Radar-based sleep stage classification in children undergoing polysomnography: a pilot-study.

STUDY OBJECTIVES: Unobtrusive monitoring of sleep and sleep disorders in children presents challenges. We investigated the possibility of using Ultra-Wide band (UWB) radar to measure sleep in children. METHODS: Thirty-two children scheduled to undergo a clinical polysomnography participated; their ages ranged from 2 months to 14 years. During the polysomnography, the children's body movements and breathing rate were measured by an UWB-radar. A total of 38 features were calculated from the motion signals and breathing rate obtained from the raw radar signals. Adaptive boosting was used as machine learning classifier to estimate sleep stages, with polysomnography as gold standard method for comparison. RESULTS: Data of all participants combined, this study achieved a Cohen's Kappa coefficient of 0.67 and an overall accuracy of 89.8% for wake and sleep classification, a Kappa of 0.47 and an accuracy of 72.9% for wake, rapid-eye-movement (REM) sleep, and non-REM sleep classification, and a Kappa of 0.43 and an accuracy of 58.0% for wake, REM sleep, light sleep and deep sleep classification. CONCLUSION: Although the current performance is not sufficient for clinical use yet, UWB radar is a promising method for non-contact sleep analysis in children.

[Therapeutic evaluation of modified supraglottoplasty for laryngomalacia].

Objective:To evaluate the therapeutic effect of modified supraglottoplasty for laryngeal malacia in children. Method: All 22 children with laryngomalacia underwent modified supraglottoplasty were retrospectively analyzed. Surgical correction of type Ⅰ involved the ablation of redundant mucosal tissue over the arytenoids, keep the part below anesthetic intubation. Type Ⅱ was treated by ablation of the shortened aryepiglottic folds and/or ablation of the lateral edge of the epiglottis, separate the epiglottis with epiglottis to enlarge the laryngeal inlet. Type Ⅲ was corrected by ablating wound surfaces on the base of the tongue and epiglottic vallecula but no more than 1/2 area of lingual surface of epiglottis. All patients were kept intubated for 5 days after surgery in the intensive care unit （ICU）. Evaluate the severity of laryngomalacia before and after surgery （extubation）, 1 month after surgery, and 6 months after surgery. Visual analogue scale （VAS） was used to score the symptoms, including stridor, reflux or feeding difficulties, aspiration, dyspnea and frequency or severity of pneumonia. Clinical score was determined by the physician on the child's laryngeal obstruction, supraglottic morphology in laryngoscope, swallowing function, weight and the result of polysomnography. Result:All 22 children with laryngomalacia were followed up for 6 months after surgery, statistically significant differences in scores before, after, 1 month after and 6 months after surgery （P<0.01）. The symptoms of stridor, dyspnea and feeding difficulties were improved in different degrees. Conclusion:Modified supraglottoplasty for children with laryngomalacia simplified the surgical procedure, and the therapeutic effect is safe and reliable. The evaluation system designed in this study is more intuitive and objective to evaluate the severity of laryngomalacia and the operative effect, which may has certain reference value for the evaluation of the condition and the treatment process.

[Establishment and preliminary application of a laryngomalacia larynx three-dimension model].

Objective:To establish and preliminarily apply a laryngomalacia larynx three-dimension finite element model. Method:The MIMCS software was employed to deal with the Dicom images of larynx CT scan by means of distinguishing material gray threshold of different tissues. 3D visualization model of larynx was also built by this software. Hyermesh software was used to handle the grid layout of larynx finite element model. Laryngeal structure parameter were added, and laryngeal mechanical analysis were carried out by Abaqus software in order to get von Mises stress. Result:A 3D model，which finely represent the morphological characteristics of laryngomalacia larynx was built using the finite element technology. Peak von Mises stress was observed to be higher in more severe laryngomalacia case. Conclusion:The 3D finite element model of the laryngomalacia larynx provides the foundation for further study．Peak von Mises stress may be a useful indicator of laryngomalacia severity assessment.

A diarylethene-derived probe for colorimetric detection of CN- and highly selective fluorescent recognition of I.

A new photochromic diarylethene derivative with 2-hydrazinobenzothiazole was synthesized, and its multi-controllable switch behavior was investigated in detail when triggered by light and anions. When triggered by CN-, the absorption spectra of the diarylethene showed a new band at 474 nm with an obvious color change from colorless to bright yellow. Upon addition of I-, the diarylethene compound displayed a new absorption band at 297 nm and the original absorption at 370 nm also increased, and the fluorescence intensity exhibited obvious fluorescence quenching with fluorescence color change from a light royal blue to dark. The results indicated that the diarylethene derivative exhibited naked-eye detection of CN- and the fluorescent recognition of I-.

Protection against cognitive impairment and modification of epileptogenesis with curcumin in a post-status epilepticus model of temporal lobe epilepsy.

Epileptogenesis is a dynamic process initiated by insults to the brain that is characterized by progressive functional and structural alterations in certain cerebral regions, leading to the appearance of spontaneous recurrent seizures. Within the duration of the trauma to the brain and the appearance of spontaneous recurrent seizures, there is typically a latent period, which may offer a therapeutic window for preventing the emergence of epilepsy. Previous animal studies have shown that curcumin can attenuate acute seizure severity and brain oxidative stress, but the effect of curcumin on epileptogenesis has not been studied. We examined the effect of continued administration of curcumin during the latent period on epileptogenesis and the deleterious consequences of status epilepticus in adult rats in a post-status epilepticus model of temporal lobe epilepsy induced by kainic acid. We demonstrate that, while administration of curcumin treatment during the latent period does not prevent occurrence of spontaneous recurrent seizures after status epilepticus, it can attenuate the severity of spontaneous recurrent seizures and protect against cognitive impairment. Thus, treatment with curcumin during the latent period following status epilepticus is beneficial in modifying epileptogenesis.

Impact of carbapenem heteroresistance among clinical isolates of invasive Escherichia coli in Chongqing, southwestern China.

Although heteroresistance is common in a wide range of microorganisms, carbapenem heteroresistance among invasive Escherichia coli infections has not been reported. The objective of this study was to evaluate the clinical significance of carbapenem heteroresistance and to identify risk factors for its acquisition. A case-control study was conducted at a 3200-bed teaching hospital in Chongqing, southwestern China. Successive and non-duplicate nosocomial E. coli isolates (n = 332) were obtained from July 2011 to June 2013. Bloodstream isolates made up 50.6% of the strains collected. The rates of heteroresistance were 25.0% to imipenem, 17.2% to ertapenem, and 3.9% to meropenem. The population analysis profile revealed the presence of subpopulations with higher carbapenem resistance, showing MICs ranging from 2.0-128.0mg/L. Male gender, invasive intervention, antibiotic use and bacterial extended-spectrum ß-lactamase (ESBL) production contributed to invasive infections by carbapenem-heteroresistant E. coli (CHEC). The production of ESBL was identified as the common independent risk factor for heteroresistance to both ertapenem and imipenem. Pulsed-field gel electrophoresis revealed clonal diversity among the CHEC isolates. Most importantly, characterization of two successive E. coli strains isolated from the same patient indicated that carbapenem resistance evolved from heteroresistance. In conclusion, the high prevalence of heteroresistance to carbapenem among invasive E. coli merits great attention. Routine detection of ESBLs and the prudent use of imipenem and ertapenem are advocated. The early targeted intervention should be formulated to reduce CHEC infection and carbapenem resistance of E. coli.

Brain-derived neurotrophic factor-activated astrocytes produce mechanical allodynia in neuropathic pain.

Neuropathic pain management is challenging for physicians and a vexing problem for basic researchers. Recent studies reveal that activated spinal astrocytes may play a vital role in nerve injury-induced neuropathic pain, although the mechanisms are not fully understood. We have found increased glial fibrillary acidic protein (GFAP) expression, a hallmark of reactive gliosis, and elevated brain-derived neurotrophic factor (BDNF) expression in the dorsal horn in a rat model of allodynia induced by spinal nerve ligation (SNL). The high GFAP expression and mechanical allodynia that SNL induces were prevented by the intrathecal injection of the BDNF-sequestering fusion protein TrkB/Fc. Additionally, mechanical allodynia and GFAP overexpression was induced by the spinal administration of exogenous BDNF to naive rats, and exogenous BDNF given together with fluorocitrate, an astrocytic metabolism inhibitor, inhibited allodynia and GFAP upregulation. Exogenous BDNF also activated the astrocytes directly when tested in vitro. Furthermore, intrathecal administration of BDNF-stimulated astrocytes also induced mechanical allodynia in naive rats. All of these results indicate that astrocytes activated by BDNF might contribute to mechanical allodynia development in neuropathic pain in rats.

The characteristics of placental transfer and tissue concentrations of nickel in late gestational rats and fetuses.

The dynamics of nickel (Ni) uptake, transfer, retention and clearance in fetuses and late gestational rats were investigated by assessing its distributions in placenta, maternal and fetal organs and tissues during the 24 h period after a single dose of (63)Ni intraperitoneal injection on gestational day 20. Peak (63)Ni radioactivity was detected at 0.5 h in maternal blood, at 3 h in placenta, fetal membranes, fetal blood, fetal heart, maternal kidney, lung, stomach, liver and brain, at 9 h in fetal kidney, stomach, liver and brain, and lastly at 24 h in fetal lung and amniotic fluid. The maximal (63)Ni radioactivity among all samples was detected consistently in the fetal membranes and placenta. The (63)Ni radioactivity in fetal blood was higher than that in maternal blood from 3 to 24 h. The fetal liver, heart, stomach and brain exhibited higher (63)Ni radioactivity than the corresponding maternal organs from 6 to 24 h. However, maternal kidney consistently exhibited significantly higher (63)Ni radioactivity than the fetal kidney. The (63)Ni in fetal lung and amniotic fluid increased throughout the period of experimental observation. These observations corroborated previous finding that nickel is actively transferred across the blood-placenta-barrier into fetus, but hardly from fetus to mother. Moreover, these results suggest that the placenta has a high affinity for nickel and its barrier does not protect the fetus from nickel exposure. The fact that nickel concentrations are higher in most fetal organs and tissues than in corresponding maternal organs and tissues in late gestation indicates that, unlike the dam, fetuses lack effective means for getting rid of excessive nickel due to its confined environment and relatively weak kidney functions. The situation is exacerbated by mother-to-fetus unidirectional transfer. Consequently, the fetuses are particularly vulnerable to the damaging effects of nickel.

Subinhibitory concentrations of licochalcone A decrease alpha-toxin production in both methicillin-sensitive and methicillin-resistant Staphylococcus aureus isolates.

AIM: To evaluate the effect of subinhibitory concentrations of licochalcone A (LicA) on alpha-toxin secretion in Staphylococcus aureus. METHODS AND RESULTS: A haemolysin assay was used to investigate the haemolytic activities in culture supernatants of both methicillin-sensitive and methicillin-resistant Staph. aureus isolates cultured with graded subinhibitory concentrations of LicA. Alpha-toxin secretion was detected by immunoblot analysis. Moreover, quantitative RT-PCR was performed to assess the influence of LicA on the transcription of hla (the gene encoding alpha-toxin) and agr (accessory gene regulator). Growth in the presence of LicA markedly inhibited the mRNA levels of hla and agr in Staph. aureus, resulting in a reduction of alpha-toxin secretion and, thus, haemolytic activities. CONCLUSION: The secretion of alpha-toxin in Staph. aureus is decreased by LicA; this effect may be partially dependent upon inhibition of the Agr two-component system. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings in our study may support the use of LicA as a lead compound in the design of more potent antibacterial agents that are based on the chalcone template.

Synthesis and pharmacokinetic evaluation of novel N-acyl-cordycepin derivatives with a normal alkyl chain.

For slowing down the too fast metabolic velocity and increasing the bioavailability of cordycepin, four N-acyl-(propionyl-, octanoyl-, lauroyl- and stearoyl-) cordycepin derivatives were synthesized chemically and their pharmacokinetic profiles were investigated in this study. The results show that time of maximum concentration (T(max)) and half-life (t(1/2)) would be elongated with the increase of the alkyl chain length, but maximum concentration (C(max)) and area under concentration-time curve (AUC) increased initially, then decreased when the number of alkyl carbon exceeded eight. The T(max), C(max) and AUC of N-octanoyl-cordycepin were nearly 4, 30 and 68 times, respectively, higher than that of cordycepin. All derivatives could be transformed into cordycepin in vivo and the concentration of transformed cordycepin was proportional to that of derivatives. It indicated that N-octanoyl modification could decrease the metabolic velocity and increase the bioavailability of cordycepin to the maximum, thus it might be a promising prodrug of cordycepin.

Codeposition of dNTPs detection for rapid LAMP-based sexing of bovine embryos.

Loop-mediated isothermal amplification (LAMP) is a novel nucleic acid amplification method with high specificity and rapidity under isothermal conditions. According to the LAMP method, a rapid and simple detection system was established for bovine embryo sexing. Two sets of primers were designed by targeting the bovine male-specific sequence and bovine common sequence respectively. The reaction condition of the detection system was optimized within 60 min under isothermal conditions of 65 degrees C by detection of the reaction mixture on agarose gel. Especially, the primers F2 and B2 could replace the F3 and B3 as outer primers, making the primer design simpler and the amplification efficiency higher. Additionally, codeposition of dNTPs was firstly performed to detect the reaction products by addition of 1 microl 0.1 mM CuSO(4), the visible ring-shaped deposit was found in the middle of the reaction tube with negative mixture. It could be employed as an alternative method in the detection of the reaction products in place of the time-consuming electrophoresis or the turbidity meter. Furthermore, the embryo sexing system was carried out in the embryo transfer and achieved 98% of efficiency and 99.5% of accuracy.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like PET scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

A pilot study on the effects of testosterone in hypogonadal aging male patients with Alzheimer's disease.

The male aging process brings about declines in hormonal function including a gradual decline in bioavailable testosterone levels. Animal studies suggest that testosterone modulates cognitive function through enhancing acetylcholine release and up-modulation of nicotinic receptors. Tau protein deposition is also affected by androgen supplementation in animals. We hypothesize that testosterone replacement in elderly hypogonadal males may improve cognition, in particular the visual-spatial domain. Thirty-six male patients with a new diagnosis of Alzheimer's disease had their total and bioavailable testosterone levels measured. None of the patients had been on acetylcholinesterase inhibitors. Ten of the 36 patients (28%) were deemed biochemically hypogonadal (total testosterone < 240 ng/dl or 7 nmol/l). Five of the hypogonadal patients were randomized to testosterone and five to placebo. Initial Alzheimer's Disease Assessment Scale cognitive subscale (ADAScog) and Mini Mental Status Examination (MMSE) ranged from 31 to 19 and from 17 to 22, respectively. The clock drawing test (CDT) and the pentagon-tracing portion of the MMSE were used as measures of visual-spatial abilities. Normal prostate-specific antigen (PSA) levels were essential before treatment with intramuscular testosterone, 200 mg every 2 weeks. Measurement of testosterone, complete blood count, lipids, PSA and neuropsychological cognitive tests were repeated at 3, 6, 9 and 12 months of treatment. In the testosterone-treated group, levels of total testosterone increased from a mean of 126.4 ng/dl to 341 ng/dl or 3.6 nmol/l to 9.7 nmol/l (p = 0.11). Bioavailable testosterone also increased from a mean of 48.7 ng/dl to 142 ng/dl or 1.39 nmol/l to 4.05 nmol/l (p = 0.10). PSA levels were also elevated from a mean of 0.98 to 1.37 ng/ml (p = 0.07). ADAScog improved from a mean of 25 to 16.3 (p = 0.02); MMSE improved from a mean of 19.4 to 23.2 (p = 0.02), CDT also improved from 2.2 to 3.2 (p = 0.07). One patient stopped treatment because of hypersexual behavior. The placebo-treated group deteriorated gradually. This small pilot study performed in aging male patients suggests that testosterone could indeed improve cognition, including visual-spatial skills in mild to moderate Alzheimer's disease.

Role of androgens in mild cognitive impairment and possible interventions during andropause.

Mild cognitive impairment (MCI) is becoming fashionable as a diagnosis, representing a state of cognitive decline associated with negligible functional loss. MCI is important as it often precedes Alzheimer's disease (AD). Recognizing MCI may lead to preventive strategies that can delay the onset of AD. Many patients who transition into andropause report problems with their memory. There is strong evidence from basic sciences and epidemiological studies that both estrogens and androgens play a protective role in neurodegeneration. The evidence from small prospective clinical trials lends support to the role of hormones in improving cognitive function. The improvement in cognitive function with hormones is subtle and often not measurable on standard neuropsychological batteries. Patients have reported memory improvements in both declarative and procedural domains after being on hormonal replacement. Functional changes and vascular changes can be detected after hormonal replacement with more sophisticated imaging of the brain like positron emission tomography (PET) scans. We hypothesize androgens and perhaps selective androgen receptor modulators as future treatment options for MCI in aging males.

Impact of obesity on hypogonadism in the andropause.

Obesity is an issue that is increasingly affecting ageing men. With ageing, there is a decline in androgens as well. There are implications for the health of ageing men as a result of hypogonadism. Overall, there seems to be an inverse relationship between body mass index and testosterone levels, as is also demonstrated in our cross-sectional study. Obesity seems to depress the production of testosterone. It has been hypothesized that there is increased aromatization of testosterone to oestradiol and alteration of the hypothalamic-pituitary-adrenal axis in obese older men. Some hormones can affect obesity in ageing men including leptin, insulin, dehydroepiandrostenedione and growth hormone. The relationship of obesity to these hormones in ageing men will be reviewed. Testosterone replacement in ageing men can alter body composition whereby fat is exchanged for muscle. These studies will also be reviewed. Further studies in this field are recommended to evaluate long-term benefits and risks.

The andropause and memory loss: is there a link between androgen decline and dementia in the aging male?

Studies demonstrate a decline in androgens with age and this results in the andropause. The objective of this paper is to review the literature on hormonal changes that occur in the aging males and determine if there are associations between decreased testosterone, dehydroepiandrosterone (DHEA) and decreased cognitive function. Trials of androgen replacement and its impact on cognitive function will also be analyzed. Method of analysis will be by a thorough search of articles on MEDLINE, the Internet and major abstract databases. Results of the author's own research in 302 men of the association of memory loss as a symptom in the andropause will be presented. In addition, the authors open trial of testosterone replacement in hypogonadic men with Alzheimer's disease will also be presented. The results of the author's trial will be compared with other investigators. High endogenous testosterone level predicted better performance on visual spatial tests in several studies, but not in all studies. Likewise, testosterone replacement in hypogonadic patients improved cognitive functions in some but not all studies. Testosterone has also been shown to improve cognitive function in eugonadal men. Several studies have shown that declines in DHEA may contribute to Alzheimer's disease and the results of double blind studies with DHEA replacement and its effect on cognition will also be presented. In summary, there is still no consensus that androgen replacement is beneficial in cognitive decline but this option may prove promising in some patients.

A GABA-neuropeptide Y (NPY) interplay in LH release.

Neuropeptide Y (NPY) stimulates and gamma-amino butyric acid (GABA) inhibits LH release in the rat. Since a sub-population of NPY-producing neurons in the arcuate nucleus (ARC) of the hypothalamus co-express GABA, the possibility of an interplay between NPY and GABA in the release of LH was investigated in two ways. First by employing light and electron microscopic double staining for NPY and GABA, using pre and post-immunolabeling on rat brain sections, we detected GABA in NPY immunoreactive axon terminals in the MPOA, one of the primary sites of action of these neurotransmitters/neuromodulators in the regulation of LH release. These morphological findings raised the possibility that inhibitory GABA co-released with NPY may act to restrain the excitatory effects of NPY on LH release. Muscimol (MUS, 0.44 or 1.76 nmol/rat), a GABA(A) receptor agonist, administered intracerebroventricularly (icv), alone failed to affect LH release, but NPY (0.47 nmol/rat icv) alone stimulated LH release in ovarian steroid-primed ovariectomized rats. On the other hand, administration of MUS blocked the NPY-induced stimulation of LH release in a dose-dependent manner. Similarly, administration of MUS abolished the excitatory effects on LH release of 1229U91, a selective NPY Y4 receptor agonist. These results support the possibility that in the event of co-release of these neurotransmitters/neuromodulators, GABA may act to restrain stimulation of LH release by NPY during the basal episodic and cyclic release of LH in vivo.