[Effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis].

OBJECTIVE: To evaluate the effectiveness of a whole-process health education model among inpatients with ascites type of advanced schistosomiasis. METHODS: A "admission-hospitalization-discharge" whole-process health education model was created, 101 inpatients with ascites type of advanced schistosomiasis were given the whole-process health education. The scores of schistosomiasis control knowledge, attitudes towards schistosomiasis control and healthy behaviors, and awareness of schistosomiasis control knowledge, correct rate of attitudes towards schistosomiasis control and correct rate of healthy behaviors were compared among inpatients with ascites type of advanced schistosomiasis before and after implementation of the whole-process health education. RESULTS: The scores of schistosomiasis control knowledge, schistosomiasis control attitudes and healthy behaviors were all significantly higher among inpatients with ascites type of advanced schistosomiasis after implementation of the whole-process health education than before implementation (Z = -7.688, -3.576 and -4.328, all P values < 0.01). In addition, the awareness of schistosomiasis control knowledge increased from 54.3% to 82.7% (χ2 = 188.886, P < 0.01), and the correct rate of attitudes towards schistosomiasis control increased from 88.4% to 98.0% (χ2 = 22.001, P < 0.01), while the correct rate of healthy behaviors increased from 48.2% to 59.7% (χ2 = 11.767, P < 0.01). CONCLUSIONS: The whole-process health education model may remarkably improve the awareness of schistosomiasis control knowledge and promote the formation of positive attitudes towards schistosomiasis control and correct behaviors among inpatients with ascites type of advanced schistosomiasis, which is of great significance to facilitate patients' cure.

Laser vibrational excitation of radicals to prevent crystallinity degradation caused by boron doping in diamond.

Pursuing high-level doping without deteriorating crystallinity is prohibitively difficult but scientifically crucial to unleashing the hidden power of materials. This study demonstrates an effective route for maintaining lattice integrity during the combustion chemical vapor deposition of highly conductive boron-doped diamonds (BDDs) through laser vibrational excitation of a growth-critical radical, boron dihydride (BH2). The improved diamond crystallinity is attributed to a laser-enabled, thermal nonequilibrium suppression of the relative abundance of boron hydrides (BH), whose excessive presence induces boron segregation and disturbs the crystallization. The BDDs show a boron concentration of 4.3 × 1021 cm-3, a film resistivity of 28.1 milliohm·cm, and hole mobility of 55.6 cm2 V-1 s-1, outperforming a commercial BDD. The highly conductive and crystalline BDDs exhibit enhanced efficiency in sensing glucose, confirming the advantages of laser excitation in producing high-performance BDD sensors. Regaining crystallinity with laser excitation in doping process could remove the long-standing bottlenecks in semiconductor industry.

Metabolomics and its application in the mechanism analysis on diabetic bone metabolic abnormality.

OBJECTIVE: This study is aimed at analysing the endogenous metabolites profiling of patients with diabetic osteoporosis, so as to provide the reference for pathogenesis research of diabetic osteoporosis. PATIENTS AND METHODS: The 1H-NMR metabolomics technology, combined with pattern recognition analysis and SIMCA-P 12.0 statistical analysis, were employed to identify the metabolites differences between diabetic patients with disordered bone metabolism (research group) and healthy volunteers (normal group) in this study. RESULTS: Compared with normal group, the results show that in research group, the levels of O-acetyl glycoprotein, proline, 1-methyl histidine, tricarboxylic acid cycle (TCA cycle) product (citric acid and α-ketoglutaric acid) decline, while the levels of branched chain amino acids (leucine, isoleucine, valine), glucose, choline, creatine, inositol, glutamine, aspartic acid, alanine, glycine, and citrulline increase. CONCLUSIONS: There are disordered metabolic pathways and imbalanced bone synthetic materials and regulatory substances in diabetic patients with bone metabolic abnormality. These metabolic abnormalities could be the specific indicators in early diagnosis of diabetic osteoporosis.

[Effect of rational emotive therapy on negative emotion in advanced schistosomiasis patients with repeated hospitalization].

OBJECTIVE: To examine the effect of rational emotive therapy on negative emotions among advanced schistosomiasis patients with repeated hospitalizations. METHODS: A total of 97 advanced schistosomiasis patients with anxiety and depressive emotions that were hospitalized in Xiangyue Hospital of Hunan Institute of Schistosomiasis Control for three times or more were enrolled, and given rational emotive therapy for 4 weeks in addition to routine nursing care. The scores for anxiety, depression and quality of life were estimated in patients before and after the rational emotive therapy using the Self-Rating Anxiety Scale (SRS), the Self-Rating Depression Scale (SDS) and WHOQOL-BREF Form. RESULTS: The SAS and SDS scores were significantly lower 4 weeks following rational emotive therapy than before the intervention (SAS score, 45.40 ± 7.77 vs. 59.25 ± 9.29, t = 14.021, P < 0.01; 51.48 ± 8.01 vs. 63.93 ± 9.59, t = 12.991, P < 0.01). The percentages of patients with moderate and severe anxiety and depression were significantly lower 4 weeks following rational emotive therapy than before the intervention (P < 0.01), and the scores for each item in the quality of life were all significantly greater 4 weeks following rational emotive therapy than before the intervention (P < 0.01). CONCLUSIONS: Rational emotive therapy may improve the negative emotions and the quality of life of advanced schistosomiasis patients with repeated hospitalizations.

Unexpectedly high affinity of a novel histamine H(3) receptor antagonist, GSK239512, in vivo in human brain, determined using PET.

BACKGROUND AND PURPOSE: This study aimed to investigate the relationship between the plasma concentration (PK) of the novel histamine H3 receptor antagonist, GSK239512, and the brain occupancy of H(3) receptors (RO) in healthy human volunteers. EXPERIMENTAL APPROACH: PET scans were obtained after i.v. administration of the H(3) -specific radioligand [(11) C]GSK189254. Each subject was scanned before and after single oral doses of GSK239512, at 4 and 24 h after dose. PET data were analysed by compartmental analysis, and regional RO estimates were obtained by graphical analysis of changes in the total volumes of distribution of the radioligand, followed by a correction for occupancy by the high affinity radioligand. The PK/RO relationship was analysed by a population-modelling approach, using the average PK of GSK239512 during each scan. KEY RESULTS: Following administration of GSK239512, there was a reduction in the brain uptake of [(11) C]GSK189254 in all regions, including cerebellum. RO at 4 h was higher than at 24 h, and the PK/RO model estimated a PK associated with 50% of RO of 0.0068 ng·mL(-1) . This corresponds to a free concentration of 4.50 × 10(-12 ) M (pK = 11.3). CONCLUSIONS AND IMPLICATIONS: The affinity of GSK239512 for brain H3 receptors in humans in vivo is much higher than that expected from studies in vitro, and higher than that observed in PET studies in pigs. The study illustrates the utility of carrying out PET studies in humans early in drug development, providing accurate quantification of GSK239512 RO in vivo as a function of time and dose.

Analgesic efficacy and safety of the novel p38 MAP kinase inhibitor, losmapimod, in patients with neuropathic pain following peripheral nerve injury: a double-blind, placebo-controlled study.

BACKGROUND: Inhibitors of p38 mitogen-activated protein kinase are undergoing evaluation as a novel class of anti-rheumatic drugs, by virtue of their ability to suppress the production of pro-inflammatory cytokines. Emerging data suggests that they may also attenuate peripheral or central sensitization in neuropathic pain. A double-blind, placebo-controlled study was undertaken to evaluate the analgesic efficacy of losmapimod (GW856553), a novel p38α/ß inhibitor, in subjects with neuropathic pain following traumatic peripheral nerve injury. METHODS: One hundred and sixty-eight subjects with pain of at least moderate intensity (average daily score ≥4 on an 11-point pain intensity numeric rating scale; PI-NRS) at baseline were randomized to receive oral losmapimod, 7.5 mg BID or placebo for 28 days. Efficacy and safety assessments were undertaken at weekly clinic visits. RESULTS: The mean treatment difference for the change in average daily pain score from baseline to week 4 of treatment based on the PI-NRS was -0.22 (95% CI -0.73, 0.28) in favour of losmapimod over placebo (p = 0.39). There were no statistically significant or clinically meaningful differences between the treatment groups over the 4-week dosing period for either the primary or secondary efficacy variables. There were no unexpected safety or tolerability findings following dosing with losmapimod. CONCLUSIONS: Losmapimod could not be differentiated from placebo in terms of a primary analgesia response in patients with pain following peripheral nerve injury. The lack of response could reflect inadequate exposure at central sites of action or differences between rodent and human with respect to the target or neuropathic pain mechanisms.

Combined optical and acoustical method for determination of thickness and porosity of transparent organic layers below the ultra-thin film limit.

Analysis techniques are needed to determine the quantity and structure of materials composing an organic layer that is below an ultra-thin film limit and in a liquid environment. Neither optical nor acoustical techniques can independently distinguish between thickness and porosity of ultra-thin films due to parameter correlation. A combined optical and acoustical approach yields sufficient information to determine both thickness and porosity. We describe application of the combinatorial approach to measure single or multiple organic layers when the total layer thickness is small compared to the wavelength of the probing light. The instrumental setup allows for simultaneous in situ spectroscopic ellipsometry and quartz crystal microbalance dynamic measurements, and it is combined with a multiple-inlet fluid control system for different liquid solutions to be introduced during experiments. A virtual separation approach is implemented into our analysis scheme, differentiated by whether or not the organic adsorbate and liquid ambient densities are equal. The analysis scheme requires that the film be assumed transparent and rigid (non-viscoelastic). We present and discuss applications of our approach to studies of organic surfactant adsorption, self-assembled monolayer chemisorption, and multiple-layer target DNA sensor preparation and performance testing.

Multifocal electroretinography changes in patients on ethambutol therapy.

PURPOSE: To evaluate the multifocal electroretinography (mfERG) changes in patients on ethambutol therapy. METHODS: A cross-sectional observational study of 17 visually asymptomatic patients receiving antituberculosis therapy with ethambutol. Patients underwent complete ophthalmic examination and mfERG recordings. The first-order mfERG N1 and P1 response amplitudes and implicit times of six concentric rings were analysed and compared with 17 normal age-similar controls. Correlation analyses were performed between the patients' mfERG parameters with parameters of ethambutol usage (daily dose of ethambutol per body weight, duration of ethambutol therapy, cumulative dose of ethambutol, and cumulative dose of ethambutol per body weight). RESULTS: The mean duration of ethambutol therapy was 3.6 months (range: 2-9 months) and the mean daily dose per body weight was 13.2 mg/kg/day. Analysis of response amplitude measures showed no significant difference in the mfERG N1 and P1 response amplitudes between the ethambutol and control groups at all ring eccentricities (P>0.05). For implicit times, there were significant delays in the mfERG P1 implicit times of rings 4-6 in the ethambutol group compared with controls (P=0.012 to P=0.041). Correlation analyses showed no significant correlation between the mfERG and ethambutol parameters (P>0.05). CONCLUSIONS: The mfERG findings suggested that visually asymptomatic patients receiving ethambutol therapy might have localized mild electrophysiological changes involving the peripheral macula. These changes might be related to localized alteration of metabolism or physiological changes associated with ethambutol therapy.

Safety enhanced photodynamic therapy with half dose verteporfin for chronic central serous chorioretinopathy: a short term pilot study.

AIM: To evaluate short term safety of an enhanced photodynamic therapy (PDT) protocol with half dose verteporfin for treating chronic central serous chorioretinopathy (CSC). METHODS: 20 eyes of 18 patients with symptomatic chronic CSC underwent PDT using 3 mg/m2 verteporfin. Verteporfin was infused over 8 minutes followed by indocyanine green angiography guided laser application 2 minutes later. Serial optical coherence tomography (OCT) and multifocal electroretinography (mfERG) recordings were performed before PDT, at 4 days, 2 weeks, and 1 month after PDT. The best corrected visual acuity (BCVA), OCT central retinal thickness, and mean mfERG response amplitudes and peak latencies were compared longitudinally. Subgroup analysis was further performed for eyes with or without pigment epithelial detachment (PED). RESULTS: At 1 month after PDT, the median BCVA improved from 20/40 to 20/30 (p = 0.001). The mean central retinal thickness also reduced from 276 microm to 158 microm (p < 0.001) and 17 (85%) eyes had complete resolution of serous retinal detachment and/or PED. MfERG showed no significant changes in the mean N1 and P1 response amplitude and latency for all eyes. Subgroup analysis demonstrated that eyes without PED had a significant increase in the mean central mfERG P1 response amplitude with reduction in P1 peak latency at 1 month post-PDT. For eyes with PED, transient reduction in the mean central P1 response amplitude was observed at 4 days post-PDT. CONCLUSIONS: The modified safety enhanced PDT protocol with half dose verteporfin appeared to be a beneficial treatment option for patients with chronic CSC, especially in eyes without serous PED. Further controlled study is warranted to demonstrate the long term safety and efficacy of this treatment option.

Myopia progression among preschool Chinese children in Hong Kong.

INTRODUCTION: Myopia is the most common eye disorder especially in Asia. However, the information on myopic progression and ocular growth among preschool children, who undergo rapid changes, is limited. The aim of this study was to determine the prevalence, incidence of myopia and myopic progression among preschool children in Hong Kong. MATERIALS AND METHODS: A kindergarten was randomly chosen in Hong Kong, China. Preschool children aged 2 to 6 years attending the selected kindergarten were invited to participate. One hundred and eight children completed the 5-year cohort study. Refractive error and axial ocular dimensions were the main outcome measures. RESULTS: A total of 255 preschool children with a mean age of 4.96 (SD, 0.90) years were examined in the initial examination. Only 4.6% children had myopia of at least -0.50 D. The prevalence of myopia increased almost 10-fold to 43.5% after 5 years in the final examination. The annual incidence of myopia was 8.2%. The mean increase in axial length was 1.72 mm (SD, 0.80 mm) over the 5-year period (P < 0.001). The lens thickness decreased significantly from 3.80 mm (SD, 0.37 mm) to 3.74 mm (SD, 0.51 mm) whereas the vitreous chamber depth increased significantly from 15.01 mm (SD, 0.68 mm) to 16.42 mm (SD, 0.88 mm) (both P < 0.001). Children who were younger or were less hypermetropic at the initial examination was having greater myopic progression (P = 0.015, P < 0.001 respectively). CONCLUSION: This is the first prospective study to investigate the myopic progression and ocular growth among preschool children. Hong Kong has a high prevalence of myopia even in preschool children. They also experience a significant myopic shift and ocular growth. Further studies on the prevention of myopic development or progression should be targeted on this population.

Synthesis, cyclic voltammetric studies, and electrogenerated chemiluminescence of a new donor-acceptor molecule: 3,7-[Bis[4-phenyl-2-quinolyl]]-10-methylphenothiazine.

We report here the synthesis of a novel compound that contains two electron-accepting phenylquinoline groups covalently attached to the 3,7-positions of a light-emitting electron donor, 10-methylphenothiazine. The optimized geometry as determined from semiempirical MNDO calculations shows that the phenylquinoline moieties are twisted approximately 77.5 degrees from the phenothiazine central ring. As a result, no molecular orbital overlap between these two groups exists, inhibiting any delocalization of the charge upon electrochemical oxidation or reduction. Comparison between cyclic voltammograms obtained of this compound as well as of the individual compounds, 10-methylphenothiazine and 2-phenylquinonine, did indeed show no change in the electrochemical behavior of these two groups upon the covalent attachment, confirming the results obtained from the semiempirical calculations. A shift to lower energy wavelengths of phenothiazine was observed upon the addition of the electron-deficient phenylquinoline moieties. Overall, this unique geometry allows us to electrochemically produce the stable radical ions needed to generate the light-emitting excited state of phenothiazine within a potential window not obtainable with just 10-methylphenothiazine. ECL spectrum produced by annihilation between the radical cation of phenothiazine and the radical anion of phenylquinoline shows good agreement with the fluorescence emission of 10-methylphenothiazine.

Could a cycloplegic agent be replaced by a fogging or a corrective lens in the biometric measurement of the crystalline lens?

This study investigated whether a fogging or a corrective lens could be used to replace a cycloplegic agent in the ultrasonic measurement of crystalline lens thickness in myopia. A group of 28 Hong Kong Chinese adults with myopia was recruited. The crystalline lens thickness of the examined eye was measured by A-scan ultrasonography while the fixating eye was in one of three conditions: fog (+2.00 D fogging lens), full corrective lens, or cycloplegia (50 minutes after instillation of 1% cyclopentolate HCl). We found that the mean lens thickness was significantly different between the three conditions in our myopic subjects. The mean crystalline lens thickness under fogging and corrective lens conditions was significantly greater than the cycloplegic condition by 0.09 mm and 0.11 mm, respectively. The 95% limits of agreement compared to cycloplegia (fogging: -0.32 to +0.14; corrective: -0.35 to +0.13) showed marked intersubject variability, indicating that there is a risk of overestimating the lens thickness when substituting cycloplegia with either a fogging or a corrective lens.

Selective inhibition of Alzheimer disease-like tau aggregation by phenothiazines.

In Alzheimer disease (AD) the microtubule-associated protein tau is redistributed exponentially into paired helical filaments (PHFs) forming neurofibrillary tangles, which correlate with pyramidal cell destruction and dementia. Amorphous neuronal deposits and PHFs in AD are characterized by aggregation through the repeat domain and C-terminal truncation at Glu-391 by endogenous proteases. We show that a similar proteolytically stable complex can be generated in vitro following the self-aggregation of tau protein through a high-affinity binding site in the repeat domain. Once started, tau capture can be propagated by seeding the further accumulation of truncated tau in the presence of proteases. We have identified a nonneuroleptic phenothiazine previously used in man (methylene blue, MB), which reverses the proteolytic stability of protease-resistant PHFs by blocking the tau-tau binding interaction through the repeat domain. Although MB is inhibitory at a higher concentration than may be achieved clinically, the tau-tau binding assay was used to identify desmethyl derivatives of MB that have Ki values in the nanomolar range. Neuroleptic phenothiazines are inactive. Tau aggregation inhibitors do not affect the tau-tubulin interaction, which also occurs through the repeat domain. Our findings demonstrate that biologically selective pharmaceutical agents could be developed to facilitate the proteolytic degradation of tau aggregates and prevent the further propagation of tau capture in AD.

Quantitative analysis of tau protein in paired helical filament preparations: implications for the role of tau protein phosphorylation in PHF assembly in Alzheimer's disease.

In Alzheimer's disease, there is a major redistribution of the tau protein pool from soluble to PHF-bound forms. PHF-bound tau can be distinguished from normal tau by acid reversible occlusion of a generic tau epitope in the tandem repeat region and characteristic sedimentation in the if-II protocol developed in this laboratory. We show that 85% of tau bound in the PHF-like configuration can be recovered in the if-II PHF-fraction. Less than 1% of this material was phosphorylated at the mAb AT8 site in aged clinical controls or in cases with minimal or mild dementia. Of tau phosphorylated at the mAb AT8 site, only 12% was found to co-sediment with PHFs. These low levels could not be explained by postmortem dephosphorylation. As more than 95% of PHF-tau is not phosphorylated, even at early stages of pathology, it is misleading to use the terms "PHF-tau" and "phosphorylated tau" as though they were synonymous, particularly as this implies a pathogenetic role which phosphorylation need not have.

Examination of phosphorylated tau protein as a PHF-precursor at early stage Alzheimer's disease.

Hyperphosphorylated tau protein which can be isolated on the basis of insolubility in 1% sarkosyl (A68-tau fraction) is thought to represent a precursor pool for PHF assembly, associated histologically with neuritic pathology, which feeds into a more resistant tangle-associated PHF pool via cross-linking and proteolysis. We examined these predictions at the earliest detectable stages of neurofibrillary pathology. We report that there is no evidence that neuritic pathology represents an early pathologic stage, no evidence of an association between neuritic pathology and phosphorylated tau, no evidence of selective accumulation of phosphorylated tau at early stages of pathology, and no evidence for a precursor/product relationship between phosphorylated tau and PHFs during progression of pathology. We conclude that altered phosphorylation is a secondary process affecting 5% of PHFs and does not explain PHF assembly in Alzheimer's disease.

Blocking cell division does not remove the requirement for Polycomb function in Drosophila embryogenesis.

The Polycomb (Pc) gene is required from the extended germ band stage onwards, to maintain spatially restricted patterns of homeotic gene expression. It has been thought to be involved in the 'stable inheritance of the determined state'. In this paper, we have tested the notion that the Pc gene is required specifically during or after DNA replication to enable the stable transmission of states of gene activity. We found that arresting cell division using the string mutation or blocking DNA replication with aphidicolin failed to prevent ectopic expression of the homeotic gene Ultrabithorax in Pc mutants. Thus, even in the absence of DNA replication, Pc is required to maintain spatially restricted patterns of homeotic gene expression. The role of the Pc gene product in the stable repression of homeotic gene transcription is discussed.