Automated Reconstruction of Dendritic and Axonal Trees by Global Optimization with Geometric Priors

We present a novel probabilistic approach to fully automated delineation of tree structures in noisy 2D images and 3D image stacks. Unlike earlier methods that rely mostly on local evidence, ours builds a set of candidate trees over many different subsets of points likely to belong to the optimal tree and then chooses the best one according to a global objective function that combines image evidence with geometric priors. Since the best tree does not necessarily span all the points, the algorithm is able to eliminate false detections while retaining the correct tree topology. Manually annotated brightfield micrographs, retinal scans and the DIADEM challenge datasets are used to evaluate the performance of our method. We used the DIADEM metric to quantitatively evaluate the topological accuracy of the reconstructions and showed that the use of the geometric regularization yields a substantial improvement.     

SK2 channels are neuroprotective for ischemia-induced neuronal cell death

In mouse hippocampal CA1 pyramidal neurons, the activity of synaptic small-conductance Ca²⁺-activated K⁺ channels type 2 (SK2 channels) provides a negative feedback on N-methyl--aspartate receptors (NMDARs), reestablishing Mg²⁺ block that reduces Ca²⁺ influx. The well-established role of NMDARs in ischemia-induced excitotoxicity led us to test the neuroprotective effect of modulating SK2 channel activity following cerebral ischemia induced by cardiac arrest and cardiopulmonary resuscitation (CA/CPR). Administration of the SK channel positive modulator, 1-ethyl-benzimidazolinone (1-EBIO), significantly reduced CA1 neuron cell death and improved CA/CPR-induced cognitive outcome. Electrophysiological recordings showed that CA/CPR-induced ischemia caused delayed and sustained reduction of synaptic SK channel activity, and immunoelectron microscopy showed that this is associated with internalization of synaptic SK2 channels, which was prevented by 1-EBIO treatment. These results suggest that increasing SK2 channel activity, or preventing ischemia-induced loss of synaptic SK2 channels, are promising and novel approaches to neuroprotection following cerebral ischemia.     

Policy Support, Norms, and Secondhand Smoke Exposure Before and After Implementation of a Comprehensive Smoke-Free Law in Mexico City

Objectives. We assessed attitudes and beliefs about smoke-free laws, compliance, and secondhand smoke exposure before and after implementation of a comprehensive smoke-free law in Mexico City.Methods. Trends and odds of change in attitudes and beliefs were analyzed across 3 representative surveys of Mexico City inhabitants: before implementation of the policy (n = 800), 4 months after implementation (n = 961), and 8 months after implementation (n = 761).Results. Results indicated high and increasing support for 100% smoke-free policies, although support did not increase for smoke-free bars. Agreement that such policies improved health and reinforced rights was high before policy implementation and increased thereafter. Social unacceptability of smoking increased substantially, although 25% of nonsmokers and 50% of smokers agreed with smokers'' rights to smoke in public places at the final survey wave. Secondhand smoke exposure declined generally as well as in venues covered by the law, although compliance was incomplete, especially in bars.Conclusions. Comprehensive smoke-free legislation in Mexico City has been relatively successful, with changes in perceptions and behavior consistent with those revealed by studies conducted in high-income countries. Normative changes may prime populations for additional tobacco control interventions.Smoke-free policies can reduce involuntary exposure to toxic secondhand tobacco smoke (SHS), reduce tobacco consumption and promote quitting,^1,2 and shift social norms against smoking.^3–5 These policies are fundamental to the World Health Organization''s Framework Convention on Tobacco Control, an international treaty that promotes best-practices tobacco control policies across the world.⁶Evidence of successful implementation of smoke-free policies generally comes from high-income countries. Low- and middle-income countries increasingly bear the burden of tobacco use,⁷ however, and these countries may face particular challenges in implementing smoke-free policies, including greater social acceptability of tobacco use, shorter histories of programs and policies to combat tobacco-related dangers, and greater tolerance of law breaking.^8–10 There is a need for research that will help identify effective strategies for promoting and implementing smoke-free policies in low- and middle-income countries.Studies in high-income countries generally indicate that popular support for laws that ban smoking in public places and workplaces is strong and increases after such laws are passed.^11–15 Weaker laws that allow smoking in some workplaces can leave policy support unchanged.¹⁶ Policy-associated increases in support have been shown across populations that include smokers^{11,13,14,17,18} and bar owners and staff.^19,20 Beliefs about rights to work in smoke-free environments¹¹ and the health benefits of these environments²¹ have also been shown to increase with policy implementation. Support for banning smoking in all workplaces appears high in Latin American countries,²² but responses to smoke-free policies are less well known. In Uruguay, the first country in the Americas to prohibit smoking in all workplaces, including restaurants and bars,²³ support before the law was unknown. However, the level of support was high among both the general population²² and smokers²⁴ after the law''s implementation.Compliance with smoke-free laws in high-income countries has been good, particularly when laws apply across all workplaces, including restaurants and bars, and involve media campaigns. Self-reported declines in exposure in regulated venues^11,17,25 are consistent with findings from observational studies,^11,26 biomarkers of exposure,^11,25,27 and air quality assessments.^11,12Approximately 26% of Mexican adults residing in urban areas smoke.⁸ Most Mexicans recognize the harms of SHS and support smoke-free policies.^9,24,28,29 According to an opinion poll conducted before the August 2007 passage of a smoke-free law in Mexico City, about 80% of both Mexico City inhabitants and Mexicans in general supported prohibiting smoking in enclosed public places and workplaces.²⁸ In 2006, 60% of smokers reported that their workplace had a smoking ban, with Mexico City smokers reporting the lowest percentage of workplace bans at 37%.²⁴Mexico City''s smoke-free workplace law^30–32 initially allowed for designated smoking areas that were ventilated and physically separate.^22,33 Concerns about the inequity of this law for small business owners who could not afford to build designated smoking areas led the hospitality industry to support a comprehensive smoke-free law^31,32 that prohibited smoking inside all enclosed public places and workplaces, including public transport, restaurants, and bars. This law entered into force on April 3, 2008.Media coverage of the law was similar to that in high-income countries, pitting arguments about the government''s obligation to protect citizens from SHS dangers against arguments about discrimination toward smokers and the “slippery slope” of regulating behavior^4,32,34 (J. F. Thrasher et al., unpublished data, 2010). Most print media coverage was either positive or neutral, with much less coverage pitched against tobacco control policies.³⁴In the month before and after the law came into effect, the Mexico City Ministry of Health and nongovernmental organizations disseminated print materials and aired radio spots describing the dangers of SHS and the benefits of the law.³⁰ Community health promoters informed businesses about the law. From September through December 2008, a television, radio, print, and billboard campaign emphasized the law''s benefits.³⁵ We assessed, among Mexico City inhabitants, the prevalence of and increases in support, beliefs, norms, and compliance around the smoke-free law, as well as decreases in SHS exposure.     

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??Allogeneic-hematopoietic stem cell transplantation??HSCT?? is the most important or even the only radical cure for some primary immunodeficiency diseases. The long-term survival is 90% or even higher with HLA matched sibling donor transplantation. In total??the overall survival for the patients with severe combined immunodeficiency disease??Wiskott-Aldrich sydrome and chronic granulomatous disease is 70%??80% and 90%??respectively. Proper conditioning regimen promotes the success of transplantation??while severe graft versus host disease and reactivation of cytomegalovirus in patients negetively affect the overall survival and life quality after transplantation. This review summerized the rencent advances in allogeneic-HSCT for primary immunodeficiency patients with respect to alternative donor transplantation??conditiong regimen consideration??prevention and treatment of graft versus host disease and reactivation of cytomegalovirus.     

Dorsal intramedullary spinal epidermoid cysts: Report of two cases and review of literature

Intramedullary epidermoid cysts of the spinal cord are rare tumors, especially those not associated with spinal dysraphism. About 50 cases have been reported in the literature. Of these, only seven cases have had magnetic resonance imaging (MRI) studies. We report two cases of spinal intramedullary epidermoid cysts with MR imaging. Both were not associated with spina bifida. In one patient, the tumor was located at D4 vertebral level; while in the other, within the conus medullaris. The clinical features, MRI characteristics and surgical treatment of intramedullary epidermoid cyst are presented with relevant review of the literature.     

Why are children living in poverty getting fatter?

In recent decades, there has been a dramatic increase in unhealthy weight for both children and adults. The Canadian standard of living has changed in favour of more easily prepared, calorie-dense foods and sedentary practices. Many family characteristics have also changed over the past 50 years. More Canadian families are living in disadvantaged situations, forecasting a host of unhealthy behaviours and attitudes in adults. The poor are not only getting poorer, they are also becoming heavier. Children from disadvantaged families seem to be leading the trend in increasing prevalence of unhealthy weight. Because they live in neighbourhoods that are perceived as unsafe, these children are likely spending more time indoors. This is associated with watching more television, which not only displaces other forms of educational and active entertainment but also places them at risk of learning inaccurate information about proper eating. Social science research helps identify factors contributing most to the rise in excess weight within this population, thus providing essential clues for effective approaches to its eradication.     

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??Abstract??Objective To analyze the evolution of disease composition and causes of death in hospitalized children in hospitals of urban Beijing. Methods Medical data of 151 336 hospitalized children in Beijing Children's Hospital and the Sino-Japanese Friendship Hospital aged 0??18 years from 2003 to 2009 were analyzed to summarize changes of disease composition and mortality of each age group and year. According to international nosology ICD-10 classification criteria?? first diagnosis of each child was classified into five catogeries?? communicable diseases?? non-communicable diseases?? perinatal diseases?? injuries and others. Results The first three diseases of hospitalized children were respiratory infection?? congenital malformation and neonatal disease?? the top five single diseases for hospitalization were pneumonia?? inguinal hernia?? cancer?? upper respiratory tract infection and allergic purpura.The top three cause-specific death of hospitalized children were congenital heart disease?? cancer and pneumonia. Congenital heart disease was the first cause of death in infants under the age of 1 year?? while cancer as the first cause of death in more than 1 year old children.The top five diseases of hospitalized children were different in each age group. Conclusion The number of congenital malformations and cancer has significantly increased in hospitalized children in the hospitals of urban Beijing?? but pneumonia still accouns for the most common disease in these children. Congenital heart disease is the first cause of death in infants?? while cancer in more than 1 year old children?? which is basically the same in developed countries.     

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??Abstract??Objective??To explore the characteristics on molecular epidemiology of Mycobacterium tuberculosis isolates in chilidren and to analyse the relationship between drug resistance and genotype. Methods??Totally 150 M.tuberculosis isolated strains were collected from Children's Hospital of Chongqing Medical University and typed by MIRU genotyping.The relationship between genetic type and drug resistance was explored. Results??The 150 strains were divided into 89 distinct MIRU patterns’ and 65 isolates of them were unique. Totally 85 strains were grouped into 24 different MIRU clusters. The MIRU genotype of the largest cluster was 223325173533. Drug resistant M. tuberculosis wasn’t associated with cluster type. Conclusion??223325173533 genotype was perhaps the main epidemic strains for children in Chongqing. Drug-resistance might have no relationship with the clustering genotype.     

Phase I study of epirubicin, cisplatin and capecitabine plus matuzumab in previously untreated patients with advanced oesophagogastric cancer

To evaluate the safety, tolerability, efficacy, pharmacokinetics and pharmacodynamics of the humanised antiepidermal growth factor receptor monoclonal antibody matuzumab combined with epirubicin, cisplatin and capecitabine (ECX) in patients as first-line treatment for advanced oesophagogastric cancer that express epidermal growth factor receptor (EGFR). This was a phase I dose escalation study of matuzumab at 400 and 800 mg weekly and 1200 mg every 3 weeks combined with ECX (epirubicin 50 mg m⁻², cisplatin 60 mg m⁻² on day 1 and capecitabine 1000 mg m⁻² daily). Patients were treated until disease progression, unacceptable toxicity or for a maximum of eight cycles. Twenty-one patients were treated with matuzumab at three different dose levels (DLs) combined with ECX. The main dose-limiting toxicity (DLT) was grade 3 lethargy at 1200 mg matuzumab every 3 weeks and thus 800 mg matuzumab weekly was the maximum-tolerated dose (MTD). Other common toxicities included rash, nausea, stomatitis and diarrhoea. Pharmacokinetic evaluation demonstrated that the coadministration of ECX did not alter the exposure of matuzumab. Pharmacodynamic studies on skin biopsies demonstrated inhibition of the EGFR pathway. Objective response rates of 65% (95% confidence interval (CI): 43–82), disease stabilisation of 25% (95% CI: 11–47) and a disease control rate (CR+PR+SD) of 90% were achieved overall. The MTD of matuzumab in combination with ECX was 800 mg weekly, and at this DL it was well-tolerated and showed encouraging antitumour activity. At the doses evaluated in serial skin biopsies, matuzumab decreased phosphorylation of EGFR and MAPK, and increased phosphorylation of STAT-3.