Both epilepsy and anti-seizure medications affect bone metabolism in children with self-limited epilepsy with centrotemporal spikes.

OBJECTIVE: Bone metabolism can be influenced by a range of factors. We selected children with self-limited epilepsy with centrotemporal spikes (SeLECTS) and lifestyles similar to those of healthy children to control for the confounding factors that may influence bone metabolism. We aimed to identify the specific effects of epilepsy and/or anti-seizure medications (ASMs) on bone metabolism. METHODS: Patients with SeLECTS were divided into an untreated group and a monotherapy group, and the third group was a healthy control group. We determined the levels of various biochemical markers of bone metabolism, including procollagen type I nitrogenous propeptide (PINP), alkaline phosphatase (ALP), osteocalcin (OC), collagen type I cross-linked C-telopeptide (CTX), calcium, magnesium, phosphorus, parathyroid hormone (PTH), and vitamin D3 (VD3 ). RESULTS: A total of 1487 patients (from 19 centers) were diagnosed with SeLECTS; 1032 were analyzed, including 117 patients who did not receive any ASMs (untreated group), 643 patients who received only one ASM (monotherapy group), and 272 children in the healthy control group. Except for VD3 , other bone metabolism of the three groups were different (p < .001). Bone metabolism was significantly lower in the untreated group than the healthy control group (p < .05). There were significant differences between the monotherapy and healthy control group in the level of many markers. However, when comparing the monotherapy and untreated groups, the results were different; oxcarbazepine, levetiracetam, and topiramate had no significant effect on bone metabolism. Phosphorus and magnesium were significantly lower in the valproic acid group than the untreated group (adjusted p < .05, Cliff's delta .282-.768). CTX was significantly higher in the lamotrigine group than in the untreated group (adjusted p = .012, Cliff's delta = .316). SIGNIFICANCE: Epilepsy can affect many aspects of bone metabolism. After controlling epilepsy and other confounders that affect bone metabolism, we found that the effects of ASMs on bone metabolism differed. Oxcarbazepine, levetiracetam, and topiramate did not affect bone metabolism, and lamotrigine corrected some of the abnormal markers of bone metabolism in patients with epilepsy.

Establishment and utility assessment of posterior reversible encephalopathy syndrome early warning scoring (PEWS) scale establishment and utility assessment of PEWS scale.

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a complication that occurs during various diseases' treatment. Imaging examination is the gold standard for diagnosis. PRES frequently occurrence in patients with hematological malignancies results in poorer prognosis and higher mortality. We aim to establish a practical and operable scale for early prediction, assessment of the severity of the Posterior Reversible Encephalopathy Syndrome, and timely intervention for better prognosis. METHODS: The scale designed by reviewing the literature and by referring to clinical practice. We assessed the reliability and validity of the scale. Scale-based assessment of children undergoing chemotherapy for acute lymphoblastic leukemia conducted as early warning and intervention for those who may have PRES. RESULTS: Establishment of Posterior Reversible Encephalopathy Syndrome early warning scoring (PEWS) scale included three parts, as follows: (1) risk factors, including underlying disease, hypertension, Infection, and drug toxicity; (2) clinical features, including high cranial pressure, visual symptoms, seizure, and disturbance of consciousness; and (3) EEG features, including slow wave and epileptiform discharges. Utility assessment of PEWS scale showed that in 57 patients with acute lymphoblastic leukemia, 54 scored less than 10 and none of them detected as PRES. The other two had scores of 12 and 13 both diagnosed with PRES by brain MRI scan. CONCLUSIONS: PEWS scale can predict PRES early. PRES was highly suspected when the score was 10 points and more. Thus, prophylactic intervention can give to improve the prognosis of PRES.

Epileptic seizure, as the first symptom of hypoparathyroidism in children, does not require antiepileptic drugs.

OBJECTIVE: Patients with hypoparathyroidism exhibit metabolic disorders (hypocalcemia) and brain structural abnormalities (brain calcifications). Currently, studies have determined whether antiepileptic drug (AED) treatment is required for epileptic seizures in children with hypoparathyroidism. METHOD: This study aims to evaluate the data of two medical centers in Beijing based on the diagnosis of epileptic seizures as the first symptom of hypoparathyroidism in children. RESULT: A total of 42 patients were included and assigned into AED and non-AED treatment groups in a 1:2 matched case-control study. Results show that the seizure outcome after 1 year of AED treatment is not significantly different from that of the control. In the subgroup analysis of patients with subcortical calcifications, the seizure outcome is still not significantly different from that of the control. CONCLUSION: Thus, AED treatment cannot improve the seizure outcomes in children with parathyroid disorder, even in such cases as suspected structural seizure caused by subcortical calcifications. Clinicians must take adequate considerations on the use of AEDs in these patients. Epileptic seizures, as the first symptom of hypoparathyroidism in children, do not require epilepsy drugs.

Levetiracetam: Probably Associated Diurnal Frequent Urination.

Diurnal frequent urination is a common condition in elementary school children who are especially at risk for associated somatic and behavioral problems. Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that has been used in both partial and generalized seizures and less commonly adverse effects including psychiatric and behavioral problems. Diurnal frequent urination is not a well-known adverse effect of LEV. Here, we reported 2 pediatric cases with epilepsy that developed diurnal frequent urination after LEV administration. Case 1 was a 6-year-old male patient who presented urinary frequency and urgency in the daytime since the third day after LEV was given as adjunctive therapy. Symptoms increased accompanied by the raised dosage of LEV. Laboratory tests and auxiliary examinations did not found evidence of organic disease. Diurnal frequent urination due to LEV was suspected, and then the drug was discontinued. As expected, his frequency of urination returned to normal levels. Another 13-year-old female patient got similar clinical manifestations after oral LEV monotherapy and the symptoms became aggravated while in stress state. Since the most common causes of frequent micturition had been ruled out, the patient was considered to be diagnosed with LEV-associated psychogenic frequent urination. The dosage of LEV was reduced to one-third, and the frequency of urination was reduced by 60%. Both patients got the Naranjo score of 6, which indicated that LEV was a "probable" cause of diurnal frequent urination. Although a definite causal link between LEV and diurnal urinary frequency in the 2 cases remains to be established, we argue that diurnal frequent urination associated with LEV deserves clinician's attention.

The effects of total knee arthroplasty on physical functioning and health among the under age 65 population.

OBJECTIVES: This study examined the effects of total knee arthroplasty on six measures of physical functioning, self-rated health, pain, earnings, and employment status among US adults aged 51 to 63 years at baseline. METHODS: Data came from the Health and Retirement Study, a nationally representative longitudinal study conducted biannually. The analysis sample consisted of individuals aged 51 to 63 years at baseline with arthritis who were resurveyed at 2-year intervals from 1996 to 2010. Propensity score matching was used to compare outcomes of persons receiving total knee arthroplasty (TKA) with those of matched controls. Six measures of physical functioning were examined: lower-body mobility problems, instrumental activities of daily living limitations, activities of daily living limitations, and large muscle, fine motor, and gross motor limitations. Self-rated health and pain were also examined. The two employment-related outcomes were earnings and employment status. RESULTS: Receipt of TKA was associated with better outcomes for several measures of physical functioning, especially mobility limitations, pain, and self-rated health. Receipt of TKA was not associated with increased earnings or employment. CONCLUSIONS: Receipt of TKA yields important improvements in physical function among persons with an arthritis diagnosis who received the procedure before reaching the age of 65 years. This study contributes to knowledge about the benefits of TKA in a community setting among nonelderly recipients of TKA.

Exhaustive clinical examination of etiology and initial response to first-line treatment in 577 children with infantile epileptic spasm syndrome children: A 5-year retrospective observational study.

OBJECTIVE: Employing whole-exome sequencing (WES) technology to investigate the etiology of infantile epileptic spasm syndrome (IESS), and determining whether different etiologies exhibit phenotypic variations, while elucidating the potential associated factors, might improve short-term responses to first-line treatment. METHODS: We retrospectively evaluated patients with IESS admitted for treatment between January 2018 and June 2023. Clinical phenotypic differences among etiological classifications and clinical manifestations were analyzed. Variable selection using the best subset method was performed, followed by logistic regression analysis to identify the factors influencing treatment response. RESULTS: A total of 577 patients were included; 412 completed trio-WES. Magnetic resonance imaging abnormalities were detected in 387 patients (67.1%). Patients with etiology as structural abnormalities were likelier to have non-spasms at the initial seizure onset. A total of 532 patients completed the first-line treatment; 273 patients received it for the first time at our hospital (initial response rates: 30.1% and 42.1%, respectively). The response group had a lower proportion of early-onset seizures (≤3 months) than the no-response group (11.3% vs. 23.7%, p < 0.01 and 11.3% vs. 21.5%, p = 0.03, respectively). Logistic regression analysis indicated that earlier initiation of first-line treatment was associated with a higher likelihood of an initial response. However, the etiological classification did not have a significant impact on the initial response. INTERPRETATION: IESS patients with structural abnormalities are more likely to present with non-spasm seizures at initial onset. Early initiation of first-line treatment is crucial; however, initial responses may be less favorable when seizures occur in early infancy.

Dark septate endophyte Exophiala pisciphila promotes maize growth and alleviates cadmium toxicity.

Dark septate endophytes (DSE) are typical root endophytes with the ability to enhance plant growth and tolerance to heavy metals, but the underlying mechanisms are unclear. Here, the physiological and molecular mechanisms of a DSE strain, Exophiala pisciphila, in mitigating cadmium (Cd, 20 mg/kg) toxicity in maize were investigated. Our results showed, under Cd stress, E. pisciphila inoculation enhanced the biomass of maize and reduced both inorganic and soluble forms of Cd (high toxicity) by 52.6% in maize leaves, which may be potentially contributing to Cd toxicity mitigation. Besides, E. pisciphila inoculation significantly affected the expression of genes involved in the signal transduction and polar transport of phytohormone, and then affected abscisic acid (ABA) and indole-3-acetic acid (IAA) contents in maize roots, which was the main reason for promoting maize growth. In addition, E. pisciphila also made a 27% increase in lignin content by regulating the expression of genes involved in the synthesis of it, which was beneficial to hinder the transport of Cd. In addition, E. pisciphila inoculation also activated glutathione metabolism by the up-regulation of genes related to glutathione S-transferase. This study helps to elucidate the functions of E. pisciphila under Cd stress, sheds light on the mechanism of detoxifying Cd and provides new insights into the protection of crops from heavy metals.

Case Report: Chronic inflammatory demyelinating polyradiculoneuropathy rather than hemophagocytic lymphohistiocytosis-the initial phenotype of PRF1 gene mutation.

Perforin is essentially involved in the granule-dependent killing activities of cytotoxic T lymphocytes and NK cells. Monoallelic PRF1 mutation increases the risk of autoimmune diseases, and biallelic PRF1 mutation causes familial hemophagocytic lymphohistiocytosis-2. Here, we report a case of a 12-year-old girl with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), followed by a rapidly progressive onset of hemophagocytic lymphohistiocytosis (HLH) 9 months later, alongside manifestations of demyelinating encephalopathy. Genetic sequencing revealed a heterozygous nonsense mutation in the PRF1 gene (c.984G>A; p.W328*) and a heterozygous missense mutation in the PRF1 gene (c.1349C>T; p.T450M). Eventually, she died because of no suitable allogeneic hematopoietic stem cell available in time. Our observations suggest that CIPD might represent the initial phenotype of biallelic PRF1 mutation and could serve as an early sign of subsequent HLH. A comprehensive understanding of this condition is paramount for timely diagnosis, treatment, and ultimately improved patient outcomes.

Effectiveness of peer-mediated intervention on social skills for children with autism spectrum disorder: a randomized controlled trial.

Background: Peer-mediated intervention (PMI) is an intervention that teaches normally developing peers to help children with autism spectrum disorder (ASD) actively participate in social interactions. Previous studies have shown that PMI applied to school settings is effective for children with ASD, but more multiple-baseline single-subject design. Many questions are still not clear due to the large clinical variability in children with ASD. This study investigated the effectiveness of PMI on social skills of children with ASD at varying symptom levels and analyzed the specific changes. Methods: This study used a randomized, single-blind, parallel-controlled design to analyze the effect of PMI in a hospital setting. Fifty-five children aged 4-12 years were diagnosed with ASD by clinicians using the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and stratified randomly allocated to either the experimental group or the control group using the envelope method. The experimental group utilized PMI, whereas the control group utilized behavioral therapy based on applied behavior analysis (ABA) [early intensive behavioral intervention (EIBI)]. This study primarily utilized the Social Responsiveness Scale (SRS) to evaluate the social performance of autistic children prior to and after the intervention. Results: Fifty-five participants were recruited and analyzed, the experimental group (n=29; mild to moderate n=18, severe n=11) and the control group (n=26; mild to moderate n=15, severe n=11). After the intervention, the experimental group's SRS score fell significantly more than the control group's (t=-3.918, P=0.000), d=-1.043; the mild to moderate subgroup experienced the same situation (H=17.811, P=0.009), d=-1.642. At the same time, the decline in social communication scores was significantly greater in the experimental group compared to the control group (t=-3.869, P=0.000), and the 95% confidence interval was -10.067 to -3.193. The social motivation of the mild-to-moderate subgroup of the experimental group (H=16.894, P=0.011), -3.000 (25th percentile, 75th percentile: -3.000, 0.000), and the behavioral patterns of autism (H=18.150, P=0.006), -3.000 (25th percentile, 75th percentile: -5.000, 0.000), the decreased value was significantly larger. Conclusions: PMI therapy can increase social motivation in children with mild to moderate ASD, minimize undesirable behavior patterns, effectively improve overall social skills and enhance effective social communication with others. Trial Registration: Chinese Clinical Trial Registry ChiCTR2100049185.

Vigabatrin-associated brain abnormalities on MRI in tuberous sclerosis complex patients with infantile spasms: are they preventable?

Background: Vigabatrin (VGB) is currently the most widely prescribed first-line medication for individuals with infantile spasms (IS) and especially for those with tuberous sclerosis complex (TSC), with demonstrated efficacy. Meanwhile, its adverse events, such as vigabatrin-associated brain abnormalities on magnetic resonance imaging (MRI; VABAM), have also been widely reported. Objectives: The objectives of this study were to observe the occurrences of VABAM in patients with IS caused by TSC (IST) and further explore the associated risk factors. Methods: Children with IS receiving VGB were recruited from our institution; clinical, imaging, and medication data were collected. Cerebral MRI was reviewed to determine the occurrence of VABAM. Group comparisons (IS caused by TSC and other etiologies) were performed; subgroup analyses on IST were also performed. Next, a retrospective cohort study of children taking VGB was conducted to explore risk/protective factors associated with VABAM. Results: The study enrolled 172 children with IS who received VGB. VABAM was observed in 38 patients (22.1%) with a peak dosage of 103.5 ± 26.7 mg/kg/day. Subsequent analysis found the incidence of VABAM was significantly lower in the 80 patients with IST than in the 92 patients with IS caused by other etiologies (10% versus 32.6%, p-value < 0.001). In subgroup analyses within the IST cohort, VABAM was significantly lower in children who received concomitant rapamycin therapy. Univariate and multivariate logistic regression analysis of the 172 IS children showed that treatment with rapamycin was the independent factor associated with a lower risk of VABAM; similar results were observed in the survival analysis. Conclusion: The incidence of VABAM was significantly lower in IST patients. Further research is needed to examine the mechanisms that underlie this phenomenon and to determine if treatment with rapamycin may reduce the risk of VABAM.

Effect of ambroxol on pneumonia caused by Pseudomonas aeruginosa with biofilm formation in an endotracheal intubation rat model.

BACKGROUND: Pseudomonas aeruginosa, especially the mucoid phenotype, is responsible for most of the morbidity and mortality in ventilator-associated pneumonia. Although ambroxol is widely used in neonatal lung problems as a mucolytic as well as an antioxidant agent, its anti-infective role is not well demonstrated by studies in vivo. OBJECTIVE: To explore the effect of ambroxol on the biofilms of mucoid P. aeruginosa and on the associated lung infection using a rat model. METHODS: We developed a rat model of acute lung infection by endotracheal intubation with a tube covered with mucoid P. aeruginosa biofilm. Then, we studied the effect of ambroxol on the biofilm using saline treatment as a control. Subsequently, we studied the microstructure of the biofilm, bacterial count in the tubes and lungs, pathological changes that occurred in the lungs, and the cytokine response. RESULTS: Alteration of the microstructure of the biofilm with ambroxol treatment was demonstrated by scanning electron microscopy. The bacterial counts on the biofilm-covered tube in the ambroxol-treated group were significantly lower than those in the saline-treated group on both post-bacterial challenge days 4 and 7 (p < 0.05). The bacterial counts in lungs of the ambroxol-treated group and of the saline-treated group on post-bacterial challenge day 7 were not significantly different (p > 0.05). The pathological changes in lungs were milder with the effect of ambroxol. The cytokine responses, namely the level of IFN-γ and the ratio of IFN-γ and IL-10, were also reduced with the effect of ambroxol. CONCLUSION: We demonstrated that the ambroxol treatment could destroy the structure of the biofilm on the tube used for intubation and decrease the bacterial load. Further, the reduced cytokine response and milder pathological changes in lungs in an endotracheal intubation rat model indicate that ambroxol can attenuate the damage caused by biofilm-associated infection in the lung.

Off-Label Underdosing or Overdosing of Non-vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation: A Meta-Analysis.

Background: Several studies have investigated the role of off-label non-vitamin K antagonist oral anticoagulants (NOACs) in patients with atrial fibrillation (AF). We aimed to compare the effectiveness and safety outcomes between off-label underdose or overdose vs. on-label dose of NOACs in AF patients. Methods: The PubMed database was systematically searched until August 2021. Observational cohorts were included if they compared the outcomes of off-label underdose or overdose with on-label dose of NOACs in AF patients. The risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a fixed-effects model (I 2 ≤ 50%) or a random-effects model (I 2 > 50%). Results: A total of 15 observational studies were included. Compared with on-label dose of NOACs, off-label underdose of NOACs was associated with increased risks of stroke or systemic embolism (RR = 1.09, 95% CI 1.02-1.16), and all-cause death (RR = 1.29, 95% CI 1.10-1.52) but not ischemic stroke (RR = 1.34, 95% CI 0.76-2.36), myocardial infarction (RR = 1.08, 95% CI 0.92-1.28), major bleeding (RR = 0.97, 95% CI 0.89-1.05), intracranial hemorrhage (RR = 1.12, 95% CI 0.90-1.40), and gastrointestinal bleeding (RR = 0.96, 95% CI 0.85-1.07), whereas off-label overdose of NOACs was associated with increased risks of SSE (RR = 1.20, 95% CI 1.05-1.36), all-cause death (RR = 1.22, 95% CI 1.06-1.39), and major bleeding (RR = 1.33, 95% CI 1.16-1.52) but not gastrointestinal bleeding (RR = 1.18, 95% CI 0.99-1.42) and myocardial infarction (RR = 0.98, 95% CI 0.75-1.30). Conclusion: Compared with on-label dose of NOACs, off-label underdose was associated with increased risks of stroke or systemic embolism and all-cause death, whereas off-label overdose of NOACs was associated with increased risks of stroke or systemic embolism, all-cause death, and major bleeding.

Association of Direct Oral Anticoagulants vs. Vitamin K Antagonists With Fractures in Atrial Fibrillation Patients: A Systematic Review and Meta-Analysis.

Background: Current evidence regarding the application of direct oral anticoagulants (DOACs) vs. vitamin K antagonists (VKAs) on the fracture risk is inconsistent. Therefore, we conducted a meta-analysis to evaluate the fracture risk of DOACs vs. VKAs in patients with atrial fibrillation (AF). Methods: The PubMed and Embase databases were systematically searched until June 2021 for all the studies that reported oral anticoagulants in AF patients. The random-effect model with an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). Results: A total of 10 studies were included in this meta-analysis. Among AF patients receiving anticoagulants, DOAC users showed a reduced risk of any fracture compared to those with VKAs (RR = 0.80; 95% CI: 0.70-0.91) regardless of gender [males (RR = 0.79; 95% CI: 0.67-0.92) and females (RR = 0.71; 95% CI: 0.57-0.89)]. Apixaban (RR = 0.75; 95% CI: 0.60-0.92) and rivaroxaban (RR = 0.73; 95% CI: 0.61-0.88), but not dabigatran and edoxaban, were associated with a decreased risk of any fracture compared with VKAs. DOAC users had decreased risks of osteoporotic fractures (RR = 0.63; 95% CI: 0.47-0.84) and hip/pelvic fractures (RR = 0.88; 95% CI: 0.79-0.97) compared to those treated with VKAs. Conclusions: Our meta-analysis suggested that the use of DOACs was associated with a reduced risk of any fracture compared with VKAs. Further studies should confirm our findings.

Genotypes and Phenotypes of MEF2C Haploinsufficiency Syndrome: New Cases and Novel Point Mutations.

Aim: MEF2C haploinsufficiency syndrome (MCHS) is a severe neurodevelopmental disorder. We describe the clinical phenotypes and genotypes of seven patients with MCHS to enhance the understanding of clinical manifestations and genetic alterations associated with MCHS. Method: Seven patients (6 females and 1 male, aged between 2 years 5 months and 6 years) who had MEF2C mutations, and their parents underwent trio-based whole-exome sequencing; subsequently, their clinical features were assessed. A literature review of patients with MCHS was performed by searching the PubMed and Online Mendelian Inheritance in Man databases. Results: Seven mutations were identified, of which six were unreported in the past; of the reported cases, five patients had de novo mutations but two had an undefined inheritance pattern. All patients presented delays in developmental milestones, severe intellectual disabilities and lack of speech. Six patients exhibited infantile hypotonia, five patients experienced stereotypic movements and were unable to walk, four patients exhibited poor eye contact indicative of autism and two showed poor performance. While six patients experienced seizure, five among them became seizure free after receiving anti-seizure medicine. Three patients showed a regression in their development, whereas the mothers of two patients exhibited mosaicism but were healthy without any abovementioned symptoms. Interpretation: Regression was not a common phenomenon but occurred in MCHS. The prognosis of MCHS patients with epilepsy was good, but most patients can achieve a seizure-free status. Healthy people may have low-level mosaicism and carry a pathogenic MEF2C mutation.

Effect of chlorine dioxide and phosphates on the quality of tiger frog (Rana tigrina) meat during 4 °C storage.

Tiger frog (Rana tigrina) meat is extremely perishable. This study investigated the antimicrobial efficacy of chlorine dioxide (ClO2 ) on frog meat, optimized the formulation of a phosphate-based enhancement solution by response surface methodology (RSM), and determined the quality parameters (i.e., total aerobic counts [TAC], pH, drip loss, cooking loss, color measurements, shear force, total volatile basic nitrogen [TVB-N], and thiobarbituric acid-reactive substances [TBARS]) of refrigerated frog meat pretreated with ClO2 and the optimized blend of phosphates. Treatments of frog meat with 35 and 70 ppm ClO2 for 3, 5, and 10 min achieved a 0.7-, 0.9- and 0.9-, and 0.8-, 1.4- and 1.6-log CFU/g reduction of TAC, respectively, indicating the antimicrobial efficacy of ClO2 was concentration- and time-dependent with such that higher concentrations and/or longer exposure time achieved greater bacterial reductions. The concentrations of the phosphates, including sodium tripolyphosphate (STPP), sodium pyrophosphate (SPP), and sodium hexametaphosphate (SHMP), were optimized as the formula of 0.3% STPP and 0.45% SPP obtaining the highest water retention of the frog meat. After washed with 70 ppm ClO2 for 10 min and subsequently soaked with 0.3% STPP and 0.45% SPP for 30 min, the frog meat stored at 4 °C shown significantly (P < 0.05) lower TAC (<4.4 log CFU/g) and higher water holding capacity during the whole storage of 12 days, compared to the control. Results indicated that the two-step process may be applicable to slow down deterioration and maintain quality frog meat during refrigeration. PRACTICAL APPLICATION: This research provides a means to slow down deterioration, maintain quality frog meat, and improve stability during refrigeration. Refrigerated frog meat products, which are preferred by consumers with juicier and more tender texture compared to the frozen-thawed meat, could be developed by the frog industry based on the data from this study.

The Instigation of the Associations Between Melatonin, Circadian Genes, and Epileptic Spasms in Infant Rats.

Background: Infantile spasm (IS) is one of the most common catastrophic epilepsy syndromes in infancy characterized by epileptic spasm. While adrenocorticotropic hormone (ACTH) is the first-line treatment for IS, it is evident that the seizures associated with IS exhibit a clear circadian rhythm; however, the precise mechanisms underlying such seizures remain unclear. Melatonin is an important amine hormone and is regulated by circadian rhythm. Circadian proteins, especially Aryl Hydrocarbon Receptor Nuclear Trasnslocator-like Protein (ARNTL or BMAL1) and Circadian Locomotor Output Cycles Kaput (CLOCK), and their target proteins Period Circadian Regulator 1 (PER1), Period Circadian Regulator 2 (PER2), Cryptochrome 1 (CRY1), and Cryptochrome 2 (CRY2), play key roles in circadian rhythm. This study explored the relationships between melatonin, genes associated with circadian rhythm, and epileptic spasm. Materials and Methods: Eighteen female rats were mated with nine male rats and 16 became pregnant. Twelve pregnant rats were subjected to prenatal stress by forced swimming in cold water from the day of conception. Rat pups produced by stressed mothers received an intraperitoneal injection of N-methyl-D-aspartate (NMDA) on the 13th day after birth and were divided into four groups: NMDA (15 mg/kg), NMDA+ACTH (20 IU/kg), NMDA+melatonin (55 mg/kg), and NMDA+ACTH+melatonin (n = 36/group). Offspring from four dams that were not subjected to prenatal stress were used as controls. We then recorded latency and the frequency of flexion seizures. All offspring were sacrificed on the 14th day after birth and CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was analyzed by western blotting, immunohistochemistry, and immunofluorescence. Results: NMDA induced spasm-like symptoms in rats. ACTH and melatonin significantly increased seizure latency and significantly reduced the frequency of seizures (P < 0.05). CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 expression was significantly lower in the NMDA group than the controls (P < 0.05). ACTH significantly increased the expression of CLOCK, BAML1, PER1, and CRY1 (P < 0.05) and melatonin significantly increased the expression of CLOCK, BMAL1, PER1, PER2, CRY1, and CRY2 (P < 0.05) compared with those of the NMDA group. There were no significant differences in the expression of BMAL1, CRY2, PER1, and PER2 when compared between the NMDA+ACTH+melatonin and control groups (P > 0.05). Conclusion: ACTH and melatonin significantly increased the expression of circadian genes and improved NMDA-induced seizures. The anticonvulsant effects of ACTH and melatonin are likely to involve regulation of the expression of these genes.

The Efficacy of Fecal Microbiota Transplantation for Children With Tourette Syndrome: A Preliminary Study.

Therapies for Tourette syndrome (TS) are insufficient, and novel therapies are needed. Fecal microbiota transplantation (FMT) has been a potential therapy for several neurological diseases. Here, we report a preliminary study to investigate the effects of FMT on patients with TS. Five patients with TS received a single administration of FMT via endoscopy. Tic symptoms were assessed by Yale Global Tic Severity Scale-Total Tic Score (YGTSS-TTS) and adverse effects were recorded at week 8 following FMT. Lipopolysaccharide (LPS) levels and 14 cytokines levels were measured. The microbiota profile in feces were analyzed by shotgun metagenomics. Four patients (4/5) responded positively to FMT (YGTSS-TTS reduction rate >25%) at week 8 with high safety. The levels of LPS and cytokines varied after FMT. FMT shifted the composition of the gut microbiota in patients close to that of the donor and continuously changed the abundance of Bacteroides coprocola, Dialister succinatiphilus and Bacteroides vulgatus. The restoration of B.coprocola was correlated with the improvement in tic symptoms (Spearman R = -0.900, P = 0.037). In conclusion, FMT was indicated a potential effective and safe alternative for patients with TS. However, larger clinical trials are needed to confirm the influence of microbiota in TS. Trial Registration: chictr.org.cn Identifier: ChiCTR-IIR-17011871, URL: http://www.chictr.org.cn/showproj.aspx?proj=19941.

Vertical transmission of Chlamydia trachomatis in Chongqing China.

This is the first study to investigate vertical transmission of Chlamydia trachomatis in Chongqing China. For this study, 300 cervical swab samples from pregnant women and 305 nasopharygeal swab samples from their babies (605 specimens) were collected for nest polymerase chain reaction (nPCR) of the ompl gene, which encodes the major outer membrane protein (MOMP) and typed C. trachomatis using Cleavase fragment-length polymorphism (CFLP) labeled with digoxin. From these samples, 11% (33/300) of pregnant women samples were successfully amplified. The vertical transmission rate of C. trachomatis from mother to baby was 24% (8/33). The vertical transmission rates were 66.7% (6/9) for mothers with vaginal delivery and 8.3% (2/24) for those with cesarean section. The incidence of premature membrane rupture among C. trachomatis-positive pregnant women was 30.3% (10/33), which was greater than among those who were C. trachomatis-negative (13.5%, 36/267; chi(2) = 4.2; p < 0.05). Four genotypes including type E (3 pairs), type F (2 pairs), type H (2 pairs), and type D (1 pair) were observed by CFLP assay labeled with digoxin and confirmed by DNA sequencing in the 16 C. trachomatis-positive samples from eight pregnant women and their eight infants. Each pair of matched maternal-infantile samples showed identical CFLP. This study showed the incidence of C. trachomatis infection in pregnant women, the vertical transmission rate for C. trachomatis, and the genotypes of C. trachomatis in Chongqing, China. The CFLP assay labeled at the 5' end of the forward primer with digoxin was first used successfully to genotype of C. trachomatis. As a promising method for C. trachomatis genotyping, CFLP had good sensitivity, reproducibility, and simplicity and no radioactive contamination.

Phase selection controlled by sodium ions in the synthesis of FAU/LTA composite zeolite.

Zeolite faujasite (FAU), Linde type A (LTA) and FAU/LTA composite have been synthesized using tetramethylammonium cation (TMA+) as template, by adjusting only the concentration of Na+ ions in the initial solution (1.00 Al2O3 4.36 SiO2 : 2.39 (TMA)2 O : ß Na2 O : 249.00H2 O). Na+ ions alter the phase composition of the product more than TMA+ or OH- ions. When Na2 O concentration [Na2 O] increases from 0.024 to 0.168, the product gradually changes from pure FAU to pure LTA via the formation of FAU/LTA composite with increasing LTA fraction. Interestingly, the induction periods of FAU and LTA in the FAU/LTA composite zeolite ([Na2 O] is 0.072) are both 13 h, quite different from the induction periods of their individual pure phases-45 h for FAU and 4 h for LTA. During the crystallization, the LTA/(FAU + LTA) fraction in the composite zeolite decreases in a nearly linear fashion. Scanning electron microscopy, thermogravimetry and differential thermal analysis indicate some difference between the properties of the FAU/LTA composite zeolite and of the mechanical mixture.