[The study on the association of long-term ambient fine particulate matters exposure and elevated blood pressure in children].

Objective: To evaluate the association of long-term ambient fine particulate matters (PM(2.5)) exposure with elevated blood pressure in children. Methods: From April 2012 to June 2013, we used cluster randomized sampling method to investigate 9 354 children aged 5-17 years old from 68 primary and middle schools in the seven Northeastern Cities (Shenyang, Dalian, Fushun, Anshan, Benxi, Liaoyang and Dandong) in Liaoning Province, and measured their blood pressure (BP). A spatial statistical model nested by aerosol optical depth (AOD) was used to inverse PM(2.5) concentrations. Generalized additive model was used to quantify the association between PM(2.5) exposure and blood pressure in children. To examine the associations, two-level regression model was used to evaluate individual characteristics' modifying effect on the health influence of PM(2.5). Results: The prevalence of hypertension in children was 13.78% (1 289/9 354). The results showed that there was an associations between hypertension and pollutants, and the multivariable regression analysis indicated that the increase in mean systolic blood pressure (SBP), diastolic blood pressure (DBP), and the OR of hypertension associated with a 10 µg/m(3) increase for PM(2).5 were 3.12 (95%CI: 2.71-3.54) mmHg (1 mmHg=0.133 kPa), 1.45 (95%CI:1.12-1.78) mmHg, and 1.55 (95%CI: 1.10-2.19), respectively. Compared with non-breastfeeding children (OR=2.10, 95%CI: 1.39-3.17), children who were breastfeeding (OR=1.49, 95%CI: 1.00-2.20) exhibited consistently weaker effects, and the interaction effect of P value was 0.002. Conclusion: Study findings indicate that long-term exposure to PM(2.5) is associated with increased arterial BP and hypertension among the children. Breastfeeding may reduce this association.

Risk assessment of dengue fever in Zhongshan, China: a time-series regression tree analysis.

Dengue fever (DF) is the most prevalent and rapidly spreading mosquito-borne disease globally. Control of DF is limited by barriers to vector control and integrated management approaches. This study aimed to explore the potential risk factors for autochthonous DF transmission and to estimate the threshold effects of high-order interactions among risk factors. A time-series regression tree model was applied to estimate the hierarchical relationship between reported autochthonous DF cases and the potential risk factors including the timeliness of DF surveillance systems (median time interval between symptom onset date and diagnosis date, MTIOD), mosquito density, imported cases and meteorological factors in Zhongshan, China from 2001 to 2013. We found that MTIOD was the most influential factor in autochthonous DF transmission. Monthly autochthonous DF incidence rate increased by 36·02-fold [relative risk (RR) 36·02, 95% confidence interval (CI) 25·26-46·78, compared to the average DF incidence rate during the study period] when the 2-month lagged moving average of MTIOD was >4·15 days and the 3-month lagged moving average of the mean Breteau Index (BI) was ⩾16·57. If the 2-month lagged moving average MTIOD was between 1·11 and 4·15 days and the monthly maximum diurnal temperature range at a lag of 1 month was <9·6 °C, the monthly mean autochthonous DF incidence rate increased by 14·67-fold (RR 14·67, 95% CI 8·84-20·51, compared to the average DF incidence rate during the study period). This study demonstrates that the timeliness of DF surveillance systems, mosquito density and diurnal temperature range play critical roles in the autochthonous DF transmission in Zhongshan. Better assessment and prediction of the risk of DF transmission is beneficial for establishing scientific strategies for DF early warning surveillance and control.

Abnormal voiding parameters in children with severe idiopathic constipation.

OBJECTIVE: It is suggested that idiopathic constipation may associate with abnormal voiding parameters. In this study, we investigate the voiding parameters in children with constipation. METHODS: Since 2010, seventeen consecutive children (12 boys, 5 girls) aged 5-17 (median = 14) with significant constipation according to Rome III criteria and who were not responding to conventional treatment (diet, laxatives & bowel training) for over 6 months were recruited. The rectal diameter (RD) was measured by transpubic ultrasonography (USG), RD >3.5 cm was considered as dilated. Each patient had uroflow measurement and bladder USG done to measure the maximal flow rate (Vmax), voided volume (VV), and post-void residual urine (PVR). Abnormal voiding parameters were defined as Vmax <12 ml/sec, VV <65 or >150% of age-adjusted expected bladder capacity (EBC) and/or PVR >20 ml. RESULTS: Rectal diameter ranged from 1.7 to 8.2 cm (median = 3 cm) and was abnormally dilated in eight children. Vmax was normal in all children (median = 23.7 ml/sec). Voided volume ranged from 30 to 289% of EBC and was abnormal in six children (35.5%). Post-void residual urine varied from 0 to 85 ml and was abnormal in six (35.5 %) children. Three children (17.6 %) had both abnormal VV and PVR. On the whole, the prevalence of abnormal voiding parameters in constipated children was 52.9 %. Mean RD in normal and abnormal parameters groups was 2.8 and 4.7 cm, respectively. Rectal dilation was associated with abnormal voiding parameters (p = 0.015). CONCLUSION: Abnormal voiding parameters including voided volume and post-void residual urine are prevalent in constipated children. Dilated rectum is associated with abnormal voiding parameters.

Scrotal antegradesclerotherapy demonstrates anatomical variations on venous drainage in paediatric, adolescent and young adult varicoceles.

AIM OF THE STUDY: Anatomical variations on venous drainage in varicoceles are under-reported. We report our experience in scrotal antegrade sclerotherapy (SAS) for adolescent varicoceles. METHODS: Since 2011, 15 consecutive boys with left varicoceles were recruited. Under general anaesthesia, a 5-mm transverse incision was made at scrotal neck, testicular vein was cannulated at pampiniform plexus with venogram performed. Foam sclerosant by mixing sodium tetradecyl sulphate (STS), Lipiodol(®) and air was slowly injected under fluoroscopy. Postoperatively the patients were followed-up for varicocele grading, testicular size, and complications. MAIN RESULTS: Median age at operation was 14 (10-19) years. 80 % had grade three varicoceles, 33.3 % had smaller left testis before operation. Intra-operative venogram showed three different anatomical variations. Group I: eleven patients (73.3 %) had single distinct internal spermatic vein; Group II: two patients demonstrated duplication of internal spermatic vein draining into left renal vein; Group III: two patients had pampiniform plexus draining to iliac and/or paraspinal veins. SAS was performed in Group I and II patients. Sclerosant volume injected ranged from 1.5 to 4.5 ml. In Group III patients, surgical ligation of testicular veins was performed rather than SAS to avoid uncontrolled systemic sclerosant spillage. Mean length of stay was 1.13 day. One patient with scrotal haematoma and one other with minor wound dehiscence were managed conservatively. Mean follow-up period was 10.9 (1-22) months. Thirteen patients (86.7 %) achieved varicocele grading ≤ 1. There was no postoperative testicular atrophy, hydrocele and epididymo-orchitis. CONCLUSION: Scrotal antegrade sclerotherapy using STS foam is a safe and effective treatment for adolescent varicoceles. Anatomical variations on venous drainage in varicoceles are common.

TGFß modulates cell-to-cell communication in early epithelial-to-mesenchymal transition.

AIMS/HYPOTHESIS: A key pathology in diabetic nephropathy is tubulointerstitial fibrosis. The condition is characterised by increased deposition of the extracellular matrix, fibrotic scar formation and declining renal function, with the prosclerotic cytokine TGF-ß1 mediating many of these catastrophic changes. Here we investigated whether TGF-ß1-induced epithelial-to-mesenchymal transition (EMT) plays a role in alterations in cell adhesion, cell coupling and cell communication in the human renal proximal tubule. METHODS: Whole-cell and cell compartment abundance of E-cadherin, N-cadherin, snail, vimentin, ß-catenin and connexin-43 was determined in human kidney cell line (HK)2 and human proximal tubule cells with or without TGF-ß1, using western blotting and immunocytochemistry, followed by quantification by densitometry. The contribution of connexin-43 in proximal tubule cell communication was quantified using small interfering RNA knockdown, while dye-transfer was used to assess gap junctional intercellular communication (GJIC). Functional tethering was assessed by single-cell force spectroscopy with or without TGF-ß1, or by immunoneutralisation of cadherin ligation. RESULTS: High glucose (25 mmol/l) increased the secretion of TGF-ß1 from HK2 cells. Analysis confirmed early TGF-ß1-induced morphological and phenotypical changes of EMT, with altered levels of adhesion and adherens junction proteins. These changes correlated with impaired cell adhesion and decreased tethering between coupled cells. Impaired E-cadherin-mediated adhesion reduced connexin-43 production and GJIC, these effects being mimicked by neutralisation of E-cadherin ligation. Upregulation of N-cadherin failed to restore adhesion or connexin-43-mediated GJIC. CONCLUSIONS/INTERPRETATION: We provide compelling evidence that TGF-ß1-induced EMT instigates a loss of E-cadherin, cell adhesion and ultimately of connexin-mediated cell communication in the proximal tubule under diabetic conditions; these changes occur ahead of overt signs of renal damage.

Management of primary spontaneous pneumothorax in Chinese children.

OBJECTIVES: To (1) determine the demographics of Chinese children admitted with primary spontaneous pneumothorax, (2) suggest how they may be quantified radiologically, (3) compare the difference in outcomes after their primary management by thoracentesis and chest tube insertion, and (4) review the local experience with surgical intervention for such children. DESIGN: Retrospective, descriptive study. SETTING: Acute tertiary public hospital, Hong Kong. PATIENTS: Consecutive patients younger than 18 years and admitted with primary spontaneous pneumothorax between 1 January 1999 and 30 September 2007. MAIN OUTCOME MEASURES: Hospital stay and risk of recurrence after thoracentesis versus chest tube insertion. RESULTS. Seventy-seven patients with 114 episodes of primary spontaneous pneumothorax were reviewed. They were significantly taller (P<0.001) and thinner (P<0.001) than the population mean percentile. Both the Light index and Collins formula were accurate in quantifying pneumothorax volume, but as the former was simpler and more user-friendly, this was more applicable in children. Thoracentesis resulted in shorter hospital stays (mean, 4.6; standard deviation, 1.9 days) than chest tube insertion (6.9; 3.0 days), but there was no significant difference in the recurrence rates within 6 months (P=1.0), 1 year (P=0.9), and 2 years (P=0.1). Insignificant pneumothorax was treated with observation alone in 16% of the patients. For patients with a clinically significant pneumothorax, thoracentesis and chest tube insertion were successful in 78% and 67%, respectively (P=0.34). The success rate of video-assisted thoracoscopic surgery was 89%, and postoperative recurrence occurred more commonly in patients without a lung bleb. CONCLUSION: Chinese children with primary spontaneous pneumothorax exhibited similar demographic characteristics to Caucasian children. Light index is simple and accurate for quantifying pneumothorax volume in children. Conservative treatment including observation, thoracentesis, and chest tube insertion should suffice for most patients with first episode of primary spontaneous pneumothorax. Early surgery is warranted for any patient who fails conservative treatment, for which video-assisted thoracoscopic surgery is safe and effective.

A receptor in pituitary and hypothalamus that functions in growth hormone release.

Small synthetic molecules termed growth hormone secretagogues (GHSs) act on the pituitary gland and the hypothalamus to stimulate and amplify pulsatile growth hormone (GH) release. A heterotrimeric GTP-binding protein (G protein)-coupled receptor (GPC-R) of the pituitary and arcuate ventro-medial and infundibular hypothalamus of swine and humans was cloned and was shown to be the target of the GHSs. On the basis of its pharmacological and molecular characterization, this GPC-R defines a neuroendocrine pathway for the control of pulsatile GH release and supports the notion that the GHSs mimic an undiscovered hormone.

Correlations between the experimental and numerical investigations on the mechanical properties of erythrocyte by laser stretching.

The deformation and mechanical properties of the erythrocytes are studied experimentally and numerically. For the experimental part, an osmotic swollen spherical erythrocyte was attached with a pair of silica beads, and then stretched at two opposite ends by a laser trap. The purpose of this experiment is to find the empirical correlation between the stretching force and the cell deformation in terms of the transverse strain, which is a measure of the change of radius in a spherical cell along its equator. Experimental results show the cell shape become more oblate, elliptic as the stretching force increases. On the numerical front, a physical model from the original work by Pamplona and Calladine for the lipsomes was extended to simulate the deformation of the cell membrane. Numerical analyses were performed to solve the nondimensionalized governing equations with proper boundary conditions imposed to simulate the experimental conditions. The simulated results indicate that at high tensile stiffness, the cell can deform into a spindle shape with negative curvature close to the ends of stretch. Finally, the experimental data and the simulated results were correlated through optimization by minimizing their discrepancy at various values of the shear stiffness. The optimal value of shear stiffness was found in the range of 2.35 approximately 4.29 10(-6) N.m(-1), which is comparable with those values reported in the literature.

Determination of work of adhesion of biological cell under AFM bead indentation.

Hertz contact theory has been widely used for the determination of cell elasticity based on AFM indentation experiments. In light of the adhesive contact between AFM tip and cell, this study applied Johnson-Kendall-Roberts (JKR) model to fit the indentation force-displacement (F-D) curves reported previously. A MIN6 cell has been modeled as first a sphere and then a flattened cell with different thicknesses. The results have shown that both basic JKR model and "generalized" JKR model can best describe the unloading force-displacement behaviors of the indentation curves. The Young׳s modulus of the cell and the work of adhesion of the cell-indenter interface are obtained. In comparison to the Hertzian contact model, the JKR model provides obviously better fitting to the experimental results, indicating that the adhesion is significant in the cell interaction.

[Zheng Meijian's Sha yu yi yu (Random Medical Talks in Leisure Time) and his new ideas on pulse-taking].

Zheng Meijian, a doctor of Xin'an district in the reign of Qianlong Emperor of the Qing Dynasty, left his manuscript Sha yu yi yu (Random Medical Talks in Leisure Time), and was handed down in his family for generations. Sha yu yi yu was published in the Anhui Yixue of Issue 20, 1959, with horizontal layout and punctuation. The book records Zheng Meijian's understanding for the medicine, especially his new ideas on the cunkou pulse, with its underlying corresponding relationship among cun-guan-chi and zang-fu which should be combined with meridian and collateral system, claiming that the pulse taken superficially was corresponding to fu, while that taken deeply, to zang. He classified the strength of the fingers in pulse-taking into 8 levels, and advocated flexible application of pulse-taking. All his opinions had an important reference value for theoretical research and clinical application of pulse-taking.

Expression of a glutamate-activated chloride current in Xenopus oocytes injected with Caenorhabditis elegans RNA: evidence for modulation by avermectin.

Membrane currents were recorded from Xenopus laevis oocytes injected with C. elegans poly(A)+ RNA. In such oocytes glutamate activated an inward membrane current that desensitized in the continued presence of glutamate. Glutamate-receptor agonists quisqualate, kainate, and N-methyl-D-aspartate were inactive. The reversal potential of the glutamate-sensitive current was -22 mV, and exhibited a strong dependence on external chloride with a 48 mV change for a 10-fold change in chloride. The chloride channel blockers flufenamate and picrotoxin inhibited the glutamate-sensitive current. Ibotenate, a structural analog of glutamate, also activated a picrotoxin-sensitive chloride current. Ibotenate was inactive when current was partially desensitized with glutamate, and the responses to low concentrations of glutamate and ibotenate were additive. The anthelmintic/insecticide compound avermectin directly activated the glutamate-sensitive current. In addition, avermectin increased the response to submaximal concentrations of glutamate, shifted the glutamate concentration-response curve to lower concentrations, and slowed the desensitization of glutamate-sensitive current. We propose that the glutamate-sensitive chloride current and the avermectin-sensitive chloride current are mediated via the same channel.

Enzyme-catalyzed asymmetric deacylation for the preparation of lasofoxifene (CP-336156), a selective estrogen receptor modulator.

[structure] selective estrogen receptor modulator (SERM), Lasofoxifene (CP-336156), was prepared by an enzyme-catalyzed asymmetric deacylation with high optical purity and excellent yield even though the hydrolytic site is remote from the chiral centers.

Detection of intracellular calcium elevations in Xenopus laevis oocytes: aequorin luminescence versus electrophysiology.

Detection of receptor expression in Xenopus oocytes often relies upon functional coupling to second messengers such as Ca2+ or cyclic adenosine monophosphate. To detect intracellular Ca2+, electrophysiological measurement of the endogenous Ca(2+)-activated chloride current (ICl(Ca)) is often used (Dascal, 1987). An alternative utilizes the Ca2+ sensing, bioluminescent protein aequorin (Parker and Miledi(1986) Proc. R. Soc. Lond. B, 228: 307-315; Giladi and Spindel (1991) BioTechniques, 10: 744-747). In the present study the sensitivities of aequorin and electrophysiology for detecting receptor-mediated Ca2+ transients were compared. Assays were performed on the same batches of oocytes using either animal serum or ligands of exogenous receptors to generate inositol 1,4,5-trisphosphate (InsP3) and ultimately elevate intracellular Ca2+. Signal amplitudes were controlled by titrating the concentration of animal serum, or titrating the amount of receptor mRNA injected. Both assays detected signals with high concentrations of animal serum, or with high receptor density. However, aequorin signals were not detected in experiments with average ICl(Ca) current amplitudes below 200 nA. To further evaluate the differences between these two techniques, membrane current and bioluminescence were measured simultaneously. Results of these studies suggest that the signals differ due to the spatial distribution of aequorin, the chloride channels, and the calcium release sites.

Avian influenza in Hong Kong 1997-2002.

In 1997, a high-pathogenicity H5N1 avian influenza virus caused serious disease in both man and poultry in Hong Kong, China. Eighteen human cases of disease were recorded, six of which were fatal. This unique virus was eliminated through total depopulation of all poultry markets and chicken farms in December 1997. Other outbreaks of high-pathogenicity avian influenza (HPAI) caused by H5N1 viruses occurred in poultry in 2001 and 2002. These H5N1 viruses isolated had different internal gene constellations to those isolated in 1997. No new cases of infection or disease in man due to these or other H5N1 viruses have been reported. This paper provides an overview and chronology of the events in Hong Kong relating to avian influenza, covering the period from March 1997 to March 2002.

An update on avian influenza in Hong Kong 2002.

An outbreak of highly pathogenic avian influenza caused by multiple genotypes of H5N1 virus occurred in Hong Kong, commencing in January 2002. Infection in local chicken farms was preceded by the detection of virus in multiple retail markets and the main poultry wholesale market. The first case of this disease on a local farm was detected on February 1, 2002. By February 9, 2002, 15 farms were infected, and by late March a total of 22 infected farms had been identified. Three main clusters of infected farms were seen, suggesting multiple incursions of virus, and subsequent limited lateral spread to neighboring firms. Control of this disease has been effected through a combination of quarantine, tightening of biosecurity measures, and depopulation of infected and contact farms. About 950,000 birds have been destroyed. Vaccination using a killed H5 vaccine was introduced in April 2002 to farms in one zone where infection has persisted. None of the viruses isolated contained the internal genes found in the 1997 H5N1 virus.

The mechanism of action of avermectins in Caenorhabditis elegans: correlation between activation of glutamate-sensitive chloride current, membrane binding, and biological activity.

Xenopus laevis oocytes were injected with mRNA isolated from the free-living nematode Caenorhabditis elegans and the activation and potentiation of a glutamate-sensitive chloride current by a series of avermectin analogs and milbemycin D were determined. There was a strong correlation between the EC50 value determined for current activation in oocytes, the LD95 value for nematocidal activity, and also for the Ki value determined in a [3H]ivermectin competition binding assay. Four of the analogs were tested for potentiation of glutamate-sensitive current and the rank order for potentiation correlated with the EC50 for direct activation of current. We conclude that avermectins and milbemycins mediate their nematocidal effects on C. elegans via an interaction with a common receptor molecule, glutamate-gated chloride channels.

New model to characterise cell-substrate adhesion in the presence of osmosis.

A simple model of cell-substrate adhesion, in response to osmosis change, is derived to describe quantitatively the interrelationships between osmotic inflation, contact area and angle, membrane stretching and adhesion strength. As the cell inflates, the contact area shrinks in dimension, until the cell is eventually lifted off the substrate. The theoretical prediction is consistent with other published data.

Contact mechanics of a thin-walled capsule adhered onto a rigid planar substrate.

A thin-walled capsule, modelled as an incompressible liquid droplet contained in a thin flexible membrane, was allowed to adhere onto a rigid substrate. The contact mechanics were formulated, based on linear elasticity, to portray quantitatively the relationships between osmotic inflation, contact area and angle, membrane stretching and adhesion strength. The predicted results shed light on fundamental adhesive contact mechanics in a cell-substrate system.

Capsule-substrate contact deformation: determination of adhesion energy.

A study is reported of a cellular entity (liquid-filled microcapsule) adhered on a flat glass substrate in response to changes in osmotic pressure and temperature. High-resolution reflection interference contrast microscopy (HR-RICM) and phase-contrast microscopy were developed for probing the adhesion contact area, capsule-substrate separation profile and adhesion energy of the adhering microcapsule. The new technique increased the detection limit of the measured capsule wall-substrate separation in the cohesive zone from 1 to 4.5 microm and improved the spatial resolution of the heterogeneous contact zones. A theoretical model was applied to correlate quantitatively the adhesion energy to the area of the contact zone. The work demonstrated the possibility of ascertaining the quantitative interfacial adhesion energy of a liquid-filled microcapsule using the present technique and represents the first step in extending this novel approach to study more complicated systems, such as cell-substrate interactions, in the future.

The clip and drop back technique in the management of multifocal necrotizing enterocolitis: a single centre experience.

AIM: The surgical management of multifocal necrotizing enterocolitis (NEC) remains a major challenge. The "clip-and-drop" strategy with a second-look laparotomy permits re-assessment of bowel viability after optimization, thus offering the potential of both improving survival and conserving bowel length. This study reviews the outcome of this strategy in a single regional center. METHODS: Since 2000, NEC patients undergoing emergency laparotomy selectively underwent a "clip-and-drop" operation if there was peri-operative instability and/or multifocal disease with uncertain bowel viability. Bowel with full thickness gangrene was resected and bowel-ends were temporarily tied-off; a second-look definitive procedure was performed when the patient had stabilized. For this review, in-hospital and follow-up records were studied retrospectively for demographics, 30-day mortality and long-term outcome. MAIN RESULTS: Between 2000 and 2010, 16 patients underwent a "clip-and-drop" operation. The mean post-conception age was 32.8 weeks (27.7-41.7 weeks) with a median body weight of 1.4 kg (0.76-4.4 kg) at first operation. Preoperative radiograph showed free gas in 43.8% and portal venous gas in 37.5% of patients. 2 patients did not survive to the second laparotomy. 14 patients received a second laparotomy, after a mean of 51 h (35-74 h). 2 patients were found to suffer from NEC totalis on the second laparotomy and died without further procedures. All other patients (n = 12) had stoma formation. 1 patient died 4 days after stoma formation. The 30-day mortality for NEC with the "clip-and-drop" strategy was 31.6% (5/16). Among the 11 survivors, 1 died from liver failure complicated by short bowel syndrome at 5 months post operation, 2 others died from respiratory complications of prematurity despite adequate gastrointestinal function. The median follow-up time for the 8 long-term survivors was 45 months (7-129 months). Their median time to achieving full feeds was 41 days (range 21-105 days) after the second operation. CONCLUSION: The "clip-and-drop" strategy, when used in selected patients with multifocal NEC, may help bowel conservation in survivors.