title stringlengths 0 901 | abstract stringlengths 3 9.89k | PMID int64 22 25.3M | embedding listlengths 768 768 |
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Evaluation of a fully human monoclonal antibody against multiple influenza A viral strains in mice and a pandemic H1N1 strain in nonhuman primates. | Influenza virus is a global health concern due to its unpredictable pandemic potential. Frequent mutations of surface molecules, hemagglutinin (HA) and neuraminidase (NA), contribute to low efficacy of the annual flu vaccine and therapeutic resistance to standard antiviral agents. The populations at high risk of influenza virus infection, such as the elderly and infants, generally mount low immune responses to vaccines, and develop severe disease after infection. Novel therapeutics with high effectiveness and mutation resistance are needed. Previously, we described the generation of a fully human influenza virus matrix protein 2 (M2) specific monoclonal antibody (mAb), Z3G1, which recognized the majority of M2 variants from natural viral isolates, including highly pathogenic avian strains. Passive immunotherapy with Z3G1 significantly protected mice from the infection when administered either prophylactically or 1-2days post infection. In the present study, we showed that Z3G1 significantly protected mice from lethal infection when treatment was initiated 3days post infection. In addition, therapeutic administration of Z3G1 reduced lung viral titers in mice infected with different viral strains, including amantadine and oseltamivir-resistant strains. Furthermore, prophylactic and therapeutic administration of Z3G1 sustained O2 saturation and reduced lung pathology in monkeys infected with a pandemic H1N1 strain. Finally, de-fucosylated Z3G1 with an IgG1/IgG3 chimeric Fc region was generated (AccretaMab® Z3G1), and showed increased ADCC and CDC in vitro. Our data suggest that the anti-M2 mAb Z3G1 has great potential as a novel anti-flu therapeutic agent. | 25,218,949 | [
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Evaluation of levonorgestrel intrauterine system upon presumed nonintact removal. | A 51 year old woman presented for removal of her expired levonorgestrel intrauterine device (IUD). The IUD arms appeared absent upon IUD removal. Further examination of the device revealed that the arms were concealed inside the hormonal cylinder. Recognizing abnormal presentations of the levonorgestrel IUD upon removal can avoid unnecessary procedures. | 25,218,958 | [
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Time and distance to first accident and driving patterns of young drivers with pay-as-you-drive insurance. | We conducted a study of approximately 16,000 drivers under the age of 30 that had purchased a pay-as-you-drive insurance policy, where their risk of being involved in a crash was analyzed from vehicle tracking data using a global positioning system. The comparison of novice vs. experienced young drivers shows that vehicle usage differs significantly between these groups and that the time to the first crash is shorter for those drivers with less experience. Driving at night and a higher proportion of speed limit violations reduces the time to the first crash for both novice and experienced young drivers, while urban driving reduces the distance traveled to the first crash for both groups. Gender differences are also observed in relation to the influence of driving patterns on the risk of accident. Nighttime driving reduces the time to the first accident in the case of women, but not for men. The risk of an accident increases with excessive speed, but the effect of speed is significantly higher for men than it is for women among the more experienced drivers. | 25,218,977 | [
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The role of voltage-operated and non-voltage-operated calcium channels in endothelin-induced vasoconstriction of rat cerebral arteries. | Endothelin-1 has been identified as a potential mediator in the pathogenesis of ischaemic stroke and cerebral vasospasm. The aim of this study was to analyse the role of voltage-operated calcium channels (VOCC) and non-VOCC in endothelin-1 induced vasoconstriction of rat cerebral arteries. Arterial segments were dissected from different regions of the cerebral circulation and responses assessed using wire myography. Endothelin-1 concentration-contraction curves were constructed in calcium-free medium or in the presence of nifedipine, NNC 55-0396 ((1S,2S)-2-(2-(N-[(3-benzimidazol-2-yl)propyl]-N-methylamino)ethyl)-6-fluoro-1,2,3,4-tetrahydro-1-isopropyl-2-naphtyl cyclopropanecarboxylate dihydrochloride) or SK&F 96365 (1-(2-(3-(4-methoxyphenyl)propoxy)-4-methoxyphenylethyl)-1H-imidazole) to inhibit the l-type VOCC, T-type VOCC and non-VOCC, respectively. Inhibition of the calcium channels or removal of calcium from the medium variably decreased the maximum effects (Emax) of endothelin-1, however its potency (pEC50) was unaltered. Endothelin-1 caused a small contraction (<22%) in calcium-free solution. Pre-treatment with nifedipine (1µM) did not affect responses to low concentrations of endothelin-1 but decreased Emax, while NNC 55-0396 (1µM) and SK&F 96365 (30-100µM) generally attenuated the endothelin-1-induced contraction. Combination of nifedipine with SK&F 96365 further decreased the Emax. The relaxant effect of the calcium channel antagonists was also assessed in pre-contracted arteries. Only nifedipine and SK&F 96365 relaxed the arteries pre-contracted with endothelin-1. In conclusion, VOCC and non-VOCC calcium channels are involved in different phases of the endothelin-1 contraction in rat cerebral vessels. T-type VOCC may be involved in contraction induced by low concentrations of endothelin-1, while l-type VOCC mediate the maintenance phase of contraction. VOCC and non-VOCC may work in concert in mediating contraction induced by endothelin-1. | 25,218,985 | [
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Power spectral differences of electrophysiological signals detected at acupuncture points and non-acupuncture points. | In this study, we chose 10 acupoints and non-acupuncture point control groups to see if there are electrical differences between acupoints and non-acupoints. 4 adjacent non-acupoints around each acupoint were chosen as a control group in 400 trials on 10 volunteers aged 23-30 years to characterize the Power Spectral Density of acupoint electrophysiological signals, which means the differences of power and its distribution in frequency. The electrophysiological signals of acupoints and control groups were recorded simultaneously. The results show that acupoint electrophysiological signals have higher Power Spectral Density and power than nearby non-acupoint areas. Integrating the entire data, power of acupoint electrical signals are about 14.7% higher than nearby non-acupoint electrical signals, and most of the higher power is distributed from 0 to 10 Hz and 0-2 Hz is the highest. The maximum power difference between acupoints and non-acupoint is 61.5% appeared in LI 11(see text for symbol). From physiological view, the percentage is high enough to show the electrical specificity of acupoint, which is strong proof of Traditional Chinese Medicine theory and one of the bases for further research. As acupoint electrophysiological signals are driven by internal organs, they can reflect the health condition of internal organs effectively, and so analysis of acupoint electrophysiological signals may be a new way to diagnose organ diseases instead of with the experience of doctor of Traditional Chinese Medicine. | 25,219,030 | [
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[The academician Yuri Pavlovitch Lisytsyn and development of public health in Russia]. | The scientific input of academician Yu.P Lisytsyn into development of social hygiene, public health and history of medicine is discussed. | 25,219,042 | [
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Dual hybrid suite 'a first' for the UK. | A new 6.4 million pounds sterling dual hybrid endovascular theatre suite at the Manchester Royal Infirmary (MRI), which the Central Manchester University Hospitals NHS Foundation Trust (CMFT) says will 'transform the treatment of patients undergoing minimally invasive vascular and cardiac procedures', has recently come into operation. As HEJ editor, Jonathan Baillie, discovered, when he met, a few weeks before its completion, with one of the vascular surgeons who championed it, and the Trust's associate director for Surgical Services, who wrote the business case, the surgical suite makes the MRI the UK's first hospital equipped with two adjacent full hybrid theatres utilising a robotic imaging system, with a fully flexible, synchronised operating table. | 25,219,084 | [
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[NUG--necrotizing ulcerative gingivitis: a review]. | Necrotizing Ulcerative Gingivitis (NUG) is an acute and rare (0.5-11% of the population) infectious disease of the gum tissue, which is characterized by ulceration and inflammation of the inter-dental gum tissue. NUG was documented by historians since the fourth century BC, most of the reports from the ancient world were in the context of illness among fighting troops, present studies of NUG in the modern world are still common among soldiers. NUG is associated with poor oral hygiene and weakening of the host, especially in immunocompromised patients, malnutrition and poor living conditions, as well as in the context of mental stress. NUG is more common in young adults, but reports of morbidity in young children with malnutrition in the background are not uncommon. NUG diagnosis is based on three essential symptoms: sore gums, bleeding gums and the most diagnostic characteristic, ulceration and necrosis of the interdental papillae. The disease is considered to have a clear initial infectious etiology, when the main bacteria, associated with the disease, include: Bacteroides intermedius and Fusobacterium sp. The infection involves anaerobic \ aerobic bacteria with a majority of Gram-negative bacteria. The treatment of NUG is based on combining mechanical removal of tartar with local and systemic delivery of antimicrobial agents. Adequate treatment usually prevent the progression of the disease and ulcer healing is expected in a few days. Nevertheless, lack of treatment can lead to deterioration in the form NUP to Noma. | 25,219,100 | [
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Hypersensitivity reactions to biological drugs. | Strictly speaking, biological drugs are defined as drugs obtained using biotechnology that act on the immune system. They encompass monoclonal antibodies, fusion proteins, and cytokines. Although they are restricted to specific diseases, they have been increasingly used in recent years, with the consequent reporting of adverse reactions, many of which occur during the postmarketing phase. Because of the characteristics of adverse reactions, a new classification has been proposed. Hypersensitivity reactions are beta-type reactions and include infusion reactions and injection site reactions. In some cases, an immune mechanism mediated by IgE, IgG, or T cells is involved. Clinical symptoms vary widely, from skin reactions to anaphylaxis. Diagnostic studies are based on skin tests and in vitro tests (specific IgE, basophil activation test). Most are not standardized and are conducted in small groups of patients, thus making it impossible to obtain sensitivity and specificity values. With some biological drugs, desensitization protocols have proven successful. In this review, we discuss hypersensitivity reactions to biological drugs and the diagnostic tests used to assess these reactions. | 25,219,103 | [
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Oral immunotherapy in children with IgE-mediated wheat allergy: outcome and molecular changes. | IgE-mediated wheat allergy affects around 0.5% of the population, and current management is based on avoidance. We propose an active intervention to promote tolerance in wheat-allergic children. To investigate the efficacy and safety of an oral immunotherapy (OIT) protocol with wheat to treat IgE-mediated wheat-allergic children. Six wheat allergic patients assessed in a double-blind, placebo-controlled food challenge (DBPCFC) underwent wheat OIT with an up-dosing phase until 100 g of wheat was tolerated, followed by a 6-month maintenance phase. Tolerance to rye and oat was evaluated, as were specific IgE (sIgE) to wheat and other cereals and sIgE, slgG4, and sIgG1 to a panel of wheat proteins (alpha-amylase and trypsin inhibitors, wheat lipid transfer proteins, gliadins, and glutenins). Threshold doses in the wheat DBPCFC ranged from 6.6 g to 96.6 g. Five out of 6 (83%) patients successfully finished the up-dosing phase in 3 to 24 days; after a 6-month maintenance phase, all the patients maintained good tolerance of 100 g of wheat daily. Only 6.25% of doses in the up-dosing phase elicited mild adverse reactions. All 5 patients who successfully finished the up-dosing phase tolerated rye after OIT, and all but 1 tolerated oat as well. The median baseline wheat sIgE was 47.5 kU(A)/L, increasing to 84.55 kU(A)/L after up-dosing and decreasing to 28.75 kU(A)/L after 6 months of follow-up. None of the patients showed sIgE to 5-omega-gliadin, but alpha-amylase inhibitors were recognized by all patients. Specific IgG4 and sIgG1 increased in all patients. Our wheat OIT protocol was safe, efficient, and rapid. In our population, alpha-amylase was the major allergen. | 25,219,106 | [
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[Effects of acupuncture intervention on expression of glucose-regulated protein 78 and C/EBP homologous protein in hippocampal CA 1 region in rats with hyperspasmia]. | To observe the effect of acupuncture intervention on expression of glucose-regulated protein 78 (Grp 78) and C/EBP homologous protein (CHOP) in the hippocampus in epilepsy rats so as to explore its mechanism underlying improvement of hyperspasmia-induced brain injury. Forty-two SD rats were randomly divided into normal control group (n = 6), model group (n = 18), and acupuncture group (n = 18). The epileptic seizure model was established by intraperitonel injection of Pentylenetetrazol (50 mg/kg, 2 mL). Manual acupuncture stimulation of "Baihui" (GV 20) and "Dazhui" (GV 14) was conducted for rats of the acupuncture group for 30 min. Two hours (h), 12 h and 48 h after acupuncture intervention, the hippocampal tissue was sampled (6 rats at each time-point). The expression levels of Grp 78 and CHOP proteins in the hippocampal CA 1 region were detected by immunohistochemistry. Compared with the normal group, the expression levels of Grp 78 protein at time-points of 2 h and 12 h, and those of CHOP protein at 2 h, 12 h and 48 h after epilpeptic seizure were significantly increased in the model group (P < 0.01). After acupuncture treatment, the expression levels of Grp 78 at 12 and 48 h were significantly increased, and those of CHOP protein at 2 h, 12 h and 24 h in the acupuncture group were considerably downregulated (P < 0.05, P < 0.01). Acupuncture treatment can up-regulate Grp 78 protein expression and down-regulate CHOP protein expression level in epilepsy rats , which may contribute to its protective effect on seizure-induced brain injury. | 25,219,120 | [
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[Using functional brain imaging technique to study central mechanism of acupuncture therapy for chronic stable angina pectoris in view of heart-brain correlation]. | Heart-brain correlation is an important component of Chinese medicine about the theory of zang-fu organs, which is still valuable for acupuncture clinical practice. Nowadays, increasing evidence supports the close association between the heart-brain axis, central autonomic nerve network and cardiovascular diseases, as well as the extensive regulative effects of acupuncture intervention on the heart-brain axis, functional connectivity of the brain, automatic nerve activities and cardiac functions. Therefore, the authors of the present paper hold that from the viewpoint of the heart-brain relationship, and by combining non-invasive functional brain imaging techniques with the patients' subjective and objective clinical indexes, our researchers will possibly and systematically reveal the underlying central mechanisms of acupuncture therapy in the treatment of chronic stable angina pectoris. However, the concrete biochemical mechanism should be proved via other advanced biological techniques. | 25,219,133 | [
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[The influence of pH and pCO2 levels of umbilical cord blood obtained perinatally on selected parameters of stem cells]. | The aim of the study was to demonstrate a correlation between pH and pCO2 levels in umbilical cord blood and the quality of the harvested material. Additionally the effect of pH and pCO2 on the number of cord blood CD34+ cells and their vitality was analyzed. The study included 50 pregnant women after vaginal delivery at term or elective cesarean section. Umbilical cord blood was collected immediately after birth. The probes were analyzed at the Polish Stem Cell Bank in Warsaw. The number of CD34+ cells ranged from 0.1-0.2 in white blood cells count over 12 thousand/ml and pH of > 7.3. If pH ranged between 7.35-7.40, the number of CD34+ was 0.3-0.4. The highest number of CD34+ cells was noted for pH of 7.30-7.35 and amounted to 0.4-0.5. Analysis of stem cell vitality showed that the highest level, over 98%, was obtained when pH was < 7.3 and > or = 7.4. The study revealed the viability of stem cells to drop to 97-98% at pH level of 7.3-7.4. Low values of CD34+ (0.01-0.09) were related to pCO2 of > 40.0 mmHg. For pCO2 < 38 mmHg, the value of CD34+ cells was 0.2-0.3%, which is relatively high. However when pCO2 was > or = 38 mmHg, the number of CD34+ ranged between 0.1-0.2. Viability of the umbilical cord stem cells increases along with the decrease of pH and pCO2 levels. The mode of delivery does not influence the viability of the stem cells. | 25,219,137 | [
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The -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage. | Genetically determined disturbances in the activity of coagulation factor VII may lead to obstetric complications. The aim of the study was to evaluate the correlation between -323P0/P10 factor VII gene polymorphism and the risk of recurrent miscarriage. The study group consisted of 152 women with a history of > or = 2 miscarriages. The control group comprised 180 women with no history of miscarriage and > or = 1 pregnancy who gave birth to a healthy newborn at term. The study group was further subdivided twice into two subgroups: 1174 patients with a history of 2 miscarriages and 38 subjects with a history of > or = 3 miscarriages, and 123 patients with miscarriages < 13 gw. and 29 with miscarriages < 21 gw. Genetic analysis was performed with the use of PCR/RFLP. Overrepresentation of P0/P0 genotype and lower frequency of P0/P10 genotype was noted in the study group as compared to controls (P0/P0: 80.26 vs. 76.67%, p = 0.25; P0/P10: 18.42 vs. 22.78%, p = 0.20). A higher presentation of P0/P0 genotype and P0 allele, lower frequency of P0/P10 genotype and P10 allele was observed in the subgroup of women with > or = 3 miscarriages as compared to controls (P0/P0: 8.84 vs. 76.67%, p = 0.12; P0: 93.42 vs. 88.06%, p = 0.12; P0/P10:13.16 vs. 22.78%, p = 0.13; P10: 11.94 vs. 6.58%, p = 0.12). The obtained results suggest a probable protective role of -323P10 allele against the risk of miscarriage in women with > or = 3 recurrent pregnancy losses. | 25,219,139 | [
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[Safety of rush allergen-specific immunotherapy in allergic rhinitis patients]. | The safety of rush immunotherapy (RIT) in Chinese allergic rhinitis (AR)patients is unknown. The purpose of this prospective was to assess the safety differences between RIT and conventional immunotherapy in Chinese AR patients, and then discuss the clinical application feasibility of RIT. A one-year study period was set for this study. The enrolled patients were divided into 2 groups according to their preference of therapy: RIT or conventional immunotherapy using standardized house dust mite allergen vaccine. For safety evaluation, the local and systemic adverse reactions were recorded throughout the both groups initial phase. Week 0 (W0), Week 2 (W2), Week 5 (W5), Week 17 (W17) were set as observation time points for leukotriene (LT-B4) and so on. The Generalized Mixed Linear Model with SPSS13. O and the chi-square test with SAS 9. 1.3 were used for Statistics. Fifty-two cases were enrolled into the RIT group, of which 49 patients have completed the established treatment study, and 3 cases were lost to follow-up. In the conventional immunotherapy group, 35 cases were enrolled, of which 32 have completed established treatment study, and 3 cases were lost to follow-up. The local and systemic adverse events of AR RIT appeared to be similar to those of conventional therapy and LT-B4 was descended steadily in the two groups. Processed in advance Chinesear with drugs, RIT is similar to the safety of conventional immunotherapy. | 25,219,200 | [
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[Primary nasopharyngeal tuberculosis presenting as durative aural fullness: one case report and literature review]. | To study the clinical features, diagnosis and treatments of primary nasopharyngeal tuberculosis. A case report was presented, and meanwhile etiopathogenesis and differential diagnosis were also reviewed. A biopsy was taken and the histopathological examination showed tuberculosis granuloma with caseous necrosis. After anti-tuberculosis therapy, the symptoms disappeared. Not only otologic disorders but also nasopharyngeal diseases need to be considered when aural fullness exists. More importantly, primary nasopharyngeal tuberculosis should be taken as one of the differential diagnosis. | 25,219,213 | [
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[Analysis of the level and significance of IL-16 and IL-17 in nasal secretion and in serum of patients with allergic rhinitis and non-allergic rhinitis]. | To test the immunoglobulin free light chain (FLC) from nasal secretion and serum of patients with allergic rhinitis(AR)and non-allergic rhinitis(NAR) for the purpose of exploring the possible immunological mechanism. Ninety consecutive patients were selected between January 2009 and January 2012, involving 45 patients with AR and 45 patients with NAR diagnosed by symptoms,signs,skin prick tests(SPT) and specific IgE (slgE). Forty-five volunteers were chosen as healthy control (HC). According to the visual analogue scale (VAS) scores,the nasal symptoms of AR and NAR,including sneeze. Nasal discharge. Nasal obstruction and nasal itching were compared. ELISA was used to detect the total IgE, IL-16, IL-17 in nasalsecretion and serum. The data was analyzed by SPSS 17.0 software. There was no statistical difference between AR and NAR group in nasal symptoms (P > 0.05); In serum, IL-16 and IL-17 increased in AR group comparared to NAR group (P < 0.05); IL-16 and IL-17 increased in NAR group comparared to HC group (all P < 0.05); In nasal secretion, IL-16 and IL-17 increased in NAR and AR group comparared to HC group (all P < 0.05). IL-16, IL-17 takes part in the path of physiological process of AR and NAR with the immunological mechanism. | 25,219,212 | [
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[Research on increasing X-ray protection capability based on photonic crystal technology]. | Light cannot be propagated within the range of photonic crystal band gaps. Based on this unique property, we proposed a method to improve anti-radiation capability through one-dimensional photonic crystal coating. Using transmission matrix method, we determined the appropriate dielectric materials, thickness and periodic numbers of photonic crystals through Matlab programming simulation. Then, compound one-dimensional photonic crystal coating was designed which was of high anti-radiation rate within the range of X-ray. As is shown through simulation experiments, the reflection rate against X-ray was higher than 90 percent, and the desired anti-radiation effect was achieved. Thus, this method is able to help solve the technical problems facing the inorganic lead glass such as thickness, weightiness, costliness, high lead equivalent, low transparency and high cost. This method has won China's national invention patent approval, and the patent number is 201220228549.2. | 25,219,231 | [
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[Data analysis for relationship between aging and cardiothoracic ratio based on C-V segmentation algorithm]. | Cardiac enlargement is an important symptom of vascular and heart disease. The cardiothoracic ratio (CTR) is an important index used to measure the size of heart. The aim of this study was to assess the relationship between aging and cardiothoracic ratio. This paper also presents an improved C-V level set method to segment lung tissue based on X-ray image, which used to automatically compute CTR. In the investigation carried out in our school, we got more than 3 120 chest radiographs from medical examination of the working population in Beijing, and we systematically studied the effects of age and gender on the CTR to obtain reference values for each group. The reference values established in this study can be useful for recording and quantifying the cardiac enlargement, so that it may be useful for calling attention to the cardiovascular diseases and the heart diseases. | 25,219,232 | [
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[Significant genes extraction and analysis of gene expression data based on matrix factorization techniques]. | It is generally considered that various regulatory activities between genes are contained in the gene expression datasets. Therefore, the underlying gene regulatory relationship and the biologically useful information can be found by modeling the gene regulatory network from the gene expression data. In our study, two unsupervised matrix factorization methods, independent component analysis (ICA) and nonnegative matrix factorization (NMF), were proposed to identify significant genes and model the regulatory network using the microarray gene expression data of Alzheimer's disease (AD). By bio-molecular analyzing of the pathways, the differences between ICA and NMF have been explored and the fact, which the inflammatory reaction is one of the main pathological mechanisms of AD, is also emphasized. It was demonstrated that our study gave a novel and valuable method for the research of early detection and pathological mechanism, biomarkers' findings of AD. | 25,219,254 | [
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[Application of a new design of cryo-jaw and its biomechanical evaluation in rat achilles tendon in vitro]. | This study was aimed to design a new, accurate and easy-to-use water bath cryo-jaw, and try to solve the problems met in small animals achilles tendon mechanical testing. The muscle-tendon-bony units were fixed in the clamps. SD rats achilles tendon were randomly divided into group A and B. Group A was tested by the newly designed water bath cryo-jaw, while group B was treated by non-water bath cryo-jaw. The mechanical tests revealed that non of the samples of the newly-designed water bath cryo-jaw in group A slipped and fell off, and the achilles tendons were in a physiologically active state, but one of the group B samples slipped and fell off, and the others had the frozen phenomenon obviously. The maximum stress, fracture displacement and Young's modulus of the rats in group A were significantly different compared to those in group B (P < 0.05). In conclusion, the new water bath cryo-jaw has more advantages than traditional ones. It exhibits a good simulation in vivo in the environmental conditions for testing the mechanical properties of the achilles tendon. | 25,219,256 | [
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One-Health Simulation Modelling: Assessment of Control Strategies Against the Spread of Influenza between Swine and Human Populations Using NAADSM. | Simulation models implemented using a range of parameters offer a useful approach to identifying effective disease intervention strategies. The objective of this study was to investigate the effects of key control strategies to mitigate the simultaneous spread of influenza among and between swine and human populations. We used the pandemic H1N1 2009 virus as a case study. The study population included swine herds (488 herds) and households-of-people (29,707 households) within a county in Ontario, Canada. Households were categorized as: (i) rural households with swine workers, (ii) rural households without swine workers and (iii) urban households without swine workers. Seventy-two scenarios were investigated based on a combination of the parameters of speed of detection and control strategies, such as quarantine strategy, effectiveness of movement restriction and ring vaccination strategy, all assessed at three levels of transmissibility of the virus at the swine-human interface. Results showed that the speed of detection of the infected units combined with the quarantine strategy had the largest impact on the duration and size of outbreaks. A combination of fast to moderate speed of the detection (where infected units were detected within 5-10 days since first infection) and quarantine of the detected units alone contained the outbreak within the swine population in most of the simulated outbreaks. Ring vaccination had no added beneficial effect. In conclusion, our study suggests that the early detection (and therefore effective surveillance) and effective quarantine had the largest impact in the control of the influenza spread, consistent with earlier studies. To our knowledge, no study had previously assessed the impact of the combination of different intervention strategies involving the simultaneous spread of influenza between swine and human populations. | 25,219,283 | [
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Antifungal Activity of Apple Cider Vinegar on Candida Species Involved in Denture Stomatitis. | To evaluate the in vitro antifungal activity of apple cider vinegar on Candida spp. involved in denture stomatitis. The microdilution technique was used to determine the minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) of apple cider vinegar containing 4% maleic acid, and nystatin (control). Further tests of microbial kinetics and inhibition of adherence to acrylic resin were performed testing different concentrations (MIC, MICx2, MICx4) of the products at time intervals of 0, 30, 60, 120 and 180 minutes. A roughness meter was used to measure the changes in surface roughness; color change of the acrylic resin specimens exposed to the test products in different concentrations and time intervals were also evaluated. Apple cider vinegar (4%) showed MIC of 2500 μg/ml and MFC of 2500, 5000, and 10,000 μg/ml depending on the strain tested. Nystatin showed MIC of 3.125 μg/ml and strain-dependent MFC values ranging from 3.125 to 12.5 μg/ml. The microbial kinetic assay showed a statistical difference between apple cider vinegar and nystatin (p < 0.0001). After 30 minutes of exposure, apple cider vinegar showed fungicidal effect at MICx4, whereas nystatin maintained its fungistatic effect. Apple cider vinegar showed greater inhibition of adherence (p < 0.001) compared to control. Apple cider vinegar did not significantly alter the surface roughness of the acrylic resin specimens compared to nystatin (p > 0.05), and both had no influence on their color. Apple cider vinegar showed antifungal properties against Candida spp., thus representing a possible therapeutic alternative for patients with denture stomatitis. | 25,219,289 | [
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Effects of specific organs on seed oil accumulation in Brassica napus L. | Seed oil content is an important agricultural characteristic in rapeseed breeding. Genetic analysis shows that the mother plant and the embryo play critical roles in regulating seed oil accumulation. However, the overwhelming majority of previous studies have focused on oil synthesis in the developing seed of rapeseed. In this study, to elucidate the roles of reproductive organs on oil accumulation, silique, ovule, and embryo from three rapeseed lines with high oil content (zy036, 6F313, and 61616) were cultured in vitro. The results suggest that zy036 silique wall, 6F313 seed coat, and 61616 embryo have positive impacts on the seed oil accumulation. In zy036, our previous studies show that high photosynthetic activity of the silique wall contributes to seed oil accumulation (Hua et al., 2012). Herein, by transcriptome sequencing and sucrose detection, we found that sugar transport in 6F313 seed coat might regulate the efficiency of oil synthesis by controlling sugar concentration in ovules. In 61616 embryos, high oil accumulation efficiency was partly induced by the elevated expression of fatty-acid biosynthesis-related genes. Our investigations show three organ-specific mechanisms regulating oil synthesis in rapeseed. This study provides new insights into the factors affecting seed oil accumulation in rapeseed and other oil crops. | 25,219,307 | [
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HnRNP-like proteins as post-transcriptional regulators. | Plant cells contain a diverse repertoire of RNA-binding proteins (RBPs) that coordinate a network of post-transcriptional regulation. RBPs govern diverse developmental processes by modulating the gene expression of specific transcripts. Recent gene annotation and RNA sequencing clearly showed that heterogeneous nuclear ribonucleoprotein (hnRNP)-like proteins which form a family of RBPs, are also expressed in higher plants and serve specific plant functions. In addition to their involvement in post-transcriptional regulation from mRNA capping to translation, they are also involved in telomere regulation, gene silencing and regulation in chloroplast. Here, we review the involvement of plant hnRNP-like proteins in post-transcription regulation of RNA processes and their functional roles in control of plant developmental processes especially plant-specific functions including flowering, chloroplastic-specific mRNA regulation, long-distance phloem transportation and plant responses to environmental stresses. | 25,219,311 | [
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Plant regeneration and biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in Hypoxis hemerocallidea organ and callus cultures. | Micropropagation of Hypoxis hemerocallidea Fisch. and C.A. Mey was used as a model system to study the influence of cytokinins (CKs) on plant regeneration and biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in organ and callus cultures and their antioxidant activity. Fourteen free phenolic acids were detected using ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) while antioxidant activity was evaluated using oxygen radical absorbance capacity (ORAC) and 2,2-diphenyl-1-picryl hydrazyl (DPPH) radical scavenging activity. Cytokinins had a significant effect on the biochemical accumulation of hydroxybenzoic and hydroxycinnamic acid derivatives in H. hemerocallidea organ cultures. In particular, meta-topolin-treated organ cultures produced high concentrations of gallic, protocatechuic, gentisic, p-hydroxybenzoic, m-hydroxybenzoic, salicylic, chlorogenic and trans-cinnamic acids. The isoprenoid CK, N(6)-(2-isopentenyl)-adenine significantly increased the accumulation of hydroxycinnamic acid derivatives, namely, caffeic, p-coumaric, sinapic and ferulic acids. Cytokinin-treated organ cultures exhibited a significant increase in antioxidant activity, particularly in the ORAC model. In callus cultures, CKs decreased the concentrations of hydroxycinnamic acid derivatives and antioxidant activity when compared to the control. Overall, both CK type and concentration had a significant effect on plant regeneration, callus proliferation, biochemical accumulation of free phenolic acids and antioxidant activity of the resultant extracts. | 25,219,317 | [
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Beery-Buktenica Developmental Test of Visual-Motor Integration (Beery-VMI): lessons from exploration of cultural variations in visual-motor integration performance of preschoolers. | Visual-motor integration (VMI) is important in children's development because it is associated with the performance of many functional skills. Deficits in VMI have been linked to difficulties in academic performance and functional tasks. Clinical assessment experience of occupational therapists in Singapore suggested that there is a potential difference between the VMI performance of Singaporean and American children. Cross-cultural studies also implied that culture has an influence on a child's VMI performance, as it shapes the activities that a child participates in. The purpose of this study was to (1) explore if there was a difference between the VMI performance of Singaporean and American preschoolers, and (2) determine if there were ethnic differences in the VMI performance of Singaporean preschoolers. The Beery-VMI, which was standardized in America, is commonly used by occupational therapists in Singapore to assess the VMI ability of children. We administered the Beery-VMI (fifth edition) full form test (excluding the supplemental tests) to 385 preschoolers (mean age = 63.3 months) from randomly selected schools in Singapore. We compared the scores of Singaporean preschoolers with those of the American standardization norms using the one-sample t-test. Scores of different ethnic groups among the Singapore population were also compared using a one-way anova, followed by the Bonferroni post-hoc test. Singaporean preschoolers and the standardization sample of American children performed significantly differently in all age groups (P < 0.05). Among the Singapore population, the scores were also significantly different (P < 0.05) between the (i) Chinese and Malay and (ii) Chinese and Indians ethnic groups. Preschoolers from different cultural and ethnic groups had different VMI performance. Certain cultural beliefs and practices may affect VMI performance. Clinicians should exercise caution when using an assessment in communities and cultures outside the ones on which it was standardized. | 25,219,320 | [
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Pharmacokinetic interactions between topiramate and pioglitazone and metformin. | To investigate potential drug-drug interactions between topiramate and metformin and pioglitazone at steady state. Two open-label studies were performed in healthy adult men and women. In Study 1, eligible participants were given metformin alone for 3 days (500 mg twice daily [BID]) followed by concomitant metformin and topiramate (titrated to 100mg BID) from days 4 to 10. In Study 2, eligible participants were randomly assigned to treatment with pioglitazone 30 mg once daily (QD) alone for 8 days followed by concomitant pioglitazone and topiramate (titrated to 96 mg BID) from days 9 to 22 (Group 1) or to topiramate (titrated to 96 mg BID) alone for 11 days followed by concomitant pioglitazone 30 mg QD and topiramate 96 mg BID from days 12 to 22 (Group 2). An analysis of variance was used to evaluate differences in pharmacokinetics with and without concomitant treatment; 90% confidence intervals (CI) for the ratio of the geometric least squares mean (LSM) estimates for maximum plasma concentration (Cmax), area under concentration-time curve for dosing interval (AUC12 or AUC24), and oral clearance (CL/F) with and without concomitant treatment were used to assess a drug interaction. A comparison to historical data suggested a modest increase in topiramate oral clearance when given concomitantly with metformin. Coadministration with topiramate reduced metformin oral clearance at steady state, resulting in a modest increase in systemic metformin exposure. Geometric LSM ratios and 90% CI for metformin CL/F and AUC12 were 80% (75%, 85%) and 125% (117%, 134%), respectively. Pioglitazone had no effect on topiramate pharmacokinetics at steady state. Concomitant topiramate resulted in decreased systemic exposure to pioglitazone and its active metabolites, with geometric LSM ratios and 90% CI for AUC24 of 85.0% (75.7%, 95.6%) for pioglitazone, 40.5% (36.8%, 44.6%) for M-III, and 83.8% (76.1%, 91.2%) for M-IV, respectively. This effect appeared more pronounced in women than in men. Coadministration of topiramate with metformin or pioglitazone was generally well tolerated by healthy participants in these studies. A modest increase in metformin exposure and decrease in topiramate exposure was observed at steady state following coadministration of metformin 500 mg BID and topiramate 100mg BID. The clinical significance of the observed interaction is unclear but is not likely to require a dose adjustment of either agent. Pioglitazone 30 mg QD did not affect the pharmacokinetics of topiramate at steady state, while coadministration of topiramate 96 mg BID with pioglitazone decreased steady-state systemic exposure to pioglitazone, M-III, and M-IV. While the clinical consequence of this interaction is unknown, careful attention should be given to the routine monitoring for adequate glycemic control of patients receiving this concomitant therapy. Concomitant administration of topiramate with metformin or pioglitazone was generally well tolerated and no new safety concerns were observed. | 25,219,351 | [
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First use of the WAVE™ disposable rocking bioreactor for enhanced bioproduct synthesis by N2 -fixing cyanobacteria. | WAVE™ rocking disposable bioreactors have been successfully utilized for bioproduct development from bacteria, yeast, microalgae, and animal and plant cells but not from cyanobacteria so far. N2 -fixing cyanobacteria represent a prolific bioproducts source with reduced cultivation costs. In this study, 1 L cultures of the N2 -fixing cyanobacterium Anabaena siamensis grown diazotrophically in the WAVE™ bioreactor exhibited increased phosphate consumption and 37-70% higher CO2 fixation rates than those grown in conventional bubbled suspension (BS) batch cultures. This generated 40-80% increased biomass productivities in the WAVE™ bioreactor reaching 60 mg L(-1) day(-1) when supplemented with 10% CO2 . Consequently, WAVE™ generated 36-153% more protein, lipid, and carbohydrate than BS, including 47-100% increased productivity of phycocyanin and stearidonic acid (SA) with relevant biomedical applications. While the type of culture system (BS or WAVE(TM) ) did not affect the biochemical profile of cyanobacterial biomass, 10% CO2 supplementation induced a significant decrease in fatty acids and phycocyanin contents (mg g(-1) DW). Therefore, for commercial applications, the CO2 supplementation of WAVE™ should be optimized for each targeted bioproduct separately. This study opens possibilities for upgrading the WAVE™ systems to photobioreactors (PBRs) for bioproduct development from cyanobacteria, with opportunities and challenges critically evaluated herein. | 25,219,374 | [
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Physician payment methods: a focus on quality and cost control. | With rising health care costs, governments must develop innovative methods to deliver efficient and equitable health care services. With physician remuneration being the third largest health care expense, the design of remuneration methods is a priority in health care policy. Otolaryngology-Head and Neck surgeons should have an understanding of the behavioural incentives associated with different physician payment methods. This article will outline the different physician payment methods with a focus on discussing the impact on quality of care and health care costs. | 25,219,382 | [
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Effect of breeding activity on the microflora of the external genitalia and in the semen of stallions, and the relationship between micro-organisms on the skin and on the external genitalia. | A possible role of breeding activities in the composition of the microbial population in stallions' external genitalia (EG) and the relationship between micro-organisms colonizing the skin of the abdomen and the ones colonizing the EG have not been studied. In experiment 1, EG microbiological samples were collected from 41 stallions used for both natural cover and semen collection (BST) and from 18 non-breeding stallions (NBST). A higher (p < 0.05) frequency of isolation of potentially pathogenic species was found for BST. Age did not influence number of micro-organism species isolated both in BST and NBST. In experiment 2, the microbial content of the EG and semen was compared in 23 BST. Most micro-organisms isolated from the EG were present in semen, albeit with a numerically lower prevalence. In 7 stallions, six microbial species isolated from semen were absent from the EG cultures, suggesting contamination by the operator. In experiment 3, a numerically higher number of micro-organism species was isolated from the EG of 31 stallions, than from their skin of the ventral abdomen in contact with the penis or from the skin of the thorax. With the sole exception of Escherichia coli, potentially pathogenic bacteria were only isolated from the EG but not from the skin. Results suggest that breeding activity increased the number of species colonizing the EG; most species isolated from the EG were also found in semen even if with a lower frequency, and additional semen contamination seemed to occur during its manipulation. Many micro-organism species of the skin were also isolated from the penis, but independently of being or not in contact with the penis, skin did not seem to provide an adequate environment for the growth of potentially pathogenic bacteria that were isolated from EG, with the sole exception for E. coli. | 25,219,398 | [
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Anti-transforming growth factor β-induced protein antibody ameliorates vascular barrier dysfunction and improves survival in sepsis. | Sepsis is a systemic inflammatory response syndrome resulting from a microbial infection. Transforming growth factor β-induced protein (TGFBIp) is an extracellular matrix protein expressed by human endothelial cells and platelets that induces sepsis through interaction with integrin αvβ5. The aim of this study was to investigate the role of TGFBIp in vascular permeability and the underlying mechanisms using TGFBIp-neutralizing antibody. Mice were subjected to caecal ligation and puncture (CLP) with or without neutralizing anti-TGFBIp antibody (300 μg kg(-1), intravenously). Wild-type or integrin β5-null mice received TGFBIp (0.1 mg kg(-1), intravenously) or were subjected to CLP. Human umbilical vein endothelial cells were exposed to lipopolysaccharide (100 ng mL(-1)) with or without neutralizing anti-TGFBIp antibody (50 μg mL(-1)). Administration of neutralizing anti-TGFBIp antibody in mice attenuated CLP-induced secretion of TGFBIp, leucocyte migration and vascular permeability and reduced septic mortality. Injected TGFBIp did not enhance vascular barrier permeability or leucocyte migration in β5-null mice. Finally, neutralizing anti-TGFBIp antibody inhibited the specific interactions between TGFBIp and its receptor, integrin αvβ5. Our findings demonstrate that treatment with a TGFBIp-neutralizing antibody can ameliorate the deleterious effects of sepsis. | 25,219,400 | [
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Blood pressure reference values for European non-overweight school children: the IDEFICS study. | To provide oscillometric blood pressure (BP) reference values in European non-overweight school children. Cross-sectional analysis from the IDEFICS study (www.ideficsstudy.eu) database. Standardised BP and anthropometric measures were obtained from children aged 2 to 10.9 years, participating in the 2007-2008 and 2009-2010 IDEFICS surveys. Age- and height-specific systolic and diastolic pressure percentiles were calculated by GAMLSS, separately for boys and girls, in both the entire population (n=16,937) and the non-overweight children only (n=13,547). The robustness of the models was tested by sensitivity analyses carried out in both population samples. Percentiles of BP distribution in non-overweight children were provided by age and height strata, separately for boys and girls. Diastolic BP norms were slightly higher in girls than in boys for similar age and height, while systolic BP values tended to be higher in boys starting from age 5 years. Sensitivity analysis, comparing BP distributions obtained in all children with those of non-overweight children, showed that the inclusion of overweight/obese individuals shifted the references values upward, in particular systolic BP in girls at the extreme percentiles. The present analysis provides updated and timely information about reference values for BP in children aged 2 to <11 years that may be useful for monitoring and planning population strategies for disease prevention. | 25,219,411 | [
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Competitive direct vs. indirect photochromism dynamics of constrained inverse dithienylethene molecules. | State-of-the-art experimental and theoretical tools were used to investigate the gas-phase relaxation dynamics of various photoexcited photochromic dithienylethene molecules in situations where several relaxation channels are simultaneously at play. Unconstrained and constrained dynamics were addressed by considering unbridged and bridged molecules with a polyether bridge of various sizes (from 2 to 4 units). Time-resolved ultrafast ionization spectroscopy techniques were used to probe the dynamics. This revealed the existence of several relaxation pathways from the first excited state to the ground-state. Characteristic times were determined for each process. These channels compete at an early stage of the dynamics only when the initial wavepacket splits into two parts. A striking excited state wavepacket oscillation is observed in bridged molecules. A general reaction mechanism is proposed which rationalizes the carbon-carbon distance rule which is widely used as an empirical tool to predict the photoactivity of photochromic molecules in crystals. | 25,219,416 | [
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How does an undergraduate pain course influence future physicians' awareness of chronic pain concepts? A comparative study. | Pain is one of the most undertreated medical complaints, with barriers to effective pain management lying in poor education of health professionals and misconceptions regarding patients in pain. The aim of this study was to assess whether an elective undergraduate course on chronic pain offered in Greek medical schools influences knowledge and attitudes of medical undergraduates about chronic pain and helps them clarify pain-related concepts. An electronic questionnaire with 6 demographic and 21 pain-related items was uploaded on SurveyMonkey. The questionnaire was open to medical students in every Greek medical school for 1 month. Students were asked to respond to questions regarding various aspects of pain taught in the aforementioned course. In specific, they were asked to respond to questions regarding the definition, types, and adequacy of treatment of chronic cancer and non-cancer pain. They were queried about their knowledge of pain clinics, health practitioners who run them, and types of treatment available there. There were also questions about opioid use in cancer and non-cancer chronic pain patients and regarding the likelihood of opioid addiction. According to their responses, medical students had good knowledge about the definition and consequences of pain, and those who attended the pain course had greater knowledge regarding the adequacy of treatment of chronic pain and were more familiar with the recent classification of types of pain. Students who did not have exposure to the undergraduate pain course had little information regarding pain clinics and had poor knowledge regarding the use of opioids in cancer and in nonmalignant chronic pain. All students expressed concerns regarding addiction to opioids. Although students enter medical school with little knowledge about pain issues, pain awareness can be positively influenced by education. A curriculum about pain should not only teach the basic science of pain but also present treatment strategies available and address the socio-emotional dimensions of pain. Additionally, if misconceptions about opioid use and addiction are properly elucidated early in medical education, the future health practitioners will be one step forward in achieving the goal of alleviating suffering patients' pain. | 25,219,419 | [
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The STRIDE weight loss and lifestyle intervention for individuals taking antipsychotic medications: a randomized trial. | The STRIDE study assessed whether a lifestyle intervention, tailored for individuals with serious mental illnesses, reduced weight and diabetes risk. The authors hypothesized that the STRIDE intervention would be more effective than usual care in reducing weight and improving glucose metabolism. The study design was a multisite, parallel two-arm randomized controlled trial in community settings and an integrated health plan. Participants who met inclusion criteria were ≥18 years old, were taking antipsychotic agents for ≥30 days, and had a body mass index ≥27. Exclusions were significant cognitive impairment, pregnancy/breastfeeding, recent psychiatric hospitalization, bariatric surgery, cancer, heart attack, or stroke. The intervention emphasized moderate caloric reduction, the DASH (Dietary Approaches to Stop Hypertension) diet, and physical activity. Blinded staff collected data at baseline, 6 months, and 12 months. Participants (men, N=56; women, N=144; mean age=47.2 years [SD=10.6]) were randomly assigned to usual care (N=96) or a 6-month weekly group intervention plus six monthly maintenance sessions (N=104). A total of 181 participants (90.5%) completed 6-month assessments, and 170 (85%) completed 12-month assessments, without differential attrition. Participants attended 14.5 of 24 sessions over 6 months. Intent-to-treat analyses revealed that intervention participants lost 4.4 kg more than control participants from baseline to 6 months (95% CI=-6.96 kg to -1.78 kg) and 2.6 kg more than control participants from baseline to 12 months (95% CI=-5.14 kg to -0.07 kg). At 12 months, fasting glucose levels in the control group had increased from 106.0 mg/dL to 109.5 mg/dL and decreased in the intervention group from 106.3 mg/dL to 100.4 mg/dL. No serious adverse events were study-related; medical hospitalizations were reduced in the intervention group (6.7%) compared with the control group (18.8%). Individuals taking antipsychotic medications can lose weight and improve fasting glucose levels. Increasing reach of the intervention is an important future step. | 25,219,423 | [
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[Temporal-spatial scan clustering analysis on hand-foot-mouth disease in Zhejiang province, 2008-2013]. | To understand the temporal-spatial distribution of hand-foot-mouth disease in Zhejiang province, from May 2008 to June 2013. The cases number and incidence data of hand-foot-mouth disease from May 2008 to June 2013 for all the counties(cities, districts) in Zhejiang province were collected from China Information System for Disease Control and Prevention, total 511 643 cases. Temporal distribution of hand-foot-mouth disease was described, the incidence maps were drawn using Epimap software. Temporal-spatial clustering was analyzed by Satscan 9.0.1 software.Log likelihood ratio(LLR) was used to assess the clustering. The year-county (city, district)-specific relative risk(RR) of hand-foot-mouth disease were calculated. RR contour maps were drawn with Arcview GIS 3.3. In Zhejiang province, from May 2008 to June 2013, the highest incidence rate was 270.81/100 000 (147 943/54 629 996) (2012 year) and the lowest incidence rate was 135.32/100 000 (69 285/51 199 987) (2009 year). The incidence in the eastern coastal areas (217.77/100 000(286 300/131 468 746)) including Ningbo, Taizhou, Wenzhou, was higher than the western mountain areas(168.11/100 000(98 016/58 304 266)) including Quzhou, Lishui, Jinhua. The epidemic curve showed two peaks, during April to July (101.15/100 000(320 144/316 497 516)) , and during October to November (23.30/100 000 (61 088/262 148 114)) . of temporal-spatial scan showed 10 temporal spatial aggregation areas, the strongest one was in Wenzhou city, south-east Zhejiang province, from July 2009 to June 2011(RR = 2.38, LLR = 10 650.75, P < 0.01). The relative risk maps from 2009 to 2012 were similar, the highest density areas were located in the eastern coastal Zhejiang: Longwan district, Wenzhou city (RR = 4.42 and 3.30) in 2009 and 2010 year, Pingyang county, Wenzhou city(RR = 3.04) in 2011 year, and Ninghai county, Ningbo city(RR = 2.97) in 2012. The eastern coastal area had a high incidence level of hand-foot-mouth disease in Zhejiang province, 2008-2013, with the peak during April to July. Temporal-spatial clustering were observed, the disease showed a distinct regional distribution feature, eastern coastal cluster areas and mid-west cluster areas were found. | 25,219,431 | [
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[Analysis of death causes among infants in Guangzhou from 2010 to 2013]. | To analyze the main death causes among infants in Guangzhou in 2010-2013 and to provide an objective and scientific basis for risk communication of public health emergencies in the future. Descriptive epidemiological method was used to analyze the death causes among infants reported in Guangzhou from the National Death Registration Reporting Information System. The death causes among infants were classified by the 10th international classification of diseases (ICD-10). The constitution and rank order of death causes among infants were analyzed according to the underlying causes of deaths. A total of 4 880 cases of infant deaths were reported in Guangzhou from 2010 to 2013 and infant deaths in floating population were 1.8 (3 135/1 745) times of registered population. The deaths of male infants were 1.73 (3 094/1 786) times of female infants. The neonatal group accounted for 52.32% (2 553/4 880) of total infant deaths and early neonatal group accounted for 64.86% (1 656/2 553) of total neonatal deaths. The top five causes of infant deaths followed by perinatal diseases, congenital malformations, respiratory diseases (mainly pneumonia), accidental deaths and communicable diseases. The mortality ratios were respectively 44.12% (2 153 cases) , 24.73% (1 207 cases), 6.86% (335 cases), 3.48% (170 cases), 3.01% (147 cases) , and no vaccine-related death case was reported. The primary cause of infant deaths in Guangzhou 2010-2013 was perinatal diseases. | 25,219,438 | [
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[Analysis of trends and characteristics of mortality of ischemic heart disease over the age of 35 years old in China, 2004-2011]. | To analyze the features of distribution and variation trends of mortality of ischemic heart disease over the age of 35 years old in China, 2004-2011. A total of 493 274 cases were recruited in the study, the mortality data of the ischemic heart diseases were collected from the national disease surveillance point (DSP) system between 2004 and 2011. The change of ischemic heart disease standardized mortality was described, and the annual change percentage of age group mortality and standardized mortality were analyzed using log linear regression method. In 2004-2011, the standardized mortality of ischemic heart disease over the age of 35 showed an upward trend in each regions of China.In 2004, the ischemic heart disease standardized mortality over the age of 35 was 176.2/100 000 among males and 131.7/100 000 among females in urban areas, and the figures increased to 204.6/100 000 and 147.9/100 000 respectively in 2011.In 2004, the ischemic heart disease standardized mortality over the age of 35 was 164.4/100 000 among males and 122.2/100 000 among females in rural areas, and the figures increased to 236.8/100 000 and 151.5/100 000 respectively in 2011. The ischemic heart disease standardized mortality was lower in rural regions than in urban regions in 2004, but it changed to be higher in rural regions than in urban regions in 2011 both in males and female. The annual growth rate of ischemic heart disease mortality over the age of 35 was separately 5.00% in male and 3.65% in female. The annual growth rate was highest among males in rural areas (7.09%), followed by females in rural areas (5.06%). The growth rate was lowest among females in urban areas (1.69%).It was found that the increasing trends of ischemic heart disease mortality of males both in urban and rural areas, and females in rural areas was statistically significant (P < 0.05). The mortality of ischemic heart disease has still been showing an uprising trend, especially in the rural areas. | 25,219,440 | [
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[Application of multi-level model in study of relationship between soil cadmium contamination and people's urinary cadmium level]. | Based on the characteristics of hierarchical data, a multilevel model was used to analysis possible influencing factors of urinary cadmium levels in one county population, and to discuss the advantages of multilevel model for processing hierarchical data in practical problems. In May 2013, 1 460 participants aged 20 and above in 12 administrative villages in one county in central China were recruited by cluster sampling. Urinary cadmium level and its possible influencing factors were investigated, and cadmium level in farmland soil of survey area was also tested. A total of 1 410 participants completed the survey and met the inclusion criterion. 318 farmland samples in survey area were detected. According to the data, individuals were set as the level one unit, and the village was set as level two unit. the data were analyzed by MIXED procedure for hierarchical data of SAS 9.3 software. In the case of not considering the hierarchy of data, the general linear model was fitted by SAS 9.3 software, and the fitting results of the two models were compared. A total of 1 410 participants were included finally, the age was (55.2 ± 11.1) years. 645 (45.74%) were males and 765 (54.26%) were females. The amount of household per capita consumption of rice was (100.9 ± 40.3) kg/y. All 18.65% (262/1 410) of the participants had mining and mineral separation work experience. The urinary cadmium level was (9.39 ± 2.16) µg/g Cr. Most of the soil cadmium levels in villages were greater than tolerance value. The fitting results of general linear model suggested that whether doing mining and mineral separation work does not have significant difference (χ(2) = 1.05, P = 0.305). There was significant difference in the village soil cadmium levels, age, the amount of household per capita consumption of rice, and gender (χ(2) = 401.39, 34.9, 4.16 and 86.15, respectively, P < 0.01, <0.01, 0.041, <0.01, respectively). The fitting result of empty model showed the ICC was 0.435 5, the urinary cadmium had clustering at village level. The results of multilevel model showed that the explanatory variables of the village soil cadmium levels, age, the amount of household per capita consumption of rice and gender had significant difference (Wald χ(2) values 2.55, 6.34, 2.37 and 10.32, respectively, P = 0.029, <0.01, = 0.018 and <0.01), while whether doing mining and mineral separation work had no significant difference (χ(2) = 0.78, P = 0.438). To the fitting optimization index using for the comparison of models, the results of multilevel model were less than that of general linear model. The regression coefficient of level-2 explanatory variable (the village soil cadmium levels) was 0.84, which could explain the 35.26% of the total variance. Multilevel model could analyze hierarchical data more reasonably than general linear model. Urinary cadmium levels is highly influenced by the village soil cadmium levels. | 25,219,442 | [
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High frequency of posterior and combined shoulder instability in young active patients. | The purpose of this study was to describe the epidemiology and demographics of surgically treated shoulder instability stratified by direction. We hypothesized that there would be an increased frequency of posterior and combined shoulder instability in our population compared with published literature. Secondarily, we assessed preoperative magnetic resonance imaging (MRI) reports to determine how accurately they detected the pathology addressed at surgery. A retrospective review was conducted at a single facility during a 46-month period. The study included all patients who underwent an operative intervention for shoulder instability. The instability in each case was characterized as isolated anterior, isolated posterior, or combined, according to pathologic findings confirmed at arthroscopy. The findings were retrospectively compared with official MRI reports to determine the accuracy of MRI in characterizing the clinically and operatively confirmed diagnosis. A consecutive series of 231 patients (221 men, 10 women) underwent stabilization for shoulder instability over 46 months. Patients were a mean age of 26.0 years. There were 132 patients (57.1%) with isolated anterior instability, 56 (24.2%) with isolated posterior instability, and 43 (18.6%) with combined instability. Overall, MRI findings completely characterized the clinical diagnosis and arthroscopic pathology in 149 of 219 patients (68.0%). The rate of posterior and combined instability in an active population is more common than has been previously reported, making up more than 40% of operatively treated instability, including a previously unreported incidence of 19% for combined instabilities. In addition, MRI was often incomplete or inaccurate in detecting the pathology eventually treated at surgery. | 25,219,471 | [
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Sensitization of ethanol-induced place preference as a result of up-regulation of type 1 inositol 1,4,5-trisphosphate receptors in mouse nucleus accumbens. | This study involved mice that received 4 days of ethanol (EtOH) vapor inhalation and then were assessed for type 1 inositol 1,4,5-trisphosphate receptor (IP3 Rs-1) expression and the development of EtOH-induced place preference at various time points in withdrawal. IP3 R-1 protein was found to be significantly increased in the nucleus accumbens (NAcc) of mice immediately after 4-day EtOH vapor inhalation, while it significantly reduced to the control level during the next 3 days of withdrawal from EtOH inhalation. EtOH (2 g/kg, i.p.)-induced place preference after 3 days of withdrawal from EtOH vapor inhalation increased dose dependently for 4 days, which was significantly inhibited by 2-aminophenoxyethane-borate, an antagonist for IP3 Rs. EtOH conditioning significantly increased, compared to alcohol-naïve control mice, both IP3 R-1 protein and the release of dopamine in the NAcc of mice after 3 days of withdrawal from EtOH vapor inhaled for 4 days, and this increase of IP3 R-1 protein was completely abolished by intracerebroventricular injection of FK506, an inhibitor for calcineurin. These results indicate that the sensitization of EtOH-induced place preference is due to up-regulated IP3 R-1 via calcineurin-mediated pathway after enhanced release of dopamine in the NAcc on EtOH administration during EtOH conditioning. We revealed signal transduction pathways that may promote sensitization of ethanol (EtOH)-induced place preference. EtOH facilitated the release of dopamine (DA) in the Nucleus accumbens (NAcc), enhancing calcineurin function via dopamine D1-like and D2-like receptor activation, which in turn resulted in increased NFATc4 expression. Increase in NFATc4 may further facilitate transcription factor binding to IP3 R-1 promoter domain to stimulate IP3 R-1 synthesis. Such increased IP3 R-1 elevates intracellular Ca(2+) concentration via facilitated mobilization of Ca(2+) from the intracellular Ca(2+) stores to the cytosol. | 25,219,476 | [
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Relaparotomy in colorectal cancer surgery--do any factors influence the risk of mortality? A case controlled study. | Identification of the incidence of relaparotomy after operations for colorectal cancer and finding out factors influencing the incidence of relaparotomy and risk of mortality. In the period from 2008 to 2012 the group of patients electively operated on for colorectal cancer was analysed. The database of the surgical department was reviewed retrospectively to search relaparotomies performed in perioperative period. We compared the risk of mortality and of reoperations according to clinical and demographic pre- and postoperative factors, tumour location and extend of surgery. The group of 1674 patients was electively operated on for colorectal cancer and 121 (7.2%) relaparotomies were identified and analysed (77 males, 44 females, mean age of 65.1). In the whole group the risk of relaparotomy was higher in males OR 1.68; 95%CI 1.15-2.47; p = 0.008 and in patients with ASA III/IV OR 1.54; 95% CI 1.05-2.27; p = 0.027. The overall mortality rate was higher in patients after relaparotomy than after the only initial procedure 13.2% vs. 1.4%; with higher risk of mortality OR 9.78; 95%CI 4.97-19.29; p = 0.0008. The rate of anastomotic leak requiring reoperation was 2.7%. In resection procedures the incidence of reoperation was significantly higher 8.1% vs. 3.5%; p = 0.007, without any influence on mortality OR 0.7; 95%CI 0.14-3.49; p = 0.656. In reoperated patients mortality rate was the highest if the tumour was primary located in left colon than in the rectum an right colon (44.4% vs. 10.9% vs. 6.7%; p = 0.04). Anastomotic leak significantly increased the risk of mortality OR 2.95; 95%CI 1.00-8.39; p = 0.048. The risk of mortality was also higher in patients at age >65 OR 7.70; 95%CI 1.67-35.57; p = 0.009 and when ASA score was III or IV OR 5.83; 95%CI 1.58-21.60; p = 0.008. Patients after relaparotomy for complications of colorectal cancer surgery are at very high risk of mortality. Particularly male gender, older age, poor general condition and anastomotic complications are the risk factors of high mortality. | 25,219,479 | [
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An electric-field assisted growth control methodology for integrating ZnO nanorods with microstructures. | The growth control of ZnO nanorods bridging over two microelectrodes in a three-electrode structure (the top cathode and anode, and the bottom gate) was realized using a wet chemical method with the assistance of an electric field generated by applying AC sine wave power on the top electrodes and a DC voltage on the bottom gate. A numerical control model for controlling the growth position, direction and density of ZnO nanorods on the microstructure was established based on the simulation of the electric-field distribution around the microstructures. The three input parameters in the numerical control model were defined as the peak-to-peak voltage of the AC sine wave (x1), the frequency of the AC sine wave (x2) and gate voltage (x3). Moreover, five output parameters (y1, y2, y3, y4, y5) in the model were defined as the electric field intensities at specific points on the electrodes to characterize the growth rate, direction, position and morphology of the ZnO nanorods integrated with the microelectrodes. The relationship between the defined outputs and inputs were established using 3(rd) polynomial fitting, which served as the numerical control model for the prediction of nanorod growth. The experimental results validated that growth control methodology provides us with an effective approach to integrate ZnO nanorods into devices. | 25,219,487 | [
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The serotonin transporter genotype modulates the relationship between early stress and adult suicidality in bipolar disorder. | Bipolar disorder (BD) is associated with a higher risk of suicide and with worse early life stress. A serotonin (5-hydroxytryptamine; 5-HT) transporter-linked polymorphic region (5-HTTLPR) has been shown to influence the relationship between stress and the risk of attempting suicide in the general population, but has not been investigated in BD. We studied 136 inpatients (93 females, 43 males) with a major depressive episode in the course of BD. Early and recent stressful life events were scored on the Social Readjustment Rating Scale (SRRS). Regional gray matter (GM) volumes were analyzed, acquiring T1-weighted images on a 3.0 Tesla scanner. Homozygote l/l patients attempted suicide in a higher proportion than *s carriers. A separate-slopes logistic regression showed a significant effect of 5-HTTLPR on the relationship between stress, depression, and suicide among *s carriers, but not among l/l homozygotes, early stress associated with worse probability of attempting suicide and with earlier age at onset of BD. Exposure to early stress correlated with GM volumes in the right prefrontal cortex (Brodmann area 46) - again, in *s carriers only. 5-HTTLPR modulated the relationship between early life stress and the core features of bipolar illness. 5-HTTLPR*s carriers showed a higher sensitivity to the effects of stress; when exposed to low levels of early stress, they were protected against suicide in respect to l/l, but higher levels of stress progressively increased their risk of suicide and reduced the age at onset of illness. | 25,219,494 | [
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WT1 expression in endocrine mucin-producing sweat gland carcinoma: a study of 13 cases. | Endocrine mucin-producing sweat gland carcinoma (EMPSGC), a low-grade sweat gland carcinoma with a predilection for the eyelids, often shows areas of benign eccrine cysts, atypical intracystic proliferation and associated mucinous carcinoma, suggesting tumor progression. Wilms tumor 1 (WT1) protein, a transcription factor, is overexpressed in many tumors and plays a role in oncogenesis. A computer-based search for tumors diagnosed between 1989 and 2009 was conducted. Clinical data were obtained from pathology reports and patient records. Biopsies were reviewed for histologic features. Immunostaining was performed for WT1, chromogranin, synaptophysin, estrogen receptor (ER), epithelial membrane antigen (EMA), polyclonal carcinoembryonic antigen (P-CEA), cytokeratin 7 (CK7), cytokeratin 20 (CK20) and MIB-1. Eight women and five men (mean age: 61.2 years; range: 40-77 years) presented with slow-growing eyelid nodules. Cases of EMPSGC were characterized by the presence of dermal nodules with various growth patterns. Adjacent eccrine cysts were present in five patients, atypical epithelial proliferation within the cyst wall in four patients, and an associated mucinous carcinoma in one patient. All tumors were positive for WT1, CK7, ER, P-CEA and EMA and negative for CK20. Tumors were positive for synaptophysin in 12 cases and chromogranin in nine cases. The MIB-1 proliferation index was low in most cases. No WT1 staining was observed in the overlying epidermis, adnexal structures or areas of benign eccrine cyst. WT1 expression was observed in areas of atypical epithelial proliferation, and the neoplastic cells. The present study shows WT1 expression in the neoplastic epithelial cells of EMPSGC, areas of atypical intraductal proliferations, and mucinous carcinoma. The absence of WT1 expression in areas of benign eccrine cyst and cutaneous sweat glands suggests WT1 upregulation plays a role in tumor cell proliferation and progression of EMPSGC. | 25,219,513 | [
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Origin of high photoconductive gain in fully transparent heterojunction nanocrystalline oxide image sensors and interconnects. | A technique for invisible image capture using a photosensor array based on transparent conducting oxide semiconductor thin-film transistors and transparent interconnection technologies is presented. A transparent conducting layer is employed for the sensor electrodes as well as interconnection in the array, providing about 80% transmittance at visible-light wavelengths. The phototransistor is a Hf-In-Zn-O/In-Zn-O heterostructure yielding a high quantum-efficiency in the visible range. | 25,219,518 | [
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Deep sequencing of the ancestral tobacco species Nicotiana tomentosiformis reveals multiple T-DNA inserts and a complex evolutionary history of natural transformation in the genus Nicotiana. | Nicotiana species carry cellular T-DNA sequences (cT-DNAs), acquired by Agrobacterium-mediated transformation. We characterized the cT-DNA sequences of the ancestral Nicotiana tabacum species Nicotiana tomentosiformis by deep sequencing. N. tomentosiformis contains four cT-DNA inserts derived from different Agrobacterium strains. Each has an incomplete inverted-repeat structure. TA is similar to part of the Agrobacterium rhizogenes 1724 mikimopine-type T-DNA, but has unusual orf14 and mis genes. TB carries a 1724 mikimopine-type orf14-mis fragment and a mannopine-agropine synthesis region (mas2-mas1-ags). The mas2' gene codes for an active enzyme. TC is similar to the left part of the A. rhizogenes A4 T-DNA, but also carries octopine synthase-like (ocl) and c-like genes normally found in A. tumefaciens. TD shows a complex rearrangement of T-DNA fragments similar to the right end of the A4 TL-DNA, and including an orf14-like gene and a gene with unknown function, orf511. The TA, TB, TC and TD insertion sites were identified by alignment with N. tabacum and Nicotiana sylvestris sequences. The divergence values for the TA, TB, TC and TD repeats provide an estimate for their relative introduction times. A large deletion has occurred in the central part of the N. tabacum cv. Basma/Xanthi TA region, and another deletion removed the complete TC region in N. tabacum. Nicotiana otophora lacks TA, TB and TD, but contains TC and another cT-DNA, TE. This analysis, together with that of Nicotiana glauca and other Nicotiana species, indicates multiple sequential insertions of cT-DNAs during the evolution of the genus Nicotiana. | 25,219,519 | [
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Characterization of the starvation-induced chitinase CfcA and α-1,3-glucanase AgnB of Aspergillus niger. | The common saprophyte Aspergillus niger may experience carbon starvation in nature as well as during industrial fermentations. Starvation survival strategies, such as conidiation or the formation of exploratory hyphae, require energy and building blocks, which may be supplied by autolysis. Glycoside hydrolases are key effectors of autolytic degradation of fungal cell walls, but knowledge on their identity and functionality is still limited. We recently identified agnB and cfcA as two genes encoding carbohydrate-active enzymes that had notably increased transcription during carbon starvation in A. niger. Here, we report the biochemical and functional characterization of these enzymes. AgnB is an α-1,3-glucanase that releases glucose from α-1,3-glucan substrates with a minimum degree of polymerization of 4. CfcA is a chitinase that releases dimers from the nonreducing end of chitin. These enzymes thus attack polymers that are found in the fungal cell wall and may have a role in autolytic fungal cell wall degradation in A. niger. Indeed, cell wall degradation during carbon starvation was reduced in the double deletion mutant ΔcfcA ΔagnB compared to the wild-type strain. Furthermore, the cell walls of the carbon-starved mycelium of the mutant contained a higher fraction of chitin or chitosan. The function of at least one of these enzymes, CfcA, therefore appears to be in the recycling of cell wall carbohydrates under carbon limiting conditions. CfcA thus may be a candidate effector for on demand cell lysis, which could be employed in industrial processes for recovery of intracellular products. | 25,219,534 | [
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[Enhancement of gastric cancer MKN28 cell line radiosensitivity induced by β-elemene]. | To study radiation-enhancing effects on human gastric cancer MKN28 cell line and underlying mechanisms of β-elemene. Inhibition of MKN28 cell proliferation at different concentrations of β-elemene was assessed using the methyl thiazolyl blue colorimetric method (MTT method), with calculation of IC50 value and choice of 20% of the IC50 as the experimental drug concentration. Irradiation group and β-elemene+irradiation group were established, and the cell survival fraction (SF) was calculated from flat panel colony forming analysis, and fitted by the 'multitarget click mathematical model'. Draw the survival curve and get the radiobiological parameters D0, Dq, SF2, N and SER. Flow cytometry (FCM) was used to detect changes in the cell cycle and cell apoptosis rates was detected by Annexin-V/PI assay. β-elemene exerted inhibitory effects on proliferation of gastric cancer MKN28 cells, with an IC50 of 45.6 mg/L and we chose 8 mg/L as the experimental concentration. The cell survival fraction of MKN28 cells with irradiation decreased significantly after treated with β-elemene; D0, Dq decreased, SER = 1.3. After combined treatment of β-elemene+irradiation, the results of FCM showed that cells could be arrested in the G2/M phase and the cell apoptosis increased significantly. β-elemene can enhance the radiosensitivity of gastric cancer MKN28 cell line. Mechanistically, β-elemene mainly influences the cell cycle distribution of MKN28 cells by inducing G2/M phase arrest, inhibits the repair of sublethal damage and induces cell apoptosis to enhance the killing effects of radioactive rays. | 25,219,560 | [
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Relationships between obesity management and depression management in a university-based family medicine center. | The purpose of this study is to describe and examine relationships among sociodemographics, obesity, and depression management in Appalachian adults. This study was conducted in a primary care center and used a cross-sectional, quantitative, nonexperimental descriptive, and predictive design. Data were obtained from a random sample of 240 adult records that were stratified by gender. Analysis included exploration of all variables for descriptive information followed by bivariate analyses to determine significant relationships between variables, and regression analysis using variables with significant relation to obesity and depression management. Obesity was prevalent (48%) though less than 1% had documented diagnosis. Over 98% of the 65 participants diagnosed with depression did not have documentation of use of a depression screening tool. Diagnosis of depression correlated significantly with elevated body mass index (BMI) and diagnosis of obesity. Gender bias was evident with males having more documentation of weight-loss discussions and planning, and women receiving more referrals to behavioral health for counseling. Innovations to enhance the diagnosis of obesity could lead to consistent provider-led management. Implementation studies of valid depression screening tools in the electronic medical record could enhance the identification of depressive symptoms and could promote health equity. | 25,219,571 | [
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Shape analysis of the proximal humerus in orthograde and semi-orthograde primates: correlates of suspensory behavior. | "Suspensory locomotion" is an expression that encompasses a series of specialized forms of locomotion that mainly orthograde primates use to achieve below-branch traveling. It implies a number of features in the entire body associated with the use of the forelimb in overhead positions. The glenohumeral joint is one of the main joints involved in effective suspensory locomotion, being subject to a delicate balance between the high degree of mobility and stabilization needed to successfully engage in suspensory behaviors. Here, we present a 3D geometric morphometric study that explores the form of the proximal humerus of six orthograde and semi-orthograde genera (Hylobates, Pongo, Pan, Gorilla, Ateles, and Lagothrix) and a pronograde genus, Colobus, to determine to what extent suspensory locomotor requirements are driving the shape of this epiphysis. Results show the presence of a morphocline related to degree of suspension in the shape of the articular surface, with highly suspensory taxa (i.e., Hylobates) exhibiting particular morphological traits at the articular surface that provide a greater range of circumduction. The placement and orientation of the rotator cuff muscles' insertion sites on the tubercles appear associated with the divergent forces operating at the joint in quadrupedal or above-head use of the hand. | 25,219,580 | [
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A genetic analysis of the validity of the Hypomanic Personality Scale. | Studies of mania risk have increasingly relied on measures of subsyndromal tendencies to experience manic symptoms. The measures of mania risk employed in those studies have been shown to predict manic onset, to show familial associations, and to demonstrate expected correlations with psychosocial variables related to bipolar disorder. However, little work has been conducted to validate such measures against biologically relevant indices, or to consider whether early adversity, which has been shown to be highly elevated among those with bipolar disorder, is related to higher scores on mania risk measures. This study tested whether a well-used, self-report measure of vulnerability to mania is associated with several candidate genes that have previously been linked with bipolar disorder or with early adversity. Interactions of genes with early adversity in the prediction of mania vulnerability were also tested. Undergraduate students from the University of Miami (Coral Gables, FL, USA) (N = 305) completed the Hypomanic Personality Scale and the Risky Families Scale, and provided blood for genotyping. Findings indicated that the Hypomanic Personality Scale was related to a number of dopamine-relevant polymorphisms and with early adversity. A polymorphism of ANKK1 appeared to specifically increase mania risk in the context of early adversity. These results provide additional support for the validity of the Hypomanic Personality Scale. | 25,219,588 | [
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UFLC/MS-IT-TOF guided isolation of anti-HBV active chlorogenic acid analogues from Artemisia capillaris as a traditional Chinese herb for the treatment of hepatitis. | Hepatitis B induced by HBV is a serious health problem. Artemisia capillaris (Yin-Chen) has long been used to treat hepatitis in traditional Chinese medicine. Coumarins, flavonoids and organic acids were revealed as its hepatoprotective and choleretic components, but its anti-HBV active components remain unknown. This current study focused on its anti-HBV active constituents by various chromatographic methods. LC/MS and bioassay-guided fractionation on the active extract of Artemisia capillaris led to the isolation of nine chlorogenic acid analogues. Structures of the isolates were elucidated by MS/MS and NMR techniques. Anti-HBV assay was performed on HepG 2.2.15 cell line in vitro: reduction of HBsAg and HBeAg secretions was measured by an ELISA method; inhibition of HBV DNA replication was monitored by real-time quantitative PCR and cellular toxicity was assessed by a MTT method. The 90% ethanol extract of Artemisia capillaris (Fr. AC) showed significantly inhibitory activity on HBV DNA replication with an IC₅₀ value of 76.1 ± 3.9 μg/mL and low cytotoxic effects (SI>20.1). To clarify its active constituents, the extract was further separated into 3 sub-fractions (AC-1, AC-2 and AC-3), of which Fr. AC-2 was the most active fraction against HBeAg secretion and HBV DNA replication with IC50 values of 44.2 ± 2.8 and 23.2 ± 1.9 μg/mL. Nine chlorogenic acid analogues were detected from the active part (Fr. AC-2) by a LC/MS technique and further separated by a HPLC method. The isolates were determined as chlorogenic acid (1), cryptochlorogenic acid (2), neochlorogenic acid (3), 3,5-dicaffeoylquinic acid (4), 4,5-dicaffeoylquinic acid (5), 3,4-dicaffeoylquinic acid (6), chlorogenic acid methyl ester (7), cryptochlorogenic acid methyl ester (8), neochlorogenic acid methyl ester (9). Compounds 1-6 possessed potent activity against HBV DNA replication with IC50 values in the range of 5.5 ± 0.9-13.7 ± 1.3 μM. Di-caffeoyl analogues (4-6) also exhibited activity against the secretions of HBsAg and HBeAg. Esterified analogues (7-9) showed dramatically decreased anti-HBV activity, indicating that carboxyl group is closely associated to the anti-HBV activity. This investigation was focused on the active fractions of Artemisia capillaris and their active compositions, which showed that Fr. AC-2 was the main active section of Artemisia capillaris and chlorogenic acid analogues were the main constituents contributing to its anti-HBV activity. These results support the ethnopharmacological use of Artemisia capillaris as anti-HBV agents. | 25,219,603 | [
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Factors which can influence the quality related to cell viability of the umbilical cord blood units. | Cell viability is an important indicator for the quality of umbilical cord blood (UCB) units that can influence the transplant final outcome. Thus, it is particularly important to identify the factors that may affect the cell quality during the banking process. The present study is a first attempt to correlate the impact of exogenous factors (time from collection to processing, collected UCB volume) and endogenous factors (TNCC--total nucleated cell count, CD34(+)cell count) on cell viability assessed before UCB units cryopreservation within a banking standardized process. Three thousand UCB units collected in 35 ml CPDA containing bags were processed by HES sedimentation within 48 h. TNCC, CD34(+) cell counts and total cell viability were determined after processing. Cell viability of 94.37 ± 4.67%, TNCC of 73.17 ± 36.73 × 10(7) and CD34(+)cell count of 2.61 ± 2.29 × 10(6) was obtained after processing of units with UCB collected volume of 80.23 ± 28.52 ml. A significant negative correlation was found between cell viability and the time from collection to processing (r = -0.7228; P < 0.0001). The cell viability decreasing rate of 20.54%, 15.18% and 3-10% were achieved for units with collected UCB volume <40 ml, (40-80 ml) and >80 ml, to 48 h versus 12 h. There were no differences considering cell viability for the UCB units with similar collected UCB volume that had various CD34(+)cell count or TNCC (P > 0.05). The extension of the time from collection to processing of UCB units can reduce the quality by decreasing cell viability. The cell viability decreasing rate owing to the time influence is determined by the collected UCB volume being inversely proportional to it. Endogenous factors do not affect the cell viability. | 25,219,638 | [
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Comparison of double dose plateletpheresis on the Fenwal Amicus, Fresenius COM.TEC and Trima Accel cell separators. | A variety of apheresis instruments are now available on the market for double dose plateletpheresis. We compared three apheresis devices (Fenwal Amicus, Fresenius COM.TEC and Trima Accel) with regard to processing time, platelet (PLT) yield, collection efficiency (CE) and collection rate (CR). The single-needle or double-needle double plateletpheresis procedures of the three instruments were compared in a retrospective, randomized study in 135 donors. In the pre-apheresis setting, 45 double plateletpheresis procedures performed with each instrument revealed no significant differences in donor's age, sex, weight, hemoglobin, white blood cell and PLT count between three groups. The blood volume processed to reach a target PLT yield of ≥ 6 × 10(11) was higher in the COM.TEC compared with the Amicus and Trima (4394 vs. 3780 and 3340 ml, respectively; p < 0.001). Also there was a significantly higher median volume of ACD used in collections on the COM.TEC compared with the Amicus and Trima (426 vs. 387 and 329 ml, respectively; p < 0.001). There was a significantly higher median time needed for the procedures on the COM.TEC compared with the Amicus and Trima (66 vs. 62 and 63 min, respectively; p = 0.024). The CE was significantly higher with the Trima compared with the Amicus and COM.TEC (83.57 ± 17.19 vs. 66.71 ± 3.47 and 58.79 ± 5.14%, respectively; p < 0.001). Also, there was a significantly higher product volume on the Trima compared with the Amicus and COM.TEC (395.56 vs. 363.11 and 386.4 ml, respectively; p = 0.008). Additionally, the CR was significantly lower with the COM.TEC compared with the Amicus and Trima (0.092 ± 0.011 vs. 0.099 ± 0.013 and 0.097 ± 0.013 plt × 10(11)/min, respectively; p = 0.039). There was no significant differences in PLT yield between the three groups (p = 0.636). Trima single-needle device collected double dose platelets more efficiently than Amicus and COM.TEC double-needle devices. Blood volume processed, ACD-A volume, and median separation time was significantly higher with the COM.TEC. Also, the CR was significantly lower with the COM.TEC. | 25,219,639 | [
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Exoming into rare skin disease: EGFR deficiency. | Dermatologists are frequently asked to see patients with pustular eruptions caused by EGFR mAbs or tyrosine kinase inhibitors. In this issue, Campbell et al. describe an infant with severely inflammed skin and bowel and lung disease caused by a homozygous mutation in the EGFR gene. This commentary discusses the power of exome sequencing in disease gene discovery within the rare genodermatoses and the role of aberrant EGFR signaling in a subset of monogenic skin and epithelial syndromes. | 25,219,648 | [
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WISP1: Clinical insights for a proliferative and restorative member of the CCN family. | As a proliferative and restorative entity, Wnt1 inducible signaling pathway protein 1 (WISP1) is emerging as a novel target for a number of therapeutic strategies that are relevant for disorders such as traumatic injury, neurodegeneration, musculoskeletal disorders, cardiovascular disease, pulmonary compromise, and control of tumor growth as well as distant metastases. WISP1, a target of the wingless pathway Wnt1, oversees cellular mechanisms that include apoptosis, autophagy, cellular migration, stem cell proliferation, angiogenesis, immune cell modulation, and tumorigenesis. The signal transduction pathways of WISP1 are broad and involve phosphoinositide 3-kinase (PI 3-K), protein kinase B (Akt), mitogen activated protein (MAP) kinase, c-Jun N-terminal kinase (JNK), caspases, forkhead transcription factors, sirtuins, c-myc, glycogen synthase kinase -3β (GSK-3β), β-catenin, miRNAs, and the mechanistic target of rapamaycin (mTOR). Ultimately, these signal transduction pathways of WISP1 can result in varied and sometimes unpredictable outcomes especially for cell survival, tissue repair, and tumorigenesis that demand increased insight into the critical role WISP1 holds for cellular biology and clinical medicine. | 25,219,658 | [
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Biochemical markers of joint tissue damage increase shortly after a joint bleed; an explorative human and canine in vivo study. | Evaluation whether biomarkers of joint damage are sensitive to change shortly after a joint bleed in hemophilia patients and in a canine model of blood-induced joint damage. Blood and urine samples were collected from 10 hemophilia patients after they reported a joint bleed: within 2 days, after 3-5 days, and 12-14 days. Additionally, 90 days after the bleed a blood and urine sample was taken and considered to represent baseline condition. Commercial serum and urine biomarker assays were performed: urinary C-terminal telopeptide of type II collagen (uCTX-II), serum cartilage oligomeric matrix protein (sCOMP), serum cartilage cleavage product C1,2C, and serum chondroitin sulfate 846 (sCS846). The same panel of biomarkers was explored in dogs (n = 7) after induction of a first joint bleed by intra-articular blood injections. Biosamples were collected at baseline, day 2, 1 and 2 weeks later. In hemophilia patients, levels of uCTX-II and sCS846 increased 5 days after joint bleeding when compared with baseline (+52%; P = 0.021 and +14%; P = 0.011, respectively). In dogs, uCTX-II increased statistically significant from day 2 to day 7 (from 75% to 155% of baseline; P = 0.018), and sCOMP from baseline to day 2 (+46%; P = 0.028). This study demonstrates that biochemical markers of joint tissue damage increase shortly after a single joint bleed, both in humans with established hemophilic arthropathy (HA) and in an animal model of joint damage upon a first joint bleed. Biomarkers might be useful in monitoring the impact of a joint bleed and in evaluation of treatment of such bleeds. | 25,219,667 | [
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Radiosensitivity in patients suffering from chronic kidney disease. | Patients suffering from chronic kidney disease (CKD) exhibit a high incidence of cancer, as well as high levels of genetic damage. We hypothesized that these patients show genomic instability detected as an increased chromosomal radiosensitivity in front of the genetic damage induced by ionizing radiation. The background levels of genetic damage and the net genetic damage after in vitro irradiation with 0.5 Gy were analyzed using the micronucleus (MN) assay in peripheral blood lymphocytes. A total number of 552 individuals (179 controls and 373 CKD patients) were included in the study. The net radiation-induced genetic damage was significantly higher in CKD patients than in controls; but no differences between those patients submitted to hemodialysis and those in pre-dialytic stages were detected. A positive correlation was observed between basal and net micronucleus frequencies in CKD patients what would indicate an underlying genetic background modulating DNA damage levels. Our results indicate that CKD patients present genomic instability, measured as an increased chromosomal radiosensitivity in front of ionizing radiation. | 25,219,678 | [
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Variants of the melanocortin-1 receptor: do they matter clinically? | The melanocortin 1 receptor (MC1R) gene encodes for a seven-pass transmembrane receptor primarily expressed on melanocytes and melanoma cells. Single nucleotide polymorphisms (SNPs, also termed variants) in MC1R frequently cause red hair, fair skin and are associated with melanoma and keratinocyte-derived skin cancer development. Activation of wild-type (WT) MC1R in skin assists cutaneous photoprotection whereas reduced MC1R signalling, seen with MC1R variants, impairs ultraviolet radiation (UVR)-protective responses. As ancestral humans migrated out of Africa, the evolutionary advantage of MC1R variants may have related to improved cutaneous vitamin D synthesis and higher birthweight reported with certain MC1R variants. Reduced photoprotection secondary to MC1R dysfunction involves pigmentary and non-pigmentary mechanisms (reduced DNA repair, effects on cell proliferation and possibly immunological parameters), leading to clonal expansion of mutated cells within skin and subsequent carcinogenesis. Recent investigations suggest an association between MC1R genotype and vitiligo, with preliminary evidence that a MC1R agonist, [Nle4-D-Phe7]-alpha-MSH, in combination with UVB, assists repigmentation. Future development of compounds to correct defective MC1R responses secondary to MC1R variants could result in photoprotective benefits for fair-skinned individuals and reduce their skin cancer risk. | 25,219,681 | [
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[Augmentation strategies in patients with schizophrenia who show partial response to clozapine treatment]. | A significant proportion of patients with schizophrenia receiving clozapine remain with partial response. In this group of patients findings regarding addition of various psychotropics to ongoing clozapine treatment for augmentation are controversial. In this review, literature regarding the efficacy and safety of adjunctive agents in clozapine resistant schizophrenic patients is examined. Augmentation agents added to clozapine in treatment resistant schizophrenic patients consist of antipsychotics, antidepressants, mood stabilizers, other agents (eg. omega 3 fatty acids and glutamatergic agents) and electroconvulsive therapy (ECT) in this review. The number of controlled studies evaluating augmentation of clozapine in schizophrenia patients are highest for risperidone and lamotrigine add on treatments. However, the results of recent meta-analyses studies do not support any benefit of either agent as adjunct to clozapine treatment. Some evidence regarding the success of clozapine augmentation with amisulpride, aripiprazole, mirtazapine, omega 3 fatty acids and ECT have been obtained which needs further clinical investigation. Current findings from relevant clinical studies point that theses studies have limitations of small sample size, variable definitions of clozapine resistance, heterogenity of outcome measures and methodological designs and that sufficient evidence does not yet exist regarding the success of various adjunctive treatments for clozapine resistant patients. | 25,219,694 | [
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Impact of dynamic transrectal ultrasonography on pelvic organ prolapse. | We developed a new method to evaluate pelvic organ prolapse dynamically in patients in supine and standing positions using transrectal ultrasonography. We visualized the descent and prolapse of pelvic organs in real time using dynamic transrectal ultrasonography. The dynamic transrectal ultrasonography findings were compared with intraoperative findings. A prospective analysis was performed including 31 women with symptomatic pelvic organ prolapse. Before surgical repair for pelvic organ prolapse, transrectal ultrasonography was performed by an operator separate from the surgeon, and the transrectal ultrasonography findings were compared with the intraoperative findings, focused on the diagnosis of pelvic organ prolapse. The patients were put on the fluoroscopic tilting table for passive postural change from supine to standing position. After injection of sonographic jelly into the vaginal lumen, the ultrasound probe was inserted into the rectum. With passive postural change from supine to standing position using the fluoroscopic tilting table, descent and prolapse of pelvic organs were dynamically evaluated in real time. Cystocele, uterine prolapse and rectocele were dynamically observed in this procedure. Morphological details of pelvic organ prolapse such as movement, sliding, eversion, descent, and looseness of vaginal wall and bladder wall were successfully demonstrated in most cases. Dynamic transrectal ultrasonography demonstrated a high sensitivity (85.0%), specificity (81.1%), and positive (77.3%) and negative (87.8%) predictive value. We successfully demonstrated morphological conditions and dynamic changes of pelvic organs during passive postural change using dynamic transrectal ultrasonography in real time. Dynamic transrectal ultrasonography can be a useful modality to visualize pelvic organ prolapse preoperatively. | 25,219,698 | [
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Contemporary surgical trends in the management of upper tract calculi. | Upper tract nephrolithiasis is a common surgical condition that is treated with multiple surgical techniques, including shock wave lithotripsy, ureteroscopy and percutaneous nephrolithotomy. We analyzed case logs submitted to the ABU by candidates for initial certification and recertification to help elucidate the trends in management of upper tract urinary calculi. Annualized case logs from 2003 to 2012 were analyzed. We used logistic regression models to assess how surgeon specific attributes affected the way that upper tract stones were treated. Cases were identified by the CPT code of the corresponding procedure. A total of 6,620 urologists in 3 certification groups recorded case logs, including 2,275 for initial certification, 2,381 for first recertification and 1,964 for second recertification. A total of 441,162 procedures were logged, of which 54.2% were ureteroscopy, 41.3% were shock wave lithotripsy and 4.5% were percutaneous nephrolithotomy. From 2003 to 2013 there was an increase in ureteroscopy from 40.9% to 59.6% and a corresponding decrease in shock wave lithotripsy from 54% to 36.3%. For new urologists ureteroscopy increased from 47.6% to 70.9% of all stones cases logged and for senior clinicians ureteroscopy increased from 40% to 55%. Endourologists performed a significantly higher proportion of percutaneous nephrolithotomies than nonendourologists (10.6% vs 3.69%, p <0.0001) and a significantly smaller proportion of shock wave lithotripsies (34.2% vs 42.2%, p = 0.001). Junior and senior clinicians showed a dramatic adoption of endoscopic techniques. Treatment of upper tract calculi is an evolving field and provider specific attributes affect how these stones are treated. | 25,219,700 | [
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A European multicenter randomized noninferiority trial comparing 180 W GreenLight XPS laser vaporization and transurethral resection of the prostate for the treatment of benign prostatic obstruction: 12-month results of the GOLIATH study. | We present the 1-year results of the GOLIATH prospective randomized controlled trial comparing transurethral resection of the prostate to GreenLight XPS for the treatment of men with nonneurogenic lower urinary tract symptoms due to prostate enlargement. The updated results at 1 year show that transurethral resection of the prostate and GreenLight XPS remain equivalent, and confirm the therapeutic durability of both procedures. We also report 1-year followup data from several functional questionnaires (OABq-SF, ICIQ-SF and IIEF-5) and objective assessments. A total of 291 patients were enrolled at 29 sites in 9 European countries. Patients were randomized 1:1 to undergo GreenLight XPS or transurethral resection of the prostate. The trial was designed to evaluate the hypothesis that GreenLight XPS is noninferior to transurethral resection of the prostate on the International Prostate Symptom Score at 6 months. Several objective parameters were assessed, including maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen, in addition to functional questionnaires and adverse events at each followup. Of the 291 enrolled patients 281 were randomized and 269 received treatment. Noninferiority of GreenLight XPS was maintained at 12 months. Maximum urinary flow rate, post-void residual urine volume, prostate volume and prostate specific antigen were not statistically different between the treatment arms at 12 months. The complication-free rate at 1 year was 84.6% after GreenLight XPS vs 80.5% after transurethral resection of the prostate. At 12 months 4 patients treated with GreenLight XPS and 4 who underwent transurethral resection of the prostate had unresolved urinary incontinence. Followup at 1 year demonstrated that photoselective vaporization of the prostate produced efficacy outcomes similar to those of transurethral resection of the prostate. The complication-free rates and overall reintervention rates were comparable between the treatment groups. | 25,219,699 | [
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Development of haemostatic decontaminants for the treatment of wounds contaminated with chemical warfare agents. 2: evaluation of in vitro topical decontamination efficacy using undamaged skin. | The risk of penetrating, traumatic injury occurring in a chemically contaminated environment cannot be discounted. Should a traumatic injury be contaminated with a chemical warfare (CW) agent, it is likely that standard haemostatic treatment options would be complicated by the need to decontaminate the wound milieu. Thus, there is a need to develop haemostatic products that can simultaneously arrest haemorrhage and decontaminate CW agents. The purpose of this study was to evaluate a number of candidate haemostats for efficacy as skin decontaminants against three CW agents (soman, VX and sulphur mustard) using an in vitro diffusion cell containing undamaged pig skin. One haemostatic product (WoundStat™) was shown to be as effective as the standard military decontaminants Fuller's earth and M291 for the decontamination of all three CW agents. The most effective haemostatic agents were powder-based and use fluid absorption as a mechanism of action to sequester CW agent (akin to the decontaminant Fuller's earth). The envisaged use of haemostatic decontaminants would be to decontaminate from within wounds and from damaged skin. Therefore, WoundStat™ should be subject to further evaluation using an in vitro model of damaged skin. | 25,219,755 | [
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Microcomputed tomographic analysis of human condyles in unilateral condylar hyperplasia: increased cortical porosity and trabecular bone volume fraction with reduced mineralisation. | Unilateral condylar hyperplasia or hyperactivity is a disorder of growth that affects the mandible, and our aim was to visualise the 3-dimensional bony microstructure of resected mandibular condyles of affected patients. We prospectively studied 17 patients with a clinical presentation of progressive mandibular asymmetry and an abnormal single-photon emission computed tomographic (SPECT) scan. All patients were treated by condylectomy to arrest progression. The resected condyles were scanned with micro-CT (18 μm resolution). Rectangular volumes of interest were selected in 4 quadrants (lateromedial and superoinferior) of the trabecular bone of each condyle. Variables of bone architecture (volume fraction, trabecular number, thickness, and separation, degree of mineralisation, and degree of structural anisotrophy) were calculated with routine morphometric software. Eight of the 17 resected condyles showed clear destruction of the subchondral layer of cortical bone. There was a significant superoinferior gradient for all trabecular variables. Mean (SD) bone volume fraction (25.1 (6) %), trabecular number (1.69 (0.26) mm(-1)), trabecular thickness (0.17 (0.03) mm), and degree of mineralisation (695.39 (39.83) mg HA/cm(3)) were higher in the superior region. Trabecular separation (0.6 (0.16) mm) and structural anisotropy (1.84 (0.28)) were higher in the inferior region. The micro-CT analysis showed increased cortical porosity in many of the condyles studied. It also showed a higher bone volume fraction, greater trabecular thickness and trabecular separation, greater trabecular number, and less mineralisation in the condyles of the 17 patients compared with the known architecture of unaffected mandibular condyles. | 25,219,775 | [
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Reliability and validity of measurements of facial swelling with a stereophotogrammetry optical three-dimensional scanner. | Volume changes in facial morphology can be assessed using the 3dMD DSP400 stereo-optical 3-dimensional scanner, which uses visible light and has a short scanning time. Its reliability and validity have not to our knowledge been investigated for the assessment of facial swelling. Our aim therefore was to assess them for measuring changes in facial contour, in vivo and in vitro. Twenty-four healthy volunteers with and without an artificial swelling of the cheek were scanned, twice in the morning and twice in the afternoon (in vivo measurements). A mannequin head was scanned 4 times with and without various externally applied artificial swellings (in vitro measurements). The changes in facial contour caused by the artificial swelling were measured as the change in volume of the cheek (with and without artificial swelling in place) using 3dMD Vultus software. In vivo and in vitro reliability expressed in intraclass correlations were 0.89 and 0.99, respectively. In vivo and in vitro repeatability coefficients were 5.9 and 1.3 ml, respectively. The scanner underestimated the volume by 1.2 ml (95% CI -0.9 to 3.4) in vivo and 0.2 ml (95% CI 0.02 to 0.4) in vitro. The 3dMD stereophotogrammetry scanner is a valid and reliable tool to measure volumetric changes in facial contour of more than 5.9 ml and for the assessment of facial swelling. | 25,219,776 | [
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Subjective-objective sleep discrepancy among older adults: associations with insomnia diagnosis and insomnia treatment. | Discrepancy between subjective and objective measures of sleep is associated with insomnia and increasing age. Cognitive behavioural therapy for insomnia improves sleep quality and decreases subjective-objective sleep discrepancy. This study describes differences between older adults with insomnia and controls in sleep discrepancy, and tests the hypothesis that reduced sleep discrepancy following cognitive behavioural therapy for insomnia correlates with the magnitude of symptom improvement reported by older adults with insomnia. Participants were 63 adults >60 years of age with insomnia, and 51 controls. At baseline, participants completed sleep diaries for 7 days while wearing wrist actigraphs. After receiving cognitive behavioural therapy for insomnia, insomnia patients repeated this sleep assessment. Sleep discrepancy variables were calculated by subtracting actigraphic sleep onset latency and wake after sleep onset from respective self-reported estimates, pre- and post-treatment. Mean level and night-to-night variability in sleep discrepancy were investigated. Baseline sleep discrepancies were compared between groups. Pre-post-treatment changes in Insomnia Severity Index score and sleep discrepancy variables were investigated within older adults with insomnia. Sleep discrepancy was significantly greater and more variable across nights in older adults with insomnia than controls, P ≤ 0.001 for all. Treatment with cognitive behavioural therapy for insomnia was associated with significant reduction in the Insomnia Severity Index score that correlated with changes in mean level and night-to-night variability in wake after sleep onset discrepancy, P < 0.001 for all. Study of sleep discrepancy patterns may guide more targeted treatments for late-life insomnia. | 25,219,802 | [
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The dual binding site of angiogenin and its inhibition mechanism: the crystal structure of the rat angiogenin-heparin complex. | The heparin complex of rat angiogenin revealed that a heparin strand is fitted into a positively charged groove formed by the dual binding site of rat angiogenin, suggesting that cell adhesion to angiogenin is facilitated by its interaction with substrates on the cell surface and can be inhibited by heparin. | 25,219,815 | [
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Combination therapy with retinaldehyde (0.1%) glycolic acid (6%) and efectiose (0.1%) in mild to moderate acne vulgaris during the period of sun exposure--efficacy and skin tolerability. | Acne vulgaris is the most common disease of the adolescence age (70-94%). Main topical treatments for acne vulgaris are retinoids, benzoyl peroxide and antibiotics in mono or combination therapy. Topical retinoids, some antibiotics and antiseptics although effective on acne lesions, can due photosensitivity or make the skin more sensitive to the sun. Our study is aimed to evaluate the efficacy and tolerability of a combination therapy with Retinaldheyde (0.1%), Glycolic acid (6%) and Efectiose (0.1%) (RGE) cream in patients affected by acne vulgaris, during the lasting period of sun exposure. We retrospectively observed 30 patients of Central Italy with mild or moderate acne between April and September. All the patients selected underwent only therapy with RGE cream once a day in the evening for 8 weeks, while in the morning they just applied SPF 50 sunscreen. We evaluate the efficacy at 30 and 60 days with the "Global Evaluation Scale" (GES) and the tolerability with a 0-3 qualitative scale. The mean GES value showed a statistically significant reduction: 1.83 (SD 0.83) at baseline 1.57 (SD 0.77) and 0.90 (SD 0.76) respectively at 30 and 60 days (p < 0.01). Side effects were very uncommon. Topical treatments with retinoids, antibiotics and antiseptics can be associated with an increased occurrence of facial dryness and erythema restricting their use in sun exposure period. RGE cream has shown a good skin tolerability and efficacy, so it can be considerate an effective maintaining therapy to treat mild to moderate acne during the sun exposure period in which retinoids, antibiotics or antiseptic treatments are not recommended. | 25,219,827 | [
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Expression of rat oligodendrocyte transcription factor 2 in COS-7 cells following its eukaryotic expression vector construction. | The basic HLH transcription factor Olig is a key regulator for differentiating the oligodendrocyte lineage cells during development. Oligodendrocyte transcription factor 2 (Olig2) plays a crucial role in differentiating the oligodendrocytes in the spinal cord. We aimed to construct and investigate the eukaryotic expression recombinant plasmid in the rat Olig2. The experiment was performed at the Laboratory of Neurobiology, Xuzhou Medical College from October 2011 to March 2012. The pEGFP-N1 vector was purchased from Invitrogen. JM101 competent cells and COS-7 cells were preserved at the Laboratory of Neurobiology, Xuzhou Medical College, China. The Olig2 cDNA fragment was cloned by RT-PCR with the total RNA from the neonatal rat spinal cord, and subsequently cloned into pGEM-T vector. The confirmed Olig2 fragment was then cloned into the pEGFP-N1 vector. The right recombinant was transfected into COS-7 cells by lipofectamine 2000. The expression of the Olig2 in COS-7 cells was detected by RT-PCR and immunoblot analysis. Enzyme digestion and sequencing of the recombinant plasmid; and expression of the Olig2 were analyzed by fluorescence microscope and western blot. The correct pEGFP-N1-Olig2 cloning was verified by restriction endonuclease digestion and sequencing. The western blot analysis indicated that the Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells at 72 h. The pEGFP-N1-Olig2 vector was constructed successfully. The Olig2-GFP fusion protein was expressed in the COS-7/pEGFP-N1-Olig2 cells. This study lays the foundation for further research in gene therapy for central nervous system demyelinating diseases. | 25,219,831 | [
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Minimally invasive (sinus tarsi) approach for open reduction and internal fixation of intra-articular calcaneus fractures in children: surgical technique and case report of two patients. | Calcaneus fractures in children differ from those in adults. Most calcaneus fractures in children can be managed nonoperatively, with good long-term results expected. The width and height of the calcaneus can remodel with time in children. Recently, there has been a trend toward operative treatment of displaced intra-articular fractures of the calcaneus in children to correct the articular deformity. Studies of calcaneal fracture fixation in children used an extended lateral approach, with its possible complications. In the present report, we describe the operative treatment of 2 children (12 and 13 years old), who had a displaced intra-articular fracture of the calcaneus, using a minimally invasive sinus tarsi approach. Adequate reduction was obtained in both cases with no soft tissue complications or implant discomfort. Fixation was obtained using 3.5-mm cortical screws. Anatomic joint alignment was restored. The children were followed up until they had both resumed their full activities with no complications. We recommend this approach for operative treatment of displaced intra-articular fractures of the calcaneus, because it addresses the intra-articular displacement, which is the most important element of the deformity in children. | 25,219,845 | [
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Asian monsoons in a late Eocene greenhouse world. | The strong present-day Asian monsoons are thought to have originated between 25 and 22 million years (Myr) ago, driven by Tibetan-Himalayan uplift. However, the existence of older Asian monsoons and their response to enhanced greenhouse conditions such as those in the Eocene period (55-34 Myr ago) are unknown because of the paucity of well-dated records. Here we show late Eocene climate records revealing marked monsoon-like patterns in rainfall and wind south and north of the Tibetan-Himalayan orogen. This is indicated by low oxygen isotope values with strong seasonality in gastropod shells and mammal teeth from Myanmar, and by aeolian dust deposition in northwest China. Our climate simulations support modern-like Eocene monsoonal rainfall and show that a reinforced hydrological cycle responding to enhanced greenhouse conditions counterbalanced the negative effect of lower Tibetan relief on precipitation. These strong monsoons later weakened with the global shift to icehouse conditions 34 Myr ago. | 25,219,854 | [
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Planar bioadhesive microdevices: a new technology for oral drug delivery. | The oral route is the most convenient and least expensive route of drug administration. Yet, it is accompanied by many physiological barriers to drug uptake including low stomach pH, intestinal enzymes and transporters, mucosal barriers, and high intestinal fluid shear. While many drug delivery systems have been developed for oral drug administration, the physiological components of the gastro intestinal tract remain formidable barriers to drug uptake. Recently, microfabrication techniques have been applied to create micron-scale devices for oral drug delivery with a high degree of control over microdevice size, shape, chemical composition, drug release profile, and targeting ability. With precise control over device properties, microdevices can be fabricated with characteristics that provide increased adhesion for prolonged drug exposure, unidirectional release which serves to avoid luminal drug loss and enhance drug permeation, and protection of a drug payload from the harsh environment of the intestinal tract. Here we review the recent developments in microdevice technology and discuss the potential of these devices to overcome unsolved challenges in oral drug delivery. | 25,219,863 | [
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Design of bioartificial pancreas with functional micro/nano-based encapsulation of islets. | Type I diabetes mellitus (TIDM), a devastating health issue in all over the world, has been treated by successful transplantation of insulin secreting pancreatic islets. However, serious limitations such as the requirement of immunosuppressive drugs for recipient patients, side effects as a result of long-term use of drugs, and reduced functionality of islets at the transplantation site remain. Bioartificial pancreas that includes islets encapsulated within semi-permeable membrane has been considered as a promising approach to address these requirements. Many studies have focused on micro or nanobased islet immunoisolation systems and tested the efficacy of encapsulated islets using in vitro and in vivo platforms. In this review, we address current progress and obstacles for the development of a bioartificial pancreas using micro/nanobased systems for encapsulation of islets. | 25,219,869 | [
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Clinical treatment of cutaneous leishmaniasis in dogs with furazolidone and domperidone. | Cutaneous leishmaniasis (CL) is a zoonosis and a public health problem in countries of subtropical America. The aim of this study was to investigate the efficacy of furazolidone and domperidone treatment of dogs naturally infected with Leishmania (Viannia) braziliensis. Infection was confirmed by PCR and parasite culture of tissue collected from skin scrapings of the lesion borders of dogs. Naturally infected animals were divided into control (n=4) and treatment (n=8) groups. The treatment group was administered furazolidone for 21 days interspersed with domperidone for 10 days by oral gavage. Dogs that showed no lesion healing during this period were administered the same treatment cycle for up to 93 days. Among the eight treated animals, seven were clinically cured without recurrence of skin lesions during the 12-month study period. However, during lesion healing, skin scrapings were positive for L. (V.) braziliensis by PCR; no growth of the protozoan in NNN-LIT medium occurred until the end of follow-up. These results suggest that treatment with furazolidone and domperidone is effective for epithelialisation and lesion healing of dogs with clinical CL caused by L. (V.) braziliensis. | 25,219,877 | [
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Maternal kin bias in affiliative behavior among wild adult female blue monkeys. | Kin-biased cooperative and affiliative behavior is widespread in social mammals and is expected to increase fitness. However, despite evolutionary benefits of cooperating with relatives, demographic circumstances may influence the strength of kin bias. We studied the relationship between maternal kinship and affiliative behavior among 78 wild adult female blue monkeys (Cercopithecus mitis) from 8 groups monitored for 1-5 years. We compared behavior and kinship matrices, controlling for rank differences. Using multivariate models, we examined effects of demographic variables on the extent to which females groomed disproportionately with close adult female kin. Female blue monkeys, like other cercopithecine primates, generally preferred closer maternal kin for grooming and spatial association, although there was also substantial variation. Kin bias was weakest for association (at 7 m) while feeding, intermediate for closer (1 m) association while resting, and most intense for grooming. Grooming kin bias was stronger when a female had more very close relatives (either her mother or daughters), when her group contained more adult females, when she groomed with a lower percentage of group-mates, and when she had fewer total kin. Dominance rank did not predict variation in kin bias. Females generally groomed with all kin, but in larger groups they increased the number of unrelated grooming partners and total grooming time. The increased kin bias intensity in larger groups resulted from the addition of unrelated partners with whom grooming occurred less often than with kin, rather than from time constraints that drove females to select kin more strongly. In natural-sized groups, it may be common that females groom with all their adult female kin, which are present in limited numbers. The addition of grooming partners in larger groups may benefit female blue monkeys who rely on collective action in territorial defense; group-wide cooperation may thus influence grooming decisions in this species. | 25,219,933 | [
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Genome-wide association studies of suicidal behaviors: a review. | Suicidal behaviors represent a fatal dimension of mental ill-health, involving both environmental and heritable (genetic) influences. The putative genetic components of suicidal behaviors have until recent years been mainly investigated by hypothesis-driven research (of "candidate genes"). But technological progress in genotyping has opened the possibilities towards (hypothesis-generating) genomic screens and novel opportunities to explore polygenetic perspectives, now spanning a wide array of possible analyses falling under the term Genome-Wide Association Study (GWAS). Here we introduce and discuss broadly some apparent limitations but also certain developing opportunities of GWAS. We summarize the results from all the eight GWAS conducted up to date focused on suicidality outcomes; treatment emergent suicidal ideation (3 studies), suicide attempts (4 studies) and completed suicides (1 study). Clearly, there are few (if any) genome-wide significant and reproducible findings yet to be demonstrated. We then discuss and pinpoint certain future considerations in relation to sample sizes, the units of genetic associations used, study designs and outcome definitions, psychiatric diagnoses or biological measures, as well as the use of genomic sequencing. We conclude that GWAS should have a lot more potential to show in the case of suicidal outcomes, than what has yet been realized. | 25,219,938 | [
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Autism in DSM-5 under the microscope: implications to patients, families, clinicians, and researchers. | The changes in the diagnostic classification of the pervasive developmental disorders from the 4th edition of the Diagnostic and Statistical Manual for Mental Disorders (DSM-IV) to DSM-5 are expected to affect patients with autism, their families, as well as clinicians and researchers in the field of autism. This article reviews the new DSM-5 diagnostic criteria for Autism Spectrum Disorder (ASD) and Social Communication Disorder (SCD), and discusses potential consequences in the perspectives of major stakeholders. | 25,219,947 | [
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Granulosa cell tumor of the ovary--an incidental finding during caesarean section--a rare case report. | Approximately one-fourth of the ovarian neoplasms and cysts are diagnosed incidentally during caesarean section. The possibility of borderline tumor or cancer should be considered although existence of ovarian malignancy in pregnancy is rare. We report a case of a rare solid malignant tumor of the ovary incidentally found during caesarean section. Intraoperatively, it was thought to be a variant of the common ovarian teratoma. Ovariectomy was done but histopathology revealed it to be granulosa cell tumor. The diagnosis changed the prognosis and future treatment plan drastically. Equipped with this knowledge physicians can be made aware of the existence of this little-known ovarian neoplasm along with its rare association with pregnancy. Also one can better manage, counsel and follow-up the patients after delivery, given the knowledge of the tumours' inevitable malignant potential and its high incidence of recurrence. | 25,219,997 | [
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NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy. | N-glycanase 1 (NGLY1) is a conserved enzyme that is responsible for the deglycosylation of misfolded N-glycosylated proteins in the cytoplasm prior to their proteasome-mediated degradation. Disruption of this degradation process has been associated with various neurologic diseases including amyotrophic lateral sclerosis and Parkinson's disease. Here, we describe two siblings with neuromotor impairment, apparent intellectual disability, corneal opacities, and neuropathy who were found to possess a novel homozygous frame-shift mutation due to a 4 base pair deletion in NGLY1 (c.1533_1536delTCAA, p.Asn511LysfsX51). We hypothesize that this mutation likely limits the capability of neuronal cells to respond to stress due to accumulation of misfolded proteins, thereby impairing their survival and resulting in progressive loss of neurological function. | 25,220,016 | [
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Effects of anxiety sensitivity on alcohol problems: evaluating chained mediation through generalized anxiety, depression and drinking motives. | To test whether the relations between anxiety sensitivity (AS), a transdiagnostic risk factor, and alcohol problems are explained by chained mediation models, from AS through anxiety or depressive symptoms then drinking motives in an at-risk sample. It was hypothesized that AS would influence alcohol problems through generalized anxiety or depression symptoms and then through negatively reinforced drinking motives (i.e. drinking to cope with negative affect and drinking to conform). Cross-sectional single- and chained-mediation models were tested. Self-report measures were completed in clinics at Florida State University and the University of Vermont, USA. Participants consisted of 523 adult daily cigarette smokers [mean age = 37.23, standard deviation (SD) = 13.53; 48.6% female]. As part of a larger battery of self-report measures, participants completed self-report measures of AS, generalized anxiety, depression, drinking motives and alcohol problems. Chained mediation was found from AS to alcohol problems through generalized anxiety then through drinking to cope with negative affect [B = 0.04, 90% confidence interval (CI) = 0.004, 0.10)]. Chained mediation was also found from AS to alcohol problems through depression then through drinking to cope with negative affect (B = 0.11, 90% CI = 0.05, 0.21) and, separately, through socially motivated drinking (B = 0.05, 90% CI = 0.003, 0.11). Anxiety sensitivity and alcohol problems are indirectly related through several intervening variables, such as through generalized anxiety or depression and then through drinking to cope with negative affect. | 25,220,033 | [
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Cohesin's ATPase activity couples cohesin loading onto DNA with Smc3 acetylation. | Cohesin mediates sister chromatid cohesion by topologically entrapping sister DNA molecules inside its ring structure. Cohesin is loaded onto DNA by the Scc2/NIPBL-Scc4/MAU2-loading complex in a manner that depends on the adenosine triphosphatase (ATPase) activity of cohesin's Smc1 and Smc3 subunits. Subsequent cohesion establishment during DNA replication depends on Smc3 acetylation by Esco1 and Esco2 and on recruitment of sororin, which "locks" cohesin on DNA by inactivating the cohesin release factor Wapl. Human cohesin ATPase mutants associate transiently with DNA in a manner that depends on the loading complex but cannot be stabilized on chromatin by depletion of Wapl. These mutants cannot be acetylated, fail to interact with sororin, and do not mediate cohesion. The absence of Smc3 acetylation in the ATPase mutants is not a consequence of their transient association with DNA but is directly caused by their inability to hydrolyze ATP because acetylation of wild-type cohesin also depends on ATP hydrolysis. Our data indicate that cohesion establishment involves the following steps. First, cohesin transiently associates with DNA in a manner that depends on the loading complex. Subsequently, ATP hydrolysis by cohesin leads to entrapment of DNA and converts Smc3 into a state that can be acetylated. Finally, Smc3 acetylation leads to recruitment of sororin, inhibition of Wapl, and stabilization of cohesin on DNA. Our finding that cohesin's ATPase activity is required for both cohesin loading and Smc3 acetylation raises the possibility that cohesion establishment is directly coupled to the reaction in which cohesin entraps DNA. | 25,220,052 | [
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Lgl regulates Notch signaling via endocytosis, independently of the apical aPKC-Par6-Baz polarity complex. | The Drosophila melanogaster junctional neoplastic tumor suppressor, Lethal-2-giant larvae (Lgl), is a regulator of apicobasal cell polarity and tissue growth. We have previously shown in the developing Drosophila eye epithelium that, without affecting cell polarity, depletion of Lgl results in ectopic cell proliferation and blockage of developmental cell death due to deregulation of the Hippo signaling pathway. Here, we show that Notch signaling is increased in lgl-depleted eye tissue, independently of Lgl's function in apicobasal cell polarity. The upregulation of Notch signaling is ligand dependent and correlates with accumulation of cleaved Notch. Concomitant with higher cleaved Notch levels in lgl- tissue, early endosomes (Avalanche [Avl+]), recycling endosomes (Rab11+), early multivesicular bodies (Hrs+), and acidified vesicles, but not late endosomal markers (Car+ and Rab7+), accumulate. Colocalization studies revealed that Lgl associates with early to late endosomes and lysosomes. Upregulation of Notch signaling in lgl- tissue requires dynamin- and Rab5-mediated endocytosis and vesicle acidification but is independent of Hrs/Stam or Rab11 activity. Furthermore, Lgl regulates Notch signaling independently of the aPKC-Par6-Baz apical polarity complex. Altogether, our data show that Lgl regulates endocytosis to restrict vesicle acidification and prevent ectopic ligand-dependent Notch signaling. This Lgl function is independent of the aPKC-Par6-Baz polarity complex and uncovers a novel attenuation mechanism of ligand-activated Notch signaling during Drosophila eye development. | 25,220,057 | [
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Achieving minimum caseload requirements: an analysis of hospital quality control reports from 2004-2010. | Legally mandated minimum hospital caseload requirements for certain invasive procedures, including pancreatectomy, esophagectomy, and some types of organ transplantation, have been in effect in Germany since 2004. The goal of such requirements is to improve patient care by ensuring that patients undergo certain procedures only in hospitals that have met the corresponding minimum caseload requirement. We used the case numbers published in legally mandated hospital quality control reports to determine whether the hospitals actually met the stipulated requirements. We performed a secondary analysis of data supplied by hospitals in their quality control reports for the years 2004, 2006, 2008, and 2010 with respect to six procedures that have a minimum caseload requirement: complex interventions on the esophagus and pancreas, total knee replacement, and hepatic, renal, and stem-cell transplantation. The total case numbers for these six different procedures rose from 22 064 (0.1% of all procedures) in 2004 to 170 801 (0.9% of all procedures) in 2010. From 2006 onward, procedures to which minimum caseload requirements apply have been carried out in half of all hospitals studied. These procedures account for 0.9% of all inpatient cases in Germany. The percentage of hospitals that continue to perform certain procedures despite not having met the minimum caseload requirement ranged from 5% to 45%, depending on the type of procedure, and the percentage of cases carried out in such hospitals ranged from 1% to 15%. These values remained nearly constant for each of the six minimum caseload requirements over the 4 reporting years for which data were examined. The establishment of minimum caseload requirements in Germany in 2004 did not lessen the number of cases performed in violation of these requirements over the period 2004 to 2010. | 25,220,064 | [
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Achieving minimum caseload requirements--an analysis of hospital discharge data from 2005-2011. | The German Federal Joint Committee (the highest decision-making body of physicians and health insurance funds in Germany) has established minimum caseload requirements with the goal of improving patient care. Such requirements have been in place for five types of surgical procedure since 2004 and were introduced for total knee endoprosthesis surgery in 2006 and for the care of low-birth-weight neonates (weighing less than 1250 g) in 2010. We analyzed data from German nationwide DRG statistics (DRG = diagnosis-related groups) for the years 2005-2011. The procedures that were performed were identified on the basis of their operation and procedure codes, and the low-birth-weight neonates on the basis of their birth weight and age. The treating facilities were distinguished from one another by their institutional identifying numbers, which were contained in the DRG database. In 2011, there were 172 838 hospitalizations to which minimum caseload requirements were applicable. 4.5% of these took place in institutions that did not meet the minimum requirement for the procedure in question. The percentage of institutions that did not meet the minimum caseload requirement for complex pancreatic surgery fell significantly from 64.6% in 2006 to 48.7% in 2011, and the percentage of pancreatic surgery cases treated in such institutions fell over the same period from 19.0% to 11.4%. A significant reduction in the number of institutions treating low-birth-weight neonates was already evident before minimum caseload requirements were introduced. For all other types of procedure subject to minimum caseload requirements, there has been no significant change either in the percentage of institutions meeting the requirements or in the percentage of cases treated in such institutions. After taking account of the potential bias due to the identification of institutions by their institutional identifying numbers, we found no discernible effect of minimum caseload requirements on care structures over the seven-year period of observation, with the possible exception of a mild effect on pancreatic procedures. | 25,220,065 | [
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A novel TMEM16A splice variant lacking the dimerization domain contributes to calcium-activated chloride secretion in human sweat gland epithelial cells. | Sweating is an important physiological process to regulate body temperature in humans, and various disorders are associated with dysregulated sweat formation. Primary sweat secretion in human eccrine sweat glands involves Ca(2+) -activated Cl(-) channels (CaCC). Recently, members of the TMEM16 family were identified as CaCCs in various secretory epithelia; however, their molecular identity in sweat glands remained elusive. Here, we investigated the function of TMEM16A in sweat glands. Gene expression analysis revealed that TMEM16A is expressed in human NCL-SG3 sweat gland cells as well as in isolated human eccrine sweat gland biopsy samples. Sweat gland cells express several previously described TMEM16A splice variants, as well as one novel splice variant, TMEM16A(acΔe3) lacking the TMEM16A-dimerization domain. Chloride flux assays using halide-sensitive YFP revealed that TMEM16A is functionally involved in Ca(2+) -dependent Cl(-) secretion in NCL-SG3 cells. Recombinant expression in NCL-SG3 cells showed that TMEM16A(acΔe3) is forming a functional CaCC, with basal and Ca(2+) -activated Cl(-) permeability distinct from canonical TMEM16A(ac). Our results suggest that various TMEM16A isoforms contribute to sweat gland-specific Cl(-) secretion providing opportunities to develop sweat gland-specific therapeutics for treatment of sweating disorders. | 25,220,078 | [
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School-based interventions for elementary school students with ADHD. | Children with attention-deficit/hyperactivity disorder (ADHD) experience significant difficulties with behavior, social functioning, and academic performance in elementary school classrooms. Although psychotropic medication may enhance classroom behavior, pharmacologic treatment is rarely sufficient in addressing the many challenges encountered by individuals with ADHD in school settings. This article describes 3 evidence-based strategies including behavioral, academic, and self-regulation interventions. Future directions for research on school-based interventions are discussed. | 25,220,080 | [
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Lifestyle interventions to reduce risk of diabetes among women with prior gestational diabetes mellitus. | While lifestyle interventions involving exercise and a healthy diet in high-risk adults have been found to reduce progression to type 2 diabetes by >50%, little attention has been given to the potential benefits of such strategies in women with a history of gestational diabetes mellitus (GDM). We conducted a literature search of PubMed for English language studies of randomized controlled trials of lifestyle interventions among women with a history of GDM. In total, nine studies were identified which fulfilled the eligibility criteria. The majority of randomized trials of lifestyle interventions in women with GDM have been limited to pilot or feasibility studies. However, preliminary findings suggest that such interventions can improve diabetes risk factors in women with a history of GDM. Larger, well-designed controlled randomized trials are needed to assess the effects of lifestyle interventions on preventing subsequent progression to type 2 diabetes among women with GDM. | 25,220,104 | [
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-0.02598114,
... |
Air/water interfacial formation of freestanding, stimuli-responsive, self-healing catecholamine Janus-faced microfilms. | A catecholamine freestanding film is discovered to be spontaneously formed at the air-water interface, and the film has unique properties of robust surface adhesiveness, self-healing, and stimuli-responsive properties. The interfacial film-producing procedure is a simple single step containing polyamines and catechol(amine)s. It is found that oxygen-rich regions existing at an air-water interface greatly accelerate the catecholamine crosslinking reaction. | 25,220,108 | [
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0.07452085,
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-0.4172759,
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0.004838515,
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0.0285011,
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0.1220522,
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-0.3998244,
0.04932297,
-0.1093794,
-0.07488007,
0.2836216,
-0.3156684,
-0.18167... |
Administration of surfactant using less invasive techniques as a part of a non-aggressive paradigm towards preterm infants. | Traditional treatment of respiratory distress syndrome in preterm infants consisted of early intubation, mechanical ventilation and intra-tracheal administration of exogenous surfactant. Recently, non-invasive ventilation, which has shown some advantages in short- and long-term outcomes, has gained popularity for the initial management of respiratory insufficiency in preterm infants. However, non-invasive ventilation from the outset poses difficulties in relation to administration of exogenous surfactant. The customary INSURE technique requires tracheal intubation, surfactant administration, and rapid extubation, but the latter is not always possible. As a more elegant approach, several minimally invasive techniques of delivering surfactant have been developed for babies spontaneously breathing on CPAP. The most extensively studied have been those in which the trachea is briefly catheterized with a nasogastric tube or vascular catheter, and exogenous surfactant is administered. Although results seem promising they are not yet conclusive, and further studies will be needed to answer a number of outstanding questions. | 25,220,131 | [
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0.03291475,
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0.11716... |
Flow- and voltage-dependent blocking effect of ethosuximide on the inward rectifier K⁺ (Kir2.1) channel. | Absence seizures are manifestations of abnormal thalamocortical oscillations characterized by spike-and-wave complexes in EEG. Ethosuximide (ETX) is one of the principal medications against absence seizures. We investigate the effect of ETX on the Kir2.1 channel, a prototypical inward rectifier K(+) channel possibly playing an important role in the setting of neuronal membrane potential. We demonstrate that the outward currents of Kir2.1 channels are significantly inhibited by intracellular ETX. We further show that the movement of neutral molecule ETX in the Kir2.1 channel is accompanied by ∼1.2 K(+), giving rise to the vivid voltage dependence of ETX unbinding rate. Moreover, the apparent affinity (K d ) of ETX in the channels are decreased by single-point mutations involving M183, E224, and S165, and especially by double mutations involving T141/S165, which always also disrupt the flux-coupling feature of ETX block. Molecular dynamics simulation demonstrates narrowing of the pore at ∼D172 by binding of ETX to S165 or T141. ETX block of the Kir2.1 channels may cause a modest but critical depolarization of the relevant neurons, decreasing available T-type Ca(2+) channels and consequently lessening pathological thalamocortical burst discharges. | 25,220,134 | [
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0.1694597,
0.1753568,
-0.0924168... |
3.0 T MRI arterial spin labeling and magnetic resonance spectroscopy technology in the application of Alzheimer's disease. | The purpose of this study was to investigate the changes in the cerebral blood flow (CBF) and spectrum variables in the posterior cingulate region of patients with AD under the detection of arterial spin labeling (ASL) and magnetic resonance spectroscopy (MRS). A total of 20 AD patients (8 males and 12 females; mean age, 64.84±8.82 years) and 20 healthy controls (9 males and 11 females; mean age, 64.94±7.93 years) were included in this study for analysis. All images were obtained using a 3.0-T MR imager and an 8-channel head array receiving coil. MRS measurements were conducted exploring variables of metabolite ratios. Statistical analyses were conducted with the SPSS 11.0 statistical software package. Findings in the present study revealed a significant difference in the mean MMSE scores between the AD group and the healthy control group (16.21±4.01 vs. 27.35±1.01, P<0.01). Compared with the healthy control group, CBF in the bilateral frontal region showed a significant decrease in the AD group (right frontal: 83.5±7.2 vs. 110±11.5, P<0.05; left frontal: 85.6±8.1 vs. 108.7±12.2, P<0.05, respectively), and a similar association was also observed in the TL, TPJ, parietal, and hippocampal regions (all P<0.05). MRS imaging in the posterior cingulate region showed a significant reduction in the NAA/Cr ratio in the AD group (1.43±0.1 vs. 1.49±0.0, P<0.05). Additionally, we found that the MI/Cr and Cho/Cr ratios were higher than normal controls in patients with AD (all P<0.05). Our results suggested that 3D ASL detection combined with MRS in studying AD could show the regional hypo-perfusion with the decrease of CBF and the abnormal metabolic changes of the posterior cingulate cortex. | 25,220,149 | [
0.09166846,
0.230282,
0.13457,
0.2846744,
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0.1010819,
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0.4809569,
0.08839565,
0.2310075,
0.02197146,
0.0... |
Present simple and continuous: emergence of self-regulation and contextual sophistication in adolescent decision-making. | Sophisticated, intentional decision-making is a hallmark of mature, self-aware behaviour. Although neural, psychological, interpersonal, and socioeconomic elements that contribute to such adaptive, foresighted behaviour mature and/or change throughout the life-span, here we concentrate on relevant maturational processes that take place during adolescence, a period of disproportionate developmental opportunity and risk. A brief, eclectic overview is presented of recent evidence, new challenges, and current thinking on the fundamental mechanisms that mature throughout adolescence to support adaptive, self-controlled decision-making. This is followed by a proposal for the putative contribution of frontostriatal mechanisms to the moment-to-moment assembly of evaluative heuristics that mediate increased decision-making sophistication, promoting the maturation of self-regulated behaviour through adolescence and young adulthood. | 25,220,166 | [
-0.279642,
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0.2063762,
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0.1480295,
0.2445608,
0.3567536,
-0.023001... |
Randomness and preserved patterns in cancer network. | Breast cancer has been reported to account for the maximum cases among all female cancers till date. In order to gain a deeper insight into the complexities of the disease, we analyze the breast cancer network and its normal counterpart at the proteomic level. While the short range correlations in the eigenvalues exhibiting universality provide an evidence towards the importance of random connections in the underlying networks, the long range correlations along with the localization properties reveal insightful structural patterns involving functionally important proteins. The analysis provides a benchmark for designing drugs which can target a subgraph instead of individual proteins. | 25,220,184 | [
0.1742563,
0.05817573,
0.04285529,
0.04789797,
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0.3376655,
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0.02421561,
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0.03042623,
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0.03393852,
0.07498304,
-0.1218677... |
Socio-economic analysis for the authorisation of chemicals under REACH: a case of very high concern? | Under the European chemicals' legislation, REACH, substances that are identified to be of "very high concern" will de facto be removed from the market unless the European Commission grants authorisations permitting specific uses. Companies who apply for an authorisation without demonstrating "adequate control" of the risks have to show by means of a socio-economic analysis (SEA) that positive impacts of use outweigh negative impacts for human health and ecosystems. This paper identifies core challenges where further in-depth guidance is urgently required in order to ensure that a SEA can deliver meaningful results and that it can effectively support decision-making on authorisation. In particular, we emphasise the need (i) to better guide the selection of tools for impact assessment, (ii) to explicitly account for stock pollution effects in impact assessments for persistent and very persistent chemicals, (iii) to define suitable impact indicators for PBT/vPvB chemicals given the lack of reliable information about safe concentration levels, (iv) to guide how impacts can be transformed into values for decision-making, and (v) to provide a well-balanced discussion of discounting of long-term impacts of chemicals. | 25,220,186 | [
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0.1235985,
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0.02788001,
0.3027422,
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0.7230977,
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... |
Senescence-associated-gene signature identifies genes linked to age, prognosis, and progression of human gliomas. | Senescence-associated genes (SAGs) are responsible for the senescence-associated secretory phenotype, linked in turn to cellular aging, the aging brain, and the pathogenesis of cancer. We hypothesized that senescence-associated genes are overexpressed in older patients, in higher grades of glioma, and portend a poor prognosis. Forty-seven gliomas were arrayed on a custom version of the Affymetrix HG-U133+2.0 GeneChip, for expression of fourteen senescence-associated genes: CCL2, CCL7, CDKN1A, COPG, CSF2RB, CXCL1, ICAM-1, IGFBP-3, IL-6, IL-8, SAA4, TNFRSF-11B, TNFSF-11 and TP53. A combined "senescence score" was generated using principal component analysis to measure the combined effect of the senescence-associated gene signature. An elevated senescence score correlated with older age (r=0.37; P=.01) as well as a higher degree of malignancy, as determined by WHO, histological grade (r=0.49; P<.001). There was a mild association with poor prognosis (P=.06). Gliosarcomas showed the highest scores. Six genes independently correlated with either age (IL-6, TNFRSF-11B, IGFBP-3, SAA4, and COPG), prognosis (IL-6, SAA4), or the grade of the glioma (IL-6, IL-8, ICAM-1, IGFBP-3, and COPG). We report: 1) a novel molecular signature in human gliomas, based on cellular senescence, translating the concept of SAG to human cancer; 2) the senescence signature is composed of genes central to the pathogenesis of gliomas, defining a novel, aggressive subtype of glioma; and 3) these genes provide prognostic biomarkers, as well as targets, for drug discovery and immunotherapy. | 25,220,188 | [
0.2648368,
0.3275004,
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-0.5960678,
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0.2705479,
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0.0698259,
0.332652,
0.2776722,
0.3227538,
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0.... |
CD8αα⁺ innate-type lymphocytes in the intestinal epithelium mediate mucosal immunity. | Innate immune responses are critical for mucosal immunity. Here we describe an innate lymphocyte population, iCD8α cells, characterized by expression of CD8α homodimers. iCD8α cells exhibit innate functional characteristics such as the capacity to engulf and kill bacteria. Development of iCD8α cells depends on expression of interleukin-2 receptor γ chain (IL-2Rγc), IL-15, and the major histocompatibility complex (MHC) class Ib protein H2-T3, also known as the thymus leukemia antigen or TL. While lineage tracking experiments indicated that iCD8α cells have a lymphoid origin, their development was independent of the transcriptional suppressor Id2, suggesting that these cells do not belong to the family of innate lymphoid cells. Finally, we identified cells with a similar phenotype in humans, which were profoundly depleted in newborns with necrotizing enterocolitis. These findings suggest a critical role of iCD8α cells in immune responses associated with the intestinal epithelium. | 25,220,211 | [
0.008168847,
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0.02036805,
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0.1676559,
0.1212717,
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0.2054133,
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0.09346438,
0.4076821,
0.3900236,
-0.0842747... |
Isolation of the copper redox steps in the standard selective catalytic reduction on Cu-SSZ-13. | Operando X-ray absorption experiments and density functional theory (DFT) calculations are reported that elucidate the role of copper redox chemistry in the selective catalytic reduction (SCR) of NO over Cu-exchanged SSZ-13. Catalysts prepared to contain only isolated, exchanged Cu(II) ions evidence both Cu(II) and Cu(I) ions under standard SCR conditions at 473 K. Reactant cutoff experiments show that NO and NH3 together are necessary for Cu(II) reduction to Cu(I). DFT calculations show that NO-assisted NH3 dissociation is both energetically favorable and accounts for the observed Cu(II) reduction. The calculations predict in situ generation of Brønsted sites proximal to Cu(I) upon reduction, which we quantify in separate titration experiments. Both NO and O2 are necessary for oxidation of Cu(I) to Cu(II), which DFT suggests to occur by a NO2 intermediate. Reaction of Cu-bound NO2 with proximal NH4(+) completes the catalytic cycle. N2 is produced in both reduction and oxidation half-cycles. | 25,220,217 | [
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0.393488,
0.01645229,
0.1001156,
-0.03246976... |
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