Efficacy comparison of oxcarbazepine and levetiracetam monotherapy among patients with newly diagnosed focal epilepsy in China: A multicenter, open-label, randomized study.

AIMS: This multicenter, open-label, randomized study (Registration No. ChiCTR-OCH-14004528) aimed to compare the efficacy and effects of oxcarbazepine (OXC) with levetiracetam (LEV) as monotherapies on patient quality of life and mental health for patients with newly diagnosed focal epilepsy from China. METHODS: Patients with newly diagnosed focal epilepsy who had experienced 2 or more unprovoked seizures at greater than a 24-h interval during the previous year were recruited. Participants were randomly assigned to the OXC group or LEV group. Efficacy, safety, quality of life, and mental health were evaluated over 12-week and 24-week periods. RESULTS: In total, we recruited 271 newly diagnosed patients from 23 centers. Forty-four patients were excluded before treatment for reasons. The rate of seizure freedom of OXC was significantly superior to that of LEV at 12 weeks and 24 weeks (p < 0.05). The quality of life (except for the seizure worry subsection) and anxiety scale scores also showed significant differences from before to after treatment in the OXC and LEV groups. CONCLUSIONS: OXC monotherapy may be more effective than LEV monotherapy in patients with newly diagnosed focal epilepsy. Both OXC and LEV could improve the quality of life and anxiety state in adult patients with focal epilepsy.

Corrigendum: The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

[This corrects the article DOI: 10.3389/fphar.2021.684898.].

The Role of High-Content Complex Dietary Fiber in Medical Nutrition Therapy for Gestational Diabetes Mellitus.

Objectives: A controlled open clinical study was conducted to evaluate the role of Ricnoat, a high-content complex dietary fiber powder produced by Zhuhai Aimed Biotechnology Co. Ltd., in medical nutrition therapy (MNT) to treat gestational diabetes mellitus (GDM). The study aimed to investigate glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM, as well as evaluate the clinical safety of Ricnoat. Methods: A total of 120 patients with GDM who were admitted to three hospitals in Shanghai between January 2019 and January 2020 were enrolled. Ricnoat was used for intervention for patients in the experimental group. Using a χ2 test and t-test, respectively, comparisons were conducted between the measurement data and countable data of the demographics and baseline disease characteristics of the experimental group and control group. Results: Fasting blood glucose, 2-h postprandial blood glucose, glycated hemoglobin, total cholesterol, triglycerides, low-density lipoprotein, maternal gestational weight gain, neonatal weight, serum creatinine, glutamate transaminase, and aspartate aminotransferase were lower in the experimental group than in the control group, whereas high-density lipoprotein was higher in the experimental group than in the control group. Ricnoat intervention resulted in satiety higher than the expected 80% and more common occurrence of type 4 (smooth and soft, like salami or a snake) and type 5 (a soft mass with clear edges) stools. Conclusion: Ricnoat intervention had a significant effect on glycemic control, lipid control, weight control, and pregnancy outcomes (neonatal weight) in patients with GDM by enhancing maternal satiety and improving the stool features of pregnant women. It was also found to be safe for application during pregnancy.

Correlation of Seizure Increase and COVID-19 Outbreak in Adult Patients with Epilepsy: Findings and Suggestions from a Nationwide Multi-centre Survey in China.

OBJECTIVES: To investigate the impact of the COVID-19 outbreak on the behaviours, mental health and seizure control of adult patients with epilepsy (PWE) and to identify the correlation of seizure increase and the COVID-19 outbreak to guide the medical care of individuals with epilepsy during a public health crisis. METHODS: This study was conducted at 28 centres from February 2020 to April 2020. Participants filled out a 62-item online survey including sociodemographic, COVID-19-related, epilepsy-related and psychological variables and were divided into two groups based on whether their seizure frequency increased during the COVID-19 pandemic. Chi-square tests and t-tests were used to test differences in significant characteristics. Multiple logistic regression analyses were used to identify risk factors for seizure worsening. RESULTS: A total of 1,237 adult PWE were enrolled for analysis. Of this sample, 31 (8.33%) patients experienced an increase in seizures during the pandemic. Multivariate logistic regression suggested that feeling nervous about the pandemic (P < 0.05), poor quality of life (P = 0.001), drug reduction/withdrawal (P = 0.032), moderate anxiety during the COVID-19 outbreak (P = 0.046) and non-seizure free before the COVID-19 outbreak (P < 0.05) were independently related to seizure increase during the pandemic. CONCLUSIONS: During the COVID-19 pandemic, PWE with poor quality of life and mental status, as well as AED reduction/withdrawal, were more likely to experience seizure increase. This observation highlights the importance of early identification of the population at high risk of seizure worsening and implementation of preventive strategies during the pandemic.

A new non-invasive procedure for refractory PPH after vaginal delivery and caesarean section.

Worldwide, the incidence of postpartum haemorrhage (PPH) is ∼6% and it is the leading cause of maternal mortality. The present study introduces a non-invasive procedure called bilateral cervix apex clamping (BCAC) as a new treatment for refractory PPH. A total of 13 vaginal deliveries and 5 caesarean section patients received the BCAC procedure to stop bleeding. During the procedure, the anterior and posterior walls of the cervical apex were clamped using toothless ovum forceps from the left and right side. The procedure was terminated when the bleeding had nearly stopped without clamping. The success rate of the procedure was 94.4% (17/18) overall, and 92.3% for vaginal delivery and 100% in caesarean section patients. Only one case of vaginal delivery did we resort to exploratory laparotomy and hysterectomy as amniotic fluid embolism occurred. The time spent on the procedure was 2-4 min for vaginal delivery cases and 5-7 min for caesarean section patients. The blood loss reduced significantly after the procedure, before the BCAC and after it was 875(450) ml versus 100(80)ml (p < .0001). There was a reduction in the need for UAE (uterine artery embolisation) from 13 in 22,817 deliveries (2013-2015) to 0 in 18,212 deliveries (2016-2017 (p < .001). But no change in the rate of hysterectomy (5/22817 versus 5/18212) (p = .76). BCAC is a simple, easy, safe, effective and non-invasive procedure that can decrease bleeding in patients with PPH.Impact statementWhat is already known on this subject? The BCAC clamping procedure was first described in Russia 80 years ago as the Genkel-Tikanadze method. But a PUBMED search did not identify and previous studies published on use of the technique.What do the results of this study add? The results of this study show that the BCAC clamping procedure can reduce bleeding significantly in refractory postpartum haemorrhage, when the uterine body is well contracted. The procedure can be performed after both in vaginal delivery and caesarean section. It can also reduce the necessity for UAE and balloon tamponade.What are the implications of these findings for clinical practice and/or further research? BCAC can be used after the failure of regular first line therapy for postpartum haemorrhage.

Shedding lights on the flexible-armed porphyrins: Human telomeric G4 DNA interaction and cell photocytotoxicity research.

DNA polymorphism exerts a fascination on a large scientific community. Without crystallographic structural data, clarification of the binding modes between G-quadruplex (G4) and ligand (complex) is a challenging job. In the present work, three porphyrin compounds with different flexible carbon chains (arms) were designed, synthesized and characterized. Their binding, folding and stabilizing abilities to human telomeric G4 DNA structures were comparatively researched. Positive charges at the end of the flexible carbon chains seem to be favorable for the DNA-porphyrin interactions, which were evidenced by the spectral results and further confirmed by the molecular docking calculations. Biological function analysis demonstrated that these porphyrins show no substantial inhibition to Hela, A549 and BEL 7402 cancer cell lines under dark while exhibit broad inhibition under visible light. This significantly enhanced photocytotoxicity relative to the dark control is an essential property of photochemotherapeutic agents. The feature of the flexible arms emerges as critical influencing factors in the cell photocytotoxicity. Moreover, an ROS-mediated mitochondrial dysfunction pathway was suggested for the cell apoptosis induced by these flexible-armed porphyrins. It is found that the porphyrins with positive charges located at the end of the flexible arms represent an exciting opportunity for photochemotherapeutic anti-cancer drug design.

Daunomycin-loaded superparamagnetic iron oxide nanoparticles: Preparation, magnetic targeting, cell cytotoxicity, and protein delivery research.

The clinical use of daunomycin is restricted by dose-dependent toxicity and low specificity against cancer cells. In the present study, modified superparamagnetic iron oxide nanoparticles were employed to load daunomycin and the drug-loaded nanospheres exhibited satisfactory size and smart pH-responsive release. The cellular uptake efficiency, targeted cell accumulation, and cell cytotoxicity experimental results proved that the superparamagnetic iron oxide nanoparticle-loading process brings high drug targeting without decreasing the cytotoxicity of daunomycin. Moreover, a new concern for the evaluation of nanophase drug delivery's effects was considered, with monitoring the interactions between human serum albumin and the drug-loaded nanospheres. Results from the multispectroscopic techniques and molecular modeling calculation elucidate that the drug delivery has detectable deleterious effects on the frame conformation of protein, which may affect its physiological function.

MRI and clinical manifestations of delayed encephalopathy after carbon monoxide poisoning.

To explore the relationship between the clinical manifestations and functional magnetic resonance images of delayed encephalopathy after carbon monoxide intoxication. Six patients received the MRI were diagnosed with delayed encephalopathy after carbon monoxide (CO) poisoning. Clinical manifestations were observed in each patient. MRI revealed multiple lesions. The majority of the lesions were located in the globus pallidus, sub cortical white matter, and basal ganglia. The cognitive injury, akinetic mutism, fecal and uroclepsia, forced crying, forced laughing and extra pyramidal syndromes such as chorea and parkinsonism were manifested in clinic. Cognitive impairment improved greatly while involuntary movements only improved slightly after several months. Meanwhile brain MRI suggested remarkable improvement. Neuroimaging directly correlated with the clinical manifestations.

[Long-term Efficacy and Ocular Surface of Pterygium Excision Combined with Autologous Corneal Limbal Stem Cell Transplantation in Treatment of Pterygium].

PURPOSE: To evaluate the long-term efficacy of pterygium excision combined with autologous corneal limbal stem cell transplantation in the treatment of pterygium. METHODS: Fifty five patients (57 eyes) diagnosed with primary pterygium undergoing pterygium excision combined with autologous corneal limbal stem cell transplantation between December 2003 and December 2008 were enrolled in this study. Postoperative follow-up endured for 2-8 years, 5.3 years on average. The wound healing, clinical efficacy and postoperative complications were observed. RESULTS: During early stage after surgery, all patients presented with varying degree of hyperemia, edema and sense of foreign body, which were gradually mitigated 3-5 d later and completely recovered in approximately 1 week. The corneal wound was completely epithelized within 4-7 d, 4.83 d on average. Seven patients had persistent ocular surface irritation symptoms after surgery, one case had residual fibrous tissues and four patients developed superficial corneal scars. Postoperative follow-up endured for 2-8 years, 5.3 years on average. Eight patients (8 eyes) recurred with a recurrence rate of 13.11%. In all patients, postoperative OSDI score was significantly decreased at 1-year reexamination. OSDI score and constitution ratio significantly differed between two groups (both P < 0.05). At postoperative 5 years, OSDI score was slightly lower compared with that in last year with no statistical significance (P > 0.05). At post-operative 1- and 5-year, basic tear secretion was (12.95 ± 4.03) mm and (12.68 ± 4.77) mm, tear film break-up time was (10.55 ± 4.13) s and (10.03 ± 4.64) s. Both indexes were significantly improved compared with (9.48 ± 3.34) mm and (8.14 ± 3.57) s before surgery (all P < 0.05). CONCLUSION: Pterygium excision combined with autologous corneal limbal stem cell transplantation is an efficacious treatment of pterygium with mild postoperative symptoms, rapid recovery, low long-term recurrence rate and high efficacy.

A PARK2 polymorphism associated with delayed neuropsychological sequelae after carbon monoxide poisoning.

BACKGROUND: Delayed neuropsychological sequelae (DNS) are the most severe and clinically intractable complications following acute carbon monoxide (CO) poisoning. Symptoms of DNS often resemble those of Parkinson's disease (PD), suggesting shared neurological deficits. Furthermore, Parkinson protein 2 (PARK2) mutations are associated with PD and other neurodegenerative diseases. The association signal was detected between PARK2 and DNS after acute CO poisoning in our DNA pooling base genome-wide association study. METHODS: Two PARK2 single nucleotide polymorphisms (SNPs), rs1784594 (C/T allele) and rs1893895 (G/A allele), selected from DNA pooling base genome-wide association study, were genotyped by in 514 CO poisoning patients using polymerase chain reaction restriction fragment length polymorphisms (PCR-RFLPs). The patient group consisted of 231 patients with DNS and 283 patients with no signs of lasting neurological damage (control population). RESULTS: The frequency of the rs1784594 T allele was significantly lower in the DNS population (OR = 1.42, 95%CI: 1.08 - 1.87), as was the TT vs. CC genotype (OR = 1.95, 95%CI: 1.15 - 3.23) and the TT vs. CT + CC frequency (OR = 1.68, 95%CI: 1.32 - 2.49) compared to controls. Association analysis revealed a significant association between DNS and rs1784594 (P < 0.01) but not rs1893895 (P > 0.05). In female cases, the T allele frequency of rs1784594 was significantly lower in DNS patients compared to female controls (OR = 1.48, 95%CI: 1.01 - 2.17). CONCLUSION: These data suggest that the allelic variant of rs1784594 is a risk factor for DNS following acute CO poisoning, especially in females. The PARK2 protein may modulate the susceptibility to DNS, underscoring the importance of examining the relationship between other PARK2 polymorphisms and clinical outcome following CO poisoning.

Long-term outcomes of domestic hunan aqueous drainage implantation in refractory glaucoma.

PURPOSE: To evaluate the long-term outcomes of a non-valved, Chinese-made Hunan aqueous drainage device (HAD) in patients with refractory glaucoma, compared to trabeculectomy. METHODS: This was a retrospective observational case series, including 27 patients with refractory glaucoma who either underwent HAD implantation (n=11) or trabeculectomy (n=16). The mean follow-up was 27.9±13.5 (mean±SD) months. Intraocular pressure (IOP), visual acuity and postoperative complications were measured. RESULTS: IOP was significantly lower at the last follow-up in both two groups compared with the baseline IOP (HAD: 58.4 to 10.0 mmHg, P>0.001; trabeculectomy:58.4 to 23.7 mmHg, P<0.001). One week, 1 month and 1 year after the operation, the average IOP of the HAD group was significantly lower than that of trabeculectomy group (P<0.05 at all time points). However, , the IOP did not differ significantly between the two groups at the time of last follow-up. CONCLUSION: HAD implantation serves as a good option to control IOP in refractory glaucoma.

[Clinical significance of 5-HT and DA levels in serum and cerebrospinal fluid of the patients with delayed encephalopathy after acute carbon monoxide poisoning].

OBJECTIVE: To explore the changes and the clinical significance of 5-hydroxytryptamine (5-HT), dopamine (DA) levels in serum and cerebrospinal fluid (CSF) of patients with delayed encephalopathy (DEACMP) after acute carbon monoxide poisoning. METHODS: The dynamic detection of 5-HT and DA levels in serum and CSF from 42 patients with DEACMP was performed with high performance liquid chromatography (HPLC). The condition changes of patients with DEACMP were analyzed with three types of scales: the activity of daily living scale (ADL), information memory concentration test (IMCT) and Hasegawa's dementia scale (HDS); these changes were compared with those from 38 other encephalopathy patients and 38 non-encephalopathy patients, respectively. RESULTS: Before treatment, the serum 5-HT and DA levels [(662.61 ± 178.50) and (155.74 ± 60.32) nmol/L, respectively] of DEACMP group were both significantly lower than those [(914.08 ± 198.04) and (225.70 ± 48.53) nmol/L] of non-encephalopathy group (P < 0.05); the serum DA level of DEACMP group was also significantly lower than that [(243.57 ± 66.94) nmol/L] of other encephalopathy group (P < 0.05); the serum 5-HT level of DEACMP group was not significantly different from that [(729.54 ± 299.87) nmol/L] of other encephalopathy group (P > 0.05). After treatment, the serum 5-HT and DA levels [(714.08 ± 170.47) and (192.18 ± 33.07 nmol/L, respectively)] of DEACMP group elevated to various extent, but only serum DA level was significantly higher than that before treatment (P < 0.05). Before treatment, the CSF 5-HT and DA levels of DEACMP group were significantly lower than those of non-encephalopathy group and those of other encephalopathy group (P < 0.05). After treatment, the CSF 5-HT level (232.44 ± 54.28 nmol/L) was similar to normal level and significantly higher than that before treatment (P < 0.05); the CSF DA level [(56.83 ± 12.85) nmol/L] of DEACMP group increased only slightly (P > 0.05). In DEACMP group, ADL score (50.64 ± 7.23), HDS score (8.55 ± 8.08) and IMCT score (4.95 ± 7.30) before treatment were significantly different from those (8.5 ± 8.08, 4.95 ± 7.30 and 15.64 ± 10.90) after treatment (P < 0.01). In DEACMP group, there wasa negative correlation between DA level changes and HDS score changes, when the DA levels and HDS scores before treatment were compared with those after treatment (P < 0.05). CONCLUSION: The dynamic changes of 5-HT and DA levels in serum and CSF of patients with DEACMP consisted basically with the patient's condition change. The dynamically detected 5-HT and DA levels can be used as the biological indicators to reflect the condition change and treatment effects of DEACMP patients.

Notes from the heterogeneous: a few observations on the implications and necessity of affinity.

The problem of who is mixing with whom is of great theoretical importance in the context of heterosexual mixing. In this article, we publish for the first time, data from a study carried out in 1989 that had the goal of estimating who is mixing with whom, in heterosexually active college populations in the presence of co-factors like drinking. The gathering of these data and the challenges involved in modelling the interaction between and among heterosexually active populations of individuals are highlighted in this manuscript. The modelling is based on the assumptions that at least two processes are involved: individual affinities or preferences determine 'what we want' while mixing patterns describe 'what we get'. We revisit past results on the role of affinity/preference on observed mixing patterns in one- and two-sex mixing populations. Some new results for homosexually active populations are presented. The study of mixing is but the means to an end and consequently, we also look at the role of affinity on epidemics as filtered by observed mixing patterns. It would not be surprising to observe that highly distinct preference or mixing structures may actually lead to quite similar epidemic patterns.

Human brain processing and central mechanisms of pain as observed by electro- and magneto-encephalography.

We review the recent progress of electroencephalography (EEG) and magnetoencephalography (MEG) to elucidate pain perception mechanisms in humans, since EEG and MEG have an excellent temporal resolution in order of msec. MEG is more useful to detect activated areas following painful stimulation, because the spatial resolution of EEG is not very high. For recording activities following Adelta fiber stimulation relating to the first pain, painful CO2 laser stimulation is now widely used, but our new method, epidermal stimulation (ES), is also very useful. The primary small activity was recorded from the primary somatosensory cortex (SI), probably in area 1, in the hemisphere contralateral to the stimulation. Then, secondary somatosensory cortex (SII) and insula were activated with the second activity in SI. These 3 regions were activated in parallel with almost the same time period. This is a very characteristic finding in pain perception. Then, the cingulate cortex and medial temporal area (MT) around the amygdala and hippocampus were activated. In the hemisphere ipsilateral to the stimulation as well, the above regions were activated, except for SI. Therefore, we speculated that SI plays a main role in localization of the stimulus point, the SII and insula are important sites for pain perception, and the cingulate and MT are mainly responsible for cognitive or emotional aspects of pain perception. For recording activities following C fiber stimulation relating to the second pain, we recently developed a new method, that is, applying weaker CO2 laser stimuli to tiny areas of the skin. MEG findings following C fiber stimulation were also similar to those following Adelta fiber stimulation. However, the effects of sleep and attention on MEG following C fiber stimulation was much larger than that following Adelta fiber stimulation. This finding may suggest greater effects of cognitive or emotional functions on second pain than the first pain.

Localization of isoketal adducts in vivo using a single-chain antibody.

Isoketals are highly reactive gamma-ketoaldehydes formed by the oxidation of arachidonic acid that rapidly adduct to proteins. To investigate the formation of isoketal adducts in vivo, we isolated and characterized a single-chain antibody from a phage displayed recombinant ScFv library that bound a model peptide adducted with synthetic 15-E2-isoketal. Recognition of isoketal adduct by this anti-isoketal adduct single-chain antibody was essentially independent of the amino acid sequence of adducted peptides or proteins. The antibody did not cross-react with 4-hydroxynonenal or 4-oxononanal adducts or with 15-F2t-isoprostane (8-iso-prostaglandin F2alpha). We investigated the formation of isoketal adducts in a well-established model of oxidative injury, hyperoxia. Exposure to >98% oxygen for 7 h dramatically increased both the number of immunoreactive airway epithelial cells and the intensity of immunoreactivity compared with animals exposed to normal room air (21% oxygen). We conclude that isoketal adducts form in epithelial cells as a result of high oxygen exposure and that this single-chain antibody provides a valuable tool to localize the formation of isoketal adducts in tissues in vivo.

Evidence for CD4-enchanced signaling through the chemokine receptor CCR5.

The chemokine receptor CCR5 is constitutively associated with the T cell co-receptor CD4 in plasma cell membranes, but the physiological role of this interaction has not been elucidated. Here we show that detergent-solubilized, purified CCR5 can directly associate with purified soluble fragments of the extracellular portion of CD4. We further demonstrate that the physical association of CCR5 and CD4 in membrane vesicles results in the formation of a receptor complex that exhibits macrophage inflammatory protein 1beta (MIP-1beta) binding properties that are distinct from CCR5. The affinity of the CD4-CCR5 complex for MIP-1beta was 3.5-fold lower than for CCR5, but the interaction of CD4 and CCR5 resulted in a receptor complex that exhibited enhanced G-protein signaling as compared with CCR5 alone. MIP-1beta-induced G-protein activation was further increased by simultaneous stimulation of CD4 with its natural agonist, interleukin-16. Thus, the physical association of CD4 and CCR5 results in receptor cross-talk with allosteric CD4-dependent regulation of the binding and signaling properties of CCR5. Although the precise physiological role of the CD4 effects on CCR5-mediated signaling remains unknown, one can speculate that the cross-talk is a component of mechanisms involved in the fine tuning of immune system cell responses.