluR5 was increased significantly in the astrocyte induced by ATPA (P < 0.05), however, there was no alteration of GluR6 expression. The expression of GluR5 and GluR6 were decreased significantly in CL-treated group (P < 0.05). CONCLUSION: The present study showed ATPA up-regulated mRNA and protein levels of GluR5, but coriaria lactone down-regulated the GluR5 and GluR6 of astrocyte. The results indicate that there are different pathologic mechanisms of GluR5 and GluR6 in different neurotoxicants inducing model of epilepsy. The molecular mechanism need to be studied further in the future.

Imaging foci of epileptic discharges from simultaneous EEG and fMRI using the canonical HRF.

PURPOSE: Simultaneous electroencephalography and functional magnetic resonance imaging (EEG-fMRI) is considered as a powerful and non-invasive method that allows definition of the irritative zone. However, the complex interictal epileptic discharge (IED) may be present in some patients, and sometimes no active foci can be localized using General Linear Model (GLM) which is a widely adopted tool in EEG-fMRI study. The purpose of this study is to develop a new scheme to improve the detectability and localize the canonical HRF localizable foci. METHOD: Various IEDs are classified using a combination of an independent component analysis (ICA) and a temporal correlation analysis between the independent components and the raw EEG channel; and the classified IEDs are then separately used for foci localization. This scheme is tested by ten patients with variable IEDs, including two patients whose activity could not be identified by common method. RESULT: Applying this scheme to the two patients, some foci consistent with electroclinical data were localized. When it was applied to the remaining eight patients with positive results using common method, 2-4 types of IEDs were classified, and the activity could be identified from at least one type of IED. The results were similar to that received from common method. CONCLUSION: These results indicate that the proposed scheme could enhance the imaging of the localizable foci by isolating its IEDs. This scheme is potentially a useful tool for epilepsy clinic.

The operational model of a network for managing patients with convulsive epilepsy in rural West China.

OBJECTIVE: To establish an operational model of a network for managing patients with convulsive epilepsy in rural areas of West China. METHODS: The network is under unified leadership of the public health administration departments, who liaised with medical institutions and disease control and prevention organizations to foster local communities to participate. Patients with convulsive epilepsy were treated with phenobarbital. Trained local primary health care physicians carried out screening, treatment, and follow-up. Political, financial, and technological support was incrementally provided through the network. Efficacy was assessed as the percentage reduction in seizure frequency and the retention of patients on treatment. RESULTS: Two thousand five hundred fourteen patients with active convulsive epilepsy were enrolled. After more than 1 year of treatment, 78.4% of the patients had a 50% or greater reduction in seizure frequency and 43.3% remained seizure free. Probability of retention was 85.8% at 750 days. Nearly 20% patients withdrew from the project, and most of them migrated out of the study areas. Some regular training and educational programs were also carried out. CONCLUSION: This pragmatic procedure suggests that the network could be suitable for managing convulsive epilepsy in resource-poor regions. Such a network could depend on existing primary health services to ensure its sustainability.

EEG-fMRI study on the interictal and ictal generalized spike-wave discharges in patients with childhood absence epilepsy.

BACKGROUND: Absence epilepsy is characterized clinically by the impairment of consciousness and 3 Hz generalized spike-wave discharges (GSWDs) on EEG. Clinical absence can be observed with ictal GSWDs, but interictal GSWD bursts are usually clinically silent. Simultaneous EEG and blood-oxygen-level-dependent (BOLD) functional MRI (EEG-fMRI) has been successfully used to link the changes in regional neuronal activity to the occurrence of GSWDs. METHODS: We used EEG-fMRI to investigate and compare the BOLD signal changes during interictal and ictal GSWDs in patients with childhood absence epilepsy (CAE). RESULTS: Fifteen drug-naïve children with newly diagnosed CAE were studied using continuous EEG-fMRI. BOLD signal changes associated with interictal (nine sessions with six patients) and ictal (eight sessions with six patients) GSWDs were analyzed at the individual and group levels. GSWDs were associated with widespread and symmetrical deactivation in the cortex and caudate nucleus with a frontal maximum, and predominant activation in the thalamus bilaterally during ictal GSWDs and in the cortex during interictal GSWDs. The BOLD response was characterized by a higher statistical significance and a more widespread extent at the time of the ictal GSWDs as compared to the time of interictal GSWDs. CONCLUSIONS: Both interictal and ictal GSWDs in patients with CAE are associated with BOLD signal changes in the basal ganglia-thalamocortical loop. Ictal GSWDs showing predominant thalamic activation and widespread cortical deactivation might cause a complete suspension of the normal brain's default state and manifest clinically as abrupt loss of consciousness (absence seizures).

Lateral sinus thrombosis and intracranial hypertension associated with primary hypothyroidism: case report.

Several cases of hypothyroidism have been reported to develop idiopathic intracranial hypertension not directly precisely linked with cerebral venous sinus thrombosis (CVT). A 31-year-old Chinese woman presented with bilateral blurred vision and paroxysmal amaurosis for about 6 months without headache. Neurological examination revealed normal expect for the sixth cranial nerve palsy and bilateral papilledema. Laboratory tests showed pronounced hypothyroidism and greatly increased serum triglyceride. Cerebral spinal fluid showed the increased opening and closing pressure. Digital subtraction angiography (DSA) disclosed a filling defect in the adjunction of bilateral transverse sinuses and sigmoid sinuses. Her symptoms gradually improved with levothyroxine, mannitol and anticoagulants treatment. In presenting the rare case of lateral sinus thrombosis associated with primary hypothyroidism, we wish to alert physicians that patients presenting with papilledema and hypothyroidism may require investigations of DSA for CVT, even in the absence of headache.

Discovery and characterization of orthosteric and allosteric muscarinic M2 acetylcholine receptor ligands by affinity selection-mass spectrometry.

Screening assays using target-based affinity selection coupled with high-sensitivity detection technologies to identify small-molecule hits from chemical libraries can provide a useful discovery approach that complements traditional assay systems. Affinity selection-mass spectrometry (AS-MS) is one such methodology that holds promise for providing selective and sensitive high-throughput screening platforms. Although AS-MS screening platforms have been used to discover small-molecule ligands of proteins from many target families, they have not yet been used routinely to screen integral membrane proteins. The authors present a proof-of-concept study using size exclusion chromatography coupled to AS-MS to perform a primary screen for small-molecule ligands of the purified muscarinic M2 acetylcholine receptor, a G-protein-coupled receptor. AS-MS is used to characterize the binding mechanisms of 2 newly discovered ligands. NGD-3350 is a novel M2-specific orthosteric antagonist of M2 function. NGD-3366 is an allosteric ligand with binding properties similar to the allosteric antagonist W-84, which decreases the dissociation rate of N-methyl-scopolamine from the M2 receptor. Binding properties of the ligands discerned from AS-MS assays agree with those from in vitro biochemical assays. The authors conclude that when used with appropriate small-molecule libraries, AS-MS may provide a useful high-throughput assay system for the discovery and characterization of all classes of integral membrane protein ligands, including allosteric modulators.

Plasmon-waveguide resonance studies of ligand binding to the human beta 2-adrenergic receptor.

Plasmon-waveguide resonance (PWR) spectroscopy is an optical technique that can be used to probe the molecular interactions occurring within anisotropic proteolipid membranes in real time without requiring molecular labeling. This method directly monitors mass density, conformation, and molecular orientation changes occurring in such systems and allows determination of protein-ligand binding constants and binding kinetics. In the present study, PWR has been used to monitor the incorporation of the human beta(2)-adrenergic receptor into a solid-supported egg phosphatidylcholine lipid bilayer and to follow the binding of full agonists (isoproterenol, epinephrine), a partial agonist (dobutamine), an antagonist (alprenolol), and an inverse agonist (ICI-118,551) to the receptor. The combination of differences in binding kinetics and the PWR spectral changes point to the occurrence of multiple conformations that are characteristic of the type of ligand, reflecting differences in the receptor structural states produced by the binding process. These results provide new evidence for the conformational heterogeneity of the liganded states formed by the beta(2)-adrenergic receptor.