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[ "a recent systematic analysis showed that in 2011 , 314 ( 296 - 331 ) million children younger than 5 years were mildly , moderately or severely stunted and 258 ( 240 - 274 ) million were mildly , moderately or severely underweight in the developing countries .", "in iran a study among 752 high school girls in sistan and baluchestan showed prevalence of 16.2 % , 8.6 % and 1.5 % , for underweight , overweight and obesity , respectively .", "the prevalence of malnutrition among elementary school aged children in tehran varied from 6 % to 16 % .", "anthropometric study of elementary school students in shiraz revealed that 16 % of them suffer from malnutrition and low body weight .", "snack should have 300 - 400 kcal energy and could provide 5 - 10 g of protein / day . nowadays , school nutrition programs are running as the national programs , world - wide . national school lunch program in the united states", "there are also some reports regarding school feeding programs in developing countries . in vietnam ,", "school base program showed an improvement in nutrient intakes . in iran a national free food program ( nffp )", "is implemented in elementary schools of deprived areas to cover all poor students . however , this program is not conducted in slums and poor areas of the big cities so many malnourished children with low socio - economic situation are not covered by nffp . although the rate of poverty in areas known as deprived is higher than other areas , many students in deprived areas are not actually poor and can afford food .", "hence , nutritional value of the nffp is lower than the scientific recommended snacks for this age group .", "furthermore , lack of variety of food packages has decreased the tendency of children toward nffp . on the other hand ,", "the most important one is ministry of education ( moe ) of iran , which is responsible for selecting and providing the packages for targeted schools .", "the ministry of health ( moh ) is supervising the health situation of students and their health needs .", "welfare organizations , along with charities , have the indirect effect on nutritional status of students by financial support of their family .", "provincial governors have also the role of coordinating and supervising all activities of these organizations .", "parent - teacher association is a community - based institution that participates in school 's policy such as nffp .", "in addition to these organizations , nutritional literacy of students , their parents and teachers , is a very important issue , which could affect nutritional status of school age children .", "therefore , the present study was conducted with the aim of improving the nffp , so that by its resources all poor children will be covered even in big cities .", "moreover , all food packages were replaced by nutritious and diverse packages that were accessible for non - poor children . according to the aim of this study and multiple factors that could affect the problem ,", "public health advocacy has been chosen as the best strategy to deal with this issue .", "therefore , the present study determines the effects of nutrition intervention in an advocacy process model on the prevalence of underweight in school aged children in the poor area of shiraz , iran ." ]

[ "background : the present study was carried out to assess the effects of community nutrition intervention based on advocacy approach on malnutrition status among school - aged children in shiraz , iran.materials and methods : this case - control nutritional intervention has been done between 2008 and 2009 on 2897 primary and secondary school boys and girls ( 7 - 13 years old ) based on advocacy approach in shiraz , iran .", "the project provided nutritious snacks in public schools over a 2-year period along with advocacy oriented actions in order to implement and promote nutritional intervention . for evaluation of effectiveness of the intervention growth monitoring indices of pre- and post - intervention were statistically compared.results : the frequency of subjects with body mass index lower than 5 % decreased significantly after intervention among girls ( p = 0.02 ) .", "however , there were no significant changes among boys or total population .", "the mean of all anthropometric indices changed significantly after intervention both among girls and boys as well as in total population .", "the pre- and post - test education assessment in both groups showed that the student 's average knowledge score has been significantly increased from 12.5 3.2 to 16.8 4.3 ( p < 0.0001 ) .conclusion : this study demonstrates the potential success and scalability of school feeding programs in iran .", "community nutrition intervention based on the advocacy process model is effective on reducing the prevalence of underweight specifically among female school aged children ." ]

[ [ 19, 1, 2, 8, 12, 5, 18 ], [ 19, 1, 2, 8, 12, 5, 17 ], [ 19, 1, 2, 8, 18, 12 ], [ 19, 1, 15, 3, 8, 5, 18 ], [ 19, 1, 2, 8, 18, 3 ], [ 19, 1, 2, 18, 12, 4 ], [ 19, 1, 15, 3, 8, 18 ], [ 19, 1, 15, 3, 8, 5, 17 ], [ 19, 1, 15, 18, 3 ], [ 19, 1, 15, 18, 8 ] ]

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[ "it occurs in more than 50 % of patients and may reach 90 % in certain types of cancers , especially in patients undergoing chemotherapy and/or radiation therapy.1 anemia is defined as an inadequate circulating level of hemoglobin ( hb ) ( hb < 12 g / dl ) and may arise as a result of the underlying disease , bleeding , poor nutrition , chemotherapy , or radiation therapy .", "preliminary studies suggest that survival and loco - regional control after radiation therapy , especially in head and neck cancers , may be compromised by anemia.24 anemia often worsens symptoms such as fatigue , weakness , and dyspnea , and thus may have a negative effect on quality of life ( qol ) and performance status in patients with cancer .", "thus , to improve physical functioning , qol , and prognosis in patients with cancer , it would be reasonable to take a proactive approach in identifying populations who need treatment for cancer - associated anemia ( caa ) and provide timely management .", "blood transfusion is an effective way to replace depleted hb within a short period , but the effect is , unfortunately , temporary and can cause serious adverse risks and increased mortality . in randomized clinical trials in patients with caa", ", erythropoiesis - stimulating agents ( esas ) produced significant increases in hb level , decreased transfusion requirements , and improved qol.57 however , 30 % 50 % of patients do not respond to such agents .", "in addition , the use of esas often causes concern about severe adverse reactions.6,8 in several studies , esas were found to shorten overall survival time , or time to tumor progression in patients whose hb level reached more than 12 g / dl .", "these studies included patients with different primary cancers , such as breast , lung , head and neck , cervix , and lymphomas.911 the lack of response to erythropoietin stimulation in patients with cancer is partly attributed to the functional iron deficiency state , in which the high rate of erythropoiesis exceeds the delivery of usable iron , despite adequate iron stores.12 absolute iron deficiency , in contrast , occurs when iron delivery is impaired because iron stores are depleted ( serum ferritin , < 100 ng / ml ; transferring saturation , < 20 % ) .13 hepcidin , a peptide hormone produced by the liver , is up - regulated in chronic inflammatory states including cancer .", "hepcidin inhibits iron transport across cell membranes , thus decreasing the accessibility of stored iron and gastrointestinal absorption of dietary iron , leading to an increased frequency of iron - restricted erythropoiesis.1416 many randomized trials examined the role of intravenous ( iv ) iron in addition to esas in the treatment of anemia in patients with cancer .", "many of these studies showed improvement in esa response , time to maximal response , reduction in esa dose , and improvement in qol parameters ( when measured ) in favor of the combination over esas alone .", "the observed benefit was independent of baseline iron parameters.1721 one study found a 36 % reduction in the number of patients transfused.21 this pilot study assessed the efficacy and feasibility of iv iron monotherapy in patients with cancer who have anemia and who are undergoing treatment with chemotherapy and/or radiation therapy without the use of esas ." ]

[ "backgroundanemia in patients with cancer who are undergoing active therapy is commonly encountered and may worsen quality of life in these patients . the effect of blood transfusion is often temporary and may be associated with serious adverse events .", "erythropoiesis - stimulating agents are not effective in 30 % 50 % of patients and may have a negative effect on overall survival.aimsto assess the efficacy and feasibility of intravenous iron therapy in patients with cancer who have non - iron - deficiency anemia and who are undergoing treatment with chemotherapy without the use of erythropoiesis - stimulating agents.methodsadult patients with solid cancers and non - iron - deficiency anemia were included .", "ferric sucrose at a dose of 200 mg was given in short intravenous infusions weekly for a total of 12 weeks .", "hemoglobin level was measured at baseline , every 3 weeks , and 2 weeks after the last iron infusion ( week 14 ) .", "adverse events related to intravenous iron were prospectively reported.resultsof 25 patients included , 19 ( 76.0 % ) completed at least three iron infusions and 14 ( 56.0 % ) finished the planned 12 weeks of therapy .", "the mean hemoglobin level of the 25 patients at baseline was 9.6 g / dl ( median , 9.9 g / dl ; range , 6.9 g / dl 10.9 g / dl ) . the mean change in hemoglobin level for the 15 patients who completed at least 9 treatments was 1.7 g / dl ( median , 1.1 g / dl ; range , 1.9 g / dl to 3.2 g / dl ) ; it reached 2.1 g / dl ( median , 1.3 g / dl ; range , 0.2 g / dl to 4.6 g / dl ; p = 0.0007 ) for the 14 patients who completed all 12 weekly treatments .", "five ( 20.0 % ) patients were transfused and considered as treatment failures .", "no treatment - related adverse events were reported.conclusionintravenous iron treatment alone is safe and may reduce blood transfusion requirements and improve hemoglobin level in patients with cancer who are undergoing anticancer therapy .", "further randomized studies are needed to confirm these findings ." ]

[ [ 9, 0, 1, 4, 3 ], [ 9, 1, 6, 3, 4 ], [ 9, 0, 3, 4, 2 ], [ 9, 0, 1, 4, 7 ], [ 9, 0, 1, 3 ], [ 9, 1, 6, 3, 0 ], [ 9, 1, 6, 4 ] ]

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[ "tardive dystonia ( td ) , a rarer side effect after longer exposure to antipsychotics , is characterized by local or general , sustained , involuntary contraction of a muscle or muscle group , with twisting movements , generally slow , which may affect the limbs , trunk , neck , or face .", "td has been shown to develop in about 3 % of patients who have had long - term exposure to antipsychotics .", ". the low risk of td for atypical antipsychotics is thought to result from their weak affinity for dopamine receptors . compared with typical ,", "atypical antipsychotic agents have a greater affinity for serotonin 5-ht2a than dopamine d2 receptors , with a low propensity to induce td . among this olanzapine", "is thought to have preferential action at mesolimbic over nigrostriatal dopaminergic pathways and is , therefore , associated with a very low incidence of extrapyramidal symptom ( eps ) .", "furthermore , a retrospective analysis of controlled multicentric trials suggested that olanzapine also improves preexisting symptoms of tardive movements ." ]

[ "tardive dystonia ( td ) is a serious side effect of antipsychotic medications , more with typical antipsychotics , that is potentially irreversible in affected patients .", "studies show that newer atypical antipsychotics have a lower risk of td . as a result , many clinicians may have developed a false sense of security when prescribing these medications .", "we report a case of 20-year - old male with hyperthymic temperament and borderline intellectual functioning , who developed severe td after low dose short duration exposure to atypical antipsychotic risperidone and then olanzapine .", "the goal of this paper is to alert the reader to be judicious and cautious before using casual low dose second generation antipsychotics in patient with no core psychotic features , hyperthymic temperament , or borderline intellectual functioning suggestive of organic brain damage , who are more prone to develop adverse effects such as td and monitor the onset of td in patients taking atypical antipsychotics ." ]

[ [ 0, 3, 2, 4, 1 ], [ 0, 3, 2, 1 ], [ 0, 3, 1, 4, 5, 2 ], [ 0, 3, 2, 4, 5 ], [ 0, 2, 1, 4 ] ]

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[ "lepidoptera include agricultural pests that , through feeding and other activities , negatively affect stored grains , food and fiber crops [ 2 , 3 ] . since a single lepidoptera adult can produce hundreds of eggs , and their primary food source is typically plant material , they can cause significant damage to agricultural crops . although biological agents can help manage these insect pests , insecticides currently are essential for large - scale effective and economical pest control .", "these insecticides can also affect non - target organisms , including pollinators , and their application not only disrupts natural ecosystems but also reduces yields of crops that rely on pollination [ 5 , 6 ] .", "the non - target effect of some pesticides is in part due to their effects on insect immunity , which is necessary for insect survival in natural environments .", "for example , currently used pesticides have been shown to affect cellular [ 710 ] and humoral [ 11 , 12 ] immune responses and interfere with grooming behavior [ 13 , 14 ] .", "these effects on immunity are likely non - specific and negatively impact the health of both the target pest and beneficial arthropods .", "therefore , there is a need for novel target - specific approaches to control insect pests without affecting beneficial arthropods .", "although immune pathways can be generally and non - specifically inhibited by pesticides , they also are a likely source of candidate molecules that could be inhibited for target - specific insect control since multiple classes of insect immunity genes , including signaling pathways , can be under strong selection for diversification .", "fundamental mechanisms of innate immunity comprising cellular and humoral pathways are conserved throughout the animal kingdom and are controlled by signaling pathways activated by various stimuli [ 17 , 18 ] , including pathogen recognition by immune surveillance systems . despite this overall conservation ,", "aspects of immune systems are subject to strong selection to evolve in response to varying pathogen exposure and to pathogen evolution of virulence determinants that modulate immunity [ 15 , 1921 ]", ". such co - evolutionary dynamics can promote diversification of conserved elements of immunity as well as the recruitment of novel effectors .", "as such , the investigation of insect immune pathways and mechanisms of pathogen modulation can yield insights into components that may be susceptible to inhibition .", "for example , the insect pathogen xenorhabdus nematophila suppresses cellular and humoral immunity in the lepidopteran moths manduca sexta and spodoptera exigua [ 23 , 24 ] but not in the dipteran fly drosophila melanogaster , suggesting the stage of immunity suppressed by x. nematophila may be absent from d. melanogaster , but present in lepidoptera .", "since dipteran flies serve as pollinators [ 26 , 27 ] , decomposers , food sources for other animals , and pest control agents , capitalizing on the possible differences between dipteran and lepidopteran immune signaling cascades will help in the identification of targets for pest - specific inhibition . with this knowledge in hand ,", "pest management can be achieved by developing small molecule inhibitors of these targets that will suppress pest insect immunity and lead to increased susceptibility to environmental pathogens .", "indeed , many insecticides may contribute to insect ( target and non - target ) death by modulating aspects of immunity .", "the feasibility of targeted pest control via insect immune inhibition has been established for termites ; a small molecule inhibitor of an immune surveillance protein led to faster termite death upon exposure to various pathogens .", "much of our current knowledge of insect immune signaling pathways and receptor and effector function is based on the premiere model organism d. melanogaster , for which there are extensive genetic tools and several fully sequenced genomes .", "well - established lepidopteran insect models such as the silkworm bombyx mori and the tobacco hornworm m. sexta also have been widely used to study insect immunity .", "these organisms have been particularly useful for investigating hemolymph proteins and hemocyte function because of their relatively large larval size and hemolymph volume .", "many insects in the order lepidoptera are easy to rear in laboratory conditions , and new tools such as rna interference have been implemented successfully to study genetics of their immune systems [ 30 , 31 ] . also , their immune signaling pathways are gradually being revealed by genomic and transcriptomic data [ 3238 ] .", "based on these model insect systems a fairly detailed picture of immunity , from pathogen detection to effector function , is emerging , though many gaps remain , particularly with regard to components that are unique to different insect orders . here", "we review aspects of insect immunity with an emphasis on the similarities and distinctions between d. melanogaster and representative lepidoptera ." ]

[ "many lepidopteran insects are agricultural pests that affect stored grains , food and fiber crops .", "these insects have negative ecological and economic impacts since they lower crop yield , and pesticides are expensive and can have off - target effects on beneficial arthropods", ". a better understanding of lepidopteran immunity will aid in identifying new targets for the development of specific insect pest management compounds .", "a fundamental aspect of immunity , and therefore a logical target for control , is the induction of antimicrobial peptide ( amp ) expression .", "these peptides insert into and disrupt microbial membranes , thereby promoting pathogen clearance and insect survival .", "pathways leading to amp expression have been extensively studied in the dipteran drosophila melanogaster . however , diptera are an important group of pollinators and pest management strategies that target their immune systems is not recommended .", "recent advances have facilitated investigation of lepidopteran immunity , revealing both conserved and derived characteristics .", "although the general pathways leading to amp expression are conserved , specific components of these pathways , such as recognition proteins have diverged . in this review", "we highlight how such comparative immunology could aid in developing pest management strategies that are specific to agricultural insect pests ." ]

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[ "syncope is caused by transient diffuse cerebral hypoperfusion and is characterized by transient loss of consciousness with a rapid onset followed by spontaneous and complete recovery .", "clinical features of syncope may include myoclonic jerks which are often multifocal and asynchronous , convulsions , and urinary incontinence , making it difficult to differentiate from epileptic seizure by clinical features alone .", "significant fluctuations in cerebral perfusion pressure are prevented by autoregulation of cerebral circulation , but there may be conditions where such mechanism may not compensate adequately .", "cough syncope , a rare form of syncope , may be a result of transient failure of the cerebral autoregulatory mechanism to cope with sudden decrease in cerebral blood flow .", "we present an unusual case of recurrent cough syncope , which was initially diagnosed and treated as seizures , in the context of a left - sided glomus jugulare tumor , a benign paraganglioma ." ]

[ "we present an unusual case of recurrent cough syncope in a 43-year - old woman , which was initially thought to be seizures .", "syncopal episodes were triggered by paroxysms of cough and were characterized by unresponsiveness and myoclonic jerks in her extremities .", "she had a left - sided glomus jugulare tumor that extended into the posterior cranial fossa with evidence of worsening communicating hydrocephalus on brain imaging .", "we postulate that bouts of cough produced increased intracranial pressure both by raising intrathoracic and intraabdominal pressures as well as by transient obstruction to cerebrospinal fluid flow secondary to intermittent tonsillar herniation during cough .", "this resulted in diffuse decrease in cerebral blood flow causing syncope .", "the patient 's syncopal episodes decreased in frequency once an external ventricular drain was placed followed by a ventriculoperitoneal shunt .", "search for factors that can increase intracranial pressure seems warranted in patients with recurrent cough syncope ." ]

[ [ 4, 3, 0 ], [ 3, 0, 1, 4 ], [ 4, 3, 1 ] ]

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[ "midwife - led primary delivery care for low - risk pregnant women during labor has been reported to have various advantages , such as increased odds of high maternal satisfaction and a decrease of unnecessary medical interventions [ 18 ] .", "although the maternity care system for low - risk pregnant women peculiar to one country can not easily be compared with those in other countries , consumer demands for the humanization of obstetric care have arisen in various countries [ 18 ] . to date , we have found no evidence that midwife - led primary obstetric care is unsafe for low - risk pregnant women in comparison with obstetric care with the favorable cooperation of obstetricians and midwives in japan [ 912 ] .", "in addition , about 85 % of low - risk pregnant women request that they give birth while receiving midwife - led primary delivery care .", "therefore , safe midwife - led delivery care with the backup of obstetricians may also be required for low - risk pregnant women in japan . if complications occur or threaten to occur during the primary midwife - led delivery care , the midwives have to refer the woman to obstetricians at the same or a neighboring hospital or private obstetric clinic as soon as possible .", "this is because , in deliveries managed by independent midwives in japan , many intervention measures , such as oxytocin infusion , epidural anesthesia , episiotomy , suture , and instrumental delivery , are not available based on japanese legal restrictions . in our institute , one of the main tokyo city perinatal centers , there are 3 japanese systems of midwife - led delivery care , as follows : ( 1 ) those intending to give birth at home managed by midwives who do not belong to our hospital , ( 2 ) those planning to give birth on futons", "( i.e . , japanese - style bedding ) in japanese tatami mat delivery rooms in our hospital managed by the same midwives who do not belong to our hospital , and ( 3 ) those planning to give birth in japanese tatami mat delivery rooms managed by midwives who belong to our hospital .", "the objective of this study was to describe trends in transfers and perinatal outcomes among labors using these 3 japanese systems of midwife - led primary delivery care ." ]

[ "objective .", "the objective of this study was to describe the recent clinical characteristics of labor using 3 systems of japanese midwife - led primary delivery care , as follows : ( 1 ) those intending to give birth at home managed by midwives who do not belong to our hospital , ( 2 ) those planning to give birth in our hospital managed by the same midwives , and ( 3 ) those planning to give birth managed by midwives who belong to our hospital .", "methods . a retrospective cohort study was performed .", "results .", "there were no significant differences in the obstetric or neonatal outcomes among the 3 groups .", "the rate of transfers during labor with the system involving midwives belonging to our hospital was higher than those with the other 2 systems .", "in addition , the timing of transfers in the system with the midwives belonging to our hospital was earlier than with the other 2 systems . among the 3 groups ,", "there were no significant differences in the rate of the main 2 indications for transfers : fetal heart rate abnormality and failure to progress . conclusion .", "there were no significant differences in perinatal outcomes among the 3 systems ; however , there were some differences in the status of transfers to obstetric shared care ." ]

[ [ 4, 5, 6 ], [ 4, 5, 3, 6 ] ]

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[ "diabetes decreases the overall life expectancy and cause a heavy burden on public health ( 1 ) .", "moreover , the asia - pacific region is considered to be on the verge of an emerging diabetes epidemic ( 2 ) .", "the development of type 2 diabetes is affected by genetic and environmental determinants ( 3 ) .", "recently , one study investigated whether common variants of functional and positional candidate genes , including adrb3 , pparg , enpp1 and capn10 , were determinants of type 2 diabetes ( 4 ) .", "enpp1 , also called k121q , has a glutamine substitution for lysine at codon 121 ( 5 ) .", "type 2 diabetes is characterized by insulin resistance ( 6 ) , and enpp1 plays an important role in insulin resistance ( 7 , 8 ) .", "enpp1 interacts with -subunit of the insulin receptor to interrupt signaling ( 9 ) . in previous studies , the k121q polymorphism of the human pc-1 gene was strongly associated with insulin resistance ( 1 , 3 , 7 , 10 - 12 ) . however , there was no association between insulin resistance and the k121q variant ( 13 , 14 ) .", "in addition , there were discrepancies for the impact of enpp1 polymorphism on obesity between ethnic groups ( 5 , 10 , 13 , 15 - 19 ) .", "obesity increases the concentration of insulin in plasma and is the major contributor of insulin resistance ( 20 ) .", "obesity appears to be an effect modifier of type 2 diabetes in d1057 carriers ( 21 ) .", "the association of obesity with the genetic variant of the insulin receptor substrate was identified in other studies ( 21 , 22 ) . in the chinese han population ,", "the pc-1 q121 allele was associated with insulin resistance . in women , carriers of the q allele", "had an increased risk for obesity development ( 3 ) . in caucasians and african - americans , 121q carriers had an association with increased body mass index ( bmi ) ( 23 ) , and the three - allele risk type haploid qdeltg with the q allele increased the risk for obesity ( 24 )", "however , in the danish population , there were no differences in the distribution of frequencies of dominant types ( kk wild type and kq / qq variant type ) and alleles ( 19 ) .", "the complexity of type 2 diabetes is related to factors such as genetic heterogeneity , interactions between genes , and the modulating role played by the environment ( 4 ) . in spite of these limitations , studies of type 2 diabetes and genetic factors of obesity", "can predict the risks for development of both type 2 diabetes and obesity in order to assist primary prevention , and korea is an appropriate country for such studies because of the homogeneity of racial composition and lifestyle ( 25 ) .", "therefore , the aim of this study was to analyze the presence of the enpp1 polymorphism , not studied yet in korean population , to identify the association between genotypes and allele with type 2 diabetes and obesity ." ]

[ "type 2 diabetes is characterized by insulin resistance , and enpp1 plays an important role in insulin resistance .", "we investigated the association of the enpp1 k121q polymorphism with both diabetes and obesity ( body mass index [ bmi ] ) in korean male workers .", "the study design was case - control .", "subjects were 1,945 male workers ( type 2 diabetes , 195 ; non - diabetes , 1,750 ) of nuclear power plants who received examinations from march to october in 2004 .", "we collected venous blood samples under fasting ( 8 hr ) conditions , calculated bmi by height and weight , and assessed relevant biochemical factors .", "the results of this study demonstrated that the enpp1 121q genotype ( kq+qq types ) was not associated with type 2 diabetes ( odds ratios [ or ] , 0.854 ; 95 % confidence interval [ ci ] , 0.571 - 1.278 ) or obesity ( or , 0.933 ; 95 % ci , 0.731 - 1.190 ) .", "in addition , the frequency of the q allele was not related to type 2 diabetes ( or , 0.911 ; 95 % ci , 0.630 - 1.319 ) or obesity ( or , 0.962 ; 95 % ci , 0.767 - 1.205 ) .", "we concluded that the enpp1 121q allele is not a critical determinant for either diabetes or obesity in korean males .", "the discordance between the results of this study and those derived from studies of dominican , south asian , caucasian , finnish , and french populations might be due to differences in genetic backgrounds between these populations ." ]

[ [ 16, 5, 12, 13, 14 ], [ 16, 14, 5, 12 ], [ 16, 14, 12, 2, 11, 5 ], [ 16, 14, 12, 2, 5 ], [ 16, 14, 12, 2, 11, 13, 5 ], [ 16, 14, 5, 11 ], [ 16, 5, 12, 13, 2 ] ]

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[ "lipid apheresis provides a safe and effective means of treating patients with severe hyperlipidemia . it", "functions by first separating plasma from blood cells with a cell separator and then using either the adsorption of apolipoprotein b by affinity columns containing anti - apolipoprotein b antibodies or dextran sulphate , or their precipitation at low ph by heparin .", "lipid apheresis allows patients to attain lower levels of low - density lipoprotein ( ldl ) , which are usually not attainable with traditional drug therapy alone , while leaving high - density lipoprotein ( hdl ) levels generally unaffected . when used in conjunction with statins and other lipid - lowering drugs", ", lipid apheresis may also induce the regression of coronary atherosclerotic plaque in familial hypercholesterolemia ( fh ) patients .", "fh is a group of autosomal dominant genetic defects resulting in elevated serum ( ldl ) cholesterol levels . in the heterozygous state ,", "fh is a relatively common but serious genetic disorder , with an incidence of about 1 in 500 persons in the general population .", "fh has been associated with an increased risk for atherosclerosis , premature coronary heart disease , and heart failure [ 3 , 4 ] .", "fh is caused by a mutation affecting apolipoprotein b , proprotein convertase subtilisin kexin type 9 ( pcsk9 ; an enzyme involved in ldl receptor degradation ) , or , most commonly , the ldl receptor gene , resulting in defective ldl receptors and/or a diminished number of ldl receptors [ 7 , 8 ] .", "these mutations cause ldl to be catabolized at a slower rate and thus accumulate in the circulation .", "currently , fh is treated using a variety of cholesterol - lowering drugs , most notably statins or hmg - coa reductase inhibitors . for many patients , however , statins are not a viable treatment option , because of either intolerance or ineffectiveness .", "lipid apheresis is an alternative form of treatment for these fh patients as well as those who have persistently elevated ldl levels despite treatment .", "because apheresis is performed at only a few highly specialized centers in relatively low volume , there is very little literature discussing the effectiveness of lipid apheresis on the reduction of lipid profiles and the prevention of future cardiac events .", "this study , therefore , reports the experience in a single metropolitan center of treating patients with hyperlipidemia with lipid apheresis ." ]

[ "lipid apheresis is used to treat patients with severe hyperlipidemia by reducing low - density lipoprotein cholesterol ( ldl - c ) .", "this study examines the effect of apheresis on the lipid panel and cardiac event rates before and after apheresis .", "an electronic health record screen of ambulatory patients identified 11 active patients undergoing lipid apheresis with 10/11 carrying a diagnosis of fh .", "baseline demographics , pre- and postapheresis lipid levels , highest recorded ldl - c , cardiac events , current medications , and first apheresis treatment were recorded .", "patients completed a questionnaire and self - reported risk factors and interest in alternative treatment .", "there were significant reductions in mean total cholesterol ( 58.4 % ) , ldl - c ( 71.9 % ) , triglycerides ( 51 % ) , high - density lipoprotein ( hdl ) cholesterol ( 9.3 % ) , and non - hdl ( 68.2 % ) values .", "thirty - four cardiac events were documented in 8 patients before apheresis , compared with 9 events in 5 patients after apheresis .", "our survey showed a high prevalence of statin intolerance ( 64 % ) , with the majority ( 90 % ) of participants indicating an interest in alternative treatment options .", "our results have shown that lipid apheresis primary effect is a marked reduction in ldl - c cholesterol levels and may reduce the recurrence of cardiac events .", "apheresis should be compared to the newer alternative treatment modalities in a randomized fashion due to patient interest in alternative options ." ]

[ [ 11, 12, 10, 0, 4, 8, 2 ], [ 11, 2, 0, 10, 8, 12 ], [ 11, 12, 10, 0, 4, 2 ], [ 11, 2, 0, 10, 8, 4 ], [ 11, 12, 10, 0, 4, 8, 6 ], [ 11, 2, 0, 10, 12 ], [ 11, 2, 12, 0 ], [ 11, 2, 12, 10 ] ]

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[ "an exponential rise in alzheimer 's disease ( ad ) prevalence rates is predicted to parallel the aging of baby boomers creating a potentially unsustainable economic burden to the healthcare system . delaying the onset or progression of ad , even modestly , by earlier pharmacological intervention could substantially reduce the economic and psychosocial impact of the illness [ 1 , 2 ] . unfortunately", ", many ad patients remain undiagnosed or go undetected until the later stages of disease .", "insights into the underlying pathological mechanisms involving beta - amyloid plaque deposition within the brain have led to the development of a host of antiamyloid agents that are in various stages of clinical investigation .", "there is now a scientific consensus that the pathological events in ad initiate decades before clinical symptoms become apparent , and if disease modification is realized in the coming decades , the need for improved methods of early detection prior to the overt clinical signs will be accentuated . traditionally , neuropsychological measures , particularly those that tap cognitive abilities subsumed by the hippocampal formation such as episodic memory , have shown usefulness in identifying cognitively normal elders who subsequently develop ad [ 4 , 5 ] .", "decrements in semantic memory and concept formation have been shown to occur nearly a decade before the development of ad .", "performance on visual - spatial and verbal memory measures in midlife have also been shown to predict later memory loss .", "however , individuals with very high premorbid intellectual abilities experiencing incipient cognitive decline may go undetected , and false positives are possible in individuals with a low level of intellectual abilities . also appropriate", "interpretation of extensive neuropsychological testing requires a high degree of expertise and training , which limits its use in routine clinical settings . the advancement of molecular imaging tracers that bind to amyloid , such as pittsburgh compound b ( pib ) or longer - lived probes ( e.g . , fddnp ) , offers a non - invasive in vivo method to detect and quantify brain amyloid deposition [ 8 , 9 ] . however , this approach for presymptomatic detection is economically impractical for routine use given the current costs and restrictions on medically necessary use .", "similarly , biomarkers including a142 and phosphorylated tau ( also implicated in ad pathology ) in cerebral spinal fluid ( csf ) can predict subsequent cognitive decline [ 10 , 11 ] , but lumbar puncture carries risks and is inconvenient for wide - scale use in cognitively impaired elderly subjects .", "blood - based biomarkers have more practical applicability for routine use and are likely to be more cost effective than both csf and imaging procedures . consequently , measurement of a140 and a142 in blood is increasingly being explored and shows potential in identifying individuals at the preclinical stage of ad [ 1214 ] .", "it has been reported that csf a levels are subject to high diurnal fluctuations with extremely high variability reported over 12 hours . over days and weeks ,", "furthermore , serum contains more a than plasma , possibly due to the release of bound a during the clotting process .", "hence , serum a appears suitable for use in predicting mci / ad and optimal sensitivity , and specificity is probably achievable if combined with current diagnostic procedures , such as brief neuropsychological testing . in this study", ", we examined the usefulness of brief neuropsychological tests in combination with blood a140 and a142 as a predictive test for detecting mci / ad in at - risk older adults at a pre - symptomatic stage .", "such an approach will be more practical for clinical use and be germane in designing large - scale prevention trials ." ]

[ "we examined the usefulness of brief neuropsychological tests and serum a as a predictive test for detecting mci / ad in older adults .", "serum a levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw .", "twenty - eight of the subjects subsequently developed mci ( n = 18 ) or ad ( n = 10 ) over the follow - up period .", "baseline measures of global cognition , memory , language fluency , and serum a142 and the ratio of serum a142/a140 were significant predictors for future mci / ad using cox regression with demographic variables , apoe 4 , vascular risk factors , and specific medication as covariates . an optimal sensitivity of 85.2 % and specificity of 86.5 % for predicting mci / ad was achieved using roc analyses .", "brief neuropsychological tests and measurements of a142 obtained via blood warrants further study as a practical and cost effective method for wide - scale screening for identifying older adults who may be at - risk for pathological cognitive decline ." ]

[ [ 13, 8, 9, 12 ], [ 13, 8, 9, 4, 12 ], [ 13, 12, 8 ], [ 13, 12, 9 ], [ 12, 3, 9, 13 ], [ 12, 3, 9, 8, 13 ], [ 12, 3, 13 ], [ 12, 3, 9, 8, 10, 13 ] ]

[ 0.37007168458781364, 0.3678349762687112, 0.3604931796881449, 0.3522590616240735, 0.3479682584246468, 0.34729051017710805, 0.3426099925428785, 0.341601635079896 ]

[ "the wnt/-catenin pathway has been implicated in the development and progression of melanoma and a wide range of cancer types , including colorectal cancer , breast cancer , esophageal carcinoma , and liver cancer [ 13 ] . under normal conditions ,", "increases in expression and binding of certain wnt ligands to frizzled receptor or mutations in specific components of the -catenin degradation assembly deactivate this regulatory mechanism .", "nuclear -catenin stimulates transcription of a large number of tcf/-catenin responsive genes that include cyclin d1 , c - myc [ 5 , 6 ] , and the melanocyte - specific gene , microphthalmia - associated transcription factor mitf - m .", "thus , accumulation of nuclear -catenin as observed in several cancer types is considered a marker of canonical wnt/-catenin pathway deregulation and unfavorable prognosis [ 3 , 8 ] .", "previous studies have reported an association between nuclear -catenin accumulation and melanoma progression and suggested nuclear -catenin to be a marker of poor prognosis [ 1 , 7 ] .", "however , recent studies have shown that contrary to breast and colon cancer , metastatic progression of melanoma is associated with decreases in nuclear and cytoplasmic -catenin expression [ 9 , 10 ] . moreover , clinical , genetic , and histological studies suggest that nuclear and cytoplasmic -catenin may be used as biomarkers of good prognosis in melanoma [ 1114 ] . recently , hhr6 , a human homologue of the yeast rad6 gene and a principal component of the postreplication dna repair pathway , has been identified as an important regulator of canonical wnt/-catenin signaling [ 15 , 16 ] .", "hhr6 , referred hereafter as rad6 , stabilizes -catenin by polyubiquitin modifications that render -catenin resistant to 26s proteasomal degradation .", "furthermore , rad6 is a transcriptional target of -catenin , thus revealing a positive feedback loop between -catenin - mediated activation of rad6 gene expression and rad6-induced -catenin stabilization .", "rad6 expression is low in normal breast tissues ; however , increases in rad6 protein expression are detected in hyperplastic , ductal carcinoma in situ ( dcis ) and invasive breast carcinomas .", "we have previously demonstrated a role for rad6 in breast cancer progression through its regulatory effect on the canonical wnt/-catenin pathway . since the decrease / loss of nuclear -catenin [ 9 , 10 ] , rather than increases as in breast cancer ,", "is linked to melanoma progression , it is not known whether rad6 and -catenin work in concert to promote melanoma pathogenesis .", "furthermore , rad6 expression in the skin has not been investigated , and there are no data on the role of rad6 in the pathogenesis of benign ( nevi ) and malignant ( melanoma ) melanocytic lesions .", "it is important to address this gap in knowledge because of the unmet medical need for new effective antimelanoma therapies and because rad6 and -catenin have been identified as therapeutic targets [ 19 , 20 ] . in this study , we examined rad6 and -catenin expressions in serial sections of nevi , primary , and metastatic melanomas to determine their potential roles in melanoma development and metastatic progression .", "our data suggest that membranous relocation of -catenin and upregulation of rad6 are independent markers of melanoma development and progression .", "we also offer a hypothesis that explains the role of membranous -catenin relocation and decreasing cytoplasmic -catenin in melanoma development , a phenomenon that has been linked to unfavorable prognosis [ 9 , 21 , 22 ] ." ]

[ "we have previously demonstrated that rad6 and -catenin enhance each other 's expression through a positive feedback loop to promote breast cancer development / progression . while -catenin has been implicated in melanoma pathogenesis , rad6 function has not been investigated . here", ", we examined the relationship between rad6 and -catenin in melanoma development and progression .", "eighty - eight cutaneous tumors", ", 30 nevi , 29 primary melanoma , and 29 metastatic melanomas , were immunostained with anti -- catenin and anti - rad6 antibodies . strong expression of rad6 was observed in only 27 % of nevi as compared to 100 % of primary and 96 % of metastatic melanomas .", "-catenin was strongly expressed in 97 % of primary and 93 % of metastatic melanomas , and unlike rad6 , in 93 % of nevi .", "none of the tumors expressed nuclear -catenin .", "-catenin was exclusively localized on the cell membrane of 55 % of primary , 62 % of metastatic melanomas , and only 10 % of nevi .", "cytoplasmic -catenin was detected in 90 % of nevi , 17 % of primary , and 8 % of metastatic melanoma , whereas 28 % of primary and 30 % of metastatic melanomas exhibited -catenin at both locations .", "these data suggest that melanoma development and progression are associated with rad6 upregulation and membranous redistribution of -catenin and that -catenin and rad6 play independent roles in melanoma development ." ]

[ [ 12, 5, 13, 11, 7 ], [ 12, 11, 13, 7, 0 ], [ 12, 5, 13, 7, 0 ], [ 12, 5, 13, 11, 10 ], [ 12, 5, 11, 7, 0 ] ]

[ 0.3974522106679537, 0.39717250178243085, 0.38142405971863336, 0.38029694045884616, 0.3734586385344205 ]

[ "the guanine heterocyclic ring is rich in chemical reactivity toward oxidants and adduct - forming species . in dna , 2-deoxyguanosine ( dg , mass = m ) is the chief site for base oxidation due to its low redox potential leading to many products that are characterized by their mass signatures .", "the principal products characterized with one - electron oxidants in aqueous solutions can be grouped based on the site of reaction on the radical intermediate resulting from one - electron oxidation of dg .", "the 2-deoxyribonucleoside products arising from initial reactivity at c5 of dg include a four - electron oxidation product , an imidazolone ( diz , m-39 ) that hydrolyzes to an oxazolone ( dz , m-21 ) , and the two - electron oxidation product 5-carboxamido-5-formamido-2-iminohydantoin ( d2ih , m+34 ; scheme 1 ) .", "when the initial reaction occurs at c8 of dg , either 2,6-diamino-4-hydroxy-5-formamidopyrimidine ( fapy - dg , m + 18 ) is observed under reducing conditions or 8-oxo-7,8-dihydroguanine ( dog , m+16 ) is observed under oxidizing conditions , in which the latter compound is a key marker for monitoring oxidative stress in cells ( scheme 1 ) .", "the two - electron oxidation product dog is stable but is highly susceptible to further oxidation leading to two hydantoin compounds .", "the yield for the thermodynamically preferred product spiroiminodihydantoin ( dsp , m + 32 ) is greatest in nucleoside reactions at ph > 6 or in unencumbered reaction contexts ( i.e . , single - stranded dna or g - quadruplexes ) , while the yield of 5-guanidinohydantoin ( dgh , m + 6 ) is greatest in nucleoside reactions at ph < 6 or in sterically demanding duplex contexts ( scheme 1 ) .", "the hydantoins are also readily formed from direct four - electron oxidation with o2 .", "this list of products represents those that are consistently observed from many oxidant systems conducted by several laboratories ; however , other compounds have been reported in lower yield . in the cellular context", ", oxidation reactions with dg can have other nucleophilic participants such as amines or phenols . in most cases , when amines or phenols participate in the reaction , products", "are observed with similar backbone structures as characterized with water serving as the nucleophile .", "for example , when dg is oxidized in the presence of lysine , products retaining the dg heterocycle and those with a core similar to dgh or dsp have been observed .", "the adducts characterized by our laboratory and others show lysine competing with water for sites of covalent bond formation , where a single lysine is observed at c8 analogous to dog , at either c5 or c8 of a spirocyclic core similar to dsp , and last a bis - adduct at c5 and c8 with a spirocyclic ring structure has been identified ( figure 1 ) .", "the lysine adducts are all stable allowing their quantification and characterization . as a last example", ", the polyamine spermine has been adducted to dg and dog under oxidative conditions . in the dg oxidation studies , a spermine adduct at c8", "is observed retaining the dg heterocyclic core , while dog oxidations yield an adduct at c5 that does not undergo acyl migration to create a spirocycle , but instead the polyamine can generate an unstable hemiaminal intermediate that decomposes leaving a ribosylurea lesion at the adduct formation site .", "moreover , the facile formation of spermine adducts to dog oxidation intermediates has been harnessed for quantification of dog from dna samples .", "in contrast to amines , phenols ( i.e . , tyrosine ) are more redox active than amines and better able to compete with dg for oxidant during reactions .", "the products observed when phenols participate with dg during oxidation have more variability in their structures compared to amine adducts .", "these model studies aid in understanding the chemical nature of dna protein cross - links that are detrimental to cellular processes . in the current work ,", "oxidations that allowed dg to react with nh3 were conducted while the full product and diastereomer distributions were monitored .", "after careful characterization of the nucleoside reactions , similar oxidations were conducted in the single - stranded and duplex oligodeoxynucleotide ( odn ) contexts . the purified ammonia adducts were also studied with respect to their decomposition pathways leading to end products that have not been previously determined .", "lastly , polymerase insertion studies were conducted to test the hypothesis that amine adducts might have altered base - pairing preferences ; every substitution of an oxo group on a base for an amino group converts a hydrogen bond acceptor into a potential hydrogen bond donor .", "these results provide a fundamental understanding of the stability and base - pairing properties of amine adducts to dg that result during oxidation , which may occur in vivo due to the high concentration of nucleophilic amines in the vicinity of the genome .", "adducts observed when dg and lysine are allowed to react in the presence of oxidant ." ]

[ "upon oxidation of the heterocyclic ring in 2-deoxyguanosine ( dg ) , the initial electrophilic intermediate displays a wide range of reactivities with nucleophiles leading to many downstream products . in the present study ,", "the product profiles were mapped when aqueous solutions of dg were allowed to react with nh4cl in the presence of the photooxidants riboflavin and rose bengal as well as the diffusible one - electron oxidant na2ircl6 .", "product characterization identified the 2-deoxyribonucleosides of spiroiminodihydantoin , 5-guanidinohydantoin , and oxazolone resulting from h2o as the nucleophile .", "when nh3 was the nucleophile , a set of constitutional isomers that are diastereotopic were also observed , giving characteristic masses of dg + 31 .", "esi+-ms / ms of these nh3 adducts identified them to be spirocycles with substitution of either the c5 or c8 carbonyl with an amine .", "the nh3 adducts exhibit acid - catalyzed hydrolysis to spiroiminodihydantoin .", "quantification of the nh3 and h2o adducts resulting from oxidation of dg in the nucleoside , single - stranded , and duplex oligodeoxynucleotide contexts were monitored allowing mechanisms for product formation to be proposed .", "these data also provide a cautionary note to those who purify their oligonucleotide samples with ammonium salts before oxidation because this will lead to unwanted side reactions in which ammonia participates in product formation ." ]

[ [ 20, 22, 1, 0, 23 ], [ 20, 22, 1, 0, 19 ], [ 20, 22, 1, 23, 2 ], [ 20, 22, 0, 23, 2 ] ]

[ 0.38801633713914424, 0.3874254653868528, 0.38594654174703774, 0.3780718256119206 ]

[ "agriculture has been one of the primary economic avenues in the philippines contributing to about 20 % to the gross domestic product ( gdp ) .", "crops comprise about 47.56 % of the total agricultural sector and have contributed to about 510 billion pesos ( p510b ) to the country 's national income .", "benguet is a province in the northern portion of the philippines belonging to the cordillera administrative region .", "there are about 27.5 thousand farms covering 30 thousand hectares of agricultural land in benguet .", "it is also the largest producer of vegetables and fruits , supplying the capital cities in the philippines .", "the province is known as the salad bowl of the philippines as its major crops are tubers , roots , bulbs , leafy vegetables , stems , and flowers . in 2005 , benguet was the top producer of brocolli and carrots producing about 1.2 thousand and 13.7 metric tons contributing to 87.4 % and 81.4 % , respectively , to the national output . however , growing vegetables is considered a risk occupation in some areas in developing countries .", "soogarun et al . in 2003 found significantly low / abnormal mean blood cholinesterase levels among vegetable growers in thailand .", "health impacts of pesticide misuse on the other hand greatly affect the farming communities in the philippines questioning the economic advantages of its use .", "many researchers have correlated the extent of direct and indirect pesticide exposure and health hazards such as increased mortality , dermal contamination , depression in cholinesterase level , fetal abnormalities , and spontaneous abortion among pregnant women [ 36 ] .", "it is a discouraging fact though , that with knowledge of health risks , many filipino families still perceive that crop yield outweighs the health risks associated with pesticide use .", "pesticide poisoning is one of the most prevalent health problems in the philippines . in a study by the department of health ( doh ) from 19911995 , organophosphates accounted for the highest number of poisoning cases while organochlorines caused the most number of deaths .", "cheng in 1994 studied 2000 benguet vegetable farmers and found that the most common complaints were allergic reactions both in the skin and the eyes , abdominal pain , dizziness , chest pain , headache , and nose bleed .", "meanwhile , a study on pesticide poisoning in selected hospitals in four philippines regions in 2001 found that cases of acute poisoning were more prevalent than chronic cases .", "this study aimed to identify the pesticide exposure and risk factors among vegetable farmers . the data can be used as baseline data on the vegetable industry in the philippines ." ]

[ "this was a cross - sectional study that investigated pesticide exposure and its risk factors targeting vegetable farmers selected through cluster sampling .", "the sampling size calculated with p = .05 was 211 vegetable farmers and 37 farms .", "the mean usage of pesticide was 21.35 liters .", "risk factors included damaged backpack sprayer ( 34.7 % ) , spills on hands ( 31.8 % ) , and spraying against the wind ( 58 % ) .", "the top 3 pesticides used were pyrethroid ( 46.4 % ) , organophosphates ( 24.2 % ) , and carbamates ( 21.3 % ) .", "those who were exposed to fungicides and insecticides also had higher total pesticide exposure .", "furthermore , a farmer who was a pesticide applicator , mixer , loader , and who had not been given instructions through training was at risk of having higher pesticide exposure .", "the most prevalent symptoms were headache ( 64.1 % ) , muscle pain ( 61.1 % ) , cough ( 45.5 % ) , weakness ( 42.4 % ) , eye pain ( 39.9 % ) , chest pain ( 37.4 % ) , and eye redness ( 33.8 % ) .", "the data can be used for the formulation of an integrated program on safety and health in the vegetable industry ." ]

[ [ 13, 7, 9, 11 ], [ 13, 7, 9, 8, 11 ], [ 13, 11, 7 ], [ 5, 13, 9, 7, 11 ], [ 5, 13, 9, 11 ], [ 5, 11, 9, 7, 12, 13 ], [ 13, 11, 9 ], [ 5, 13, 11 ], [ 5, 13, 9, 7, 8 ] ]

[ 0.28466134804162974, 0.283582285115304, 0.2793927648578811, 0.2747096960850068, 0.27449201467328355, 0.27100603548574753, 0.2700332746134273, 0.2647261447456221, 0.2522796912192107 ]

[ "primary diffuse leptomeningeal gliomatosis ( pdlg ) is diagnosed when a glioma is located in the subarachnoid space , while intraparenchymal tumor lesions are absent .", "pdlg must be distinguished from secondary meningeal gliomatosis resulting from a primary gliomatous cns tumor .", "pdlg , especially when caused by malignant astrocytic cells , is associated with very poor survival .", "we describe a patient with pdlg consisting of malignant astrocytic cells who underwent combined radio- and chemotherapy leading to the longest survival time described in the literature thus far ." ]

[ "objectiveprimary diffuse leptomeningeal gliomatosis ( pdlg ) is a rare neoplasm with a short survival time of a few months .", "there is currently no standardized therapeutic approach for pdlg.materials and methodswe report on a 53-year - old male patient who presented with epileptic seizures , gait disturbance , paraparesis and sensory deficits in the dermatomes t8-10.resultsmagnetic resonance imaging ( mri ) revealing numerous spinal and cranial gadolinium - enhancing nodules in the meninges and histopathology led us to diagnose primary diffuse leptomeningeal gliomatosis with who grade iii astrocytic cells .", "consecutively , the patient underwent craniospinal radiotherapy ( 30 gy ) and 11 sequential cycles of temozolomide .", "this regimen led to partial tumor regression .", "thirteen months later , spinal mri revealed tumor progression . second - line chemotherapy with 5 cycles of irinotecan and bevacizumab did not prevent further clinical deterioration .", "the patient died twenty - two months after diagnosis , being the longest survival time described thus far with respect to pdlg consisting of astrocytic tumor cells.conclusionsradiochemotherapy including temozolomide , as established standard therapy for brain malignant astrocytomas , might be valid as a basic therapeutic strategy for this pdlg subtype ." ]

[ [ 3, 1, 2, 0 ], [ 3, 1, 0 ], [ 0, 2, 3 ], [ 3, 0 ] ]

[ 0.2535327842377261, 0.23804362552499667, 0.23628115590617513, 0.21872535251909278 ]

[ "in past years , numerous studies have described the role of microalbuminuria ( mau ) as a predictor of cardiovascular disease ( cvd ) and death among subjects with type 2 diabetes ( t2d ) .13 mau is one of the earliest clinical signs for diabetic nephropathy and a significant risk factor for progression to proteinuria.1 additionally , hypertensive t2d individuals with mau have an increased risk of developing end - stage renal disease ( esrd ) .4 risk factors known to be associated with cvd and diabetic nephropathy are high blood pressure ( bp ) and elevated glycosylated hemoglobin ( a1c ) .5,6 achieving adequate bp and glycemic control ( gc ) plays an essential role in preventing renal and cvd events in individuals with t2d . a current secondary analysis from the hispanic health and nutritional examination survey ( hhanes ) 7 indicated that cuban americans have higher serum cholesterol and systolic bp than puerto ricans and mexican americans . furthermore , compared with other hispanic subgroups , cuban americans have the highest proportion of hypertension ( htn ) and mean serum creatinine levels.8 smith and barnett9 examined the national center for health statistics ( nchs ) from 1996 to 1997 and concluded that cuban americans 35 years of age and older have the highest percentage of diabetes - related deaths compared with other hispanics . although previous studies have shown significant differences and diversity within hispanics , further studies conducted in the cuban american population are scarce . over the past decade ,", "the prevalence of t2d has increased , especially among cuban americans who have a higher incidence of diabetes ( 8.2 % ) compared with 6.6 % of non - hispanic whites.10 the high incidence of t2d combined with an increased risk for developing diabetes complications warrants further examination of the cuban american population .", "screening for mau can detect individuals at risk for renal dysfunction and cvd events and possibly reduce the burden associated with diabetes complications .", "therefore , the purpose of this study was to investigate to what degree the coexistence of htn and poor gc influences the likelihood of having mau among cuban americans with t2d .", "it was hypothesized that individuals with t2d , htn , and poor gc will have an increased likelihood to test positive for mau .", "it was further hypothesized that this association will be stronger after controlling for confounding variables ." ]

[ "purpose : to investigate to what degree the presence of hypertension ( htn ) and poor glycemic control ( gc ) influences the likelihood of having microalbuminuria ( mau ) among cuban americans with type 2 diabetes ( t2d ) .methods : a cross - sectional study conducted in cuban americans ( n = 179 ) with t2d .", "participants were recruited from a randomly generated mailing list purchased from knowledge - base marketing , inc .", "blood pressure ( bp ) was measured twice and averaged using an adult size cuff .", "glycosylated hemoglobin ( a1c ) levels were measured from whole blood samples with the roche tina - quant method .", "first morning urine samples were collected from each participant to determine mau by a semiquantitative assay ( immunodip ) .results : mau was present in 26 % of cuban americans with t2d .", "a significantly higher percentage of subjects with ma had htn ( p = 0.038 ) and elevated a1c ( p = 0.002 ) than those with normoalbuminuria .", "logistic regression analysis showed that after controlling for covariates , subjects with poor gc were 6.76 times more likely to have mau if they had hypertension compared with those without hypertension ( p = 0.004 ; 95 % confidence interval [ ci ] : 1.83 , 23.05 ) .conclusion : the clinical significance of these findings emphasizes the early detection of mau in this hispanic subgroup combined with bp and good gc , which are fundamentals in preventing and treating diabetes complications and improving individuals renal and cardiovascular outcomes ." ]

[ [ 0, 4, 3 ], [ 0, 4, 2, 3 ], [ 0, 4, 2, 5, 3 ], [ 0, 3 ], [ 3, 1, 0 ], [ 3, 1, 4 ] ]

[ 0.32287213369607465, 0.32140897956969766, 0.319880000745337, 0.31753135459193055, 0.3076316978404265, 0.30146778777136496 ]

[ "cancer is the second leading cause of mortality and morbidity in both developed and developing countries . in india ,", "cancer prevalence is estimated around 2.5 million , with over 0.8 million new cases and 0.5 million deaths occurring each year .", "there is an increase in the incidence of breast cancer and found to be gradually overtaking cancer of the cervix", ". breast self - examination ( bse ) is an important screening measure for detecting breast cancer .", "there is evidence that women who correctly practice bse monthly are more likely to detect a lump in the early stage of its development , and early diagnosis has been reported to influence early treatment , to yield a better survival rate .", "thus the present study aimed at identifying the level of knowledge and practice of bse among degree female students who are the citizen of the future and they can teach their family members , neighbors , friends and the community which helps the people to detect breast cancer in early stage . thus the morbidity or mortality can be reduced . in the current study", "only one participant was practicing bse occasionally so incorporating the bse concept in the degree education curriculum is very useful and helpful . the present study aimed at assessing the level of knowledge and the effectiveness of planned teaching program among degree female students on bse .", "it is a patient - centred , inexpensive and noninvasive method of screening for breast cancer .", "based on increased incidence of breast cancer and unawareness of bse among young women , researcher felt a need to provide awareness of bse among young women and can be reduced the incidence and prevalence of breast cancer in future .", "the objectives of the study were to : to assess the level of knowledge of degree college female students on bse.to determine the effectiveness of planned teaching program among degree college female students on bse.to find the association between pretest knowledge and selected demographical variables . to assess the level of knowledge of degree college female students on bse . to determine the effectiveness of planned teaching program among degree college female students on bse .", "the study attempted to test following hypotheses all the hypotheses were tested at 0.05 level of significance .", "there will be a significant difference between pretest and post - test score on knowledge of bse among degree college female students.there will be a significant association between pretest knowledge score and selected demographical variables", ". there will be a significant difference between pretest and post - test score on knowledge of bse among degree college female students .", "the study assumed that : the degree college female students will have some knowledge on bse.feel free to express their attitude toward bse.bse helps in early detection of breast cancer .", "the degree college female students will have some knowledge on bse . feel free to express their attitude toward bse .", "independent variables : teaching program on bse . selected variables : age , education , parent 's education and exposure to mass media ." ]

[ "introduction : breast cancer accounts for 19 - 34 % of all cancer cases among women in india .", "there is high mortality due to late stage diagnosis as patients usually present at an advanced stage because of lack of awareness and nonexistent breast cancer screening programs .", "early detection and prompt treatment offer the greatest chance of long - term survival and breast self - examination ( bse ) seems to be a important viable optional substitute for early detection of cancer.objectives:1 ) to assess the level of knowledge of degree college female students on bse .", "2 ) to determine the effectiveness of planned teaching program among degree college female students on bse .", "3 ) to find the association between pretest knowledge and selected demographic variables.materials and methods : pre - experimental one group pretestpost - test design was carried out among 40 degree female students by using cluster sampling method from selected colleges of udupi district.results : the data analyzed showed that majority ( 52 % ) of them was in the age group of 18 - 19 years and 72 % of them were had average knowledge on bse in the pretest score .", "out of 40 participants only one student was performing bse occasionally.conclusions : awareness regarding breast self examination among young generations is useful and it is the most important viable tool for early detection ." ]

[ [ 9, 6, 8, 7, 3 ], [ 9, 6, 3, 7 ], [ 9, 6, 3, 8 ], [ 6, 11, 9, 7, 3 ], [ 9, 6, 8, 7, 2 ], [ 9, 8, 2, 3 ], [ 9, 8, 2, 7 ], [ 9, 8, 3 ], [ 6, 11, 9, 3 ] ]

[ 0.45550489430220326, 0.44557780428096166, 0.44431195447827515, 0.44318194143461126, 0.439354383199514, 0.43810809114305443, 0.43315153359393904, 0.42457969381046307, 0.42437052226880273 ]

[ "alzheimer 's disease ( ad ) is a neurodegenerative disorder that is clinically characterized by progressive mental decline and histopathologically defined by highly abundant amyloid deposits and neurofibrillary tangles in the brain parenchyma .", "the identification of mutations within the amyloid precursor protein ( app ) and presenilin ( ps ) genes that cause autosomal dominantly inherited ad and that result in increased production of amyloid - prone forms of a established beyond doubt that the processing of app and the production of a peptides are intimately involved in the disease process and led to the proposal and the reinforcement of the alzheimer amyloid cascade hypothesis [ 1 , 2 ] .", "the role of amyloid in neuronal dysfunction has recently been extended by the discovery of small , soluble , oligomers of the a peptide , some forms of which have been termed addls ( a-derived diffusible ligands ) , protofibrils , or a*56 [ 36 ] .", "these a oligomers are not only potential intermediates in the formation of amyloid filaments , but they also have been shown to be neurotoxic themselves and to inhibit long - term potentiation ( ltp ) , a cellular model of memory , in hippocampal slices [ 4 , 7 , 8 ] .", "thus , the amyloid cascade hypothesis now includes the essential role of a oligomers in the neurodegeneration process . despite its strength", ", the amyloid cascade hypothesis is incomplete without including the essential role of amyloid - associated inflammatory proteins .", "for example , biochemical and histological studies first showed that , in addition to a , amyloid deposits also contained the inflammation / acute phase protein 1-antichymotrypsin ( act ) and , later , apolipoprotein e ( apoe ) [ 10 , 11 ] , which were both hypothesized to serve as catalysts or", "pathological chaperones of amyloid formation [ 9 , 11 , 12 ] . these and other results also indicated that alzheimer 's disease and its manifestation in middle - aged down syndrome may include an inflammatory process , for both act and apoe are inflammatory and/or acute phase proteins in other contexts , and both are overexpressed in affected regions of the ad brain ( for reviews see [ 1315 ] ) .", "indeed , alzheimer himself first identified the inflammatory component of alzheimer 's disease when he described reactive astrocytes and microglia in affected brain regions of his first patient .", "however , until inflammatory proteins such as act , il-1 , hla , and apoe were found to be overexpressed in ad and ds brains , the term inflammation was explicitly excluded from the clinical and pathological description of ad because of the lack of edema and lymphocyte infiltration [ 911 , 17 , 18 ] .", "the significance of these biochemical results instigated and was reinforced by parallel genetic discoveries implicating a role for inflammation in ad .", "in particular , inheritance of the apoe 4 allele was found to be the strongest known risk factor for ad besides age , with one copy increasing ad risk 35-fold and two copies over 10-fold [ 1921 ] .", "because of apoe 's essential genetic , and therefore presumably biochemical , contribution to ad pathology and cognitive decline , it is critical that its role in the ad pathogenic pathway / amyloid cascade be elucidated in order for therapeutics based on apoe to be designed . while recent excellent and encyclopedic literature reviews describe the many potential roles that apoe plays in ad [ 2326", "] , this focused review will concentrate on the interaction between a and apoe and other inflammatory proteins , on the effects of such interactions , and on their implications for designing apoe - based ad therapies .", "the central question we try to answer is whether increasing or decreasing apoe level and/or function will serve best to reduce ad / ds pathology and cognitive decline .", "lack of a clear answer may lead to the development of drugs that , rather than serving as an ad therapy , instead potentially exacerbate the disease ." ]

[ "the amyloid cascade hypothesis remains a robust model of ad neurodegeneration .", "however , amyloid deposits contain proteins besides a , such as apolipoprotein e ( apoe ) .", "inheritance of the apoe4 allele is the strongest genetic risk factor for late - onset ad .", "however , there is no consensus on how different apoe isotypes contribute to ad pathogenesis .", "it has been hypothesized that apoe and apoe4 in particular is an amyloid catalyst or", "pathological chaperone .", "alternatively it has been posited that apoe regulates a clearance , with apoe4 been worse at this function compared to apoe3 .", "these views seem fundamentally opposed .", "the former would indicate that removing apoe will reduce ad pathology , while the latter suggests increasing brain apoe levels may be beneficial .", "here we consider the scientific basis of these different models of apoe function and suggest that these seemingly opposing views can be reconciled . the optimal therapeutic target may be to inhibit the interaction of apoe with a rather than altering apoe levels .", "such an approach will not have detrimental effects on the many beneficial roles apoe plays in neurobiology .", "furthermore , other a binding proteins , including act and apo j can inhibit or promote a oligomerization / polymerization depending on conditions and might be manipulated to effect ad treatment ." ]

[ [ 12, 11, 6, 15, 13 ], [ 12, 11, 13, 15, 14 ], [ 12, 11, 6, 15, 5 ], [ 12, 6, 13, 15, 14 ], [ 12, 11, 6, 13 ], [ 1, 12, 14, 13 ], [ 1, 12, 6, 13 ], [ 1, 12, 14, 6 ] ]

[ 0.33438552859526616, 0.3300610820244328, 0.32742147337123756, 0.32409344838351833, 0.31743679163034005, 0.28927263212977494, 0.28823739648112406, 0.28278510074021296 ]

[ "musculoskeletal tissues show increased bone fragility , loss of cartilage resilience , reduced ligament elasticity , loss of muscular strength , and fat redistribution decreasing the ability of the tissues to carry out their normal functions .", "the loss of mobility and physical independence resulting from arthropathies and fractures can be particularly devastating in this population , not just physically and psychologically , but also in terms of increased mortality rates .", "the aim of this article is to present some of the most frequent musculoskeletal disorders of the elderly , including some misleading presentations .", "we used the following terms and some of its combinations : elderly , aged , epidemiology , fracture , osteoporosis , vertebral , hip , pelvis , arthritis , neoplasm , malignancy , myeloma , paget , gout , infection , microcrystal , and radiology .", "articles without english abstracts were excluded . besides , certain relevant rheumatological , orthopedic , and radiological books were also used .", "fractures are frequent in the elderly and result mainly from the effects of falls and osteoporosis .", "low - impact falls , even from standing height , are the most common cause of injury in geriatric patients . falling is a multi - factorial problem due to both extrinsic ( e.g . , environmental and housing conditions ) and intrinsic risk factors ( e.g . , impaired mobility , loss of muscular strength , poor visual acuity , and medication , for instance corticoids ) . [ 46 ] osteoporosis , which is characterized by qualitatively normal , but quantitatively deficient bone , leads to bone fragility and increased risk of fractures .", "the general prevalence of osteoporosis in women is approximately 50 % at the age of 85 years , while in men the prevalence is about 20 % at that age .", "ethnic differences also exist : mineral bone density is higher in black women and lower in asian women , while in white women evidence shows an intermediate value .", "due to its precision , the most widely used quantitative technique is dual energy x - ray absorptiometry , which makes it possible to diagnose osteoporosis early , predict the risk of fracture , determine therapeutic intervention , and monitor response to treatment . this method grades bone loss according to standard deviations ( sd ) from the mean young adult value .", "a value less than 2.5 times the sd below the young adult mean , is considered to indicate osteoporosis .", "the main radiographic features of osteoporosis are increased radiolucency and cortical thinning , mainly in the spine , giving rise to a well - demarcated outline of the vertebral body , which has been described as ,", "picture framing . besides , in the spine , an increased biconcavity of the vertebral end plates , with a protrusion of the intervertebral disk into the vertebral body can be observed .", "however , early radiographic changes are subtle , as a bone loss of approximately 30 % must occur before it can be detected .", "vertebral compression fractures are the most common osteoporotic fractures , with a greater incidence in women over 60 years of age .", "they can be observed in up to 25 % of women over 70 years of age and 40 % of those over 80 years .", "after one episode , the risk of subsequent vertebral fracture increases at least four - fold , with substantially increased rates during the first year . these fractures are associated with higher mortality and significant morbidity , even though they are afforded little clinical attention .", "they often appear as multiple fractures with anterior wedging , and may be associated with significant deformity , leading to kyphosis .", "they are usually well demonstrated on radiographs , but can be better assessed with computed tomography ( ct ) or magnetic resonance ( mr ) imaging , when necessary .", "the latter imaging modality may be indicated in case of associated neurological symptoms a rare event or when a vertebroplasty is discussed , in order to better localize the recently fractured vertebra .", "vertebral compression fractures in the elderly may involve several problems : first is differentiating between osteoporotic and malignant vertebral collapse ( vc ) , particularly metastatic vc , as the latter is by far the most common malignant tumor affecting the skeleton in the elderly . in most patients ,", "multiple , relatively symmetrical thoracolumbar vcs , associated with diffuse increased radiolucency are suggestive of osteoporosis [ figure 1a ] .", "the whole vertebral endplate is impacted , sometimes in association with increased or decreased radiolucency of the subjacent trabecular bone ( band - like distribution of the abnormalities under the fractured vertebral end plate ) .", "gas can also be seen under the fracture and is nearly pathognomonic of the benign nature of the collapse .", "there is no cortical osteolysis , although fractures can be identified with retropulsion of a bone fragment .", "conversely , the following are a cause for concern : a single vc , involvement of the cervical spine , heterogeneous increased or decreased radiolucency that can not be explained by an underlying end plate fracture , a focal collapse ( on the ap or lateral view ) , or a bulging of the vertebral body or cortical osteolysis [ figure 1b ] . if in doubt or for a better assessment of the spinal canal and soft tissue , ct , or better yet , an mri can be performed , in order to differentiate between these two disorders . in benign fractures ,", "an mri may show a band distribution of abnormal signal intensities on t1 and t2 weighted images , spared normal bone marrow signal intensity , retropulsion of a posterior bone fragment , and multiple compression fractures ; on the contrary , signs such as a convex posterior border of the vertebral body , abnormal signal intensity of the posterior elements , an epidural mass or a focal paraspinal mass are suggestive of spinal metastasis . [ 1921 ] second , vertebral fractures can be missed following moderate trauma , because the fracture may be difficult to identify in an osteoporotic radiolucent bone and / or because the pain is attributed to another painful condition , such as degenerative changes .", "this is observed in particular in the cervical spine , particularly at c2 , and may lead to secondary neurological complications [ figure 2 ] .", "ankylosis may be related to ankylosing spondylitis and diffuse idiopathic skeletal hyperostosis , which especially affect males and they have an estimated frequency of 5 to 15 % in the elderly . [ 2225 ] these ankylosed spines become increasingly susceptible to injury , even in the event of low - energy impacts , and are prone to unstable vertebral fractures with an increased frequency of neurological complications , either primary or secondary , after unprotected transfers and manipulation .", "these lesions may be missed on plain films when non - displaced or mildly displaced , especially in hyperextension , whereas , they are well demonstrated on ct or mr imaging . however", ", the mri features can sometimes be misleading and mimic infectious spondylitis when signal abnormalities of the disco - vertebral junction are present .", "caution is required when an elderly patient presents with an ankylosed spine , minor trauma or acute pain , especially if signal abnormalities of the anterior and posterior spine are observed [ figure 3 ] .", "usual benign vertebral compression ( a ) multiple levels , diffuse radiolucency , and whole vertebral endplate involvement ( arrows ) ; usual malignant vertebral compression characteristics ( b ) single vertebral involvement , focal and bulging of the posterior wall ( arrowheads ) . missed fracture of the odontoid process and vertebral body of c2 ( arrows ) in a patient with a history of fall one month before .", "transverse fracture of thoracic vertebral body ( arrow ) and posterior arch ( arrowhead ) with posterior epidural hematoma ( curved arrow ) in an ankylosed spine depicted on ( a ) t1- and ( b ) t2-weighted sequences .", "other important sites of fractures are the hip and the pelvis , which are associated with increased mortality and specific diagnostic problems in the elderly population .", "they are common and frequently result from lateral falls directly on the greater trochanter , in the case of hip fractures , and forward or backward falls in the case of pelvic fractures .", "most fractures are easily diagnosed by conventional radiography , particularly fractures of the proximal femur .", "however , non - displaced fractures may be negative or equivocal , particularly if the bone is osteoporotic .", "if a clinical suspicion of a fracture persists , ct or better still mr imaging is advocated , as this modality can show the fracture line surrounded by bone marrow edema .", "they may occur everywhere , but are particularly common in the hip and pelvis , the majority being located in the sacrum and pubic ramus [ figure 4 ] .", "radiographic findings are often subtle or unremarkable , and in suspected cases mr imaging is indicated due to its superior accuracy as compared to other radiological methods .", "all the images should be carefully analyzed , as multiple insufficiency fractures are frequent [ figure 5 ] .", "subchondral fractures are particularly difficult to identify on radiographs , but the thin hypointense line that represents the fracture , surrounded by a variable degree of edema , is well demonstrated on an mri [ figure 6 ] . this kind of fracture can be complicated by a necrosis of the subchondral bone , which is hypointense on t2 weighted images , and is not enhanced following gadolinium administration .", "insufficiency fractures ( arrows ) located in the sacrum with adjacent edema ( arrowheads ) , better depicted on ( a ) t1- and ( b ) t2- weighted sequences , respectively .", "multiple fractures ( white arrows ) in ( a ) the proximal femur and ( b ) pubic ramus on coronal t1-weighted images subchondral fracture of the femoral head : ( a ) conventional radiography and ( b ) fat saturated sagittal t2-weighted image ( white arrow ) .", "osteoarthritis ( oa ) can be defined as a group of distinct , but overlapping diseases , which may have different etiologies , but similar biological , morphological , and clinical outcomes affecting the articular cartilage , subchondral bone , ligaments , joint capsule , synovial membrane , and periarticular muscles .", "pathological changes can include fibrillation of cartilage , disruption of collagen fibers , changes in proteoglycan staining , chondrocyte proliferation , necrosis , and neovascularization .", "oa is the most common joint disease in persons 65 years of age and above , with a radiographic prevalence as high as approximately 90 % in women and 80 % in men . [ 3335 ] its etiology is not fully understood , although there are several related factors , such as female gender , genetics , metabolism , and excessive mechanical stress .", "it frequently leads to decreased function and loss of independence . although the joints of the hand are the most commonly affected , they are less likely to be symptomatic than the knee or hip [ figure 7 ] . the diagnosis of oa is primarily based on clinical history and physical examination .", "plain radiographs can help confirm both the diagnosis and grade the severity of the condition .", "the cardinal radiographic features of oa are focal / non - uniform narrowing of the joint space in the areas subjected to the most pressure , subchondral cysts , subchondral sclerosis , and osteophytes .", "however , the severity of the spondylolisthesis of the radiographic changes does not correlate with the clinical symptoms .", "shoulder oa and rotator cuff disease are also fairly common in the elderly and are associated with significant shoulder pain and disability related to decreased shoulder movement .", "direct signs of oa and indirect signs of large rotator cuff tears can be seen on plain films , including superior humeral head migration and remodeling of the acromion and the greater tuberosity .", "ultrasound is another valuable tool for easy assessment of the rotator cuff tendons due to its good sensitivity and specificity [ figure 8 ] .", "however , when surgical treatment is considered , arthro - ct , or mri may be preferred , in order to improve its planning .", "the lumbar and cervical spine is also frequently affected , with degenerative changes of the disk spaces , facet joints , and spinous processes , and sometimes with progressive scoliosis .", "although the intervertebral disks are not synovial joints , the pathological changes are similar to those seen in the articular cartilage .", "ct and mri are routinely used for the evaluation of narrowing of the central canal , lateral recesses , and neural foramina , when such an assessment is required ( percutaneous or surgical treatment ) . besides , mri can be useful in evaluating marrow changes in the vertebral plate , especially inflammatory changes ( type i modic ) , which present a positive correlation with low back pain . typical osteoarthritis of ( a ) the distal and proximal interphalangeal joints and ( b ) hip joint : joint space narrowing ( arrows ) , subchondral cysts ( arrowheads ) , osteophytes ( curved arrows ) , and subchondral sclerosis ( thick arrow ) .", "ultrasound images in ( a ) the long and ( b ) short axis of the supraspinatus tendon demonstrating a complete tear ( arrowheads ) .", "the frequency of microcrystal disorders also increases with age ; this is mainly true of gout and calcium pyrophosphate dihydrate deposition ( cpdd ) arthropathy .", "gout is the most common inflammatory arthritis in the elderly and is characterized by a disturbance of purine metabolism , with deposits in the joints , cartilage , and kidneys .", "the first metatarsophalangeal joint is the most common site of involvement in gouty arthritis [ figure 9 ] , but any joint can be involved .", "the typical radiographic features include eccentric nodular soft tissue masses ( particularly suggestive of tophus when they are dense ) , close erosions ( also suggestive when located at a distance from the joint and when associated with an elevated bony margin ) , preservation of the joint space , exuberant bony proliferation , and lack of periarticular osteoporosis .", "when the clinical , biological , and radiographic findings are uncertain , an ultrasound may be particularly helpful , as this technique may demonstrate more tophi [ figure 10 ] and erosions than plain films , more synovitis than a clinical examination , suggestive hyperechoic aggregates in the synovium or in the joint fluid , which may be aspirated , and the double contour sign ( an irregular hyperechoic band over the superficial margin of the articular cartilage , related to crystal deposition ) . [ 4244 ] calcium pyrophosphate dihydrate deposition ( cpdd ) disease is characterized by articular and periarticular tissue deposits ( hyaline cartilage , fibrocartilage , and other soft - tissue structures ) , even in the spine [ figure 11 ] . unlike gout , in which the increase in serum urates leads to supersaturation and deposits in the joints , in cpdd , the calcium deposits usually appear in the cartilage in the absence of any serum abnormality .", "even though such deposits may be seen in asymptomatic patients , they may be associated with the development of severe arthropathies or with acute pain related to the migration of the crystals in the synovial fluid , mimicking septic arthritis .", "gout of the first mtp joint in conventional radiography : excentric dense nodular soft tissue mass ( arrows ) , large erosions ( arrowhead ) , lack of periarticular osteoporosis , and exuberant bony proliferation ( curved arrow ) . gout involvement of the mtp ( a ) shows the tophus ( arrow ) with hyperechogenic microcrystal deposits ( arrowheads ) and a thickened synovium ( curved arrows ) . another patient with tophus deposition in the dorsal midfoot ( b ) demonstrates microcrystal deposits ( arrowhead ) with acoustic shadows ( thick arrows ) .", "calcium pyrophosphate dihydrate deposition disease demonstrated by deposits of microcrystals in the menisci ( arrow ) , articular cartilage ( arrowhead ) , and periarticular soft tissue ( curved arrow ) .", "elderly patients are more prone to infection because of an increased incidence of predisposing disorders ( diabetes mellitus , peripheral vascular disease , poor dentition , ) , immunosuppression and surgical procedures in this population ( dental extractions , open heart surgery , prosthetic joint replacement , ) .", "the infectious agents affecting elderly patients are similar to those found in the younger population ; although in the elderly , evidence shows an increased incidence of infection by nosocomial organisms ( due to institutionalization and hospitalization ) .", "these infections can have a relatively benign course , as in the case of cellulitis , or serious consequences , as with necrotizing fasciitis .", "in patients over 80 years of age , the knee , shoulder , and hip are the most frequently affected joints .", "another peculiarity of the elderly , uncommon in adults , is acute hematogenous osteomyelitis that mainly affects the spine .", "attention should , moreover , be paid to the diagnosis of tuberculosis , as early manifestations are subtle and advanced disease mimics other infections , granulomatous diseases , and malignancy .", "tuberculosis may affect the spine ( about 50 % of cases ) , with potential neurological consequences , or any joint , causing deformity [ figure 12 ] .", "it should be noted that elderly men may present with bone lesions , as a manifestation of reactivation of the disease . as there are no pathognomonic imaging signs of musculoskeletal tuberculosis ,", "the most conclusive means of reaching a diagnosis is by biopsy and culture , as chest radiographs and skin tests may not be positive in the elderly . as regards imaging techniques , magnetic resonance imaging is the modality of choice for musculoskeletal infection , as it best delineates the extension of soft tissue infections .", "computed tomography , ultrasound , radiography , and nuclear medicine studies are considered to be ancillary . in some circumstances ultrasound", "can be very useful , as it allows the aspiration of fluid collected in the joints or soft tissue , the evaluation of structures adjacent to orthopedic hardware , or the assessment of small peripheral joints . besides , in the case of debilitated elderly patients , a mobile ultrasound device can be easily moved close to their beds .", "( a ) on conventional radiography there is mild osteoporosis , extensive soft tissue swelling , and large marginal erosion ( arrowhead ) , ( b ) on doppler ultrasound the synovitis ( arrows ) and bone erosion ( arrowhead ) are well - depicted .", "paget 's disease is a bone disorder characterized by an increase in osteoclast - mediated bone resorption accompanied by osteoblast - mediated formation of new bone of inferior quality .", "the frequency of this condition is decreasing , but it still exists in 1 5 % of persons over 50 years of age , varying according to geographic areas . [ 5356 ] the radiographic signs include an advancing wedge of bone resorption , an accentuation and coarsening of the bone trabeculae along lines of stress , cortical thickening , and enlargement of the bone [ figure 13 ] . as a result , secondary osteoarthritis , insufficiency fractures , bowing of the bones , and even spinal cord or nerve root compression can be observed . in a minority of cases ,", "sarcomatous degeneration may develop , mainly in the humerus , pelvis , and proximal femur , with a frequency believed to range from 0.9 to 2 % .", "paget 's disease affecting the iliac bone demonstrated with coarsening of the bone trabeculae and cortical thickening ( arrows ) .", "tumors : tumors can be revealed by bone pain , pathological fractures , or disability , or be discovered as an incidental finding .", "primary bone tumors in elderly patients are not common , but , due to the risk of metastases , any newly discovered bone lesion or one developing within a known pre - existing lesion must be assumed to be malignant until proven otherwise .", "metastases : bone metastases are a common complication of malignant disease , especially of the breast , prostate , and lung .", "although they are often multiple , a solitary metastasis is still more common than a primary neoplasm .", "plain films are relatively insensitive for the detection of bone metastases , especially subtle lesions .", "mr imaging is superior to ct in the detection of malignant marrow infiltration , and it has a better contrast resolution for visualizing soft tissue and spinal cord lesions . even with the advances in mri , especially for bone marrow screening , bone scintigraphy continues to be used as an effective method for initial evaluation of the whole body for bone metastases .", "sarcomas : in the elderly population , many sarcomas are secondary to a pre - existing disorder of the bone , such as paget 's disease , or lesions treated by radiation .", "chondrosarcoma must also be kept in mind , especially when isolated osteolytic lesions of the pelvis are seen , as this is the most common primary sarcoma of bone in adults .", "the cartilaginous nature of the lesion may be suggested by the presence of calcifications or by a lobulated hyperintense lesion in an mri [ figure 14 ] .", "chondrosarcoma of the pelvis in ( a ) conventional radiography appears as an isolated osteolytic lesion ( arrows ) , ( b ) coronal t2-weighted image demonstrates a lobulated hyperintense lesion ( arrowheads ) .", "myeloma : myeloma is a characteristic disease in the elderly population , with a peak incidence in the eighth decade that results from an unregulated , progressive proliferation of neoplastic monoclonal plasma cells that accumulate in the bone marrow , leading to anemia and marrow failure .", "osteolytic lesions may be present on plain films , but differentiating osteoporotic vertebral compression fractures from those associated with myeloma is a common diagnostic dilemma , as bone loss may be the first sign revealing the latter disease .", "indeed , widespread osteoporosis , due to cytokine - mediated osteoclast activation , is common in patients with myeloma .", "this possible association must be kept in mind , particularly if other features are present , including unexplained back or bone pain ." ]

[ "musculoskeletal disorders are among the most common problems affecting the elderly .", "the resulting loss of mobility and physical independence can be particularly devastating in this population .", "the aim of this article is to present some of the most frequent musculoskeletal disorders of the elderly , such as fractures , osteoporosis , osteoarthritis , microcrystal disorders , infections , and tumors ." ]

[ [ 2, 1 ], [ 2, 5, 1 ], [ 1, 5, 23, 2 ] ]

[ 0.6020265548567436, 0.5778247840648687, 0.5054142075418672 ]

[ "migraine is the leading neurological cause for seeking medical care , and is associated with significant disability in the sufferer .", "the greatest impact is on migraineurs with headaches on more days than not , a condition defined as chronic migraine ( cm ) .", "cm is defined as at least 15 days of headache per month in which at least eight of the days fulfill migraine criteria and/or are treated with specific migraine medications , in the absence of a diagnosis of medication overuse headache .", "patients with cm often had a history of episodic migraine that began in adolescence or early adulthood , reporting a process of transformation marked by headaches that become more frequent over years . among migraineurs , defining risk factors for cm , or for the progression of episodic migraine to cm ,", "identified risk factors include medication overuse , obesity , sleep problems , and psychiatric comorbidity [ 712 ] .", "studies in both community and tertiary settings have demonstrated an association between migraine and several psychiatric conditions [ 8 , 9 ] . however ,", "the frequency of psychiatric disorders in both setting has not been compared before in a single study .", "furthermore , differences in methods of studies based in community or tertiary centers prevent appropriate comparison .", "population studies fail to conduct face - to - face assessments , while clinic - based studies carry the potential for selection bias .", "studies focusing on best methods to address this gap are of interest , and one strategy is to compare data obtained from the community with those from specialty care , where methods of collection have been virtually identical , and that was the scope of this study .", "we compared demographic data and psychiatric comorbidity in a sample of individuals with cm from the community with another from a tertiary care clinic . in light of the fact that patients suffering from migraine and comorbid psychiatric disorders are greater health - care service users", ", we hypothesized that the frequency of psychiatric disorders , notably depression , is higher in patients followed in tertiary care ." ]

[ "although the association between episodic migraine and psychiatric comorbidities is well documented , few studies have focused on the comorbidity with chronic migraine ( cm ) and discrepancies exist between population - based and clinic - based data .", "the objective of this study is to compare demographic and psychiatric comorbidity correlates between cm samples drawn from the community and tertiary care .", "all inhabitants from a city borough were interviewed for the presence of headaches occurring 15 or more days per month .", "cm was diagnosed after subjects had been interviewed and examined by a headache doctor .", "participants were also assessed with a structured interview by a psychiatrist , who assigned diagnoses based on the dsm - iv .", "the same investigators assessed all patients consecutively seen in a university - based outpatient headache center over a 4-month period .", "the samples consist of 41 individuals from the community and 43 from the headache center .", "sociodemographic profiles were similar between groups with the exception of the mean number of years of formal education . among individuals from the community , psychiatric diagnoses were present in 65.9 % of cases , relative to 83.7 % in those from the headache center ( p = 0.06 ) .", "phobias ( 41.9 vs. 29.3 % ) and depression ( 32.6 vs. 29.3 % ) were more frequent in patients from the headache center , but this difference did not reach statistical significance .", "thus the frequency of psychiatric disorders in patients with cm was elevated in both settings , being higher in the specialty care clinic ." ]

[ [ 10, 3, 6, 1, 5, 11, 9 ], [ 10, 3, 6, 1, 5, 9 ], [ 10, 9, 3, 11, 5 ], [ 10, 3, 6, 1, 9 ], [ 10, 3, 6, 1, 5, 11, 8 ], [ 10, 9, 3, 11, 6 ], [ 10, 9, 2, 6, 3 ], [ 10, 9, 2, 3, 5 ], [ 10, 9, 2, 6, 5 ], [ 10, 9, 3, 6 ] ]

[ 0.3757253122237641, 0.3728657953914219, 0.3625924362522083, 0.36024264132639733, 0.3601736203383825, 0.35712288591841707, 0.3550876144962167, 0.35110865619821663, 0.3458933681155904, 0.3446372906945719 ]

[ "m1dg ( 3- ( 2-deoxy -- d - erythro - pentofuranosyl ) -pyrimido [ 1,2- ] purine-10 ( 3h ) -one ) is one of many endogenous exocyclic lesions derived from the reaction of dna with bifunctional electrophiles generated by lipid , protein , or dna peroxidation .", "being an endogenous constituent of human and rodent genomes , m1dg is mutagenic in bacterial and mammalian cells and leads to mispairing when replicated in vitro by multiple different dna polymerases .", "we have previously developed a monoclonal antibody against m1dg and incorporated the antibody into analytical schemes using immunoaffinity purification of m1dg followed by mass spectrometric detection .", "these studies indicated that adult humans excrete m1dg at a rate of 12 fmol / kgd in urine .", "subsequent investigations into the metabolism and elimination of m1dg revealed that administration of m1dg to rodents at doses from 8 mg / kg to 6 pg / kg leads to its rapid disappearance from plasma due to oxidation and formation of the single , stable metabolite , 6-oxo - m1dg ( 3- ( 2-deoxy -- d - erythro - pentofuranosyl ) -pyrimido [ 1,2- ] purine-6,10 ( 3h,5h ) -dione ) . in both humans and rats ,", "xanthine oxidase appears to be responsible for this oxidation , while aldehyde oxidase also plays a role in m1dg metabolism in humans .", "because 6-oxo - m1dg is the sole metabolite of m1dg in rats , it appears to be an ideal surrogate for m1dg as an in vivo biomarker for oxidative stress .", "all studies of m1dg metabolism in vivo have been conducted with exogenously administered deoxynucleoside .", "thus , it is not known if 6-oxo - m1dg is actually present in unadulterated intact animals . in order to address this question", ", we developed a highly specific monoclonal antibody ( mab ) against 6-oxo - m1dg and covalently linked the antibody to sepharose beads .", "the resultant antibody - sepharose matrix ( the gel ) was used for the immunoaffinity purification of 6-oxo - m1dg from urine and feces followed by lc - ms / ms quantification against the stable isotope - labeled internal standard , [ n5 ] -6-oxo - m1dg . utilizing this method , we report for the first time that 6-oxo - m1dg is endogenously produced in rodents and is excreted in urine and feces ." ]

[ "oxidative stress triggers dna and lipid peroxidation , leading to the formation of electrophiles that react with dna to form adducts .", "a product of this pathway , ( 3- ( 2-deoxy -- d - erythro - pentofuranosyl ) -pyrimido [ 1,2- ] purine-10 ( 3h ) -one ) , or m1dg , is mutagenic in bacterial and mammalian cells and is repaired by the nucleotide excision repair pathway . in vivo , m1dg is oxidized to a primary metabolite , ( 3- ( 2-deoxy -- d - erythro - pentofuranosyl ) -pyrimido [ 1,2- ] purine-6,10 ( 3h,5h ) -dione , or 6-oxo - m1dg , which is excreted in urine , bile , and feces .", "we have developed a specific monoclonal antibody against 6-oxo - m1dg and have incorporated this antibody into a procedure for the immunoaffinity isolation of 6-oxo - m1dg from biological matrices .", "the purified analyte is quantified by lc - ms / ms using a stable isotope - labeled analogue ( [ 15n5 ] -6-oxo - m1dg ) as an internal standard .", "healthy male sprague dawley rats excreted 6-oxo - m1dg at a rate of 3501893 fmol / kgd in feces .", "this is the first report of the presence of the major metabolite of m1dg in rodents without exogenous introduction of m1dg ." ]

[ [ 10, 4, 6, 2, 3, 0 ], [ 10, 4, 6, 2, 0 ], [ 10, 4, 0, 6 ], [ 10, 4, 0, 2 ], [ 10, 0, 6, 2, 3, 1 ] ]

[ 0.5345595426164146, 0.5306375026805134, 0.519534630898474, 0.5165547843895779, 0.5101108232584917 ]

[ "central retinal vein occlusion ( crvo ) is a common sight - threatening vascular disease with prevalence rates ranging from 0.1 % 1 to 0.5 % 2 in the older adult population .", "crvo is characterized by occlusion of the central retinal vein and consecutive damming of the venous blood flow .", "the occlusion may occur at the level of or posterior to the lamina cribrosa.3 despite its prevalence , the pathogenesis of crvo is not completely understood .", "a combination of vascular , anatomic , and inflammatory factors may contribute to its pathophysiology.4 current treatment options include intravitreal injections of steroids5 or anti - vascular endothelial growth factor ( anti - vegf ) agents.68 fluorescein angiographic ( fa ) assessment is the most important tool for an adequate evaluation of the disease severity and for proper classification between the two types of crvo , ischemic and nonischemic .", "ischemic crvo is associated with a significant upregulation of vegf , a poor prognosis for visual acuity , and has a higher incidence of secondary neovascular glaucoma ( nvg ) ranging from 20 % to 60 % compared to nonischemic crvo with no risk of developing nvg.9 given these significant differences with various outcomes and risk profiles , it is crucial to differentiate between ischemic and nonischemic crvo .", "conventional fa images the retinal circulation within the posterior pole . however , it is not known if conventional fa devices are able to capture areas of interest regarding the intraocular metabolism of vegf , such as the peripheral retina .", "earlier findings suggested an association between peripheral retinal ischemia and an increased production of vegf.10,11 currently , two ultrawide - field systems are commercially available to perform fa and image the peripheral retina .", "one method uses a wide - field contact lens system ( ocular staurenghi 230 slo retina lens ; ocular instruments , inc , bellevue , wa , usa ) with the heidelberg retina angiograph ( hra ; heidelberg engineering gmbh , dossenheim , germany ) .12,13 the second available system uses the optos scanning laser ophthalmoscope ( optos plc , dunfermline , uk ) , which is a special non - contact - lens - based system that provides visualization up to the peripheral retina.1416 it has been shown that ultrawide - field fa ( uwfa ) is useful for the assessment of several retinal pathologies17 including retinal vein occlusions,18", "diabetes,19,20 uveitis,21 retinal vasculitis,22 choroidal masses,23,24 retinal detachment,25 and retinopathy of prematurity.26 the aim of this study was to evaluate a possible association between peripheral retinal nonperfusion obtained with uwfa and the number of intravitreal ranibizumab injections needed in patients with crvo ." ]

[ "purposeto evaluate the association between the size of peripheral retinal nonperfusion and the number of intravitreal ranibizumab injections in patients with treatment - nave central retinal vein occlusion ( crvo ) .methodsfifty - four patients with treatment - nave crvo and macular edema were included .", "each patient underwent a full ophthalmologic examination including optical coherence tomography imaging and ultrawide - field fluorescein angiography .", "monthly intravitreal ranibizumab injections were applied according to the recommendations of the german ophthalmologic society .", "two ophthalmologists quantified the areas of peripheral retinal nonperfusion ( group 1= less than five disc areas , group 2= more than five disc areas ) .", "correlation analyses between the size of nonperfusion with best - corrected visual acuity , central subfield thickness , and the number of intravitreal injections were performed.resultsbest-corrected visual acuity improved significantly after intravitreal injections ( p < 0.001 , both groups ) .", "final central subfield thickness after treatment did not significantly differ between both groups ( p=0.92 , p=0.96 , respectively ) .", "mean number of injections in group 1 and group 2 was 4.122.73 and 9.323.84 , respectively ( p < 0.001 ) .", "there was a significant positive correlation between areas of nonperfusion and the number of injections in each group .", "( r=0.97 , p < 0.001 ; r=0.94 , p < 0.001 , respectively ) .conclusionperipheral retinal nonperfusion in patients with crvo correlates significantly with the number of needed intravitreal ranibizumab injections .", "ultrawide - field fluorescein angiography is a useful tool for detection of peripheral retinal ischemia , which may have direct implications in the diagnosis , follow - up , and treatment of these patients ." ]

[ [ 8, 3, 6, 1, 0 ], [ 8, 3, 0, 6 ], [ 8, 3, 6, 1, 4 ], [ 8, 3, 0, 5 ], [ 8, 0, 6, 4 ] ]

[ 0.2785754382013654, 0.2699893385250081, 0.2648418016995828, 0.2581316679677335, 0.2558568581096741 ]

[ "small bowel obstruction ( sbo ) is one of the most feared complications after a gastric bypass . it can be chronic or acute and can range from a nuisance to the patient to a life - threatening emergency", "sbos related to adhesions occur after laparoscopic roux - en - y gastric bypass ( lgb ) , but ih formation , secondary to the reconstruction of the small intestine , is also of concern to bariatric surgeons .", "multiple defects in the mesentery of the bowel can occur and may lead to ih and , in an antecolic bypass , a defect is associated with the roux limb passing over the transverse colon .", "the reported incidence of sbo after lgb varies widely , perhaps because the technique used in the operation also varies widely , not only in placement of the roux limb , but regarding closure or nonclosure of the mesenteric defects .", "the disparity in reports leads to confusion regarding the true incidence and even the causes of sbo after lgb .", "in addition , the closure of mesenteric defects is questioned in a substantial body of literature .", "the objective of this study was to examine the incidence and characteristics of sbo after antecolic antegastric bypass with nonclosure of the mesenteric defect of the jejunojejunal ( jj ) anastomosis ." ]

[ "background and objectives : there is a wide variation of reported incidence of small bowel obstruction ( sbo ) after laparoscopic roux - en - y gastric bypass ( lgb ) .", "there is also wide variation in technique , not only in placement of the roux limb , but also regarding closure or nonclosure of the mesenteric defects .", "the objective of this study was to examine the incidence and characteristics of sbo after antecolic antegastric bypass with nonclosure of the mesenteric defect of the jejunojejunal anastomosis.methods : this is a retrospective review of a series of consecutive lgbs over a 3-year period .", "all procedures were performed by the same surgeon using the same technique . in no case was the mesenteric defect closed . a prospectively maintained database", "was used for data collection .", "patients who returned with an sbo were the study group , and those who underwent revisional bariatric surgery or conversion to open operation were excluded.results : there were 249 primary lgbs performed during the study period ; 15 of the operations were followed by sbo , for an incidence of 6.0 % .", "four cases were caused by an internal hernia ( ih ) , for an incidence of 1.6 % , and 11 were caused by adhesions , which accounted for 73 % of the sbos.conclusions : sbo after lgb is a relatively common complication .", "the incidence of sbo from ih with nonclosure of the mesenteric defect is similar to that in other series where the defect is closed .", "regardless of the cause of the sbo , operative treatment of the patient who has a gastric bypass remains the definitive standard and should not be delayed ." ]

[ [ 3, 6, 0, 2, 4, 5, 1 ], [ 3, 6, 0, 2, 4, 1 ], [ 3, 6, 1, 2, 0 ], [ 3, 6, 1, 2, 4 ], [ 3, 6, 1, 0 ] ]

[ 0.46915779258918766, 0.4639773140256855, 0.45174967957316153, 0.444943494639235, 0.43704867662947605 ]

[ "cigarette smoke ( cs ) is associated with the development of inflammation - related diseases such as chronic obstructive pulmonary disease and vascular diseases , including atherosclerosis and stroke .", "several studies have revealed that cs is a major contributor to vascular diseases because it accelerates the development of atherosclerotic plaques .", "the relationship between cs and the increased incidence of atherosclerosis has been reported [ 57 ] , which may be a consequence of direct endothelial damage , increased proliferation of smooth muscle in atherosclerotic lesions , and/or decreased vasodilation .", "endothelial damage has also been suggested as the initial cause of development of vascular diseases . in a previous study , it was shown that inhibition of oxidative stress exerts protection in human endothelial cells , which could be an effective strategy in the treatment of vascular diseases .", "a number of studies support that reactive oxygen species ( ros ) causing oxidative stress may play an essential role in mediating endothelial cell death .", "oxidative stress is a major factor in vascular diseases such as hypertension , stroke , and atherosclerosis .", "korean red ginseng ( krg ) is a popular traditional herbal medicine that has been widely used to treat several diseases such as cancer and vascular diseases .", "recent research shows that ginseng may have therapeutic potential in the treatment of alzheimer 's disease , diabetes , cancer , and cardiovascular diseases , through its antioxidant , antithrombotic , antihyperlipidemic , and anticancer effects [ 1215 ] . in endothelial cells", ", krg simulates no production in vivo and in vitro , suggesting that krg has antihypertensive effects .", "krg also promotes angiogenesis through the activation of the signaling pathway , indicating that krg can be implicated in potential angiogenic therapies for improving tissue repair , wound healing , and cardiovascular diseases .", "in addition , our previous study suggested that krg exerts a cytoprotective effect through the induction of heme oxygenase ( ho ) -1 expression , suggesting a possible therapeutic mechanism of krg in cardiovascular diseases .", "it is well known that chronic inflammation contributes to the pathogenesis of many human diseases such as atherosclerosis .", "accumulating evidence suggests that krg is involved in the regulation of inflammatory responses , suggesting an anti - inflammatory effect of krg .", "cyclooxygenase ( cox ) catalyzes the conversion of arachidonic acid to prostaglandins that play vital roles in multiple physiological and pathophysiological processes , including inflammation .", "in particular , cox-2 is normally undetectable in most tissues and is induced in response to numerous stimuli .", "vascular diseases may , in part , be caused by cox-2 upregulation at sites of inflammation and vascular injury .", "cox-2 plays an important role in inflammation , therefore , inhibition of cox-2 expression may participate in the treatment of inflammation - related diseases such as vascular diseases .", "the objective of our study was to investigate the vascular protective effect of krg in acrolein - stimulated human umbilical vein endothelial cells ( huvecs ) .", "therefore , we examined the involvement of cox-2 expression via p38 mitogen - activated protein kinase ( mapk ) , intracellular ros , and apoptosis in acrolein - stimulated huvecs ." ]

[ "cigarette smoke is considered a major risk factor for vascular diseases .", "there are many toxic compounds in cigarette smoke , including acrolein and other , -unsaturated aldehydes , which are regarded as mediators of inflammation and vascular dysfunction .", "furthermore , recent studies have revealed that acrolein , an , -unsaturated aldehyde in cigarette smoke , induces inflammatory mediator expression , which is known to be related to vascular diseases . in this study , we investigated whether korean red ginseng ( krg ) water extract suppressed acrolein - induced cyclooxygenase ( cox ) -2 expression in human umbilical vein endothelial cells ( huvecs ) .", "acrolein - induced cox-2 expression was accompanied by increased levels of phosphorylated p38 in huvecs and krg inhibited cox-2 expression in huvecs .", "these results suggest that krg suppresses acrolein - induced cox-2 expression via inhibition of the p38 mitogen - activated protein kinase signaling pathway .", "in addition , krg exhibited an inhibitory effect on acrolein - induced apoptosis , as demonstrated by annexin v", "propidium iodide staining and terminal deoxynucleotidyl transferase - mediated dutp nick end - labeling assay .", "consistent with these results , krg may exert a vasculoprotective effect through inhibition of cox-2 expression in acrolein - stimulated human endothelial cells ." ]

[ [ 3, 17, 16, 14, 1, 18 ], [ 3, 17, 16, 14, 1, 9, 18 ], [ 3, 18, 16, 10, 6, 1, 17 ], [ 3, 18, 16, 10, 6, 17 ], [ 3, 18, 17, 14, 16 ], [ 3, 18, 16, 10, 17 ], [ 3, 18, 17, 14, 15 ], [ 3, 18, 16, 10, 6, 1, 15 ], [ 3, 18, 17, 16 ] ]

[ 0.3796687975962883, 0.37951579875187785, 0.3785801436606641, 0.37468876195258716, 0.36912997903563943, 0.3667655570978834, 0.3605171056237144, 0.35865294309317086, 0.35582045621780717 ]

[ "ionic calcium ( ca ) controls multiple cellular signaling processes in all eukaryotic cells , including proliferation , gene expression , and neurotransmitter release .", "ca - binding proteins such as calmodulin play a pivotal role in ca signal transmission and amplification .", "increases in the concentration of intracellular ca activate specific protein targets , among which the ca / calmodulin - dependent protein kinase ii ( camkii ) is a critical signal mediator . in response to an increase in intracellular ca , thr-286 of camkii", "the coupling of ca - calmodulin to one of the camkii subunits allows for the phosphorylation of an adjacent subunit at thr .", "calmodulin trapping , confers ca - calmodulin - independent kinase activity to the complex and thus prolongs the ca signal .", "thus , calmodulin trapping represents a molecular mechanism of memory , which is defined as the capacity to acquire , store ( consolidate ) , and retrieve ( evocate ) information .", "camkii is a major synaptic protein that is activated during the induction of long - term potentiation ( ltp ) by ca influx through n - methyl - d - aspartate ( nmda ) receptors .", "calmodulin trapping allows camkii to remain activated long after the initial ca signal has dissipated , suggesting that camkii is a memory molecule crucial for ltp .", "consistent with this notion , camkii - null mice present with impaired memory formation , and camkii is essential for genesis and maintenance of ltp in postsynaptic neurons .", "following presynaptic stimulation , camkii is activated in postsynaptic neurons , which creates a physiological imprint of the initial ca signal , and increases translocation of nmda receptors to the plasma membrane .", "because of its capacity to remain activated long after the initial pulse of ca signaling , camkii perpetuates ca effects and modulates gene expression and the epigenetic profile of postsynaptic neurons .", "camkii also participates in glucose - stimulated insulin secretion ( gsis ) , as multiple insulin secretagogues increase camkii activity . in the perfused rat pancreas ,", "the dynamics of camkii activation correlate with the amplitude of gsis , and camkii activation is temporally associated with insulin secretion .", "camkii is essential for appropriate gsis and is involved in several steps of this process , including the synthesis of insulin granules , the modulation of cytoplasmic content of atp , and the activation of synapsin .", "importantly , camkii also regulates transcription factors central for - cell function such as creb and mafa . here", ", we investigated whether pancreatic - cells , like neurons , acquire and store the information contained in calcium pulses as a form of metabolic memory .", "indeed , we find that - cells retain memory of prior activation , and describe the molecular mechanism that contributes to this memory ." ]

[ "ca2+/calmodulin - dependent protein kinase ii ( camkii ) functions both in regulation of insulin secretion and neurotransmitter release through common downstream mediators .", "therefore , we hypothesized that pancreatic - cells acquire and store the information contained in calcium pulses as a form of metabolic memory , just as neurons store cognitive information . to test this hypothesis , we developed a novel paradigm of pulsed exposure of - cells to intervals of high glucose , followed by a 24-h consolidation period to eliminate any acute metabolic effects .", "strikingly , - cells exposed to this high - glucose pulse paradigm exhibited significantly stronger insulin secretion .", "this metabolic memory was entirely dependent on camkii .", "metabolic memory was reflected on the protein level by increased expression of proteins involved in glucose sensing and ca2 + -dependent vesicle secretion , and by elevated levels of the key - cell transcription factor mafa . in summary , like neurons ,", "human and mouse - cells are able to acquire and retrieve information ." ]

[ [ 2, 5, 16, 14, 0, 15 ], [ 2, 5, 16, 14, 15 ], [ 2, 5, 16, 14, 0, 13, 15 ], [ 15, 2, 16, 5 ], [ 15, 2, 16, 14 ], [ 15, 5, 13, 2 ], [ 15, 5, 13, 14 ], [ 15, 2, 5 ] ]

[ 0.3754370629370629, 0.3722113157809244, 0.3659020107618238, 0.35887018461070075, 0.3555244568839131, 0.3463393331814384, 0.34473648557106085, 0.3410561779660492 ]

[ "health is not only related to the absence of the disease , therefore we need to conceptualize and operationalize what health is . increasingly , we have come to understand that information about functional status is needed in order to appreciate the full picture regarding the health of an individual or a population .", "an individual 's health fundamentally includes their capacity to carry out the full range of actions , activities and tasks required to fully engage in all areas of human life .", "the health state of a person can be described in terms of capacity to carry out a set of tasks or actions .", "in addition , the health state also includes changes in body functions and/or structures arising from a health condition .", "the impact of the health state on a person 's life can be understood by measuring performance of tasks and actions in the person 's real - life or actual environment .", "the full picture of the health experience can further be appreciated by taking into cognizance the value that people place on levels of functioning in given domains in association with a health condition . plainly , the concept of functional status is integral to health and its achievement .", "two individuals with identical diagnoses may have utterly different levels of functioning that determine their actual health status . without fsi ,", "our picture of the health of an individual , or a population , is flawed and incomplete .", "fsi has , of course , long been collected in various ways and used clinically , especially in rehabilitative medicine ; physical , occupational and speech and language therapy ; and in nursing home and home care settings .", "fsi is essential for needs assessment as well as the development and monitoring of rehabilitative interventions to restore or maintain functions .", "it is also essential in this area of health care because the aim of therapy is to assist patients in maximizing their capacities to perform activities needed for their lives .", "although no one doubts that restoring functioning is restoring health ( the ultimate purpose of all forms of health care ) some clinicians , focusing exclusively on acute - care needs , do not see the need to collect or utilize fsi . in most countries with a sophisticated health administrative data collection and utilization infrastructure , a wide variety of information", "what is often missing is information that would link diagnosis and treatment with health outcomes that are fully meaningful to the patient 's life , namely information about the presence of decrements in capacity to carry out tasks and actions in areas of life as well as how these decrements play out in the person 's actual , real - life environment ( deyo and patrick , 1989 ; lubetkin et al . , 2003 ) .", "there is growing recognition that there is a gap in health administrative records : the failure to collect or disseminate fsi across all health care settings . unless fsi becomes an essential part of administrative records ,", "the potential value of these data will be lost , not merely to clinicians , but to health administrators concerned about management and quality of care issues , health researchers , and public health agencies .", "this insight is clearly expressed in a report by the national committee on vital and health statistics ( ncvhs ) ( 2001 ) : without functional status information , the researchers , policymakers , and others who are already using administrative data have at best a rough idea of how people , individually and collectively , are doing and at worst they are making erroneous assumptions and decisions .", "the report outlines in some detail the benefits of routinely collecting fsi across the entire health care delivery system and throughout all care settings .", "fsi can serve management needs of all the stakeholders in the health care system clinicians , providers , payers , patients , and government regulatory bodies . this is true especially with respect to evaluating outcomes , comparing treatment modalities , and predicting and managing costs .", "this links directly to debates of modes of service provision , single or multiple payer , managed care , fee - for - service , or some hybrid mixture .", "the policy and research applications of fsi are evident for local health management and quality control , and in the broader arena of public health .", "policy decisions about priorities must be made at the level of individual clinics or hospitals , local or regional health care agencies , or at the level of government planning and budgeting . given the importance of getting the complete picture of health outcomes , fsi is an essential input into evidence - based policy decisionmaking .", "researchers in all areas of health and social policy , at all levels , need valid and reliable data about functional status in order to make informed decisions .", "for example , it is a matter of debate whether , as the world 's population lives longer and ages , they will be unhealthy and pose a greater burden on health systems . there is some evidence suggesting that elderly persons today are functioning at higher levels than before .", "without reliable information on levels of functioning , this debate would be unresolvable because it would not be possible to detect functional status , since the disease morbidity may not have changed very much .", "compression of morbidity occurs when disability or decrement in functioning is postponed more than longevity is extended , as for example with the effects of exercise or better eating habits .", "the direct test of compression ( or extension ) of morbidity depends on the effects of reduced health risks on cumulative lifetime disability ( fries , 1980 , 2001 ; vita et al . ,", ", fsi is a crucial element for the description of health states and quantification of overall health status in individuals that can be aggregated to a summary measure of population health . at the who , the use of fsi is in this area , in particular , because this data ( collected by the world health survey now in the field in more than 70 countries ) feeds into ongoing endeavors to determine levels and distributions of health", "this survey would be inconceivable without information on health outcomes that describe health on multiple dimensions in terms of levels of functioning in a parsimonious set of domains .", "it is commonly known that the demographic trends toward an older population , at least in developed counties , will create unprecedented burdens on all age - sensitive social policies , such as social security and other pensions , retirement , unemployment , and long - term care .", "aging , according to a recent organization for economic cooperation and development ( oecd ) ( 2001 ) report , is the principal factor currently driving pension spending costs . since age - sensitive social programming constitutes between 40 and 60 percent of total public spending", ", the impact of aging is considerable . to comprehend the nature and magnitude of its social impact", ", those responsible for policies from transportation and housing to employment and taxation , will need reliable data on functional status and how it plays out in the lives of the aging population . for fsi to be available for this wide variety of uses , however ,", "it must be routinely and consistently collected across the entire health care delivery system , preferably in some electronic format .", "nonetheless , before contemplating the systemwide changes required to collect fsi , a classification that provides a common language and framework to describe the universe of functioning and disability is required . in order to complement the classification scheme , a comprehensive coding system that creates consistent and comparable data across all settings of care and a method of routinely capturing and disseminating these data ( in a mode and manner consistent with social interests in preserving privacy ) linked to measurement tools for clinical and related encounters", "the foundation of a new structure for collecting fsi is , therefore , a standard classification and coding system that will make it feasible for fsi to be included in administrative data . as the ncvhs report stated : while the international classification of diseases ( icd ) has served us well for more than a century in characterizing diagnoses , it is now time to complement it with a parallel system for characterizing functional status .", "although the committee argued that more research , analysis , testing , and demonstration projects are required before final recommendations can be made , it concluded that : the concepts and conceptual framework of the icf have promise as a code set for reporting functional status information in administrative records and computerized medical records . in the committee 's view , the icf is the only existing classification system that could be used to code functional status across the age span . in this article , we want to briefly describe the extensive international developmental process that lead to the revision of the original international classification of impairments , disabilities and handicaps ( icidh ) ( world health organization , 1980 ) and produced the icf .", "we also want to describe the basic principles and structure of the icf , in particular , to show its value in the context of collecting fsi for administrative records ." ]

[ "a common framework for describing functional status information ( fsi ) in health records is needed in order to make this information comparable and of value .", "the world health organization 's ( who 's ) international classification of functioning , disability and health ( icf ) , which has been approved by all its member states , provides this common language and framework . the biopsychosocial model of functioning and disability embodied in the icf goes beyond disease and conceptualizes functioning from the individual 's body , person , and lived experience vantage points , thereby allowing for planning interventions targeted at the individual 's body , the individual as a whole or toward the environment .", "this framework then permits the evaluation of both the effectiveness and cost effectiveness of these different interventions in devising programs at the personal or societal level ." ]

[ [ 33, 4, 21 ], [ 33, 4, 0 ], [ 35, 21, 4 ], [ 35, 21, 7 ], [ 35, 33 ] ]

[ 0.3035049745576061, 0.3013729246487868, 0.3007963594994312, 0.2930969510106201, 0.2723268781921699 ]

[ "the centers for disease control and prevention ( cdc ) and united states preventive services task force ( uspstf ) recommend universal hiv screening for all pregnant women entering prenatal care [ 1 , 2 ] .", "this screening enables hiv - infected women and their infants to benefit from appropriate and timely interventions such as antiretroviral medications .", "when the recommended antiretroviral and obstetric interventions are used , a woman who knows of her hiv infection early in pregnancy now has a less than 2 % chance of delivering an hiv - infected infant . without intervention , this risk is approximately 25 % in the united states [ 36 ] .", "testing for hiv began in 1985 with the introduction of the enzyme immunoassay ( eia ) . in order to account for false positive results using screening tests in a low - prevalence population", ", confirmatory testing has been implemented using a western blot or immunofluorescence assay . in a low - prevalence population ,", "the false positive rate using the eia is increased compared to a high - prevalence population , and the positive predictive value of any test will always depend on the prevalence of the condition in the population tested . in testing performed by the cdc ,", "the eia positive predictive value ranges from 71 to 83 % in populations with hiv prevalence from 0.5 to 1 % .", "some investigators believe that the presence of alloantibodies account for the increased false positive rate associated with pregnancy , transfusions , transplantation , and autoimmune diseases . however , risk factors specific to pregnancy that account for this are poorly understood .", "conversely , a recent large retrospective study found that the false positive hiv eia rate was lower in pregnant women compared to nonpregnant individuals ( 0.14 % versus 0.21 % ) .", "our objective was to determine if any maternal characteristics correlated with false positive hiv eia testing at delivery ." ]

[ "objective . to examine risk factors for false positive hiv enzyme immunoassay ( eia ) testing at delivery", ". study design .", "a review of pregnant women who delivered at parkland hospital between 2005 and 2008 was performed .", "patients routinely received serum hiv eia testing at delivery , with positive results confirmed through immunofluorescent testing .", "demographics , hiv , hepatitis b surface antigen ( hbsag ) , and rapid plasma reagin ( rpr ) results were obtained .", "statistical analyses included pearson 's chi - square and student 's t - test . results .", "of 47,794 patients , 47,391 ( 99 % ) tested negative , 145 ( 0.3 % ) falsely positive , 172 ( 0.4 % ) positive , and 86 ( 0.2 % ) equivocal or missing hiv results .", "the positive predictive value of eia was 54.3 % .", "patients with false positive results were more likely nulliparous ( 43 % versus 31 % , p", "< 0.001 ) and younger ( 23.9 5.7 versus 26.2 5.9 years , p < 0.001 ) .", "hiv positive patients were older than false positive patients and more likely positive for hbsag and rpr .", "conclusion .", "false positive hiv testing at delivery using eia is associated with young maternal age and nulliparity in this population ." ]

[ [ 5, 9, 3, 7, 8 ], [ 5, 9, 3, 7, 6, 8 ], [ 5, 9, 3, 8 ], [ 5, 9, 3, 7, 6, 0 ] ]

[ 0.29170574513623354, 0.29027563773326487, 0.2844337626216821, 0.2687786777321151 ]

[ "childhood obesity is a serious and growing public health problem that has arisen over the past three decades .", "the increasing occurrence of disorders such as type 2 diabetes during childhood is believed to be a consequence of this obesity epidemic .", "in addition to several behavioral and dietary risk factors , genetic predisposition is an important factor in the pathogenesis of childhood obesity .", "it is estimated that 4070 % of adiposity variance can be explained by direct or indirect genetic factors .", "growth arrest - specific 6 ( gas6 ) , cloned in 1988 and characterized in 1993 , is a secreted vitamin k - dependent protein present in the human circulatory system [ 4 , 5 ] .", "initially , gas6 was shown to be upregulated in growth - arrested fibroblasts , suggesting that it plays a protective role in certain cellular stresses such as during apoptosis .", "gas6 expression is widespread in many tissues , including immune cells , endothelial cells , vascular smooth muscle cells , and adipocytes [ 79 ] .", "the protein is also a ligand for the tam ( tyro-3/axl / mer ) family tyrosine kinase receptor .", "the gas6/tam system has been implicated in cell survival and proliferation , cell adhesion and migration , hemostasis , and inflammatory cytokine release [ 4 , 10 ] .", "recently , the gas6/tam pathway was found to be involved in mediating adipocyte survival and proliferation in vitro [ 11 , 12 ] .", "experiments with mice fed a high - fat diet indicated that overexpression of gas6 might enhance body - fat accumulation , but blocking gas6 signaling using an axl antagonist could reduce body - fat mass and body weight", ". interestingly , transgenic animals that ectopically express the axl tyrosine kinase receptor also develop progressive obesity with elevated circulating proinflammatory cytokines and severe systemic insulin resistance .", "this protein - array study also revealed higher levels of axl mrna in subcutaneous adipose tissue of obese humans than their lean control counterparts had .", "this indicates that the axl receptor may be involved in the development of human obesity .", "in addition , some studies in transgenic mice indicate that gas6/axl signaling might recruit macrophages and other immune cells into the adipose tissue resulting in the production and secretion of proinflammatory mediators .", "this suggests that the gas6/axl signaling might play a role in the pathogenesis of obesity - associated systemic inflammation [ 8 , 16 , 17 ] .", "recent studies have indicated that systemic inflammation , a hallmark of childhood and adult obesity , is a pivotal mechanism linking obesity to insulin resistance and type 2 diabetes [ 1821 ] . although gas6 gene polymorphisms are reported to be associated with stroke , acute coronary syndrome , and type 2 diabetes [ 2224 ] , to our knowledge , both gas6 and axl gene polymorphisms associated with childhood obesity have not yet been identified . in order to address this issue", ", we conducted a community - based study to determine whether common variations in the gas6 and axl genes correlate with adiposity , systemic inflammation , insulin resistance among adolescents ." ]

[ "the present study was designed to explore the effects of gas6 and axl gene polymorphisms on adiposity , systemic inflammation , and insulin resistance in adolescents .", "after multistage sampling from the data of the taipei children heart study - iii , we collected 358 boys and 369 girls with an average age of 13.3 years .", "we genotyped the adolescents ' gas6 rs8191973 , gas6 rs8191974 , axl rs4802113 , and axl rs2304232 polymorphisms .", "significantly higher body mass index ( bmi ) , waist circumference ( wc ) , and hscrp levels were found in boys with the gg genotype of gas6 rs8191974 than a allele carriers ; higher il-6 and insulin levels and increased homa - ir were found in boys with the gg genotype of axl rs2304232 than the a allele carriers . there was a significant difference in hscrp levels of boys with the tt , tc , and cc genotypes of axl rs4802113 .", "boys with both the gg genotype of gas6 rs8191973 and the gg genotype of gas6 rs8191974 exhibited higher bmi , wc , il-6 , and hscrp levels than the boys carrying both the c allele of the gas6 rs8191973 and the a allele of the gas6 rs8191974 . in conclusion ,", "gas6 and axl polymorphisms are associated with adiposity , systemic inflammation , and insulin resistance in adolescents , especially in boys ." ]

[ [ 16, 14, 15, 9, 10, 12, 17 ], [ 17, 15, 14, 12, 10, 16 ], [ 16, 14, 15, 9, 10, 17 ], [ 17, 15, 14, 12, 16 ], [ 16, 14, 15, 9, 17 ], [ 17, 15, 14, 12, 10, 13 ], [ 16, 14, 15, 17 ], [ 16, 14, 15, 9, 10, 12, 11 ], [ 16, 17, 14 ], [ 16, 17, 15 ] ]

[ 0.26033590000517975, 0.2584220458771987, 0.25441489500169207, 0.25170710768017657, 0.24726362823949954, 0.2429005404978893, 0.240545824522204, 0.23930519666953778, 0.22240367255472995, 0.22105198859343708 ]

[ "infertility is one of the crucial and critical events in sex life which engages 1015 % of couples all over the world , and as one of the most distressful life experiences , exposes couples to social and psychological problems .", "couples , who are faced with this critical situation , are prone to depression , anxiety , loss of self - esteem and dissatisfaction with their sex life more than others .", "however , the intensity of psychological problems resulting from cultural - social circumstances varies in different societies , to the point that the frequency of anxiety in infertile couples has been reported in a wide range from 48 % to 96 % . although , the advances in assisted reproductive techniques have opened new doors for infertile couples , but studies have shown that these treatments are accompanied with stress , anxiety and depression . but the intensity of these disorders could be defined by the cause of the infertility . evaluating the related factors of depression and anxiety among iranian infertile couples showed that women who were infertile themselves showed higher levels of anxiety and depression than women with male factor infertility . however , in societies that define women as the main source of fertility , starting assisted reproductive treatments with limited successful outcomes could be harmful to these women 's mental health .", "utilization of assisted reproductive techniques requires processes such as daily injection to stimulate ovulation , vaginal ultrasound and painful processes such as oocyte aspiration which are all too expensive and alongside with the fear of failure could become a harmful condition .", "although , fertile women , who start assisted reproductive treatments due to their husband 's infertility have natural biological conditions to get pregnant , but they have to tolerate these critical processes due to male factor infertility . also , women are under more cultural and social pressures", ". these conditions could affect the vulnerability of fertile women during assisted reproductive treatment ; therefore the aim of this study was to evaluate the effect of assisted reproductive treatments on fertile women 's mental health ." ]

[ "introduction : the process of assisted reproductive treatment is a stressful situation in the treatment of infertile couples and it would harm the mental health of women .", "fertile women who started infertility treatment due to male factor infertility have reported to experience less stress and depression than other women before the assisted reproductive process but considering the cultural and social factors and also the etiology of the assisted reproductive process , it could affect the metal health of these women . therefore , this study was conducted to evaluate the mental health of fertile women who undergo assisted reproductive treatment due to male factor infertility.materials and methods : this study was a prospective study on 70 fertile women who underwent assisted reproductive treatment due to male factor infertility .", "the exclusion criterion was to stop super ovulation induction . to assess", "mental health , anxiety and depression dimensions of the general health questionnaire were used . before starting ovulation induction and after oocyte harvesting , the general health questionnaire was filled by women who were under treatment .", "data were analyzed using multi - variable linear regression , paired t - test , and chi-square.results : the results showed that the mean score of depression and anxiety before ovulation induction and after oocyte harvesting were not significantly different ; but the rate of mental health disorder in the depression dimension was significantly decreased after oocytes harvesting ( 31.7 % vs. 39.7 % ) . also , there was a significant relation between the level of anxiety and depression before ovulation induction and after oocyte harvesting ( p < 0.05 ) .", "the anxiety level after oocyte harvesting had a positive and significant correlation with the economic situation ( p < 0.05 ) .conclusion : this study revealed that the process of assisted reproductive treatment does not affect the mental health in fertile women independently , but these women start assisted reproductive process with high levels of depression and anxiety .", "therefore , prior to the assisted reproductive treatment mental health consultation is needed ." ]

[ [ 2, 5, 3, 1, 4 ], [ 2, 5, 3, 4 ], [ 2, 4, 3, 0, 5 ], [ 2, 5, 3, 1, 0, 4 ], [ 5, 4, 0, 2 ], [ 2, 5, 4 ] ]

[ 0.37022668153102933, 0.3695816378743208, 0.3668306911153573, 0.3665047363585046, 0.36451122759175414, 0.36231496343855896 ]

[ "balance impairment is an important fall - risk factor , and increases in range of postural sway in the mediolateral direction in older adults are associated with increased fall - risk and rates .", "postural sway has been shown in older adults to be strongly related to other measures of balance .", "multivariate analysis reveals serum vitamin d levels as an independent variable associated with postural sway . in individuals with suboptimal levels of vitamin d ,", "epidemiological studies have shown that vitamin d levels show seasonal variation [ 7 , 8 ] .", "lowest levels of serum vitamin d are recorded towards the end of winter , approximately four weeks after the shortest day of the year .", "overall , vitamin d supplementation did not reduce rate of falls ( rar 1.00 , 95 % ci 0.90 to 1.11 ; seven trials ; 9324 participants ) or risk of falling ( rr 0.96 , 95 % ci 0.89 to 1.03 ; 13 trials ; 26 , 747 participants ) but may do so in people with lower vitamin d levels before treatment .", "older adults are at risk for lower levels of serum vitamin d because of age - related changes in uvb absorption and skin capacity to synthesize vitamin d , reduction in activation in the kidneys , and reduced expression of vitamin d receptors in tissues .", "there are many factors affecting fall - risk for older individuals , and although these may be different for inside and outside falls , strength and balance remain two important physical fall - risk factors .", "a recently published overview of the literature supports an assertion that age - related changes in postural reactions may be related to vitamin d status - mediated through either central nervous system integration or antigravity muscles as the effectors in postural responses . despite changes in vitamin d across the seasons , muscle strength in the quadriceps muscles has been shown to remain stable .", "the relationship of postural sway to any potential increased winter fall rate and decreased levels of vitamin d has not been investigated .", "the winter season sees an increase in injuries from falls and in the number of accidental deaths from falls .", "fracture rates from falls in older adults also increase at the end of the winter season , following two to eight weeks after the nadir in serum vitamin d levels .", "some studies report an increased rate of falls , for both inside and outside falls [ 13 , 14 ] ; however , significant seasonal variation in fall rates was not found in a three - year study while , in a second study , seasonal variation in fall rates was reported in women but not in men .", "coincident static balance changes with any potential increased fall rates in winter have not been previously reported .", "the data presented here forms part of a larger study , from which two other papers with the same clinical trial registration have been published [ 12 , 16 ] . the aim of this study was to determine differences in static balance ( postural sway ) , vitamin d , incidence of falls , and type of fall serially at the end of each season over a 12-month period , in older community - living adults .", "we hypothesised that postural sway , falls , and vitamin d would show a seasonal variation and that there would be an inverse relationship between vitamin d and the other variables ." ]

[ "introduction .", "low serum vitamin d levels are associated with increased postural sway .", "vitamin d varies seasonally .", "this study investigates whether postural sway varies seasonally and is associated with serum vitamin d and falls", ". methods . in a longitudinal observational study , eighty - eight independently mobile community - dwelling older adults ( 69.7 7.6 years ) were evaluated on five occasions over one year , measuring postural sway ( force platform ) , vitamin d levels , fall incidence , and causes and adverse outcomes .", "mixed - methods poisson regression was used to determine associations between measures . results .", "postural sway did not vary over the year .", "vitamin d levels varied seasonally ( p < 0.001 ) , peaking in summer .", "incidence of falls ( p = 0.01 ) and injurious falls ( p = 0.02 ) were lower in spring , with the highest fall rate at the end of autumn .", "postural sway was not related to vitamin d ( p = 0.87 ) or fall rates , but it was associated with fall injuries ( irr 1.59 ( ci 1.14 to 2.24 , p = 0.007 ) .", "conclusions .", "postural sway remained stable across the year while vitamin d varied seasonally .", "participants with high values for postural sway demonstrated higher rates of injurious falls .", "this study provides important evidence for clinicians and researchers providing interventions measuring balance outcomes across seasons ." ]

[ [ 14, 5, 2, 0, 15 ], [ 14, 5, 2, 12, 15 ], [ 14, 5, 2, 0, 9 ], [ 14, 5, 12, 6, 0, 2 ], [ 14, 12, 6, 15, 2 ], [ 14, 5, 2, 12, 0 ], [ 14, 5, 12, 6, 2 ], [ 14, 5, 12, 6, 0, 3 ], [ 14, 12, 6, 15, 9 ], [ 14, 12, 2, 15 ], [ 14, 12, 2, 6 ] ]

[ 0.33601231020608885, 0.33044990219517495, 0.33027929658637506, 0.33001321166037506, 0.32715533259011514, 0.32350274113615185, 0.32074650778294767, 0.3169683084789226, 0.3150694788840593, 0.3139746612232381, 0.31376444399700215 ]

[ "since the dawn of history , nature and natural sources , such as plants , animals , microbes , and minerals have remained a veritable source of bioactive compounds with medicinal values . among these sources , plants have been the most explored and exploited for their bioactive medicinal components .", "lead compounds or templates for the rational development of drugs are of more specific efficacies and fewer side effects ( 1 ) .", "one of the botanicals of interest in which the abortifacient claims in the folk medicine have been substantiated by scientific evidence ( 2 ) but with no documentation in the open scientific literature on its bioactive abortifacient agent ( s ) is senna alata .", "senna alata ( linn . ) roxb ( leguminosae ) , also known as craw - craw plant or ringworm plant ( english ) , asunwon oyinbo ( yoruba - western nigeria ) , nelkhi ( igbo - eastern nigeria ) , filisko or hantsi ( hausa - northern nigeria ) is an erect tropical , annual herb which grows up to 0.15 m high .", "the fruit is a pod , while the seeds are small and square in shape .", "the plant has been claimed to be used in the management of several diseased conditions such as hepatitis , dermatitis , jaundice , gastroenteritis , eczema , constipation and diarrhoea ( 3 , 4 ) .", "previous studies have shown that s. alata have antifungal , antibacterial and antioxidant activities ( 3 , 58 ) .", "furthermore , yakubu et al . ( 2 ) reported that the aqueous leaf extract of the plant contained saponins ( 1.22 % ) , flavonoids ( 1.06 % ) , cardiac glycosides ( 0.20 % ) , phenolics ( 0.44 % ) , alkaloids ( 0.52 % ) , cardenolides and dienolides ( 0.18 % ) .", "aqueous leaf extract of s. alata has also been scientifically validated for its acclaimed use as an abortifacient ( 2 ) .", "however , there is no study in the open scientific literature that has reported on the exact bioactive abortifacient agent ( s ) in s. alata leaves .", "therefore , the present study aimed to validate the speculation that the alkaloids in aqueous extract of s. alata leaves are responsible for its abortifacient activity .", "the focus on alkaloid was a follow - up from our previous study that speculated on alkaloids to be responsible for the abortifacient activity of the crude extract of s. alata leaves and from several studies that implicated the phytochemical property of colchicine , quinazoline alkaloids , e.g . vasicine and vasicinone in several botanicals such as xylopia aethiopica , peganum harmala epigeal parts , areca catchu nuts and gloriosa superba roots as abortifacient bioactive agents and/or their role in the contraction and relaxation of uterine muscles ( 912 ) ." ]

[ "backgroundthe abortifacient claim of senna alata ( s. alata ) was scientifically validated recently with alkaloids speculated to be the bioactive agent .", "this speculation is yet to be substantiated or refuted by scientific evidence .", "the present study was aimed to investigate the pregnancy terminating effects of the alkaloids from s. alata leaves.methodstwenty four pregnant rats ( 143.991.21 g ) allocated randomly to four groups : a , b , c and d respectively received , 0.5 ml of distilled water , 250 , 500 and 1000 mg / kg body weight of the s. alata extracted alkaloids orally , once daily from day 10 until day 18 post - coitum .", "the indices of abortifacient were evaluated at the end of the exposure period .", "the results were analyzed by both the analysis of variance and duncan 's multiple range test and p < 0.05 was considered as statistically significant.resultsthin-layer chromatographic separation produced five spots with rf values of 0.28 , 0.33 , 0.39 , 0.47 and 0.55 which gave positive reaction with meyer 's and wagner 's reagents , respectively .", "the number of implantation sites and corpora lutea , as well as the concentrations of fsh , lh , progesterone , weight of uterus , uterine/ body weight ratio , glucose and cholesterol decreased significantly ( p < 0.05 ) whereas the resorption index , pre- and post - implantation losses , uterine protein content and alkaline phosphatase activity increased significantly .", "none of the alkaloid treated animals presented with provoked vaginal opening or bleeding except fetal deaths .", "the alkaloid decreased the maternal weight gain , as well as feed and water intake.conclusionoverall , the alkaloids from s. alata leaves exhibited anti - implantation , anti - gonadotropic , anti - progesteronic , embryonic resorptive , feto - maternal toxic activities but not complete abortifacient .", "the alkaloids alone may not be the sole abortifacient bioactive agent in the leaf extract ." ]

[ [ 11, 2, 7, 9, 8, 5, 10 ], [ 11, 10, 9, 7, 5, 2 ], [ 11, 2, 7, 9, 8, 10 ], [ 11, 2, 7, 9, 10 ], [ 11, 2, 7, 10 ], [ 11, 10, 9, 7, 5, 8, 0 ], [ 11, 2, 7, 9, 8, 5, 0 ], [ 11, 10, 9, 2 ], [ 11, 2, 10 ] ]

[ 0.27433037586166414, 0.27157026539155815, 0.26934461934461934, 0.26624639831892666, 0.2614733899738865, 0.2570537491705375, 0.25612683841829226, 0.2510137253535846, 0.24502192676615064 ]

[ "erg protein expression has been recently suggested to be reflective of erg gene rearrangements in prostate cancer ( pca ) documenting remarkable concordance between the two [ 16 ] .", "the rearrangements between the androgen receptor - regulated gene tmprss2 ( 21q22.3 ) and members of the ets family member of transcription factor gene , most commonly erg ( 21q22.2 ) , are among the most common genetic alterations detected in prostate cancer [ 711 ] .", "erg gene rearrangements have been detected in roughly half ( 4060 % ) of pca of surgical cohorts compared to a rate of 12 % 15 % in incidental or watchful waiting cohorts [ 7 , 1218 ] .", "previous studies investigating the prognostic significance of erg gene rearrangements have revealed mixed results [ 1922 ] .", "however , it is becoming more evident that erg gene rearrangements signify a molecular subtype of pca .", "some studies investigating the significance of erg protein expression in localized pca failed to show association with adverse clinical outcome [ 23 , 24 ] . however , a recent report by our group demonstrated an association of erg expression with lethal disease in patients with unsuspected and advanced / castrate resistant disease who were treated by transurethral resection of prostate . moreover , we documented significant association between erg expression and both gleason score and tumor volume .", "studies from our group and others have also linked erg status to responsiveness to hormonal therapy , and longer progression time to castration resistant disease , compared to men with no erg expression [ 24 , 25 ] . in the current study , we investigated the association of erg protein expression to clinical - pathological parameters in a cohort of men with localized prostate cancer ." ]

[ "background .", "the prognostic significance of erg expression in prostate cancer ( pca ) has generated mixed results .", "we sought to investigate the prognostic significance of erg expression in a localized cohort of men with pca .", "material and methods .", "we investigated erg protein expression in a cohort of 198 men with localized pca .", "erg expression was correlated with patients ' clinical outcome and several pathological parameters , including gleason score ( gs ) , pathological stage , surgical margin , and extra - capsular extension . results .", "erg expression was detected in 86/198 ( 43.4 % ) patients exclusively in neoplastic epithelium .", "overall , erg mean expression intensity was 1.01 1.27 versus 0.37 0.83 in acinar pca compared to foamy type pca ( p < 0.001 ) . in hgpin , erg intensity levels were comparable to those in foamy type pca ( 0.13 0.56 ) but significantly lower than those in acinar pca ( p < 0.001 ) .", "erg expression was significantly associated with extra - prostatic extension and higher pathological stage and showed a trend toward seminal vesicle invasion .", "herein , erg expression was documented in 50/131 ( 38.1 % ) patients with pt2 versus 30/55 ( 54.5 % ) patients with pt3 ( p = 0.04 ) .", "erg association with higher pathological stage was more pronounced in patients with gs > 7 .", "grouping patients into those with gs 7 versus > 7 , there was no significant association between erg expression and gs .", "similarly , no association was present in relation to either surgical margins or postsurgical serum psa levels . conclusion .", "we report significant association between erg protein levels and extra - prostatic extension and higher pathological stage .", "erg expression is not associated with adverse clinical outcome and is of limited prognostic value in localized pca ." ]

[ [ 5, 2, 0, 3, 4, 6 ], [ 5, 2, 0, 3, 6 ], [ 5, 2, 0, 6 ], [ 5, 2, 6 ], [ 5, 6 ] ]

[ 0.3294618462968631, 0.32933866763653996, 0.31966620575892096, 0.3134463522422662, 0.29529313232830817 ]

[ "the three main arteries of the leg , the anterior tibial artery ( ata ) , posterior tibial artery and peroneal artery , form a dense vascular network around the distal leg , ankle , and foot , which ramifies perforators as the basis of all kinds of pedicle flaps such as lateral or medial malleolar perforator flaps .", "there is plenty of literature describing the anatomy and clinical application of perforators of the peroneal artery and posterior tibial artery around the distal lower leg .", "however , literature regarding perforator flaps of ata or anterior supramalleolar artery ( asma ) , one of the major branches of distal ata , are scant .", "these papers either mention the existence of the perforators from ata or asma , or describe their communication with the medial and lateral supramalleolar arteries . none of them have a detailed anatomical study on asma .", "the objective of this study was to identify the anatomic parameters of the asma and its perforators that would enable microsurgeons to harvest potentially multi - paddle flaps or composite flaps from the foot and ankle region .", "we try to preserve the ata intact after we harvest the composite flaps around the ankle using asma .", "we also want to use the ata as the only one pedicle and harvest multi - paddle flaps , decreasing the microsurgical risk greatly and minimizing the sacrifice of the blood supply to the ankle and foot ." ]

[ "purpose : a further understanding of the anterior supramalleolar artery ( asma ) and its potential applications in reconstructive surgery.materials and methods : a total of 24 fresh lower limbs from fresh cadavers were injected with red latex for dissection . the type of origin , course , diameter of the pedicle , and the distance between the origin of the asma from the anterior tibial artery to the extensor retinaculum ( o - r ) were recorded .", "bi - foliate fasciocutaneous flaps were harvested using the branches of the asma.results : we found four types of origin of the asma , and we have accordingly classified them into four types .", "10 of them were type a , 7 were type b , 6 were type c and 1 was type d. the mean o - r ( origin of asma to retinaculum ) distance was 2.0 0.8 cm .", "the diameter of the medial branch ( d1 ) , the diameter of the lateral branch ( d2 ) , and the diameter of artery stem ( d3 ) ( only in type a ) were 1.0 0.2 mm , 0.8 0.3 mm , 1.1 0.2 mm , respectively .", "the mean pedicle length of the lateral flap ( l1 ) and medial flap ( l2 ) were 5.1 1.0 cm and 3.7 0.6 cm , respectively.conclusions : the asma exists constantly with four different types of origin .", "its sizable diameter and lengthy pedicle make it suitable for bi - foliate fasciocutaneous flap transfer ." ]

[ [ 4, 0, 3, 6, 2 ], [ 4, 3, 6, 1, 2 ], [ 4, 0, 3, 6, 1 ], [ 4, 0, 6, 2, 1 ], [ 4, 0, 3, 2, 1 ] ]

[ 0.27013040059635046, 0.26964175652185957, 0.26257286403985675, 0.258767762437692, 0.2577295800646055 ]

[ "ankle dorsiflexion passive range of motion ( df prom ) measurements are performed in the field of physical therapy to estimate ankle motion during functional activities1 and to prevent lower extremity injuries2 .", "although in the clinical setting , ankle df prom is frequently measured under non - weight - bearing ( non - wb ) conditions1 , 3 , 4 , many researchers have stated that the wb position is more appropriate for estimating the amount of ankle df motion during functional activities5 , 6 . therefore , wb ankle df prom should be measured during interventions focused on increasing ankle df prom .", "limited ankle df prom with knee extended may result from gastrocnemius tightness and insufficient posterior talar glide7 .", "thus , gastrocnemius stretching and talocrural joint mobilization have been performed as intervention strategies to increase ankle df prom3 , 8 , 9 .", "previous studies have reported a significant increase in ankle df prom after these interventions3 , 8 , 9 ; however , to our knowledge , no study has demonstrated the combined effect of both interventions on wb ankle df prom .", "therefore , the aim of the present study was to examine the influence of gastrocnemius stretching combined with joint mobilization on wb ankle df prom ." ]

[ "[ purpose ] the purpose of this study was to investigate the effect of gastrocnemius stretching combined with talocrural joint mobilization on weight - bearing ankle dorsiflexion passive range of motion .", "[ subjects ] eleven male subjects with bilateral limited ankle dorsiflexion passive range of motion with knee extended participated in this study .", "[ methods ] all subjects received talocrural joint mobilization while performing gastrocnemius stretching .", "ankle dorsiflexion passive range of motion was measured using an inclinometer under weight - bearing conditions before and immediately after intervention .", "a paired t - test was used to analyze the difference between weight - bearing ankle dorsiflexion passive range of motion pre- and post - intervention .", "[ results ] a significant increase in weight - bearing ankle dorsiflexion passive range of motion was found post - intervention compared with pre - intervention .", "[ conclusion ] these findings demonstrate that gastrocnemius stretching combined with joint mobilization is effective for increasing weight - bearing ankle dorsiflexion passive range of motion ." ]

[ [ 5, 4, 0, 2, 3 ], [ 5, 4, 0, 3 ] ]

[ 0.3460239651416122, 0.32984577230101525 ]

[ "dox is one of the key chemotherapeutic drugs for cancer treatment , but its use is limited by chronic and acute toxic side effects .", "dox is an antibiotic anthracycline that was isolated from a pigment of streptomyces peucetius in the early 1960s and it had been employed for more than 30 years in the battle against cancer , but it is now chemically synthesized .", "renal dox - induced toxicity may be part of a multiorgan damage mediated mainly through free radical formation eventually leading to membrane lipid peroxidation .", "induction of apoptosis and modulation of nox are mechanisms that are involved in toxic adverse effects associated with dox therapy . in addition , dox has a direct renal damaging effect as it accumulates preferentially in the kidney .", "dox has toxic effects on other organs such as heart and liver which may lead to modulation of blood supply to the kidney and alter xenobiotic detoxification processes , respectively , thus indirectly contributing to dox - induced nephropathy .", "dia is a new anti - inflammatory , analgesic , and antipyretic drug that was developed specially for the treatment of osteoarthritis .", "it is highly effective in relieving the symptoms of osteoarthritis and may be able to modify the course of the disease .", "interleukin 1 is a proinflammatory and proapoptotic agent that induces cytokine production by activating nfb and mitogen activated protein kinase signaling .", "a major cause of dox - induced nephrotoxicity is the production of reactive oxygen species which induce cytokines , including interleukin 1 [ 6 , 9 , 10 ] .", "the aim of the present study was to study the effect of the interleukin 1 receptor antagonist diacerein ( dia ) on dox - induced nephropathy ." ]

[ "nephrotoxicity is one of the limiting factors for using doxorubicin ( dox ) .", "interleukin 1 has major role in dox - induced nephrotoxicity , so we investigated the effect of interleukin 1 receptor antagonist diacerein ( dia ) on dox - induced nephrotoxicity .", "dia ( 25 and 50 mg / kg / day ) was administered orally to rats for 15 days , in the presence or absence of nephrotoxicity induced by a single intraperitoneal injection of dox ( 15 mg / kg ) at the 11th day .", "we measured levels of serum urea , creatinine , renal reduced glutathione ( gsh ) , malondialdehyde ( mda ) , total nitrites ( nox ) , catalase , and superoxide dismutase ( sod ) .", "in addition , caspase-3 , tumor necrosis factor alpha ( tnf ) , nuclear factor kappa b ( nfb ) expressions , and renal histopathology were assessed .", "our results showed that dox - induced nephrotoxicity was ameliorated or reduced by both doses of dia , but diacerein high dose ( dhd ) showed more improvement than diacerein low dose ( dld ) .", "this protective effect was manifested by significant improvement in all measured parameters compared to dox treated group by using dhd .", "dld showed significant improvement of creatinine , mda , nox , gsh , histopathology , and immunohistochemical parameters compared to dox treated group ." ]

[ [ 9, 8, 3, 0 ], [ 9, 8, 3, 4 ], [ 9, 8, 0, 4 ], [ 9, 3, 0, 7 ] ]

[ 0.2753865852457402, 0.26339950977632137, 0.2614005712597262, 0.25848233609696 ]

[ "suicide is a leading cause of death among adolescents and has become a significant public health issue globally ( 1 ) .", "statistics korea report 2014 showed that suicide is the cause of 28.4 % of adolescent deaths in 2013 , and it was the number one cause of death among adolescents ( 2 ) .", "furthermore , suicide is the second to third cause of mortality among adolescents in the western world and is an important concern in developing countries ( 3 ) .", "numerous causes of suicidal behavior during adolescence have been reported , including mental disorders , peer affiliations , and level of achievement in school ( 4 ) .", "additionally , weight - related concerns are a common cause of suicidal behaviors ( 56 ) .", "this transition often leads to confusion about personal identity , especially in the context of enduring developments in identity and cognition as well as physical growth ( 7 ) .", "adolescents typically enter a period of a high level of self - consciousness about their body shape and size ( 8 ) .", "they have a greater tendency to consider how they look to others at this life stage than during any other period of life ( 9 ) .", "these weight - related issues are influenced by many factors including friends , peers , social norms , and media ( 10 ) .", "the media is a particularly strong influence because it has become a general source of information and adolescents are easily exposed to it ( 11 ) .", "the media encourages as `` ideal `` slim and thin body shapes for girls and muscular bodies for boys ( 1213 ) , and provides abundant information on the newest diet methods and quick fixes for weight control ( 14 ) .", "this may induce adolescents , who have a particularly keen interest in their figure , to distort their body image and to engage in unneeded or inappropriate weight control behaviors ( wcb ) ( 15 ) .", "many adolescents engage in inappropriate wcb such as vomiting , taking nonprescription diet pills , and taking laxatives or diuretics . among korean adolescents engaging in wcb ,", "13.4 % of boys and 18.8 % of girls took inappropriate methods to control their weight ( 16 ) . according to a study using data from national surveys , similar rates", "were also observed in the united states , with 10 % of boys and 21.3 % of girls conducting at least one inappropriate wcb ( 17 ) .", "inappropriate wcb are a harmful influence on adolescents ' physical and psychological development ( 12 ) .", "for instance , a 5-year longitudinal study reported that engagement in inappropriate wcb can be a predictor of obesity and eating disorders ( 18 ) .", "moreover , adverse outcomes of inappropriate wcb also include the onset of depression ( 19 ) and suicide ideation ( 20 ) .", "due to the high prevalence of and the possible negative side effects associated with inappropriate wcb , it is a growing serious public health concern .", "therefore , the prevention of inappropriate wcb among adolescents is imperative to protect them from negative physical and psychosocial consequences . to date", ", studies about inappropriate wcb merely suggest the association between inappropriate wcb and negative psychosocial consequences ( 212223 ) . in the present study , we investigate not only the association between inappropriate wcb and suicide ideation and attempt , but also the difference in this association with body mass index , body weight perception , and body shape misperception . moreover , we investigate the top five wcb combinations used by korean adolescents and examine the association between these five wcb combinations and suicide ideation and attempt .", "we used a cross - sectional design ; thus , the results should be interpreted with caution due to possibility of a bi - directional effect ." ]

[ "suicide is a leading cause of death among adolescents globally , and body weight is also a recognized reason for adolescent suicide .", "therefore , we investigated the association between weight control behaviors ( wcb ) and suicide ideation and attempt , focusing on inappropriate weight control measures .", "we used data from the 2014 korea youth risk behavior web - based survey , representing a total of 35,224 boys and 34,361 girls aged 12 to 18 years .", "adolescents were classified into groups based on wcb : appropriate wcb , inappropriate wcb , and no wcb .", "we performed logistic regression models to examine associations between wcb and suicide ideation and attempt , controlling for covariates .", "both boys and girls with inappropriate wcb were more likely to report suicide ideation and attempt .", "underweight and normal weight boys with inappropriate wcb were more likely to think or attempt suicide , and underweight girls with inappropriate wcb were also more likely to attempt suicide . among five common wcb combinations ,", "the combination of `` regular exercise , fasting , eating less `` was highly associated with suicide ideation and attempt .", "we confirmed that inappropriate wcb is associated with suicide ideation and attempt among korean adolescents .", "given the high incidence rate of suicide among adolescents and the adverse effect of inappropriate wcb , encouraging adolescents to control their weight in healthy ways is imperative ." ]

[ [ 20, 0, 19, 18, 13 ], [ 20, 0, 19, 18, 17 ], [ 1, 20, 19, 18, 13 ], [ 1, 20, 19, 18, 0 ], [ 20, 0, 13, 19 ], [ 20, 0, 13, 17 ], [ 1, 13, 20, 0 ], [ 20, 13, 1, 19 ] ]

[ 0.3983466519702397, 0.3903656466933043, 0.3888552655269431, 0.3823171175101803, 0.3822003222229197, 0.3770972436226674, 0.37097035073967627, 0.3707543524118257 ]

[ "in the past 15 years , green fluorescent protein ( gfp ) has changed from a nearly unknown protein to a commonly used molecular imaging tool in biology , chemistry , genetics , and medicine . in 2006 , more than 10 000 papers", "gfps and gfp - like proteins ( i.e . , chromoproteins and fluorescent proteins ) are particularly useful due to their stability and the fact that the chromophore ( see figure 1 ) is formed in an autocatalytic cyclization of the 65syg67 sequence that does not require a cofactor .", "this means that unlike most other bioluminescent reporters , gfp fluoresces in the absence of any other proteins , substrates , or cofactors .", "furthermore , it appears that fusion of gfp to a protein does not alter the function or location of the protein . by changing residue 66 and/or the amino acid residues around the chromophore", "( n1c1c2c3 ) and ( c1c2c3c4 ) dihedral angles of the gfp chromophore . in the protein ,", "r1 is gly67 and r2 is ser65 , and in hbdi , an often - used model compound , r1 = r2 = ch3 . in one - bond flips ( -obf ) the dihedral rotation occurs around the torsional angle , in a -obf it is around the dihedral angle , and in a positively correlated hula - twist ( + ht ) the and dihedral angles concertedly rotate in the same direction ( as shown above ) , while in a negatively correlated hula twist ( ht ) they concertedly rotate in opposite directions . a plot of the and dihedrals for a perfectly correlated negative ht will have a slope of 1 .", "if the chromophore cavity is complementary with a planar chromophore , then the and best fit line will pass through the origin and all the and angles will be centered around the origin .", "a nonzero intercept along the or axis ( see , for example , figure 4 ) or and dihedrals centered in quadrant ii ( > 0 ;", "< 0 ) or quadrant iv ( < 0 ; > 0 ; see , for example , figure 8 ) are indications of a cavity that is not complementary with a planar chromophore . the fluorescent emission of the chromophore within gfp occurs with high efficiency ( quantum yield fl = 0.8 ) and a respectable fluorescence lifetime ( 3 ns ) . ( 19 ) when the protein is denatured the fluorescence yield decreases by at least 3 orders of magnitude . ( 20 ) model compounds of the chromophore do not fluoresce in solution ( quantum yield fl < 10 ) , unless the rotation of the arylalkene bond is restrained . ( 21 ) fluorescence can , however , be obtained by lowering the temperature to 77 k ; this freezes the solution .", "it has been suggested that twisting between the phenolate and imadazolidinone groups of the chromophore is the mechanism for the ultrafast fluorescence quenching internal conversion process .", "neutral form ( a ) of the chromophore , with the phenolic oxygen protonated , can convert to the anionic species ( b ) by going through an intermediate state ( i ) .", "the change from forms a to i is solely a protonation change , while the change from i to b is a conformational change with most changes occurring at thr203 .", "upon excitation of the a state , an excited - state proton transfer ( espt ) occurs in which the proton is transferred from the chromophore to glu222 in a time scale of the order of picoseconds . following radiative relaxation from the excited - state intermediate ( i * ) ,", "the systems returns to the ground state a through the ground - state intermediates i1 and i2 . ( 29 ) excitation of the anionic b state results in direct emission from the excited state ( b * ) at 482 nm . recently", ", a nonfluorescent dark state , state c , has been observed that is distinct from states a and b and absorbs at higher energies . ( 30 ) the c state , perhaps the neutral trans form of the chromophore , may be populated by nonradiative decay from a * and it may be depopulated by excitation to the excited c * state with transcis isomerization to repopulate state a. fluorescent blinking has been ascribed to nonadiabatic crossing and conversions between the neutral and anionic states , ( 31 ) or a possible dark ( z ) zwitterionic state . while the ground - state minimum of the gfp chromophore is close to planar , this is not necessarily so for the excited state ; in fact , in some cases the excited state has an energy minimum with a twisted chromophore in which both rings are 90 to each other . ( 32 ) according to quantum mechanical calculations , the ground and excited states for the one - bond flip ( obf ) and hula twist ( ht ) in the neutral form ( a ) and the obf in the zwitterionic form come very close to each other .", "it has been proposed that in the absence of the protein matrix , which surrounds the chromophore and prevents twisting , this process can lead to fluorescence quenching internal crossing ; ( 32 ) see figure 3 .", "recent calculations on the gfp chromophore model compound hbdi suggest that the anionic form of hbdi may also undergo a -obf that leads to a favored radiationless decay channel , which is particularly efficient in solvent . ( 34 ) ( a ) model compounds of the gfp chromophore in the ground state ( s0 ) can be excited to the first singlet state ( s1 ) in which a ht or obf can freely occur . upon reaching the perpendicularly twisted conformation , fluorescence quenching nac ( nonadiabatic crossing ) occurs .", "( b ) in the ground state ( s0 ) , the residues surrounding the gfp chromophore exert a twisting force on the chromophore ( ) . upon excitation , the conjugation across the ethylenic bridge of the chromophore is reduced and it will twist ; however , the protein matrix prevents the chromophore from reaching the perpendicularly twisted conformation ( ) and fluorescence quenching internal crossing is prevented .", "recently , the results from a number of interesting experiments that provide evidence for chromophore twisting and/or fluorescence quenching internal crossing ( ic ) have been published .", "for example , a molecular dynamics simulation of the chromophore of cyan fluorescent protein found that the average dihedral angle was about 0 ; however , when the surrounding protein was considered in the simulation the average shifted by approximately 5 , showing that the protein matrix of cfp twists the chromophore . on the basis of their calculations , the authors concluded that the driving force for this twist comes from the strong short - range repulsion by four residues ( ile167 , val150 , phe165 , and thr203 ) surrounding the average position of the chromophore . ( 46 ) photoswitching fluorescent proteins can be switched back and forth between the naturally occurring green state and a dark state by 405 nm irradiation ( e.g . , dronpa , mtfp0.7 , kfp1 ) .", "a cistrans isomerization of the chromophore has been proposed as the structural basis for the photoswitching observed in dronpa . ( 47 ) this is supported by the fact that mutating either val157 or met159 with smaller residues accelerates photoswitching , presumably by decreasing steric hindrance to cistrans isomerization . ( 48 )", "the m159 t and v157 g mutations also decrease the quantum yield of dronpa from 0.85 to quantum yields of 0.23 and 0.77 , respectively . ( 48 ) recently , it has been suggested that adoption of a trans configuration can not solely be responsible for the nonfluorescent form . ( 49 ) on the basis of nmr analyses , miyawaki et al .", "propose that the fluorescence of the protein is regulated by the degree of flexibility of the chromophore but is not necessarily accompanied by cistrans isomerization . ( 49 ) interestingly , gfp is not unique in photoactive yellow protein ( pyp ) the protein matrix also prevents the chromophore from adopting a completely planar structure . in pyp", "the asymmetric proteinchromophore interaction probably serves as the initial accelerant for the light induced photocycle , ( 50 ) which ultimately leads to a cistrans isomerization . ( 51 ) the chromophore in wild - type gfp is planar due its extended system ( see figure 1 ) ; however , the energy barrier to deformation is low and the protein matrix in wild - type gfp exerts some strain away from planarity .", "when the chromophore is computationally permitted to freely rotate , it will adopt a conformation that complements the protein matrix .", "recently , we have used computational methods to show that wild - type gfp is not an anomaly and that all gfp and gfp - like proteins in the protein databank have a protein matrix that is not complementary with a planar chromophore . ( 54 ) in most cases the freely rotating chromophore undergoes rotations of at least 20. in some cases these rotations are accompanied by an equal but opposite rotation of the dihedral angle ( a negatively correlated ht ) .", "none of the proteins examined have a cavity that causes a rotation solely around the dihedral angle . ( 54 ) these calculations were done by minimizing , with freely rotating and dihedral angles , the crystal structure of 38 gfp analogues and mutants found in the pdb .", "they found the energy minimum conformation of a freely rotating chromophore in the protein matrix of the gfp mutant or gfp - like protein examined ; however , they did not provide any information about the range of low - energy conformations available to a freely rotating chromophore . to get this information", ", we ran molecular dynamics simulations of some of the interesting gfp mutants in the protein databank . ( 56 ) by running molecular dynamics simulations , with freely rotating and dihedrals , we have been able to determine the range of conformations available to chromophores with complete rotational freedom ." ]

[ "green fluorescent protein ( gfp ) and gfp - like fluorescent proteins owe their photophysical properties to an autocatalytically formed intrinsic chromophore . according to quantum mechanical calculations ,", "the excited state of chromophore model systems has significant dihedral freedom , which may lead to fluorescence quenching intersystem crossing .", "molecular dynamics simulations with freely rotating chromophoric dihedrals were performed on green , yellow , and blue fluorescent proteins in order to model the dihedral freedom available to the chromophore in the excited state .", "most current theories suggest that a restriction in the rotational freedom of the fluorescent protein chromophore will lead to an increase in fluorescence brightness and/or quantum yield . according to our calculations , the dihedral freedom of the systems studied ( bfp > a5 > yfp > gfp ) increases in the inverse order to the quantum yield . in all simulations ,", "the chromophore undergoes a negatively correlated hula twist ( also known as a bottom hula twist mechanism ) ." ]

[ [ 16, 28, 1 ], [ 16, 28, 15 ], [ 16, 25, 28 ], [ 16, 25, 15 ], [ 14, 28 ], [ 14, 25 ] ]

[ 0.3540307391336018, 0.3492170022371364, 0.34434251287444173, 0.3306182793230425, 0.28834584628996623, 0.2791557648700505 ]

[ "these tumors are classified as typical net ( tnet ) , goblet cell carcinoid ( gcc ) , and atypical gcc histologies .", "ex - goblet or composite - goblet are further classified into signet ring cell carcinoid ( srcc ) and poorly differentiated adenocarcinoid of the appendix .", "these tumors have a distinctive morphology showing tight clusters of cells with compact nuclei and abundant intracytoplasmic mucin resembling goblet or signet ring cells often with admixed enterochromaffin cells .", "pathologic features of gcc include presence of large mucin filled cells with crescent nuclei arranged in small clumps or rosettes mixed with cells of typical carcinoid appearance that stain positive for chromogranin a .", "patients with tnet have a 5-year survival ranging from 60 % to 84 % , with the most common site of metastasis being the liver .", "on the other hand , atypical gcc have a more aggressive clinical course with an increased incidence of lymph node and distant metastases , along with a lower 5-year survival ranging from 36 % to 56 % [ 5 - 7 ] .", "current management of gcc and atypical gcc is based on very limited data from small single institutional experiences .", "the rarity of appendiceal net , gcc , and srcc limits the ability to conduct appropriate randomized clinical trials to explore the optimal management . to assess the role of clinicopathologic features in survival of net , gcc , and srcc patients , the outcome of cases reported to the national cancer institute s surveillance epidemiology and end results ( seer ) program was evaluated .", "furthermore , to characterize the management of net , gcc , and srcc , a treatment strategy based on results of current analysis , published literature and institutional experience is suggested ." ]

[ "purposeappendiceal tumors are a heterogeneous group of diseases that include typical neuroendocrine tumors ( tnet ) , goblet cell carcinoids ( gcc ) , and atypical gcc .", "atypical gcc are classified into signet - ring cell cancers ( srcc ) and poorly differentiated appendiceal adenocarcinoids .", "the prognosis and management of these diseases is unclear because there are no prospective studies .", "the aim of this study is to assess the characteristics and outcome of appendiceal tnet , gcc , and srcc patients.materials and methodsappendiceal tnet , gcc , and srcc patients diagnosed between 1973 and 2011 were identified in the surveillance epidemiology and end results ( seer ) database .", "demographics , type of surgery , and clinicopathologic characteristics were collected .", "survival functions were estimated by the kaplan - meier method , and log - rank test was used to assess the difference in overall survival ( os ) among the three histologies.resultsthe seer database yielded 1,021 tnet patients , 1,582 with gcc , and 534 srcc patients .", "tnet presented at a younger age ( p < 0.001 ) .", "patients with srcc presented with advanced stage disease ( p < 0.001 ) . the median os ( mos ) for gcc and tnet patients was not reached ; mos for srcc was 24 months .", "multivariate analysis stratified for stage revealed significantly longer survival for tnet and gcc than srcc ( p < 0.001 ) .conclusionthis is the largest report to date for appendiceal neuroendocrine tumor patients , suggesting a spectrum of diseases with different characteristics and outcomes . in this report , we present a treatment approach for this complex spectrum of disease , based on the experience of ohio state and emory universities investigators ." ]

[ [ 7, 1, 8, 4, 6, 0 ], [ 7, 1, 8, 4, 6, 3, 0 ], [ 7, 1, 8, 4, 0 ], [ 7, 1, 0, 6, 8 ], [ 7, 1, 0, 6, 4 ], [ 7, 1, 0, 8 ], [ 7, 0, 8, 4, 6, 2 ] ]

[ 0.3466443487964291, 0.34337447043025887, 0.3404500261643119, 0.33797107285479383, 0.3319244473531123, 0.32735453603400705, 0.32082719911667285 ]

[ "an estimated 170 million people worldwide have hepatitis c virus ( hcv ) infection and over 20,000 new cases emerge every year . hcv infection frequently persists and may cause cirrhosis and hepatocellular carcinoma . in the us and most developed nations , where the prevalence of infection is 1 % 2 % , hcv is the leading cause of chronic liver disease.1 hcv infection is a serious public health problem in egypt , and is the country with the highest hcv prevalence , where 10 % 20 % of the general population is infected.2 interferons are a group of glycoproteins that modulate the activity of the immune system .", "recombinant alpha - interferon ( ifn ) has recently been approved as a therapy for chronic hepatitis c , for its antiviral effects and inhibition of cell proliferation.3 although interferon - based therapy is widely used for the treatment of chronic hcv , it is not without its disadvantages .", "treatment duration lasts for months , and is often fraught with potentially dangerous side effects . some of these side effects , such as influenza - like illness , myalgias , depression , and cytopenias can be intolerable resulting in premature treatment cessation , but have no lasting effects .", "ocular complications are among the complications of interferon therapy and include retinal hemorrhages , cotton wool spots , loss of color vision , cataracts , glaucoma , and occasionally retinal artery or vein obstruction .", "although the incidence of ophthalmological disorders while on interferon therapy is low , this can result in loss of vision.411" ]

[ "purposeto evaluate retinopathy associated with interferon therapy in patients with chronic hepatitis c.methodsone hundred patients with chronic hepatitis c undergoing interferon therapy were examined for the presence of cotton wool spots , retinal hemorrhages , cystoid macular edema , capillary non - perfusion , and arteriolar occlusion .", "complete ophthalmological examination including indirect ophthalmoscopic fundus examination was carried out for all patients and colored fundus photography and fluorescein angiography were carried out for the patients with positive fundus findings .", "the follow - up period was 9 months.resultssixteen percent of patients developed retinopathy in the form of cotton wool spots , retinal hemorrhages , cystoid macular edema , and capillary non-perfusion.conclusioninterferon therapy can lead to retinopathy which is mostly reversible and dose related .", "periodic fundoscopic examinations help in early detection and prevent progression to permanent visual loss ." ]

[ [ 1, 3 ], [ 1, 0, 3 ], [ 3, 0 ], [ 1, 0, 4 ] ]

[ 0.19727307632608715, 0.18935049651144517, 0.17257835934878737, 0.1701612151709999 ]

[ "women require special need - based health care programs as they pass through the menopausal transition . with this vision , a multisystem multispecialty health check - up and follow - up care program ( maitreyi health care program [ hcp ] )", "was initiated by our team about a decade ago , and this has been continued at the medical research center , kasturba health society , mumbai .", "the comparative effects of three plant products on perimenopausal symptoms , quality of life ( qol ) and clinical biochemistry have been reported by our group earlier .", "our observation of frequent mood changes and sleep disturbances in women in the premenopausal group prompted us to undertake a study of cyclic symptoms in maitreyi hcp .", "in this communication , we describe the preliminary findings from the analysis of premenstrual symptoms in 200 consecutive women who underwent a comprehensive check - up in the maitreyi hcp .", "diagnosis of premenstrual tension syndrome ( pmts ) is based on the following criteria as per the american association of obstetricians and gynecologists : a 30 % increase in the intensity of symptoms of premenstrual syndrome ( measured using a standardized instrument ) from cycle days 510 as compared with the 6-day interval before the onset of menses and documentation of these changes for at least two consecutive cycles .", "at least one of the following affective and somatic symptoms during the 5 days before menses in previous cycles .", "affective symptoms : depression , angry outbursts , irritability , anxiety , confusion , social withdrawal .", "somatic symptoms : breast tenderness , abdominal bloating , headache , swelling of extremities ; symptoms relieved from days 4 through 13 of the menstrual cycle . to determine the prevalence of premenstrual cyclic symptoms in women who attended the maitreyi hcp ." ]

[ "objective : to determine the prevalence of premenstrual cyclic symptoms in perimenopausal age.subjects and methods : women attending bhavan 's sparc maitreyi 's health care programme ( hcp ) for women around 40 years of age were included in the study . last 200 women who attended from april 2002 to october 2004 are included for analysis .", "out of these 107 qualified for final analysis as others were post hysterectomy or post menopausal .", "thirty five symptoms listed under premenstrual tension syndrome were analysed.results : forty one women ( 38.3 % ) had 3 or more symptoms whilst 15 ( 14.0 % ) had 5 or more cyclic symptoms .", "five women ( 4.7 % ) reported that the symptoms were severe .", "eleven women had seeked treatment for premenstrual tension syndrome ( pmts ) .", "the commonest symptom was mastalgia or heaviness of breasts .", "next was whilst also was reported by several women .", "women reported anger attacks and reported depression.conclusion : pmts was common between 36 and 55 years .", "about half of them have experienced 3 more symptoms and 1 in 20 may require treatment ." ]

[ [ 5, 3, 2, 4, 0, 8 ], [ 5, 3, 2, 4, 8 ], [ 5, 3, 2, 8 ], [ 5, 3, 2, 4, 0, 7, 8 ], [ 5, 3, 8 ], [ 8, 5 ], [ 8, 3 ], [ 5, 3, 2, 4, 0, 7, 6 ] ]

[ 0.23689205951083792, 0.23514418855574729, 0.2349046377406029, 0.2342528780513201, 0.22695504955391965, 0.21509121061359868, 0.2091670847035654, 0.20577805590321238 ]

[ "according to the korean national statistical office , the main cause of death in korea was cancer in 2012 .", "the total number of deaths due to cancer in 2012 was 267,221 , which was increased by 9,825 ( 3.8 % ) compared to 2011.1 this was the all - time high since 1983 .", "currently , the treatment of cancer patients in the medical field consists mainly of surgery , radiation therapy , and chemotherapy .", "seventy to eighty percent of cancer patients in chemotherapy experienced side effects such as anemia , the decreased number of white blood cells and/or platelets , oral mucositis , vomiting , diarrhea , hair loss , and disabled generative functions as chemotherapy also affects the rapidly proliferating normal cells.2 most side effects are temporary and patients recover fully ; but , some side effects may take months or years to completely disappear . to decrease side effects from non - specific cytotoxicity ,", "new drugs , such as targeted agents , are being developed to selectively destroy specific cancer cells . however , because of problems , such as tolerance manifestation , partly critical toxicity , decrease in sensitivity , and restriction in subjects , new drugs take only a small portion of the cancer treatment realm.3 chemoprevention is defined as the use of nontoxic or relatively safe chemical substances , such as vitamins , plant extracts , and pharmaceuticals to prevent cancer .", "it is effective in decreasing cancer risk and is helpful in early stages of cancer.4 hence , regular consumption of anticancer foods that display no or little toxicity to the body and boost efficacy of anti - tumor drugs or stop the development of tolerance would be beneficial in preventing cancer .", "thus , consumption of plant - derived natural foods to prevent cancer with few side effects and toxicity is crucial.5 recently , there has been a growing interest in probiotics due to the discovery of multidrug - resistant organisms that are tolerant to antibiotics .", "probiotics is derived from a greek word meaning for life and holds the opposite meaning from antibiotics which means against life . probiotics consist of microorganisms and substances , which modify the intestinal microflora , and when used as dietary supplement they have positive effects on health such as fortification of host immune function , suppression of diarrhea , and inhibition of carcinogenesis.6 kimchi , a korean traditional food , is fermented by probiotic lactic acid bacteria.7 kimchi lactic acid bacteria are known to suppress the activity of carcinogen - activating enzymes , such as azoreductase , nitroreductase , 7 -- dehydrogenase , -glucosidase , and -glucuronidase and inactivate or neutralize the cancer - causing agents and pathogenic microbes.8 in addition , the intake of lactic acid bacteria as part of kimchi improves bowel movement , strengthens immunity , ameliorates hepatocirrhosis , and decreases serum cholesterol levels.9,10 among lactic acid bacteria identified during the fermentation of kimchi , weissella , lactobacillus , leuconostoc and pediococcus species are known to play an important role in kimchi fermentation.1113 this commentary deals with anticarcinogenic effects of kimchi and lactic acid bacteria , weissella cibaria and lactobacillus plantarum separated from kimchi , which are known to be predominant in kimchi ." ]

[ "the number of death due to cancer has been increasing in korea .", "chemotherapy is known to cause side effects because it damages not only cancerous cells but healthy cells . recently", ", attention has focused on food - derived chemopreventive and anti - tumor agents or formulations with fewer side effects .", "kimchi , most popular and widely consumed in korea , contains high levels of lactic acid bacteria and has been shown to possess chemopreventive effects .", "this review focuses on weissella cibaria and lactobacillus plantarum , the representatives of kimchi lactic acid bacteria , in terms of their abilities to prevent cancer .", "further studies are needed to understand the mechanisms by which lactic acid bacteria in kimchi prevent carcinogenic processes and improve immune functions ." ]

[ [ 7, 6 ], [ 7, 1 ], [ 6, 5 ] ]

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