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pubmed_1026_8806 | OBJECTIVES
IL-37 has been identified as an important anti-inflammatory and immunosuppressive factor. This study was undertaken to explore how IL-37 affects M1/M2-like macrophage polarization and thus contributes to anti-inflammatory processes in the temporomandibular joint.
METHODS
Western blotting, quantitative real-time PCR (qRT-PCR) and immunofluorescence were used to verify the IL-37-induced polarization shift from the M1 phenotype to the M2 phenotype, and the related key pathways were analysed by western blotting. Human chondrocytes were stimulated with M1-conditioned medium (CM) or IL-37-pretreated M1-CM, and inflammatory cytokines were detected. siRNA-IL-1R8 and MCC-950 were used to investigate the mechanism underlying the anti-inflammatory effects of IL-37. Complete Freund's adjuvant-induced and disc perforation-induced inflammation models were used for in vivo studies. Haematoxylin and eosin, immunohistochemical and safranin-O staining protocols were used to analyse histological changes in the synovium and condyle.
RESULTS
Western blotting, qRT-PCR and immunofluorescence showed that IL-37 inhibited M1 marker expression and upregulated M2 marker expression. Western blotting and qRT-PCR showed that pretreatment with IL-37 suppressed inflammatory cytokine expression in chondrocytes. IL-37 inhibited the expression of NLRP3 and upregulated the expression of IL-1R8. Si-IL-1R8 and MCC-950 further confirmed that the anti-inflammatory properties of IL-37 were dependent on the presence of IL-1R8 and NLRP3. In vivo, IL-37 reduced synovial M1 marker expression and cartilage degeneration and increased M2 marker expression.
CONCLUSION
IL-37 shifting of the polarization of macrophages from the pro-inflammatory M1 phenotype to the beneficial anti-inflammatory M2 phenotype seems to be a promising therapeutic strategy for treating temporomandibular joint inflammation. | 10.1093/rheumatology/keaa192 |
pubmed_258_4769 | The family of van der Waals (vdW) materials is large and diverse with applications ranging from electronics and optoelectronics to catalysis and chemical storage. However, despite intensive research, there remains significant knowledge-gaps pertaining to their properties and interactions. One such gap is the interaction between these materials and hydrogen, a potentially vital future energy vector and ubiquitous processing gas in the semiconductor industry. This work reports on the interaction of hydrogen with the vdW semiconductor SnS2 , where molecular hydrogen (H2 ) and H-ions induce a controlled chemical conversion into semiconducting-SnS or to β-Sn. This hydrogen-driven reaction is facilitated by the different oxidation states of Sn and is successfully applied to form SnS2 /SnS heterostructures with uniform layers, atomically flat interfaces and well-aligned crystallographic axes. This approach is scalable and offers a route for engineering materials at the nanoscale for semiconductor technologies based on the earth-abundant elements Sn and S, a promising result for a wide range of potential applications. | 10.1002/smll.202202661 |
pubmed_254_7485 | Molecular analysis has allowed for refinement of salivary gland tumor classification and, in some cases, the recognition of entirely new tumor types. Microsecretory adenocarcinoma (MSA) is a salivary gland tumor described in 2019 characterized by microcystic growth, bland cytomorphology, luminal secretions, fibromyxoid stroma, and S100/p63 positivity with negative p40. Most important, MSA is defined by MEF2C-SS18 fusion. While this fusion has, to this point, been detected by next-generation sequencing, this is a technique that is currently inaccessible in most diagnostic laboratories. On the other hand, SS18 break-apart fluorescence in situ hybridization (FISH) is widely available and frequently used as an adjunct for diagnosing synovial sarcoma. It is not known if SS18 break-apart FISH is positive in tumors with MEF2C-SS18, or if it is entirely specific for MSA. Break apart FISH for SS18 was performed on 4 cases of MSA, as well as 8 tissue microarrays (TMAs) containing 423 various salivary gland carcinomas: 26 acinic cell carcinomas, 35 adenocarcinomas not otherwise specified, 96 adenoid cystic carcinomas, 3 basal cell adenocarcinomas, 20 epithelial-myoepithelial carcinomas, 15 hyalinizing clear cell carcinomas, 3 intraductal carcinomas, 12 myoepithelial carcinomas, 117 mucoepidermoid carcinomas, 30 polymorphous adenocarcinomas, 45 salivary duct carcinomas, 19 secretory carcinomas, and 2 undifferentiated carcinomas. SS18 break-apart FISH was also performed on whole slides of 2 tumors from the TMAs. All MSA cases demonstrated classic split patterns on SS18 break-apart FISH. On the TMAs, 374 cases were evaluable by FISH, and 372 cases were clearly negative for SS18 rearrangement. Two cases, both mucoepidermoid carcinomas, had rare split signals below the positivity threshold of 12% on their TMA cores, so FISH was performed on whole sections. On the whole sections both tumors were unequivocally negative for SS18 rearrangement. Taken together, SS18 break-apart FISH was 100% sensitive and 100% specific for a diagnosis of MSA. SS18 break-apart FISH, a diagnostic tool widely available in pathology laboratories, appears to be a highly accurate method for diagnosing MSA of salivary glands. Accordingly, this new tumor type may be molecularly confirmed without needing to resort to highly specialized techniques like next-generation sequencing. | 10.1007/s12105-020-01280-7 |
pubmed_521_14725 | We prospectively monitored our experience of lamotrigine as add-on therapy in 45 patients with refractory epilepsy. Nine patients (20%) withdrew from treatment due to adverse drug reactions and five patients (11%) withdrew because of a deterioration in seizure frequency. A further 17 patients (38%) showed little (< 25%) reduction in seizure number, eight patients (18%) showed a 25-50% reduction whilst 15 patients (33%) had a 50% or greater reduction in seizure number (P = 0.002). Lamotrigine was of greater benefit in patients with tonic-clonic seizures (seven of fourteen [50%] showed a > 50% seizure reduction; P = 0.01) than in patients with complex partial seizures (seven of 22 [32%] showed a > 50% seizure reduction; P = 0.02). Despite a high withdrawal rate due to ADRs, lamotrigine proved of significant benefit to one-third of our study group. | 10.1016/s1059-1311(05)80190-6 |
pubmed_408_650 | Chemical modification of the COOH-groups of acid alpha-glucosidase from human liver by 1-ethyl-3 (3'-dimethylaminopropyl) carbodiimide. HCl in the presence of rho-aminophenyl-beta-D-galactopyranoside was carried out. The presence of covalently bound galactose derivative in the enzyme was followed by changes in the absorption spectra and electrophoretic mobility during polyacrylamide gel electrophoresis and by the ability of modified alpha-glucosidase to interact specifically with castor-bean lectin (RCA II). The modified enzyme retained its catalytic activity towards maltose and did not differ from native alpha-glucosidase in terms of its affinity for this substrate, the Km values for maltose during 5 and 6 mM, respectively. The in vitro changes in the marker specificity of acid alpha-glucosidase against the unchanged catalytic properties of the enzyme are discussed. | pubmed_408_650 |
pubmed_526_2724 | This scoping review examines the literature to determine whether the position of the needle tip relative to the target nerve is accurately and reliably detected during ultrasound (US)-guided regional anesthesia. The requisites for successful and safe needle tip positioning relative to the target nerve include accurate and reliable needle presentation by the machine, needle interpretation by the operator, nerve presentation by the machine, and nerve interpretation by the operator. Failure to visualize the needle tip is a common occurrence, frequently prompting operators to use needle and probe maneuvers, which are not necessarily based on evidence. Needle tip interpretation often relies on surrogate indicators that have not been validated. The acoustic resolution of modern portable US machines limits the extent to which nerve microanatomy can be reliably presented. Finally, our interpretation of the sonographic end points for local anesthetic injection that best balance success and safety for US-guided regional anesthesia continues to evolve.
WHAT'S NEW
In order to determine whether or not the position of the needle tip relative to the target nerve is accurately and reliably detected during US-guided regional anesthesia, the available literature is reviewed and interpreted to address the following 4 questions. | 10.1097/AAP.0000000000000201 |
pubmed_1104_8903 | The past 20-30 years have seen major advances in our understanding of human reproduction and in our ability to manipulate it, as well as major social changes in human reproductive and sexual attitudes. Many of these advances and changes developed out of the first successful in vitro fertilisation (IVF) of the human oocyte. It is also the case that 30 years ago few foresaw what was to come, and many were at best doubtful and often were very critical of the scientific work which led to human IVF and to many of the subsequent developments. This lack of foresight provides us with a lesson about the dangers that we face in looking forward and attempting to predict the future. This review will try to convey, not comprehensively but through examples, the flavour of current activities in Assisted Reproduction clinics and research laboratories around the world and what is being talked about for the future in respect of emergent patient demands and anticipated clinical needs. This clinically driven approach will form the basis for consideration of some underlying scientific aspects of reproductive research, some of the ethicolegal issues that may arise, and the implications of this anticipated future for our current approaches to medical education. The future will be considered not simply in terms of the New Reproduction itself but also in its interaction with the opportunities and challenges presented by the New Genetics. It is perhaps in the interaction between these two fields of endeavour that some of the most difficult challenges ahead lie. | 10.1046/j.1469-7580.2001.19840385.x |
pubmed_397_6347 | Anaerobic enrichment cultures acclimated for 2 years to use a C-labeled, lignin-derived substrate with a molecular weight of 600 as a sole source of carbon were characterized by capillary and packed column gas chromatography. After acclimation, several of the active methanogenic consortia were inhibited with 2-bromoethanesulfonic acid, which suppressed methane formation and enhanced accumulation of a series of metabolic intermediates. Volatile fatty acids levels in 2-bromoethanesulfonic acid-amended cultures were 10 times greater than those in the uninhibited, methane-forming consortia with acetate as the predominant component. Furthermore, in the 2-bromoethanesulfonic acid-amended consortia, almost half of the original substrate carbon was metabolized to 10 monoaromatic compounds, with the most appreciable quantities accumulated as cinnamic, benzoic, caffeic, vanillic, and ferulic acids. 2-Bromoethanesulfonic acid seemed to effectively block CH(4) formation in the anaerobic food chain, resulting in the observed buildup of volatile fatty acids and monoaromatic intermediates. Neither fatty acids nor aromatic compounds were detected in the oligolignol substrate before its metabolism, suggesting that these anaerobic consortia have the ability to mediate the cleavage of the beta-aryl-ether bond, the most common intermonomeric linkage in lignin, with the subsequent release of the observed constituent aromatic monomers. | 10.1128/aem.49.2.350-358.1985 |
pubmed_1103_9306 | BACKGROUND
Rescue service personnel are often exposed to traumatic events as part of their occupation, and higher prevalence rates of psychiatric illness have been found among this group.
METHODS
In 65 rescue workers, salivary cortisol at 8 AM and 10 PM and serum prolactin at 8 AM were related to the psychiatric self-rating scale General Health Questionnaire (GHQ-28) measuring psychiatric health, and the Impact of Events Scale (IES) and Post Traumatic Symptom Scale (PTSS) measuring posttraumatic symptoms.
RESULTS
Seventeen percent of the study population scored above the GHQ-28 cut-off limit but none scored beyond the cut-off limit in the IES and PTSS questionnaires. Salivary cortisol concentration at 10 PM correlated with statistical significance to anxiety (p < .005) and depressive symptoms (p < .01) measured with GHQ-28, as well as to posttraumatic symptoms, with avoidance behavior measured with IES (p < .01) and PTSS (p < .005). Two of the rescue workers were followed over time with the same sampling procedure after a major rescue commission.
CONCLUSIONS
The correlation between evening salivary cortisol and anxiety, depressiveness, and posttraumatic avoidance symptoms indicates that these parameters can be used in screening and follow-up after traumatic stress events. | 10.1016/s0006-3223(98)00381-3 |
pubmed_75_17046 | Two modifications for miniaturizing the standard 51chromium release assay have been described. Using peripheral blood lymphocytes (PBL) as effectors and very few target cells, this permits longitudinal studies on NK cell activity of individual mice to be performed. The modifications are based on methods to increase the chromium uptake by the target cell. Firstly, chromium uptake by the YAC-1 target cells was enhanced to such an extent that appreciable activity could be detected against as little as 750 cells/well at an E/T ratio of 50:1. Secondly, the uptake was increased even further by labelling the target cells in the presence of isotonic sucrose, thus permitting the use of only 125 target cells/well at an E/T of 25:1. The long term pattern of NK activity in individual BALB/c mice was studied by repeated bleedings over a period of 8 months. Considerable fluctuations with time were observed in the pattern of NK activity of individual mice. However, the NK activity averaged over a large number of mice did not show a significant decrease with age. These methods may allow the study of the long term pattern of NK activity in individual mice and the response of this activity to physiological and environmental factors. | 10.1016/0022-1759(86)90188-2 |
pubmed_82_3699 | The polyphosphoinositide PtdIns(4,5)P2, best known as a substrate for phospholipase C isozymes, has recently been recognized to be involved in a variety of other cellular processes. The aim of this study was to examine whether the cellular levels of this versatile phospholipid are controlled by tyrosine phosphorylation. The studies were performed in human embryonic kidney (HEK)-293 cells stably expressing the M3 muscarinic acetylcholine receptor. Inhibition of tyrosine phosphatases by pervanadate induced an up-to-approx.-2. 5-fold increase in the total cellular level of PtdIns(4,5)P2, which was both time- and concentration-dependent. In contrast, the tyrosine kinase inhibitors, genistein and tyrphostin 23, caused a rapid and specific fall in the cellular PtdIns(4,5)P2 level and prevented the stimulatory effect of pervanadate on PtdIns(4,5)P2 formation. Inactivation of Rho proteins by Clostridium difficile toxin B caused a similar fall in the HEK-293 cell PtdIns(4,5)P2 level, which was not altered by additional genistein treatment. Furthermore, toxin B treatment abolished the pervanadate-induced increase in PtdIns(4,5)P2 levels. As PtdIns(4,5)P2 is an essential stimulatory cofactor for phospholipase D (PLD) enzymes, we finally examined the effects of the agents regulating PtdIns(4,5)P2 levels on PLD activity in HEK-293 cells. Inhibition of tyrosine phosphatases by pervanadate caused an increase in PLD activity, which was susceptible to genistein and tyrphostin 23, and which was abolished by prior treatment with toxin B. In conclusion, the data presented indicate that the cellular level of the multifunctional phospholipid, PtdIns(4,5)P2, in HEK-293 cells is controlled by a tyrosine-kinase-dependent mechanism and that this process apparently involves Rho proteins, as found similarly for tyrosine-phosphorylation-induced PLD activation. | 10.1042/bj3340625 |
pubmed_400_16358 | How does the brain distinguish actions that we perform from movements imposed on us? To study links between the representations of actions and their somatosensory consequences, we compared the perceived times of voluntary actions or involuntary movements and of a subsequent somatic effect (a TMS-induced twitch of the right index finger). Participants perceived voluntary actions as occurring later and their bodily effects as occurring earlier in the agency context, compared to single-event baseline conditions. When the voluntary action was replaced by a passive, involuntary movement this attraction effect reversed. In a second experiment, subjects rated the intensity of the same TMS-induced somatic effect, again following a voluntary action or a passive movement. When the somatic effect was caused by a voluntary action, it was perceived as significantly less intense than when it followed a passive movement. Our results suggest a binding mechanism integrating awareness of somatic consequences occurring in voluntary action. This 'intentional binding' mechanism might underlie the way in which the mind constructs a strong association between intentions, actions and consequences so as to generate the unique and private phenomenological experience of self-agency. | 10.1007/s00221-003-1386-8 |
pubmed_206_17146 | Ramelteon (Rozerem) is the first melatonin receptor agonist to be approved for the treatment of insomnia; it is not classified as a controlled substance. In patients with chronic insomnia, objectively assessed latency to persistent sleep (LPS) at week 1 was improved with oral ramelteon 8 mg administered 30 minutes before bedtime, compared with placebo, and this effect was maintained throughout the duration of 5-week and 6-month clinical studies. Subjectively assessed sleep latency (sSL) improved in some, but not all, studies. When a statistically significant improvement in sSL occurred at week 1, the effect was maintained throughout the duration of the 5-week studies, but not at all timepoints throughout a 6-month study. Improvements in objectively assessed total sleep time (TST) and sleep efficiency (SE) were only reported during the first week of treatment. Improvements in other objective or subjective measures of sleep were not consistent. Ramelteon was generally well tolerated, did not impair next-day cognitive or motor performance and was not associated with withdrawal symptoms, rebound insomnia or abuse potential. Thus, ramelteon provides a well tolerated option for the treatment of patients with insomnia characterized by difficulty in sleep onset. | 10.2165/00003495-200868130-00011 |
pubmed_1061_18740 | We have investigated the association of oral health with development of dementia in elderly Koreans. Data for subjects aged ≥65 years who underwent regular National Health Insurance Service check-ups and received dental care in 2017 were analysed. Those treated for dementia in 2017 served as the dementia group and those with no record of dementia in 2002-2017 as the control group. Explanatory variables were sex, age, household income, place of residence, smoking status, alcohol consumption, and presence of diabetes mellitus and hypertension, periodontitis, and removable dentures. Regression analysis showed that dementia was significantly more common in women than in men and in those aged ≥81 years than in those aged 65-70 years. The risk of dementia was highest in the 'upper-middle' income group and in the rural population. Smokers and those who consumed alcohol were less likely to develop dementia. Subjects with diabetes were more likely to have dementia than those without it, as were those with hypertension. Dementia was less likely in subjects with periodontitis and more likely in those with removable dentures. Therefore, loss of teeth may contribute to development of dementia. | 10.1038/s41598-019-50863-0 |
pubmed_434_8667 | Cu(2)SnS(3) nanocrystals with metastable zincblende and wurtzite structures have been successfully synthesized for the first time. Alloyed (ZnS)(x)(Cu(2)SnS(3))(1-x) and (CuInS(2))(x)(Cu(2)SnS(3))(1-x) nanocrystals with arbitrary composition (0 ≤x≤ 1) and ultra-broad tunable band gaps (3.63 to 0.94 eV) were obtained. | 10.1039/c0cc03560b |
pubmed_197_20028 | We investigated the effects of atypical antipsychotic drugs on GABA concentrations in early-stage, first-episode schizophrenia patients. Sixteen (8 males, 8 females; age, 30±11 years old) patients were followed up for six months. We also included 18 sex- and age-matched healthy control subjects. All patients were treated with atypical antipsychotic drugs (5 patients with risperidone, 5 patients with olanzapine, 4 patients with aripiprazole, and 2 patients with quetiapine). In all three regions measured (frontal lobe, left basal ganglia, and parieto-occipital lobe), no differences in GABA concentrations were observed in a comparison of pre-treatment levels and those six months after treatment. These results suggest that relatively short-term treatment with atypical antipsychotic drugs may not affect GABAergic neurotransmission; however, it is also possible that such treatment prevents further reductions in brain GABA levels in people with early-stage, first-episode schizophrenia. | 10.1016/j.pnpbp.2010.08.007 |
pubmed_1105_4262 | Type I interferons (IFN-alpha and -beta) play a key role in anti-viral immunity, and we sought to define the molecular mechanisms by which the sympathetic nervous system (SNS) inhibits their effects. In peripheral blood leukocytes and plasmacytoid dendritic cells (pDC2), induction of interferon anti-viral activity by double-stranded RNA (poly-I:C) or CpG DNA was substantially inhibited by norepinephrine and by pharmacologic activation of the cAMP/PKA signaling pathway. This effect was specific to Type I interferons and driven by PKA-mediated repression of IFNA and IFNB gene transcription. Luciferase reporter analyses identified tandem interferon response factor-binding sites in positive regulatory domains I and III of the IFNB promoter as a key target of PKA inhibition. PKA suppression of Type I interferons was associated with impaired transcription of interferon response genes supporting the "anti-viral state", and was sufficient to account for norepinephrine-induced enhancement of HIV-1 replication. Given the ubiquitous role of Type I interferons in containing viral replication, PKA-mediated inhibition of IFN transcription could explain the stimulatory effects of catecholamines on a broad range of viral pathogens. | 10.1016/j.bbi.2006.01.005 |
others_406_13155 | otransformation products of platinum anticancer drugs have been suggested to be responsible for drug efficacy and toxicity. This study was designed to determine whether the efficacy of the closely related 1,2-diaminocyclohexane-Pt (dach-Pt) compounds oxaliplatin and ormaplatin were determined primarily by the parent drugs or by one of their biotransformation products. Based on consideration of both in vitro cylotoxicity in human colon carcinoma cells (HT-29) and concentrations following oxaliplatin administration in vivo, our data suggest that the efficacy of oxaliplatin is primarily determined by the plasma levels of the parent drug, with the biotransformation products Pt(dach)Cl2, Pt(dach)(H2O)Cl, and Pt(dach)(H2O)2 making only minor contributions. The stable biotransformation products containing amino acids did not have any significant cytotoxicity. In contrast, our data suggest that the efficacy of ormaplatin is primarily determined by plasma levels of Pt(dach)Cl2. The cytotoxicity of oxaliplatin, Pt(dach)Cl2, and Pt(dach)(H2O)Cl was approximately proportional to their cellular uptake, whereas the cytotoxicity of ormaplatin, Pt(dach)(H2O)2, and Pt(dach)(Met) was less than predicted from their uptake. Treatment of HT-29 cells with equimolar external concentrations of Pt(dach)Cl2 and oxaliplatin resulted in the formation of twofold more Pt-DNA adducts following Pt(dach)Cl2 treatment than following oxaliplatin treatment. However, intracellular Pt(dach)Cl2 levels were 30-fold higher for Pt(dach)Cl2-treated cells than for oxaliplatin-treated cells. These data suggest that intracellular conversion of oxaliplatin to Pt(dach)Cl2 makes only a minor contribution to Pt-DNA adduct formation and the resultant cytotoxicity of oxaliplatin. Copyright © 1998 Cognizant Comm. Corp | others_406_13155 |
pubmed_1113_21633 | Fundamental to the surgical treatment of patients taking warfarin is the monitoring of the international normalised ratio (INR) before and after operation. A postoperative rise in INR was observed to be more common than a postoperative fall, so we decided to test the null hypothesis that there is no difference in the INR before and after minor dentoalveolar surgery. Data from the dental records of 71 patients treated consecutively over an 18-month period were examined, and INR before and after operation tested by a Friedman non-parametric test (ANOVA). Six cases were removed from the study because they required perioperative adjustment of their warfarin. There was a significant increase in the postoperative INR for the whole group. Further analysis showed that a significant increase in the postoperative INR for the multiple extraction and surgical removal group was the most likely cause for the rise in the whole group. There was no significant increase between men and women, those taking antibiotics preoperatively, and those not doing so, or in those having a single tooth extracted. We found an association between the degree of surgical intervention and the likelihood of anticoagulation being affected. Postoperative INR in this group should be monitored carefully. | 10.1016/j.bjoms.2007.06.002 |
pubmed_449_6556 | The influence of an acute physical exercise on hemorheological parameters in insulin-dependent diabetes mellitus in not actually known. We have examined the behavior of hemorheological parameters and other laboratory findings such as blood glucose, blood lactic acid, O2 and CO2 venous pressure and venous pH before and after a submaximal physical exercise standardized by ECG monitoring and by means of an 'oxygen consumption computer'. The work load was significantly lower in diabetic patients than in normal control subjects. On the other hand, changes in hemorheological parameters were more evident in diabetic patients. The significance of these findings is also discussed. | pubmed_449_6556 |
pubmed_98_4183 | Neighborhood walkability is key to promoting health, accessibility, and pedestrian safety. The Accessible, Connected Communities Encouraging Safe Sidewalks (ACCESS) project was developed to assess sidewalks throughout an urban community in Pontiac, Michigan. Data were collected from 2016 to 2018 along eighty miles of sidewalk for tripping hazards, cracking, vegetation, obstructions, overhead coverage, street lighting, buffers, and crosswalks. Data were mapped in ArcGIS with sociodemographic characteristics by U.S. Census block group. The majority of sidewalks had moderate (57.6%) or major (29.4%) sidewalk quality issues, especially maintenance-related impediments (68.6%) and inadequate street lighting or shade coverage (87.2%). The majority of crosswalks had a curb ramp to improve access for people with disabilities (84.4%), however over half lacked a detectable warning strip (55.8%). Degraded sidewalk quality was associated with lower neighborhood socioeconomic status and a higher proportion of Black and Latinx residents. Equity-centered pedestrian infrastructure improvement plans can address these disparities by increasing accessible, safe active transport options that promote physical activity and reduce health disparities. Evaluations like ACCESS can connect public health professionals with municipal planners to advance Complete Streets plans and promote healthy living. | 10.1016/j.ssmph.2021.100975 |
pubmed_299_21244 | BACKGROUND
Trauma remains a leading cause of morbidity and mortality in the UK and throughout the world. Socioeconomic deprivation has been linked with many types of ill-health and previous studies have shown an association with injury in other parts of the world. The aim of this study was to investigate the association between socioeconomic deprivation and trauma incidence and case-fatality in Scotland.
METHODS
The study included nine thousand two hundred and thirty eight patients attending Emergency Departments following trauma across Scotland in 2011-12. A retrospective cohort study was conducted using secondary data extracted from the national trauma registry. Postcode of residence was used to generate deciles using the Scottish Index of Multiple Deprivation. The incidence rate ratio (IRR) was calculated to allow comparison of incidence of trauma across SIMD deciles. For mortality, observed: expected ratios were obtained using observed mortality in the cohort and expected deaths using probability of survival based on Trauma and Injury Severity Score (TRISS) method.
RESULTS
Compared with the most deprived decile, the least deprived had an incidence rate ratio (IRR) for all trauma of 0.43 (95 % CI 0.32-0.58, p < 0.001). The association was stronger for penetrating trauma (IRR 0.07, 95 % CI .01-0.56, p = 0.011). There was a significant interaction between age, gender and SIMD. For case fatality, multivariate logistic regression showed that, severity of trauma (ISS > 15) OR 18.11 (95 % CI 13.91 to 23.58) and type of injury (Penetrating versus blunt injury) OR 2.07 (95 % CI 1.15 to 3.72) remain as independent predictors of case fatality in this dataset.
DISCUSSION
Our data shows a higher incidence of trauma amongst a socioeconomically deprived population, in keeping with other areas of the world. In our dataset, outcome, as measured by in-hospital mortality, does not appear to be associated with socioeconomic deprivation.
CONCLUSION
In Scotland, populations living in socioeconomically deprived areas have a higher incidence of trauma, especially penetrating trauma, requiring hospital attendance. Case fatality is associated with more severe trauma and penetrating trauma, but not socioeconomic deprivation. | 10.1186/s13049-016-0275-7 |
pubmed_994_8800 | INTRODUCTION
The family of inhibitor of apoptosis proteins (IAPs) plays a key role in the suppression of proapoptotic signaling; hence, a small molecule that disrupts the binding of IAPs with their functional partner should restore apoptotic response to proapoptotic stimuli in cells. The continued publication of new patent applications of IAP antagonists over the past 4 years is a testament to the continued interest surrounding the IAP family of proteins.
AREAS COVERED
This review summarizes the IAP antagonist patent literature from 2010 to 2014. Monovalent and bivalent Smac mimetics will be covered as well as two new developments in the field: IAP antagonists coupled to or merged with other targeted agents and new BIR2 selective IAP antagonists.
EXPERT OPINION
In addition to the well-explored scaffolds for monovalent and bivalent Smac-mimetics, some companies have taken more drastic approaches to explore new chemical space - for example, fragment-based approaches and macrocyclic inhibitors. Furthermore, other companies have designed compounds with alternative biological profiles - tethering to known kinase binding structures, trying to target to the mitochondria or introducing selective binding to the BIR2 domain. An overview of the status for the four small molecule IAP antagonists being evaluated in active human clinical trials is also provided. | 10.1517/13543776.2015.1041922 |
pubmed_995_16632 | Using the End-Stage Renal Disease Medical Information System and 1980 census information, the crude cumulative incidence among Blacks, Hispanics, and Whites in south central Los Angeles was determined to be 160.1, 49.28, and 55.3 per 100,000 respectively. Sex-specific rates were slightly greater in males. Among Blacks, nephrosclerosis and diabetes represented 41.5 and 30.2 per cent of the cases respectively and increased during the period 1980-85. | 10.2105/ajph.77.7.864 |
pubmed_681_24028 | The efficiency of potentiated preparations from ethanol and morphine hydrochloride in the therapy of patients with alcohol and opium withdrawal syndromes was compared in an open clinical trial. Potentiated ethanol relieved the major clinical manifestations, possessed hypnagogic properties, and reduced the severity of neurological and vegetative disorders in patients with the alcohol withdrawal syndrome. Potentiated morphine produced the anxiolytic, myorelaxing, and analgetic effects. Test preparations did not cause side effects. | 10.1023/a:1024704913575 |
pubmed_743_101 | Mathematical and computational approaches that integrate and model the concerted action of multiple genetic and nongenetic components holding highly nonlinear interactions are fundamental for the study of developmental processes. Among these, gene regulatory network (GRN) dynamical models are very useful to understand how diverse types of regulatory constraints restrict the multigene expression patterns that characterize different cell fates. In this chapter we present a hands-on approach to model GRN dynamics, taking as a working example a well-curated and experimentally grounded GRN developmental module proposed by our group: the flower organ specification gene regulatory network (FOS-GRN). We demonstrate how to build and analyze a GRN model according to the following steps: (1) integration of molecular genetic data and formulation of logical rules specifying the dynamic behavior of each gene; (2) determination of steady states (attractors) corresponding to each cell type; (3) validation of the GRN model; and (4) extension of the deterministic model with the inclusion of stochasticity in order to model cell-state transitions dependent on noise due to fluctuations of the involved gen products. The methodologies explained here in detail can be applied to any other developmental module. | 10.1007/978-1-0716-1816-5_4 |
pubmed_630_2903 | Two single-nucleotide polymorphisms (SNPs) (rs11918092 and rs9520087) were genotyped in Chinese Zhuang and Han populations. Symptoms of schizophrenic patients were assessed by the Positive and Negative Syndrome Scale. No association of any SNP with schizophrenic susceptibility was found. However, associations of rs9520087 with the total scale score (P = 0.014), positive scale score (P = 0.013), negative scale score (P = 0.032), and general psychopathology scale score (P = 0.031) were found in Zhuang patients. Additionally, rs11918092 was associated with positive scale score (P = 0.035) in Han patients. The two SNPs might influence symptoms of schizophrenia. | 10.1111/appy.12241 |
pubmed_487_17870 | A dual dipole electric field probe has been used to measure surface electric fields in vivo on a human subject over a frequency range of 0.1-800 Hz. The low-frequency electric fields were induced by natural body movements such as walking and turning in the fringe magnetic fields of a 3 T magnetic resonance whole-body scanner. The rate-of-change of magnetic field (dB/dt) was also recorded simultaneously by using three orthogonal search coils positioned near to the location of the electric field probe. Rates-of-change of magnetic field for natural body rotations were found to exceed 1 T s(-1) near the end of the magnet bore. Typical electric fields measured on the upper abdomen, head and across the tongue for 1 T s(-1) rate of change of magnetic field were 0.15+/-0.02, 0.077+/-0.003 and 0.015+/-0.002 V m(-1) respectively. Electric fields on the abdomen and chest were measured during an echo-planar sequence with the subject positioned within the scanner. With the scanner rate-of-change of gradient set to 10 T m(-1) s(-1) the measured rate-of-change of magnetic field was 2.2+/-0.1 T s(-1) and the peak electric field was 0.30+/-0.01 V m(-1) on the chest. The values of induced electric field can be related to dB/dt by a 'geometry factor' for a given subject and sensor position. Typical values of this factor for the abdomen or chest (for measured surface electric fields) lie in the range of 0.10-0.18 m. The measured values of electric field are consistent with currently available numerical modelling results for movement in static magnetic fields and exposure to switched magnetic field gradients. | 10.1088/0031-9155/53/2/005 |
pubmed_73_21330 | Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by the dys-homeostasis of biometal metabolism, the extracellular accumulation of neurotoxic amyloid-beta (Abeta) peptide, the intracellular accumulation of hyperphosphorylated tau and the loss of synapses. Copper plays a key role in AD development. The Abeta peptide and amyloid precursor protein (APP), the parental molecule of Abeta, are modulated by copper in the brain. Increased copper concentration has been found in the AD brain that implies that copper may participate in the pathophysiology of AD. Copper can bind to APP and Abeta, then affects the structure and toxic of APP and Abeta. Some researchers have reported that copper could affect the formation of beta-sheet structure that is widely accepted as toxic secondary structure of Abeta. This review explores the role of copper on the conformation and aggregation of Abeta, and the copper-induced neuroactive mechanisms. Copper may be involved in the following pathways to affect the neuroactivation of Abeta: (1) change of the secondary structure of Abeta; (2) induction of oxidative stress in AD brains, and (3) regulation of cellular signal pathway. Thus, correcting brain copper imbalance may represent a relevant therapeutic target for Alzheimer's disease. | 10.1016/j.brainresbull.2010.06.003 |
pubmed_901_2238 | A direct inhibitory effect of hydrocortisone on granulocyte chemotaxis has been demonstrated with an increasing inhibition between concentrations of 5 microgram to 12.5 microgram per ml. Washing the granulocytes after incubation with hydrocortisone did not reverse the inhibitory effect on chemotaxis indicating a direct cellular effect. Bacteriocidal capacity of the hydrocortisone treated cells was not reduced. These studies indicate corticosteroids, alter motility of granulocytes irreversibly possibly by incorporation into the cell membrane. | pubmed_901_2238 |
pubmed_743_23093 | This review has been withdrawn because it has been superceded by the Cochrane Review of Competitions for smoking cessation. | 10.1002/14651858.CD004986.pub4 |
others_395_321 | This work summarises the clinical pharmacology of quinine, a cinchona alkaloid, whose use in chloroquine resistant Plasmodium falciparum malaria is of great value considering the staggering effects the infection and its morbidity have upon social and economic development of malaria endemic areas of the world. Quinine is very effective and consistent in the treatment of falciparum malaria at all grades of severity. The effectiveness of quinine in severe malaria can be maintained and the possibility of development of resistant strains to the drug reduced by combined therapy with other drugs to which the infecting strains of P. falciparum are still sens | others_395_321 |
pubmed_34_14134 | We use computer simulation results for a dense Lennard-Jones fluid for a range of temperatures to test the accuracy of various binary collision approximations for the memory function for density fluctuations in liquids. The approximations tested include the moderate density approximation of the generalized Boltzmann-Enskog memory function (MGBE) of Mazenko and Yip [Statistical Mechanics. Part B. Time-Dependent Processes, edited by B. J. Berne (Plenum, New York, 1977)], the binary collision approximation (BCA) and the short time approximation (STA) of Ranganathan and Andersen [J. Chem. Phys. 121, 1243 (2004); J. Phys. Chem. 109, 21437 (2005)] and various other approximations we derived by using diagrammatic methods. The tests are of two types. The first is a comparison of the correlation functions predicted by each approximate memory function with the simulation results, especially for the self-longitudinal current correlation (SLCC) function. The second is a direct comparison of each approximate memory function with a memory function numerically extracted from the correlation function data. The MGBE memory function is accurate at short times but decays to zero too slowly and gives a poor description of the correlation function at intermediate times. The BCA is exact at zero time, but it predicts a correlation function that diverges at long times. The STA gives a reasonable description of the SLCC but does not predict the correct temperature dependence of the negative dip in the function that is associated with caging at low temperatures. None of the other binary collision approximations is a systematic improvement on the STA. The extracted memory functions have a rapidly decaying short time part, much like the STA, and a much smaller, more slowly decaying part of the type predicted by a mode coupling theory. Theories that use mode coupling commonly include a binary collision term in the memory function but do not discuss in detail the nature of that term. It is clear from the present work that the short time part of the memory function has a behavior associated with brief binary repulsive collisions, such as those described by the STA. Collisions that include attractive as well as repulsive interactions, such as those of the MGBE, have a much longer duration, and theories that include them have memory functions that decay to zero much too slowly to provide a good first approximation of the correlation function. This leads us to speculate that the memory function for density fluctuations can be usefully regarded as a sum of at least three parts: a contribution from repulsive binary collisions (the STA or something similar to it), another short time part that is related to all the other interactions (but whose nature is not understood), and a longer time slowly decaying part that describes caging (of the type predicted by the mode coupling theory). | 10.1063/1.2752153 |
pubmed_538_12101 | Interprofessional education in health care in general and palliative care has been the focus of increasing attention in recent years. However, there is still controversy about its outcomes and few courses have been evaluated. The aims of this evaluation were to explore (1) the career progression of former students who attended an interprofessional MSc in palliative care; (2) the activities former students were engaged in as a result of attending the course; and (3) the experience of attending an interprofessional postgraduate course in palliative care. Former students who attended the course between January 1998 and January 2004 were surveyed using a postal questionnaire. Of the 56 students who completed the course, 44 (79%) responded; 23 (52%) were doctors, 20 (45%) nurses, and one an occupational therapist. Career progression was significant for doctors (Z=-2.08, p=0.04) and for nurses (Z=-2.4, p=0.017). Thirty-nine (89%) former students believed this was due to attending the course. Former students described a wide range of clinical, research, and service development activities they were involved in as a result of attending the course. Qualitative data highlighted the benefits of attending an interprofessional course where the following themes became evident: lateral thinking, challenging misconceptions, enhancing teamwork opportunities, and professional networks and confidence. Funding should be made available to extend interprofessional education to a wide range of professionals who care for patients with advanced disease and their families. | pubmed_538_12101 |
pubmed_130_23345 | This article investigates the beliefs of Confucianism-China's authoritative philosophy-regarding same-sex behavior, by examining Confucian canonical texts-either directly or through the interpretations of other scholars-and the scholarly literature on the relationship between the Confucian ethics and same-sex behavior. Additionally, this article explores the empirical research and media focusing on the lives of Chinese homosexuals to ascertain whether Confucianism has a palpable impact on their daily existence. This article argues that compared to pre-modern China, the Confucian concept of filial piety has a profound influence on the lives of contemporary Chinese homosexuals. | 10.1080/00918369.2022.2042663 |
pubmed_340_18529 | Recent data from literature report that reactive oxygen species (ROS) seem to play a crucial role in the etiology of both types I and II diabetes. This may render diabetic individuals more prone to oxidative injury when challenged with hypoxic stress. It is in fact well known that many diabetic complications cause ischaemic episodes, with a consequent reduction in oxygen supply to various tissues and organs. To check this hypothesis, in this work we tested type I diabetic individuals' antioxidant capability towards a hypoxic-mediated oxidative challenge. In particular, spontaneously diabetic and age-matched non-diabetic biobreeding (BB) Wistar rats were submitted to chronic normobaric hypoxia, and the response of antioxidant enzymes, as well as redox-sensitive transcription factor NF-kappaB and p53, were monitored. Results show that diabetic subjects present a dramatic enhancement in the major antioxidant enzymes activities, thus supporting the notion of diabetes-related changes in cellular redox status. This allows diabetic individuals to counteract hypoxia-mediated oxidative challenge better than the non-diabetic counterpart. Also the behaviour of both the redox-sensitive nuclear transcription factor NF-kappaB and p53 protein in response to hypoxic stimulation seems to support the hypothesis of a better ROS scavenging efficiency in diabetics under hypoxic conditions. In conclusion, high levels of antioxidant enzymatic defences in diabetic BB rats reflect a positive adaptive response able to assure an efficient protection not only against chronic, diabetes-mediated reactive oxygen species (ROS) overproduction, but also versus further oxidative damage. | 10.1016/j.biocel.2006.06.011 |
pubmed_1014_6864 | Dystroglycan is a transmembrane glycoprotein whose interactions with the extracellular matrix (ECM) are necessary for normal muscle and brain development, and disruptions of its function lead to dystroglycanopathies, a group of congenital muscular dystrophies showing extreme genetic and clinical heterogeneity. Specific glycans bound to the extracellular portion of dystroglycan, α-dystroglycan, mediate ECM interactions and most known dystroglycanopathy genes encode glycosyltransferases involved in glycan synthesis. POMK, which was found mutated in two dystroglycanopathy cases, is instead involved in a glycan phosphorylation reaction critical for ECM binding, but little is known about the clinical presentation of POMK mutations or of the function of this protein in the muscle. Here, we describe two families carrying different truncating alleles, both removing the kinase domain in POMK, with different clinical manifestations ranging from Walker-Warburg syndrome, the most severe form of dystroglycanopathy, to limb-girdle muscular dystrophy with cognitive defects. We explored POMK expression in fetal and adult human muscle and identified widespread expression primarily during fetal development in myocytes and interstitial cells suggesting a role for this protein during early muscle differentiation. Analysis of loss of function in the zebrafish embryo and larva showed that pomk function is necessary for normal muscle development, leading to locomotor dysfuction in the embryo and signs of muscular dystrophy in the larva. In summary, we defined diverse clinical presentations following POMK mutations and showed that this gene is necessary for early muscle development. | 10.1093/hmg/ddu296 |
pubmed_270_3062 | Invasive candidiasis remains an important nosocomial infection that continues to present major diagnostic and therapeutic challenges to the clinician. Changes in the epidemiology of this disorder have occurred for many reasons, and included especially the extensive use of prophylactic antifungal agents, broad-spectrum antibacterial agents, and medical devices (eg, chronic indwelling intravascular catheters). The diagnosis of IC remains elusive in many patients, and there is a critical need for improved diagnostics that will provide clinicians the opportunity to intervene earlier in the course of disease. Newer antifungal agents offer promise in the treatment of candidemia and other forms of IC, but the optimal use of these agents, particularly in the approach to non-albicans Candida infections, needs to be explored in more detail. Furthermore, despite an overwhelming amount of data concerning risk factors and excess mortality associated with the development of IC, there is no consistent approach to treatment and primary prevention among individuals who are deemed to be at highest risk for this complication. Research that focuses on these important clinical areas could provide valuable insights into the diagnosis and management of this common and evolving infection. | 10.1016/j.idc.2006.07.004 |
pubmed_12_6974 | The unfolding of human apolipoprotein B-100 in its native lipid environment, low density lipoprotein (LDL), and in a soluble, lipid-free complex with sodium deoxycholate (NaDC) has been examined using differential scanning calorimetry (DSC) and near UV circular dichroic (CD) spectroscopy. High resolution DSC shows that LDL undergoes three thermal transitions. The first is reversible and corresponds to the order-disorder transition of the core-located cholesteryl esters (CE) (Tm = 31.1 degrees C, delta H = 0.75 cal/g CE). The second, previously unreported, is reversible with heating up to 65 degrees C (Tm = 57.1 degrees C, delta H = 0.20 cal/g apoB) and coincides with a reversible change in the tertiary structure of apoB as shown by near UV-CD. No alteration in the secondary structure of apoB is observed over this temperature range. The third transition is irreversible (Tm = 73.5 degrees C, delta H = 0.99 cal/g apoB) and coincides with disruption of the LDL particle and denaturation of apoB. The ratio of delta H/delta HvH for the reversible protein-related transition suggests that this is a two-state event that correlates with a change in the overall tertiary structure of the entire apoB molecule. The second protein-related transition is complex and coincides with irreversible denaturation. ApoB solubilized in NaDC undergoes three thermal transitions. The first two are reversible (Tm = 49.7 degrees C, delta H = 1.13 cal/g apoB; Tm = 56.4 degrees C, delta H = 2.55 cal/g apoB, respectively) and coincide with alterations in both secondary and tertiary structure of apoB. The changes in secondary structure reflect an increase in random coil conformation with a concomitant decrease in beta-structure, while the change in tertiary structure suggests that the conformation of the disulfide bonds is altered. The third transition is irreversible (Tm = 66.6 degrees C, delta H = 0.54 cal/g apoB) and coincides with complete denaturation of apoB and disruption of the NaDC micelle. The ratio of delta H/delta HvH for the two reversible transitions indicates that each of these transitions is complex which may suggest that several regions or domains of apoB are involved in each thermal event. | pubmed_12_6974 |
pubmed_965_13668 | The spontaneous recessive mutant mouse stargazer has a specific and pronounced deficit in brain-derived neurotrophic factor (BDNF) mRNA expression in the cerebellum. Cerebellar granule cells, in particular, show a selective and near-total loss of BDNF. The mutation involves a defect in the calcium channel subunit Cacng2. This severely reduces expression of stargazin. A stargazin-induced failure in BDNF expression is thought to underlie the cerebellar ataxia with which the mutant presents. BDNF is known to regulate plasticity at cerebellar synapses. However, relatively little is known about the mechanism involved. We previously demonstrated that the stargazer mutation affects the phenotype of cerebellar glutamatergic neurons. Stargazer neurons have less glutamate and proportionally fewer docked vesicles at presynaptic sites than controls. In the current study, we investigate the mechanism underlying BDNF-induced synaptic changes by analyzing alterations in synaptic signalling proteins in the stargazer cerebellum. Expression levels of synaptic proteins were evaluated by measuring relative density of immunogold label over granule cell terminals in ultrathin sections from ataxic stargazer mutants compared with matched nonataxic littermates. We show that there is a selective and marked depletion in the levels of vesicle-associated proteins (synaptobrevin, synaptophysin, synaptotagmin, and Rab3a) but not of plasma membrane-associated protein (SNAP-25) in the terminals of the BDNF-deficient granule cells. Changes are restricted to the cerebellum; levels in the hippocampus are unaltered. These data suggest that the BDNF deficits in the cerebellum of stargazer affect synaptic vesicle docking by selectively altering synaptic-protein distribution and abundance. | 10.1002/cne.21890 |
pubmed_972_10845 | Mutations of the inositol-5-phosphatase OCRL1 cause Lowe syndrome. Lowe syndrome is an inherited disease characterized by renal dysfunction and impaired development of the eye and the nervous system. OCRL1 is a Rab effector protein that can bind to a large number of different Rab proteins. We have recently determined the X-ray structure of the Rab-binding domain of OCRL1 in complex with Rab8. Furthermore, we have characterized point mutations that abolish binding to Rab proteins and cause Lowe syndrome. Here we shortly review our recent biophysical and structural work and discuss possible functional implications of our finding that Rab8 binds with the highest affinity to OCRL1 among the Rab proteins tested. This could direct further work on OCRL1 leading to a better understanding of the complex disease mechanism of Lowe syndrome. | 10.4161/sgtp.19380 |
pubmed_414_14332 | INTRODUCTION
Medicaid recipients are disproportionately affected by tobacco-related disease because their smoking prevalence is approximately 53% greater than that of the overall US adult population. This study estimates state-level smoking-attributable Medicaid expenditures.
METHODS
We used state-level and national data and a 4-part econometric model to estimate the fraction of each state's Medicaid expenditures attributable to smoking. These fractions were multiplied by state-level Medicaid expenditure estimates obtained from the Centers for Medicare and Medicaid Services to estimate smoking-attributable expenditures.
RESULTS
The smoking-attributable fraction for all states was 11.0% (95% confidence interval, 0.4%-17.0%). Medicaid smoking-attributable expenditures ranged from $40 million (Wyoming) to $3.3 billion (New York) in 2004 and totaled $22 billion nationwide.
CONCLUSION
Cigarette smoking accounts for a sizeable share of annual state Medicaid expenditures. To reduce smoking prevalence among recipients and the growth rate in smoking-attributable Medicaid expenditures, state health departments and state health plans such as Medicaid are encouraged to provide free or low-cost access to smoking cessation counseling and medication. | pubmed_414_14332 |
pubmed_848_18395 | 1. CSF NA levels were determined in a sample of DSM III-diagnosed schizophrenics and in a non-psychiatric control group. Schizophrenics with NA levels above and below the median were compared with respect to several clinical, historical, neuropsychological and biological variables. 2. Mean CSF NA levels were significantly higher in schizophrenics than in controls. 3. Schizophrenics with high CSF NA levels, as compared to those with low levels, had significantly higher scores on the CPRS subscale for positive symptoms. Moreover, in the former subgroup, C-EEG alpha relative activity was significantly lower and C-EEG beta relative activity was significantly higher in frontal and central leads. Two of the three patients who had been never treated with neuroleptics, and three of the six patients who had been neuroleptic-free for more than four weeks had high CSF NA levels. 4. These data support the relationship between increased CSF NA levels and the condition of overarousal of the schizophrenic patients, and suggest that prior neuroleptic treatment is not a major determinant of high CSF NA concentration in schizophrenics. | 10.1016/0278-5846(90)90063-m |
pubmed_173_16881 | Pediatric refractory status epilepticus (RSE) is a neurological emergency with significant morbidity and mortality, which lacks consensus regarding diagnosis and treatment(s). Therapeutic hypothermia (TH) is an effective treatment for RSE in preclinical models and small series. In addition, TH is a standard care for adults after cardiac arrest and neonates with hypoxic-ischemic encephalopathy. The purpose of this study was to identify the feasibility of a study of pediatric RSE within a research group (Pediatric Neurocritical Care Research Group [PNCRG]). Pediatric intensive care unit (PICU) admissions at seven centers were prospectively screened from October 2012 to July 2013 for RSE. Experts within the PNCRG estimated that clinicians would be unwilling to enroll a child, unless the child required at least two different antiepileptic medications and a continuous infusion of another antiepileptic medication with ongoing electrographic seizure activity for ≥2 hours after continuous infusion initiation. Data for children meeting the above inclusion criteria were collected, including the etiology of RSE, history of epilepsy, and maximum dose of continuous antiepileptic infusions. There were 8113 PICU admissions over a cumulative 52 months (October 2012-July 2013) at seven centers. Of these, 69 (0.85%) children met inclusion criteria. Twenty children were excluded due to acute diagnoses affected by TH, contraindications to TH, or lack of commitment to aggressive therapies. Sixteen patients had seizure cessation within 2 hours, resulting in 33 patients who had inadequate seizure control after 2 hours and a continuous antiepileptic infusion. Midazolam (21/33, 64%) and pentobarbital (5/33, 15%) were the most common infusions with a wide maximum dose range. More than one infusion was required for seizure control in four patients. There are substantial numbers of subjects at clinical sites within the PNCRG with RSE that would meet the proposed inclusion criteria for a study of TH. The true feasibility of such a study depends on the sample size necessary to achieve therapeutic effects on justifiable clinical outcomes. | 10.1089/ther.2015.0016 |
pubmed_398_14847 | Systolic anterior motion of the mitral valve leaflets (SAM) is a disease of the left ventricle which results from an abnormal force balance on the mitral valve. The mechanism by which is initiated is poorly understood, and a complete understanding of this mechanism is required for effective treatment of SAM. There are currently two theories for the initiation mechanism of SAM, the Venturi hypothesis and the altered papillary muscle-mitral valve geometry theory (PM-MV). The Venturi hypothesis states that abnormally high ejection velocities create Venturi forces which initiate SAM. The PM-MV theory asserts that SAM is the result of abnormally distributed chordal forces which are incapable of preventing SAM. To investigate the initiation mechanism of SAM, a computer model of early systolic flow in an anatomically-correct human left ventricle was developed using Peskin's immersed boundary algorithm. The computer model was used to determine the effect of chordal force distribution and septal thickness of the intraventricular flow field. The results show that the degree of SAM is inversely proportional to the amount of chordal restraint applied to the central portion of the leaflets. Also, the results support the PM-MV theory and indicate the following: (i) fluid forces capable of initiating SAM as always present in a normal human ventricle; (ii) SAM does not occur normally because of the presence of chordal forces on the central portion of the mitral leaflet; (iii) SAM will occur when these central chordal forces are sufficiently low; (iv) the extent of SAM is inversely proportional to these central chordal forces; and (v) Venturi forces alone can not cause SAM. | 10.1115/1.2792276 |
pubmed_726_17287 | For the preparation of nanocomposites, we conducted environmentally benign foaming processing on polypropylene (PP) copolymer/clay nanocomposites via a batch process in an autoclave. We investigated the dispersion and the exfoliation of the nanoclay particles. Full exfoliation was achieved by the foamability of the matrix PP copolymer using supercritical carbon dioxide (sc CO2) and subcritical carbon dioxide (sub CO2). More and smaller cells were observed when the clay was blended as heterogeneous nuclei and sc CO2 was used. Small angle X-ray scattering showed that highly dispersed states (exfoliation) of the clay particles were obtained by the foaming process. Since the clay particles provided more nucleating sites for the foaming of the polymer, a well dispersed (or fully exfoliated) nanocomposite exhibited a higher cell density and a smaller cell size at the same clay particle concentration. Expansion of the adsorbed CO2 facilitated the exfoliation of the clay platelets; thus, sc CO2 at lower temperature was more efficient for uniform foaming-cell production. Fully dispersed clay platelets were, however, re-aggregated when subjected to a further melting processing. The reprocessed nanocomposites still had some exfoliated platelets as well as some aggregated intercalates. The dual role of the nanoclay particles as foaming nucleus and a crystallization nucleus was confirmed by cell growth observation and nonisothermal crystallization kinetics analysis. A low foaming temperature and a high saturation pressure were more favorable for obtaining a uniform foam. The PP copolymer was found to be foamed more easily than polypropylene. A small amount of other olefin moieties in the backbone of the polymer facilitated better foamability than the neat polypropylene. | 10.1039/c3cp51068a |
pubmed_498_24389 | AIM
This study's objective was to assess the risk of severe in-hospital complications of patients admitted for COVID-19 and diabetes mellitus (DM).
DESIGN
This was a cross-sectional study.
SETTINGS
We used pseudonymised medical record data provided by six general hospitals from the HM Hospitales group in Spain.
OUTCOME MEASURES
Multiple logistic regression analyses were used to identify variables associated with mortality and the composite of mortality or invasive mechanical ventilation (IMV) in the overall population, and stratified for the presence or absence of DM. Spline analysis was conducted on the entire population to investigate the relationship between glucose levels at admission and outcomes.
RESULTS
Overall, 1621 individuals without DM and 448 with DM were identified in the database. Patients with DM were on average 5.1 years older than those without. The overall in-hospital mortality was 18.6% (N=301), and was higher among patients with DM than those without (26.3% vs 11.3%; p<0.001). DM was independently associated with death, and death or IMV (OR=2.33, 95% CI: 1.7 to 3.1 and OR=2.11, 95% CI: 1.6 to 2.8, respectively; p<0.001). In subjects with DM, the only variables independently associated with both outcomes were age >65 years, male sex and pre-existing chronic kidney disease. We observed a non-linear relationship between blood glucose levels at admission and risk of in-hospital mortality and death or IMV. The highest probability for each outcome (around 50%) was at random glucose of around 550 mg/dL (30.6 mmol/L), and the risks flattened above this value.
CONCLUSION
The results confirm the high burden associated with DM in patients hospitalised with COVID-19 infection, particularly among men, the elderly and those with impaired kidney function. Moreover, hyperglycaemia on admission was strongly associated with poor outcomes, suggesting that personalised optimisation could help to improve outcome during the hospital stay. | 10.1136/bmjopen-2021-051237 |
pubmed_390_2370 | An in vitro study of the relationship between benzo[a]pyrene (BaP) association with serum lipoproteins (LP) and LP composition was conducted using human subjects. BaP partitioning into different serum LP ranged from 53 to 71% of available BaP. Efficiency of BaP partitioning was examined for the relationship with lipid components of different sera. The data indicate that triglyceride (TG) concentrations were more directly correlated with BaP uptake than were concentrations of other LP components. Adjusting sera to a uniform TG concentration (96.5 mg/dl) resulted in the same BaP uptake for each serum type, while adjusting sera to contain a uniform cholesteryl ester concentration (104.6 mg/dl) did not result in similar BaP uptake among serum types. Analysis of serum LP composition suggested that marked differences in both BaP uptake and serum TG concentrations among the subjects were due mainly to differences in serum very low density lipoprotein (VLDL) concentrations. A correlation study using 14 human subjects showed that serum TG concentration was the best predictor (r = 0.973, P less than 0.001) for BaP uptake by serum, followed by phospholipid (r = 0.658, P less than 0.01) and total cholesterol (r = 0.514, P less than 0.05) concentrations. The results indicate that serum TG concentration (typically VLDL-TG) may be the primary factor affecting BaP uptake by serum LP, and suggest that a small change in serum TG concentration could cause a significant increase in BaP uptake by serum LP, contributing to an increased level of circulating carcinogen. | 10.3181/00379727-177-41969 |
pubmed_192_15649 | BACKGROUND
The recent description of the first plasmid-mediated colistin-resistant gene mcr-1, conferring transferable and low-level resistance to colistin, raised concern about the need to implement a rapid and reliable screening method to detect colistin-resistant clinical isolates. The only valid method to assess the MIC of colistin is the broth microdilution according to the joint CLSI-EUCAST Polymyxin Breakpoints Working Group. UMIC Colistine is a ready-to-use broth microdilution kit developed to easily assess colistin MIC by proposing unitary polystyrene strips containing 11 concentrations of dehydrated colistin. Here, we evaluated the UMIC Colistine kit on 235 Gram-negative rods (176 Enterobacterales, including 70 harboring a mcr gene, and 59 non-fermentative), through comparison to the reference broth microdilution method prepared in accordance with EN ISO 20776-1:2006 standard. Reproducibility of the UMIC Colistine was assayed with the three recommended quality control strains E. coli ATCC 25922, E. coli NCTC 13846 (mcr-1 positive), and P. aeruginosa ATCC 27853, as for stability testing.
RESULTS
Categorical agreement was 100% with 63.4% (n = 149) of colistin-resistant strains, and 36.6% (n = 86) of colistin-susceptible strains with both methods (S ≤ 2 μg/mL and R > 2 μg/mL). No major error or very major error was reported. Essential agreement was 94.0% (n = 221), and 100% for detection of colistin-resistant strains as compared to the reference method. Pearson's correlation between UMIC Colistine and the reference method was 0.98. Reproducibility of the UMIC Colistine system was 97.8% with MICs of the quality control strains within the target ranges. However, some isolates had lower MIC with UMIC Colistine, but that did not change their categorization as colistin-susceptible, and this phenomenon should be further explored.
CONCLUSIONS
The UMIC Colistine kit is an easy to perform unitary device that showed excellent results when compared to the reference method. The UMIC Colistine system is a rapid and reliable broth microdilution method that is suitable to assess the colistin MIC of clinical isolates in clinical microbiology laboratories. | 10.1186/s12866-019-1424-8 |
pubmed_641_5975 | Variation in mutation rate, attributed to differences in both generation time and in metabolic rate, has been invoked under the neutral theory of molecular evolution to account for differences in substitution rate among mammalian lineages. We show that substitution rates at fourfold-degenerate sites and at sites in noncoding regions do not vary between the primate and rodent lineages, implying mutation-rate uniformity. In contrast, the substitution rates at nondegenerate sites vary both within and between lineages. This difference in substitution-rate pattern between the two types of site is incompatible with neutral theory but may result from substitutions occurring by fixation of slightly deleterious mutations. Variation in the rate of protein evolution among mammalian lineages appears to be due more to differences in population fixation rates than to biochemical or physiological differences affecting mutation rates. | 10.1093/oxfordjournals.molbev.a040142 |
pubmed_215_22452 | The orbital cellulitis is an infection of the soft tissues located behind of the orbital setum. It is presented as a complication of an acute sinusitis although it can appear as consequence of other infectious processes. We present a series of 20 cases diagnosed and treated in our center of orbital cellulitis. We expose the diagnostic criteria that we have followed, as well as the complementary tests used and the different treatments both medical and surgical. | pubmed_215_22452 |
pubmed_1096_10285 | Splice-site selection is controlled by secondary structure through sequestration or approximation of splicing signals in primary transcripts but the exact role of even the simplest and most prevalent structural motifs in exon recognition remains poorly understood. Here we took advantage of a single-hairpin exon that was activated in a mammalian-wide interspersed repeat (MIR) by a mutation stabilizing a terminal triloop, with splice sites positioned close to each other in a lower stem of the hairpin. We first show that the MIR exon inclusion in mRNA correlated inversely with hairpin stabilities. Employing a systematic manipulation of unpaired regions without altering splice-site configuration, we demonstrate a high correlation between exon inclusion of terminal tri- and tetraloop mutants and matching tri-/tetramers in splicing silencers/enhancers. Loop-specific exon inclusion levels and enhancer/silencer associations were preserved across primate cell lines, in 4 hybrid transcripts and also in the context of a distinct stem, but only if its loop-closing base pairs were shared with the MIR hairpin. Unlike terminal loops, splicing activities of internal loop mutants were predicted by their intramolecular Watson-Crick interactions with the antiparallel strand of the MIR hairpin rather than by frequencies of corresponding trinucleotides in splicing silencers/enhancers. We also show that splicing outcome of oligonucleotides targeting the MIR exon depend on the identity of the triloop adjacent to their antisense target. Finally, we identify proteins regulating MIR exon recognition and reveal a distinct requirement of adjacent exons for C-terminal extensions of Tra2α and Tra2β RNA recognition motifs. | 10.1080/15476286.2015.1017207 |
pubmed_229_17403 | OBJECTIVE
Incontinence-specific and generic measures of well-being were regressed on potential predictors to identify incontinent respondents at risk for psychosocial distress and to understand the relationship between urinary incontinence (UI) and other determinants of social and emotional status.
DESIGN
Survey data were collected May 1994 through April 1996.
SETTING
Telephone interviews as a supplement to a nationally representative monthly consumer survey.
PARTICIPANTS
Analyses were based on 1,116 continent and 206 incontinent respondents age 40 and older.
MEASUREMENTS
Incontinent respondents self-reported the extent to which urine loss restricted social activities or affected their feelings about themselves. All respondents were asked whether they felt depressed, lonely, or sad. Covariates included sex, age, race, education, social desirability, health status, frequency of urine loss, quantity of loss, and urgency.
RESULTS
The majority of incontinent respondents reported that urine loss did not restrict activities or diminish self-esteem. Incontinent respondents who were younger, male, less educated, lower in social desirability, in poorer health, or losing greater quantities of urine were more likely to report psychosocial distress, although these correlates were not consistently significant. Compared with continent respondents, significantly higher percentages of incontinent respondents reported feeling depressed, lonely, or sad. In the multivariate models, incontinence retained an independent association with loneliness, but not with sadness or depression.
CONCLUSION
Even though the direct psychosocial impact of urine loss may be minor in many cases, UI is associated with a constellation of physical and behavioral factors that can impose a social and emotional burden. This suggests that UI cannot be adequately evaluated or treated without consideration of the patient's overall quality of life. | 10.1046/j.1532-5415.2001.49179.x |
pubmed_556_19686 | BACKGROUND
Zinc is a trace element with potent immunoregulatory and antiviral properties, and is utilized in the treatment of coronavirus disease 2019 (COVID-19). However, we do not know the clinical significance of serum Zinc levels in COVID-19 patients. The aim of this study was to determine the clinical significance of serum zinc in COVID-19 patients and to establish a correlation with disease severity.
METHODS
This was a prospective study of fasting zinc levels in COVID-19 patients at the time of hospitalization. An initial comparative analysis was conducted between COVID-19 patients and healthy controls. COVID-19 patients with zinc deficiency were compared to those with normal zinc levels.
RESULTS
COVID-19 patients (n = 47) showed significantly lower zinc levels when compared to healthy controls (n = 45): median 74.5 (interquartile range 53.4-94.6) μg/dl vs 105.8 (interquartile range 95.65-120.90) μg/dl (p < 0.001). Amongst the COVID-19 patients, 27 (57.4%) were found to be zinc deficient. These patients were found to have higher rates of complications (p = 0.009), acute respiratory distress syndrome (18.5% vs 0%, p = 0.06), corticosteroid therapy (p = 0.02), prolonged hospital stay (p = 0.05), and increased mortality (18.5% vs 0%, p = 0.06). The odds ratio (OR) of developing complications was 5.54 for zinc deficient COVID-19 patients.
CONCLUSIONS
The study data clearly show that a significant number of COVID-19 patients were zinc deficient. These zinc deficient patients developed more complications, and the deficiency was associated with a prolonged hospital stay and increased mortality. | 10.1016/j.ijid.2020.09.014 |
pubmed_271_16585 | We demonstrate a new compact CN-PPV dot, which emits in the orange wavelength range with high brightness. The small particle size, high brightness, and the ability to highly specifically target subcellular structures make the CN-PPV dots promising probes for biological imaging and bioanalytical applications. | 10.1039/c2cc16486h |
pubmed_716_19177 | Since its discovery, cadmium (Cd) has played an important role in industry and brought certain conveniences to mankind, used for electroplating and making rechargeable batteries, etc. Cd is also a harmful pollutant, which will enter the food chain and cause damage to human tissues and organs. Food is the main source of Cd in the human body, so various technologies for removing Cd from food have been studied. These technologies are based on the binding mechanism between Cd and proteins. In this work, the enrichment of Cd and the harm of Cd are described. And the binding mechanism between Cd and protein is summarized. Finally, the removal technologies of Cd are prospected. This review analyzes the methods of removing cadmium from food from the perspective of the combination of cadmium and protein, which provides insights for ensuring food safety and reducing the harm of heavy metals to the human body. | 10.1016/j.foodchem.2022.134666 |
pubmed_498_1095 | BACKGROUND
Naratriptan, marketed in a low oral dose of 2.5 mg, is generally regarded as a less-effective triptan with a slower onset of action than most other triptans in the treatment of migraine attacks. In this review, naratriptan will be compared with sumatriptan, the standard triptan.
METHODS
Papers on pharmacodynamics and pharmacokinetics and results from comparative clinical trials with oral and subcutaneous naratriptan versus other triptans were retrieved from PubMed.
RESULTS
Naratriptan and sumatriptan have similar effects in relevant animal models. In a randomized controlled trial, oral naratriptan 2.5 mg is less effective than oral sumatriptan 100 mg after both 2 h and 4 h. In contrast, oral naratriptan 10 mg has a similar time-effect curve as oral sumatriptan 100 mg, in both its steepness and the efficacy at 2 h and 4 h. Subcutaneous naratriptan 10 mg (88% pain free at 2 h) was in one trial superior to subcutaneous sumatriptan 6 mg (55% pain free at 2 h).
CONCLUSION
Naratriptan was marketed for the treatment of migraine attacks as the "gentle triptan" in a low oral dose of 2.5 mg, a dose with no more adverse events than placebo. This low dose results in the slow onset of action and low efficacy of oral naratriptan, but in high doses oral naratriptan is similar to oral sumatriptan. Based on one randomized controlled trial, subcutaneous naratriptan has probably the greatest effect of any triptan. | 10.1177/03331024211028959 |
pubmed_579_21254 | Microwave-assisted hydrothermal approach was developed as a general strategy to decorate copper nanowires (CuNWs) with nanorods (NRs) or nanoparticles (NPs) of metal oxides, metal sulfides, and metal organic frameworks (MOFs). The microwave irradiation induced local "super hot" dots generated on the CuNWs surface, which initiated the adsorption and chemical reactions of the metal ions, accompanied by the growth and assembly of NPs building blocks along the metal nanowires' surfaces. This solution-processed approach enables the NRs (NPs) @CuNWs hybrid structure to exhibit three unique characteristics: (1) high coverage density of NRs (NPs) per NWs with the morphology of NRs (NPs) directly growing from the CuNWs core, (2) intimate contact between CuNWs and NRs (NPs), and (3) flexible choices of material composition. Such hybrid structures also increased light absorption by light scattering. In general, the TiO2/CuNWs showed excellent photocatalytic activity for H2 generation. The corresponding hydrogen production rate is 5104 μmol h(-1) g(-1) with an apparent quantum yield (AQY) of 17.2%, a remarkably high AQY among the noble-metal free TiO2 photocatalysts. Such performance may be associated with the favorable geometry of the hybrid system, which is characterized by a large contact area between the photoactive materials (TiO2) and the H2 evolution cocatalyst (Cu), the fast and short diffusion paths of photogenerated electrons transferring from the TiO2 to the CuNWs. This study not only shows a possibility for the utilization of low cost copper nanowires as a substitute for noble metals in enhanced solar photocatalytic H2 generation but also exhibits a general strategy for fabricating other highly active H2 production photocatalysts by a facile microwave-assisted solution approach. | 10.1021/acs.nanolett.5b00082 |
pubmed_364_24824 | The ecology of a biofilm is a complex function of different factors, including the presence of microbial metabolites excreted by the inhabitants of the biofilm. This study aimed to assess the effect of patulin, and N-(3-oxododecanoyl)-L-homoserine lactone (3-oxo-C12-HSL) on inter-kingdom biofilm formation between a filamentous fungus and bacteria isolated from drinking water. The filamentous fungus Penicillium expansum and the bacteria Acinetobacter calcoaceticus and Methylobacterium oryzae were used as model species. M. oryzae biofilm formation and development was more susceptible to the presence of the quenching molecules than A. calcoaceticus biofilms. Patulin reduced M. oryzae biofilm growth while 3-oxo-C12-HSL caused an increase after 48 h. The presence of P. expansum had a detrimental effect on M. oryzae cell numbers, while an advantageous effect was observed with A. calcoaceticus. The overall results reveal that quorum sensing and quenching molecules have a significant effect on inter-kingdom biofilm formation, especially on bacterial numbers. | 10.1080/08927014.2020.1836162 |
pubmed_540_4324 | Wind has a significant yet complex effect on bird migration speed. With prevailing south wind, overall migration is generally faster in spring than in autumn. However, studies on the difference in airspeed between seasons have shown contrasting results so far, in part due to their limited geographical or temporal coverage. Using the first full-year weather radar data set of nocturnal bird migration across western Europe together with wind speed from reanalysis data, we investigate variation of airspeed across season. We additionally expand our analysis of ground speed, airspeed, wind speed, and wind profit variation across time (seasonal and daily) and space (geographical and altitudinal). Our result confirms that wind plays a major role in explaining both temporal and spatial variabilities in ground speed. The resulting airspeed remains relatively constant at all scales (daily, seasonal, geographically and altitudinally). We found that spring airspeed is overall 5% faster in Spring than autumn, but we argue that this number is not significant compared to the biases and limitation of weather radar data. The results of the analysis can be used to further investigate birds' migratory strategies across space and time, as well as their energy use. | 10.1002/ece3.9146 |
pubmed_533_10098 | The increased Lewis acidity in organotin-functionalized crown ethers X3SnCH2[19]-crown-6 (5, X = I; 6, X = Br; 7, X = Cl) not only resulted in ditopic complexation of sodium/potassium halides, but also offers an excellent strategy to manipulate through intramolecular O→Sn interactions the selectivity of the crown ether moiety towards Na+/K+ depending on the solvent. | 10.1039/c7cc09263f |
pubmed_64_24270 | Rosuvastatin (RST) is primarily used to treat high cholesterol levels. As it has potentially harmful but not well-documented effects on embryos, RST is contraindicated during pregnancy. To demonstrate whether RST could induce molecular epigenetic events in the brains of newborn rats, pregnant mothers were treated daily with oral RST from the 11th day of pregnancy for 10 days (or until delivery). On postnatal day 1, the brains of the control and RST-treated rats were removed for Western blot or immunohistochemical analyses. Several antibodies that recognize different methylation sites for H2A, H2B, H3, and H4 histones were quantified. Analyses of cell-type-specific markers in the newborn brains demonstrated that prenatal RST administration did not affect the composition and cell type ratios as compared to the controls. Prenatal RST administration did, however, induce a general, nonsignificant increase in H2AK118me1, H2BK5me1, H3, H3K9me3, H3K27me3, H3K36me2, H4, H4K20me2, and H4K20me3 levels, compared to the controls. Moreover, significant changes were detected in the number of H3K4me1 and H3K4me3 sites (134.3% ± 19.2% and 127.8% ± 8.5% of the controls, respectively), which are generally recognized as transcriptional activators. Fluorescent/confocal immunohistochemistry for cell-type-specific markers and histone methylation marks on tissue sections indicated that most of the increase at these sites belonged to neuronal cell nuclei. Thus, prenatal RST treatment induces epigenetic changes that could affect neuronal differentiation and development. | 10.3390/ijms22073412 |
pubmed_1094_13781 | Long at odds, the interests of payers and providers are becoming more compatible and aligned. Both stakeholders need to collaborate to manage costs. Encouraging use of generics and biosimilars is one way they can slow down the soaring drug spend. | pubmed_1094_13781 |
pubmed_149_23472 | Many drugs exert serious cytotoxic effects on pulmonary tissues. Although several reports have shown an association of epithelial-mesenchymal transition (EMT) with anticancer drug-induced lung injury, mechanisms of these effects are poorly understood. In the present study, we evaluated mechanisms of anticancer drug-induced EMT, with a focus on involvement of cell cycle arrest. We found that methotrexate (MTX) altered mRNA expression levels of many genes as determined by microarray analysis. Gene set enrichment analysis revealed that cell cycle arrest pathways may be associated with MTX-induced EMT. In addition, thymidine (THY) and nocodazole (NOC), which induce cell cycle arrest at S-phase and G2/M-phase, increased mRNA expression levels of α-smooth muscle actin (SMA), an EMT marker. Furthermore, α-SMA protein expression in cells arrested at S- and G2/M-phases by MTX and paclitaxel (PTX) was significantly higher than that in cells at G1. Notably, co-treatment of cells with THY or NOC and EMT-inducing anticancer drugs did not result in additional upregulation of α-SMA mRNA expression. These findings suggested that cell cycle arrest may be closely associated with anticancer drug-induced EMT in alveolar epithelial cells. | 10.1016/j.tox.2019.06.002 |
pubmed_656_12685 | Photosystem II (PSII) is a multisubunit pigment-protein complex that uses light-induced charge separation to power oxygenic photosynthesis. Its reaction center chromophores, where the charge transfer cascade is initiated, are arranged symmetrically along the D1 and D2 core polypeptides and comprise four chlorophyll (PD1, PD2, ChlD1, ChlD2) and two pheophytin molecules (PheoD1 and PheoD2). Evolution favored productive electron transfer only via the D1 branch, with the precise nature of primary excitation and the factors that control asymmetric charge transfer remaining under investigation. Here we present a detailed atomistic description for both. We combine large-scale simulations of membrane-embedded PSII with high-level quantum-mechanics/molecular-mechanics (QM/MM) calculations of individual and coupled reaction center chromophores to describe reaction center excited states. We employ both range-separated time-dependent density functional theory and the recently developed domain based local pair natural orbital (DLPNO) implementation of the similarity transformed equation of motion coupled cluster theory with single and double excitations (STEOM-CCSD), the first coupled cluster QM/MM calculations of the reaction center. We find that the protein matrix is exclusively responsible for both transverse (chlorophylls versus pheophytins) and lateral (D1 versus D2 branch) excitation asymmetry, making ChlD1 the chromophore with the lowest site energy. Multipigment calculations show that the protein matrix renders the ChlD1 → PheoD1 charge-transfer the lowest energy excitation globally within the reaction center, lower than any pigment-centered local excitation. Remarkably, no low-energy charge transfer states are located within the "special pair" PD1-PD2, which is therefore excluded as the site of initial charge separation in PSII. Finally, molecular dynamics simulations suggest that modulation of the electrostatic environment due to protein conformational flexibility enables direct excitation of low-lying charge transfer states by far-red light. | 10.1021/jacs.0c08526 |
pubmed_1057_10351 | In the clinical diagnosis of epileptic diseases, the intelligent diagnosis of epileptic electroencephalogram (EEG) signals has become a research focus in the field of brain diseases. In order to solve the problem of time-consuming and easily influenced by human subjective factors, artificial intelligence pattern recognition algorithm has been applied to EEG signals recognition. However, at present, the common empirical mode decomposition (EMD) signal decomposition algorithm does not consider the problem of mode aliasing. The EEG features obtained by feature extraction may be mixed with some unimportant features that affect the classification accuracy. In this paper, we proposed a new method based on complementary ensemble empirical mode decomposition (CEEMD) combined with iterative feature reduction for aided diagnosis of epileptic EEG. First of all, the evaluation indexes of decomposing and reconstructing signals by several methods were compared. The CEEMD was selected as the decomposition method of the signals. Then, the support vector machine recursive elimination (SVM-RFE) was used to reduce 9 features extracted from EEG data. The support vector classification of the gray wolf optimizer (GWO-SVC) recognition model was established for different feature subsets. By comparing the classification accuracy of training set and test set of different feature subsets, and considering the complexity of the model reflected by the number of features selected by SVM-RFE, the analysis showed that the 6 feature subsets with fewer features and higher classification accuracy could reflect the key information of epileptic EEG. The accuracy of the training set classification was 99.38% and the test set was as high as 100%. The recognition time was only 1.6551 s. Finally, in order to verify the reliability of the algorithm proposed in this paper, the proposed algorithm compared with the classification model established by the raw EEG signals and the optimization model established by other intelligent optimization algorithms. It is found that the algorithm used in this paper has higher classification accuracy and faster recognition time than other processing methods. The experimental results show that CEEMD combined with SVM-RFE is feasible for rapid and accurate recognition of EEG signals, which provides a theoretical basis for the aided diagnosis of epilepsy. | 10.3389/fbioe.2020.00669 |
pubmed_658_12824 | A Computational Fluid Dynamic (CFD) model of flow in a high-pressure homogenizing valve (APV Gaulin model 30CD) was developed with the Fluent software. The 2D model consists of an unstructured hexagonal mesh, dense in the regions of high gradients. The flow (single-phase) was modeled as laminar upstream of and in the channel (gap) and turbulent downstream of the channel exit. Applying a realizable kappa-epsilon turbulence model, the CFD model accurately predicted the effect of gap space on fluid dynamic conditions upstream (inlet pressure and pressure gradient) and downstream (impact pressure) of the channel for a valve with a standard (CD-0) impact distance (0.25 mm) and a 1 cP fluid. This CFD model was then used to estimate the magnitude of the fluid dynamic parameters (except cavitation effects) presumed to be responsible for cell breakage, as a function of gap space, impact distance and fluid viscosity. The CFD models predicted that for a given volumetric flowrate the upstream fluid conditions (inlet pressure gradient, maximum channel strain rate) and the maximum energy dissipation rate in the post-gap jet depend only on the gap space and the fluid viscosity and not on the impact distance. The impact pressure however depends on the gap spacing, the fluid viscosity and especially the impact distance. Experimental results indicate that higher inlet pressures are required to break cells, if the impact distance is increased. By conducting experiments to isolate individual cell breakage mechanisms for a single pass, threshold values were identified for breaking Escherichia coli cells: pressure gradient, 1.2 x 10(12) Pa/m; energy dissipation rate, 1.0 x 10(10) m(3)/s(2); and impact pressure, 160 psig. By isolating the wall impact as the sole mechanism responsible for breaking the E. coli cells between 3000 and 6000 psig inlet pressure, a relationship between E. coli cell breakage rate and maximum wall impact pressure was established (eq 5). | 10.1021/bp020010z |
pubmed_601_19666 | Significant numbers of mast cells have been demonstrated histologically around the periphery of the invasive rat mammary adenocarcinoma 13672NF. The number of mast cells at microfoci along the tumour:host tissue junction was significantly greater than that found in normal mammary tissues, and few mast cells were detected within the tumour itself. Mast cell degranulation, often associated with disruption and lysis of the connective tissue matrix, was a common feature in later stages of tumour proliferation. When soluble products derived from purified rat peritoneal mast cells were added to monolayer cultures of rat stromal fibroblasts or tumour cells they stimulated a significant increase in total collagenase production, and the mast cell products were also capable of activating the latent collagenases thus produced. Histological examination indicated that degradation of local collagenous matrix was a common feature of mast cell degranulation, an observation possibly explained by the release of mast cell enzymes and/or the potential of this cell to modulate the expression of collagenolytic activity by surrounding cells. These observations suggest that, at least in some tumours, mast cells contribute to the connective tissue breakdown commonly associated with tumour invasiveness and metastatic spread. | 10.1038/bjc.1986.198 |
pubmed_987_4816 | Mitigating the impacts of COVID-19 comes with the evaluation of tradeoffs. However, the exact magnitude of the tradeoffs being made cannot be known ahead of time. There are three major concerns to balance: life, liberty, and economy. Here, we create a multi-attribute utility function including those three attributes and provide reasonable bounds on the weights of each. No one set of weights on the utility function can be considered "correct." Furthermore, the outcomes of each mitigation strategy are deeply uncertain. Not only do we need to take into account the characteristics of the disease, but we also need to take into account the efficacy of the mitigation strategies and how each outcome would be evaluated. To handle this, we use Robust Decision Making methods to simulate plausible outcomes for various strategies and evaluate those outcomes using different weights on the multi-attribute utility function. The simulation is done with a compartmental epidemiological model combined with a simple economic model and a model of liberty costs. Rather than trying to optimize likely outcomes for a particular version of the utility function, we find which strategies are robust across a wide range of plausible scenarios even when there is disagreement about how to weigh the competing values of life, liberty, and economy. | 10.1007/s10479-022-04592-9 |
pubmed_1052_17094 | BACKGROUND
Diet and exercise interventions for cancer survivors result in health benefits; however, few studies have examined health outcomes in relation to adherence.
PURPOSE
We examined associations between adherence to components of a diet-exercise intervention and survivors' physical and mental health.
METHODS
A randomized controlled trial tested a telephone and mailed print intervention among 641 older, overweight, long-term survivors of breast, prostate, and colorectal cancer. Dietary and exercise behaviors were assessed at 14 time points throughout the year-long intervention; health outcomes were examined postintervention.
RESULTS
Telephone session attendance had significant indirect relationships with health outcomes through intervention-period exercise and dietary behavior. Attendance showed positive indirect relationships with physical function (β = 0.11, p < 0.05), basic and advanced lower extremity function (β = 0.10, p < 0.05/β = 0.09, p < 0.05), and mental health (β = 0.05, p < 0.05), and a negative indirect relationship with body mass index (β = -0.06, p < 0.05).
CONCLUSIONS
Session attendance is vital in facilitating improvement in health behaviors and attendant outcomes (Clinicaltrials.gov number NCT00303875). | 10.1007/s12160-014-9598-7 |
pubmed_51_2668 | India has approximately 335 medical colleges, which produce around 40,000 medical graduates annually. Even though medical professional have a critical role in prevention and control of noncommunicable diseases (NCDs) including injuries, it has been observed that the present medical and nursing curriculum in India does not adequately cover prevention and control of NCDs. The topics for specific approach to prevent NCDs and various strategies can be incorporated into public health and clinical courses in undergraduate medical education, with brief optional courses in residency and continuing medical education for established practitioners. High-level expert group instituted by Planning Commission of India on Universal Health Coverage recommended that medical education requires greater orientation of providers to the social determinants of health as well as to gender and equity issues. Curricula in medical schools should keep pace with the changing dynamics of public health, health policy, and health demographics. Medical education and training should be reoriented by introducing competency-based, health system connected curricula, and continuous education. There is a need to review of medical curriculum, introducing innovative integrated teaching methods, and capacity building of teachers for meeting the challenge of rising burden of NCDs in India. | 10.4103/0970-0218.94711 |
pubmed_378_455 | BACKGROUND
The management and outcomes of muscle-invasive bladder cancer are described in this article.
METHODS
A retrospective survey of medical practitioners involved in the management of bladder cancer was conducted. The survey obtained at least 5 years of follow-up data on all patients. The sample was taken from the public and private health sectors in Victoria. All were cases of muscle-invasive bladder cancer diagnosed between 1990 and 1995. The main outcome measures included reported management by staging, treatment and survival.
RESULTS
Completed questionnaires were returned for 743 (89.6%) of 829 cases. Of these, 523 (70.4%) were men, and the mean age was 72.7 years. More than 75% of the cases (560) presented with macroscopic haematuria. The majority (696, 94%) had transitional cell carcinoma. A variety of treatments were given in various sequences, with 231 cases (31.1%) having initial surveillance. Eventually, 303 cases (40.8%) proceeded to 'definitive' management with either radiotherapy (132, 17.8%) or cystectomy (171, 23.0%). In addition, chemotherapy was given to 254 patients (34.2%) at some time. Most patients (613, 82.5%) have subsequently died; 402 (54%) died from bladder cancer. Crude 5-year survival was 13.0%, and disease-specific survival was 27.7%. Multivariate analysis identified the following predictors of greater disease-specific survival: grade 1 or 2 histopathology (P = 0.0003), T2 primary (P < 0.0001), N0 disease (P = 0.04), M0 disease (P < 0.0001), radiation dose in BED(10) >70 Gy and cystectomy (P < 0.0001).
CONCLUSION
Muscle-invasive bladder cancer in Victoria typically occurs in elderly patients, and a notable proportion of these patients do not proceed onto 'definitive' treatment. Disease stage, cystectomy and the use of high doses of radiation are associated with better outcomes. Chemotherapy was given to approximately one-third of patients at some point in their disease management. Our data are similar to population-based data from North America, and provide a baseline against which potential changes in management of bladder cancer can be compared. | 10.1111/j.1445-2197.2006.03665.x |
pubmed_933_16516 | Four copper(II) complexes, [Cu(4)(O)(L(n))(2)(CH(3)COO)(4)] with N(2)O-donor Schiff-base ligands, where HL(1) = 4-methyl-2,6-bis(cyclohexylmethyliminomethyl)phenol for complex 1, HL(2) = 4-methyl-2,6-bis(phenylmethyliminomethyl)phenol for complex 2 x CH(3)CN, HL(3) = 4-methyl-2,6-bis(((3-tri-fluoromethyl)phenyl)methyliminomethyl)phenol for complex 3, HL(4) = 4-methyl-2,6-bis(((4-tri-fluoromethyl)phenyl)methyliminomethyl)phenol for complex 4, were synthesized and characterized by elemental analysis, FT-IR, UV-vis spectroscopy and finally by single crystal X-ray diffraction study. X-Ray analysis reveals that all of these are mu(4)-oxo-bridged tetrameric copper(II) complexes. Four copper atoms arrange themselves around an oxygen atom tetrahedrally. Magnetic susceptibility measurements show the existence of very strong antiferromagnetic coupling among these ions (J = -210.1 to -271.3 cm(-1)), mediated by the oxygen atoms. Catalysis of the epoxidation of cyclohexene, styrene, alpha-methylstyrene and trans-stilbene by these complexes has been carried out homogeneously as well as heterogeneously by immobilizing the metal complexes over 2D-hexagonal mesoporous silica. The results obtained in both the catalytic conditions show that the olefins are converted to the respective epoxides in good yield together with high selectivity. | 10.1039/b913556a |
pubmed_809_18674 | A text mining system is presented for automatically extracting information from the literature on chemical-CYP3A4 interactions (i.e., substrate, induction, inhibition). The system identifies chemicals and CYP3A4 forms according to a combination of name dictionaries and context features. In addition, it transforms sentences into multiple simple clauses each containing a single event and extracts information on chemical-CYP3A4 interactions using a simple but effective pattern matching method based on the order of three keywords (chemicals, CYP3A4, key verbs). Using this system, 2990 relations including 2700 identified interactions with CYP3A4 for 600 chemicals were extracted from a corpus of 2900 PubMed abstracts. In an evaluation test using 100 randomly selected abstracts, it achieved 87.4% recall and 92.3% precision for identification of the chemical name and 85.2% recall and 92.0% precision for the extraction of chemical-CYP3A4 interactions, respectively. This system will be applicable to interactions of chemicals with any functional proteins, such as enzymes and transporters, simply by changing the list of key verbs. | 10.1021/ci700091m |
pubmed_1018_16146 | The nucleotide sequence was determined for 2.75 kbp of phage Mu DNA encoding the contractile tail sheath protein L. N-terminal sequence analysis of Mu tail tube and sheath proteins identified the open reading frame just downstream of gene L as the tube gene. This clustering and order of the sheath and tube genes appear to be common among the myoviridae. Database homology searches revealed high similarity between the Mu sheath and tube proteins and two proteins in a Haemophilus influenzae Mu-like prophage, suggesting that they are the sheath and tube proteins of that prophage. | 10.1016/s0167-4781(98)00102-x |
pubmed_618_12973 | Synchrotron radiation computed laminography (SR-CL) is presented as an imaging method for analyzing the three-dimensional (3D) anatomy of leaves. The SR-CL method was used to provide 3D images of 1-mm² samples of intact leaves at a pixel resolution of 750 nm. The method allowed visualization and quantitative analysis of palisade and spongy mesophyll cells, and showed local venation patterns, aspects of xylem vascular structure and stomata. The method failed to image subcellular organelles such as chloroplasts. We constructed 3D computer models of leaves that can provide a basis for calculating gas exchange, light penetration and water and solute transport. The leaf anatomy of two different tomato genotypes grown in saturating light conditions was compared by 3D analysis. Differences were found in calculated values of tissue porosity, cell number density, cell area to volume ratio and cell volume and cell shape distributions of palisade and spongy cell layers. In contrast, the exposed cell area to leaf area ratio in mesophyll, a descriptor that correlates to the maximum rate of photosynthesis in saturated light conditions, was no different between spongy and palisade cells or between genotypes. The use of 3D image processing avoids many of the limitations of anatomical analysis with two-dimensional sections. | 10.1111/tpj.12701 |
pubmed_844_7706 | The role of sigmoidoscopic examination in the diagnosis, evaluation, and treatment of minor lower gastrointestinal bleeding was investigated. A hundred patients with minor rectal bleeding were examined by rigid sigmoidoscopy under general anaesthesia between January 1989 and July 1996. Patients who had bleeding secondary to infections, anal fissure, or haemorrhoids were excluded from study. Patients were reviewed retrospectively according to their diagnosis and endoscopic and histopathological findings. Twenty nine of these patients were girls and 71 boys; their ages ranged between 8 month and 14 years (mean 7.2 years). Endoscopic pathological findings were established in 60 patients; 32 had rectal polyps, 16 non-specific proctitis, four solitary rectal ulcers, three internal haemorrhoids, two ulcerative colitis, two Hirschsprung's enterocolitis, and one haemangioma. It is concluded that sigmoidoscopic examination should be performed for the diagnosis, prognosis, and choice of treatment in patients with minor rectal bleeding and the diagnosis should be confirmed histopathologically. | 10.1136/adc.78.3.267 |
pubmed_242_23611 | We report two patients with myasthenia gravis (MG) who showed dropped head as an early myasthenic manifestation. They had elevated anti-acetylcholine receptor antibody and showed improvement of the symptoms after intravenous injection of edorophonium chloride. One patient had thymoma and developed myasthenic crisis two weeks after thymectomy. The patient recovered from the crisis after a combination of immunoadsorption plasmapheresis (IAPP) and initiation of steroid and tacrolimus. The other patient without thymoma initiated treatment with steroid, tacrolimus and IAPP and showed complete recovery one month later. Dropped head in MG can recover well with immunosuppression therapy using steroid, and IAPP is helpful in getting a rapid improvement of dropped head as well as recovery from myasthenic crisis. When we consider treatment for MG with dropped head, we should take into account that MG of this type can develop myasthenic crisis and use the same treatment strategy as that for generalized MG. | pubmed_242_23611 |
pubmed_743_8826 | Serotonin (5-hydroxytryptamine, 5-HT) is a crucial signal in the neurogenic niche of the hippocampus, where it is involved in antidepressant action. Here, we utilized a new transgenic rat model (TetO-shTPH2), where brain 5-HT levels can be acutely altered based on doxycycline (Dox)-inducible shRNA-expression. On/off stimulations of 5-HT concentrations might uniquely mirror the clinical course of major depression (e.g., relapse after discontinuation of antidepressants) in humans. Specifically, we measured 5-HT levels, and 5-HT metabolite 5-HIAA, in various brain areas following acute tryptophan hydroxylase 2 (Tph2) knockdown, and replenishment, and examined behavior and proliferation and survival of newly generated cells in the dentate gyrus. We found that decreased 5-HT levels in the prefrontal cortex and raphe nuclei, but not in the hippocampus of TetO-shTPH2 rats, lead to an enduring anxious phenotype. Surprisingly, the reduction in 5-HT synthesis is associated with increased numbers of BrdU-labeled cells in the dentate gyrus. At 3 weeks of Tph2 replenishment, 5-HT levels return to baseline and survival of newly generated cells is unaffected. We speculate that the acutely induced decrease in 5-HT concentrations and increased neurogenesis might represent a compensatory mechanism. | 10.3390/cells10113240 |
pubmed_472_19235 | A better understanding of the biology of tissue-resident stem cell populations is essential to development of therapeutic strategies for regeneration of damaged tissue. Here, we describe the isolation of glandular stem cells (GSCs) from a small biopsy specimen from human parotid glands. Single colony-forming unit-derived clonal cells were isolated through a modified subfractionation culture method, and their stem cell properties were examined. The isolated clonal cells exhibited both epithelial and mesenchymal stem cell (MSC)-like features, including differentiation potential and marker expression. The cells transiently displayed salivary progenitor phenotypes during salivary epithelial differentiation, suggesting that they may be putative multipotent GSCs rather than progenitor cells. Both epithelial and mesenchymal-expressing putative GSCs, LGR5+CD90+ cells, were found in vivo, mostly in inter-secretory units of human salivary glands. Following in vivo transplantation into irradiated salivary glands of mice, these cells were found to be engrafted around the secretory complexes, where they contributed to restoration of radiation-induced salivary hypofunction. These results showed that multipotent epitheliomesenchymal GSCs are present in glandular mesenchyme, and that isolation of homogenous GSC clones from human salivary glands may promote the precise understanding of biological function of bona fide GSCs, enabling their therapeutic application for salivary gland regeneration. | 10.1038/srep36303 |
pubmed_277_21892 | UNLABELLED
The cardiac responses to exercise are influenced by a complex interplay of changes in diastolic filling, intrinsic myocardial contractility, heart rate, and ventricular afterload.
PURPOSE
To characterize these responses in children, findings are reported from two studies utilizing Doppler echocardiographic assessment of stroke volume and cardiac output during maximal upright and semisupine cycle exercise.
METHODS
In study 1, stroke volume, heart rate, and peak aortic velocity were assessed during upright cycle exercise to exhaustion in 39 sixth-grade boys. In study 2, similar methods were used to examine cardiac responses to semisupine exercise with measurement of left ventricular dimensions by two-dimensional echocardiography.
RESULTS
The findings support patterns similar to that previously described in adults, with an initial rise in stroke volume reaching a plateau at mild-moderate exercise intensities.
CONCLUSIONS
The observations in these two studies also suggest 1) peripheral vasodilatation plays an important role in the early rise in stroke volume, 2) increasing heart rate acts to maintain a stable stroke volume and left ventricular diastolic dimension at high workloads, and 3) improvements in contractility serve to maintain stroke volume as the systolic ejection period shortens. | 10.1097/00005768-200002000-00001 |
pubmed_1128_18731 | The medical records of 43 hemodynamically stable children with elevated serum transaminase levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT]) who underwent abdominal computed tomographic (CT) scan for blunt abdominal trauma were reviewed. Nineteen patients (44.2%) had AST levels greater than 450 IU/L and ALT levels greater than 250 IU/L, and 17 of these 19 patients had hepatic injury identified on abdominal CT scan. Of the 43 patients, 25 (58.1%) had AST and ALT levels of less than 450 IU/L and 250 IU/L, respectively, and none of these patients had evidence of hepatic injury on CT scan. Elevated serum transaminase levels (AST greater than 450 IU/L and ALT greater than 250 IU/L) identified all of the patients with hepatic injury visible on abdominal CT scan. The sensitivity and specificity of elevated serum transaminase levels were 100% and 92.3%, respectively, for predicting hepatic injury. It is recommended that hemodynamically stable pediatric patients with blunt abdominal trauma and AST levels greater than 450 IU/L and/or ALT levels greater than 250 IU/L undergo abdominal CT scan to determine the presence and extent of hepatic injury. Children with serum transaminase levels below these values are at decreased risk of liver injury. | pubmed_1128_18731 |
pubmed_1091_15794 | OBJECTIVES
We aimed to assess whether postural abnormalities in Progressive Supranuclear Palsy (PSP) and Idiopathic Parkinson's Disease (IPD) are qualitatively different by analysing spontaneous and reactive postural control.
METHODS
We assessed postural control upon platform tilts in 17 PSP, 11 IPD patients and 18 healthy control subjects using a systems analysis approach.
RESULTS
Spontaneous sway abnormalities in PSP resembled those of IPD patients. Spontaneous sway was smaller, slower and contained lower frequencies in both PSP and IPD as compared to healthy subjects. The amount of angular body excursions as a function of platform angular excursions (GAIN) in PSP was qualitatively different from both IPD and healthy subjects (GAIN cut-off value: 2.9, sensitivity of 94%, specificity of 72%). This effect was pronounced at the upper body level and at low as well as high frequencies. In contrast, IPD patients' stimulus-related body excursions were smaller compared to healthy subjects. Using a systems analysis approach, we were able to allocate these different postural strategies to differences in the use of sensory information as well as to different error correction efforts.
CONCLUSIONS
While both PSP and IPD patients show abnormal postural control, the underlying pathology seems to be different.
SIGNIFICANCE
The identification of disease-specific postural abnormalities shown here may be helpful for diagnostic as well as therapeutic discriminations of PSP vs. IPD. | 10.1016/j.clinph.2018.03.002 |
pubmed_143_4855 | The objective of this study were to assess the pulmonary function in patients with ethmoidal polyposis who did not respond to medical treatment; to evaluate the effect of Functional Endoscopic Sinus Surgery on the lung function of these patients and to compare the total nasal symptom score in these patients. A prospective observational study was conducted in Department of ENT, KMC Manipal on 50 subjects with ethmoidal polyposis who were unresponsive to medical treatment and hence underwent FESS. Pulmonary function tests were assessed using spirometry and nasal symptoms were scored as per TNSS system prior to surgery and 3 months post-surgery and compared with the pre-operative values and analysed. Pre operatively majority (35 patients) had TNSS value of 6-9 whereas post operatively the score was reduced to 2-3 in many patients (38 patients). The mean TNSS was 7.24 before surgery which declined to 2.82 after surgery with a p value < 0.0001 indicating a statistically significant improvement in the nasal symptoms post FESS. The mean pre-operative FVC, FEV1, MEFR were 2.94, 2.41 and 2.51 L respectively whereas the mean post-operative values were 2.95, 2.39 and 2.49 L respectively. There was no statistically significant change in lung function tests following FESS. Our study shows that FESS benefits patients with nasal polyposis by improving the symptoms and there by the quality of life without any adverse effects on the lower airways. | 10.1007/s12070-018-1422-4 |
pubmed_755_7864 | This investigation aimed to develop a biologically relevant murine model of colorectal liver metastases and determine if Kupffer cells (KC) and hepatic natural killer cells (hNKC) regulate tumor growth. The model involves the injection of murine colon adenocarcinoma 26 (MCA 26) tumor cells into the portal vein of female-specific pathogen-free BALB/c mice. Metastases developed in all animals, and the growth was limited entirely to the liver. To determine if KC and hNKC control the development of liver metastases, the in vivo function of these hepatic effector cells was modulated. Tumor growth was quantitated by the uptake of 125I into tumor DNA. Stimulation of the KC and hNKC produced a significant (P less than 0.01) dose-dependent decrease in 125I uptake in the liver in both treatment groups, which was associated with a significant improvement in survival (P less than 0.05). The in vivo cytotoxic function of the liver was inhibited with an intravenous injection of gadolinium chloride (for KC) or asialo GM1 antiserum (for hNKC). Inhibition of KC and hNKC cytotoxic function led to a significant (P less than 0.01) increase in 125I uptake in the liver and a significant decrease in survival (P less than 0.05). | 10.1007/BF00058171 |
pubmed_591_22955 | BACKGROUND
Single nucleotide polymorphisms (SNPs) located in the vascular endothelial growth factor (VEGF) gene may be correlated with the susceptibility to coronary artery disease (CAD) - although results have been controversial. The aim of this meta-analysis is to clarify the effects of VEGF -2578A/C (rs699947), -1154G/A (rs1570360), +405C/G (rs2010963), and + 936C/T (rs3025039) polymorphisms on CAD risk.
METHODS
Pooled odds ratio (OR) and corresponding 95% confidence intervals (CIs) were calculated to estimate the strength of the association between VEGF gene polymorphisms and CAD risk. Fixed- or random-effects model was used depending on the heterogeneity between studies.
RESULTS
In total, 13 eligible articles containing 29 studies were analysed. The pooled analysis indicated that the VEGF gene polymorphisms of rs699947, rs2010963, and rs3025039 were associated with an increased risk of CAD, whereas no significant associations were observed with the rs1570360 polymorphism. A subgroup analysis stratified by ethnicity revealed that the rs699947 and rs3025039 polymorphisms were associated with CAD risk in Asian populations. In addition, stratification by control source indicated an increased risk of CAD susceptibility with the rs699947 polymorphism for population-based studies of reduced heterogeneity.
CONCLUSIONS
In summary, we concluded that the VEGF gene polymorphisms rs699947, rs2010963, and rs3025039 are correlated with an elevated CAD risk. | 10.1186/s12881-018-0628-3 |
pubmed_50_20967 | Background Classical management of small infants with tetralogy of Fallot has involved placement of a Blalock-Taussig shunt followed later by complete repair, rather than primary complete repair which is the strategy adopted in larger infants. Some advantages of early complete repair compared to a staged strategy have been shown. We sought to review our institutional outcomes. Methods Patients under 3-months old undergoing complete surgical repair of tetralogy of Fallot in our institution between 2005 and 2015 were retrospectively reviewed and compared with an older control group matched by anatomical diagnosis and outflow tract intervention. Results Fourteen index cases (group A) and 14 controls (group B) were identified. At surgery, the median age was 43 days and weight 4.2 kg in group A, and 130 days and 6.1 kg in group B. Nine of 14 in group A were admitted for surgery as emergencies compared to none in group B. Peak inotrope score (22.3 vs. 12.8, p = 0.02) and intensive care unit stay (4.4 vs. 2.6 days, p = 0.02) were higher in group A. Bypass and crossclamp times, duration of intubation, and total length of stay did not differ. Conclusions We conclude that although babies undergoing early repair of tetralogy of Fallot have an increased need for intensive care support in the early postoperative period, the total length of stay is not prolonged despite more emergency admissions. As it is known that early repair may reduce long-term morbidity, we propose consideration of earlier complete repair of tetralogy of Fallot. | 10.1177/0218492318803037 |
pubmed_974_19829 | PURPOSE
Subarachnoid hemorrhage is an acute neurological emergency requiring urgent confirmation of the diagnosis for planning definitive management. Due to altered consciousness, most patients require sedation for conducting this procedure smoothly. Currently, it is unclear if any one particular sedative drug has a favorable profile in patients undergoing cerebral angiography. The aim of this study was to compare the traditionally used sedative drug propofol with a newer alternative, dexmedetomidine, in patients with subarachnoid hemorrhage undergoing cerebral angiography.
METHODS
Sixty adult patients with good grade subarachnoid hemorrhage undergoing diagnostic cerebral angiography were prospectively randomized to receive either propofol (n = 30) or dexmedetomidine (n = 30) following ethics committee approval and informed consent.
RESULTS
Compared to dexmadetomidine, propofol was associated with an earlier time for onset of sedation (2.3 ± 1.9 min vs. 15.4 ± 5.7 min; P < 0.001), but with an increased number of adverse respiratory events (11/30 vs 1/30; P = 0.003) and movement during the procedure (5/30 vs. 0/30; P = 0.05), necessitating additional supplementation of sedation (13/30 vs. 7/30; P = 0.17) and repetition of the imaging sequences. The total procedure time and time for recovery were similar for the propofol and dexmedetomidine groups, while the heart rate was lower in patients in the dexmedetomidine group.
CONCLUSION
Dexmedetomidine appears to be superior to propofol as a sole sedative agent for sedation during cerebral angiography in patients with subarachnoid hemorrhage. | 10.1007/s00540-014-1952-1 |
pubmed_438_11339 | There is a preoccupation with linearity and absorbed dose as the basic quantifiers of radiation hazard. An alternative is the fluence approach, whereby radiation hazard may be evaluated, at least in principle, via an appropriate action cross section. In order to compare these approaches, it may be useful to discuss them as quantitative descriptors of survival and transformation-like endpoints in cell cultures in vitro--a system thought to be relevant to modelling radiation hazard. If absorbed dose is used to quantify these biological endpoints, then non-linear dose-effect relations have to be described, and, e.g. after doses of densely ionising radiation, dose-correction factors as high as 20 are required. In the fluence approach only exponential effect-fluence relationships can be readily described. Neither approach alone exhausts the scope of experimentally observed dependences of effect on dose or fluence. Two-component models, incorporating a suitable mixture of the two approaches, are required. An example of such a model is the cellular track structure theory developed by Katz over thirty years ago. The practical consequences of modelling radiation hazard using this mixed two-component approach are discussed. | 10.1093/oxfordjournals.rpd.a006828 |
pubmed_299_7418 | BACKGROUND
Published work suggests a survival benefit for patients with trauma who undergo total-body CT scanning during the initial trauma assessment; however, level 1 evidence is absent. We aimed to assess the effect of total-body CT scanning compared with the standard work-up on in-hospital mortality in patients with trauma.
METHODS
We undertook an international, multicentre, randomised controlled trial at four hospitals in the Netherlands and one in Switzerland. Patients aged 18 years or older with trauma with compromised vital parameters, clinical suspicion of life-threatening injuries, or severe injury were randomly assigned (1:1) by ALEA randomisation to immediate total-body CT scanning or to a standard work-up with conventional imaging supplemented with selective CT scanning. Neither doctors nor patients were masked to treatment allocation. The primary endpoint was in-hospital mortality, analysed in the intention-to-treat population and in subgroups of patients with polytrauma and those with traumatic brain injury. The χ(2) test was used to assess differences in mortality. This trial is registered with ClinicalTrials.gov, number NCT01523626.
FINDINGS
Between April 22, 2011, and Jan 1, 2014, 5475 patients were assessed for eligibility, 1403 of whom were randomly assigned: 702 to immediate total-body CT scanning and 701 to the standard work-up. 541 patients in the immediate total-body CT scanning group and 542 in the standard work-up group were included in the primary analysis. In-hospital mortality did not differ between groups (total-body CT 86 [16%] of 541 vs standard work-up 85 [16%] of 542; p=0.92). In-hospital mortality also did not differ between groups in subgroup analyses in patients with polytrauma (total-body CT 81 [22%] of 362 vs standard work-up 82 [25%] of 331; p=0.46) and traumatic brain injury (68 [38%] of 178 vs 66 [44%] of 151; p=0.31). Three serious adverse events were reported in patients in the total-body CT group (1%), one in the standard work-up group (<1%), and one in a patient who was excluded after random allocation. All five patients died.
INTERPRETATION
Diagnosing patients with an immediate total-body CT scan does not reduce in-hospital mortality compared with the standard radiological work-up. Because of the increased radiation dose, future research should focus on the selection of patients who will benefit from immediate total-body CT.
FUNDING
ZonMw, the Netherlands Organisation for Health Research and Development. | pubmed_299_7418 |
pubmed_680_21698 | Agility is a sport in which dogs compete on an obstacle course for both accuracy and time. Dogs that participate in competitions must negotiate a complex course of approximately 20 obstacles. We describe a literature review of the biomechanics of canine agility and our preliminary results. The number of articles that have reported biomechanics of canine agility has gradually increased since 2010. Most previous studies have focused on the bar jump, which is a basic obstacle to agility. In our preliminary study, we investigated the roll motion of the head and trunk using inertial sensors for Border Collies that completed weave poles (obstacles in which dogs weave through approximately 10 poles placed 0.6 m apart in a straight line). The roll angles of the head and trunk were measured based on the angular velocity and linear acceleration data using a sensor fusion algorithm. The head and trunk rotated about the roll axis nearly in unison. The roll amplitude of the head was lower than that of the trunk. We discuss the importance of biomechanical studies on canine agility to gain a deeper understanding of mammalian quadrupedal locomotion. | 10.11477/mf.1416202184 |
pubmed_1023_9756 | The ATP content in human erythrocytes depleted without glucose falls down to half of the initial value within 2-3 hours and reaches practically zero within more than 10 hours. The ADP content increases 2-3-fold during the 1st hour after depletion and then slowly decreases. The AMP content increases 10-fold during several hours, but the rate of this process constantly decreases. The adenylate pool decreases at a constant rate ranging from 0.13 to 0.25 mmol/l cell. h; this is accompanied by accumulation of IMP. Addition of glucose to depleted erythrocytes results in partial recovery of the ATP level within 1-2 hours. The sooner glucose addition after the depletion, the greater the recovery. Simultaneously the ADP and AMP levels drastically decrease to new constant values. The decline of the adenylate pool ceases and the rate of IMP accumulation increases. Normally, the [ATP]/adenylate pool ratio lies within the small interval 0.85-0.94 irrespective of significant individual differences in the absolute values of [ATP]. This ratio is decreased during depletion and restored to the initial value after glucose addition. The mass-action ratio of the adenylate kinase reaction changes greatly during depletion and restoration of erythrocyte ATP. | pubmed_1023_9756 |
pubmed_3_15781 | Ultrasmall light modulators have been made by sandwiching a polymer-dispersed liquid crystal (PDLC) between two ferrules with optical fibers. The device can modulate light independent of the state of polarization, because the PDLC becomes transparent or opaque when either sufficient or no voltage is applied to the film. The PDLC was prepared by mixing and annealing a prepolymer and nematic liquid crystal with large anisotropy. An optical fiber modulator with a 30-microm thick PDLC film had an extinction ratio of 8:1-33:1, an insertion loss of 1.3 dB, and rise and decay times of 4 ms at a wavelength of 1.3 microm. | 10.1364/ao.37.003181 |
others_199_4828 | : Over the last decade, a few cases of visceral leishmaniasis (VL) have been reported in some provinces of northeastern Iran. We aimed to investi-gate clinical and laboratory findings of VL among children who admitted to the pediatric ward in a referral hospital in Mashhad, northeastern Iran. Methods: A retrospective study, between 1997 and 2017, was performed on the data sheet registered for children with confirmed VL at the referral Emam Reza Hospital in Mashhad. Hematological and biochemical profiles of the patients were analyzed. Results: Thirty-five children with VL, confirmed by the presence of amastigotes of Leishmania in Giemsa stained smears of the bone marrow, had been recorded through 20 yr. The mean age of patients was 3.7±4 yr. The majority of the patients suffered from hepatosplenomegaly (100%, n=35/35), followed by pro-longed fever and pallor (91%, n=32/35), weight loss (85%, n=30/35). The main laboratory findings were anemia (94.1%), leukopenia (52.9%) and thrombocyto-penia (70.5%). Almost one-third (37.1%; 13/35) of VL patients inhabited in rural areas of the Bojnoord district as a known VL endemic focus in northeastern Iran. Conclusion: Our preliminary data showed that the origin of VL is still in some districts other than Mashhad, where VL just will be diagnosed. © 2020, Tehran University of Medical Sciences. All rights reser | others_199_4828 |
pubmed_942_19757 | Two hundred and forty eight self-identified Asian-American college students participated in this study that examined the prevalence rates and sociodemographic factors of substance use among Asian Americans in college. Using a Basic Demographic Questionnaire, Family of Origin Measure, Acculturation Lifestyle Survey, and Substance Use Checklist (all instruments were in English), prevalence rates were found to be comparable to or higher than a national sample: 94.5% lifetime prevalence and 78.6% current prevalence (past 30 days) of alcohol use; and higher current prevalence (past 30 days) of illicit drug use (9.5%) and of cigarette use (22.8%) than other Asians aged 12 and older (3.5% for illicit drugs and 17.7% for cigarettes) in a national survey. Male students and those who were employed were more likely to be current users (past 30 days) of drugs in general (15%) and marijuana (13.2%), and users of wine coolers (76.0%) and cigarettes (61.1%) in their lifetime. Being born overseas, years in the U.S., and preference for American TV/movies are associated with substance use. Asian Americans are not immune from substance use (or abuse) while in college. Culture-specific prevention is necessary. | 10.1080/02791072.2006.10399826 |
pubmed_108_2932 | A 3-year survey was conducted in Iowa to characterize the distribution and frequency of species of Fusarium associated with soybean roots. Ten plants were collected from each of 40 to 57 fields each year at V2 to V5 and R3 to R4 soybean growth stages. Fusarium colonies were isolated from symptomatic and symptomless roots and identified to species based on cultural and morphological characteristics. Species identification was confirmed by amplification and sequencing of the translation elongation factor (EF1-α) gene. Fifteen species were identified; Fusarium oxysporum was isolated most frequently, accounting for more than 30% of all isolates. F. acuminatum, F. graminearum, and F. solani were also among the most frequent and widespread species. Eleven other species were recovered from few fields, accounting for less than 10% of all isolates in a given year. No consistent trends were observed in geographic distribution of species. Variability in species frequency was found between soybean growth stages. Fusarium oxysporum was recovered at higher frequency during vegetative stages (40%) than reproductive stages (22%). Conversely, species such as F. acuminatum, F. graminearum, and F. solani were recovered more often from reproductive-stage plants. No significant differences in species composition were observed among fields differing in tillage practices and row spacing. | 10.1094/PDIS-11-12-1059-RE |
pubmed_466_16772 | The response of protodifferentiated and differentiated bone cells to bovine bone morphogenetic protein (bBMP) was observed in implants in the adult rabbit distal femoral metaphysis. Bovine serum albumin and denatured bBMP were implanted in the contralateral femur of controls. The changes of the bone marrow reflected the reaction of protodifferentiated cells. The changes in preexisting trabecular bone tissue reflected the reaction of differentiated cells to bBMP. 45Ca radioisotope quantitative methods demonstrated that the bone morphogenetic response was superimposed upon the reaction to the injury of surgical implantation. By the end of the fourth week, roentgenograms and histologic sections showed larger deposits of intrametaphyseal cartilage and bone in bBMP than in control implanted femurs. By the end of the eighth week, bone formation was associated with remodeling of the entire distal femur and expansion of the external diameter of the metaphysis. These observations indicate the need for investigation of perisinusoid and perivascular cells of periosteum, endosteum, and marrow stroma that are undifferentiated with respect to cartilage and bone but are principal target tissues for BMP. | pubmed_466_16772 |
pubmed_926_5606 | INTRODUCTION
Childhood obesity is associated with cardiovascular abnormalities but little is known on the potential correlation between early cardiovascular and metabolic alterations.
AIM
Aims of this study were 1) to evaluate early cardiovascular abnormalities in a large population of obese children and adolescents compared with a normal weight counterpart, 2) to investigate their potential association with insulin resistance (IR), serum uric acid (sUA) and metabolic syndrome (MetS).
METHODS
This was a single-center case-control study. Eighty obese (OB) subjects (6-16years) and 20 normal weight (NW) matched controls were consecutively recruited. In the whole population we performed an anthropometric and a cardiovascular assessment. OB patients also underwent an OGTT and biochemical evaluations.
RESULTS
OB children showed greater left atrial (LA) and ventricular (LV) dimensions and mass and higher carotid artery intima-media thickness (CIMT), compared with NW controls. The BMI z-score, waist circumference, IR and sUA were positively related with LA and LV dimensions and mass. OB subjects with MetS (46.3%) showed greater LA diameter (p=0.001) and LV area (p=0.01) and volume (p=0.04) compared with OB children without MetS. LA diameter and LV dimensions and mass were significantly dependent on the number of criteria for MetS. Mets, sUA and IR were significant predictors of left heart dimensions and mass in obese children.
CONCLUSIONS
Obesity and MetS are associated with abnormal cardiovascular response during childhood. Hyperuricemia can be an early marker of cardiovascular dysfunction and the routine determination of circulating levels of sUA should be implemented during risk stratification among pediatric age. | 10.1016/j.ijcard.2017.09.031 |
pubmed_346_9270 | A noninvasive, computed tomography (CT) stereoadapter was used for stereotactic localization of small brain tumors in 16 patients scheduled for open surgery. The stereotactic CT study was carried out 1 day to 3 months before surgery. On the day of surgery, the adapter was remounted on the patient's head. The tumor in relation to the adapter, as shown on the CT study, was drawn on the scalp of the patient. The tumor could be found and removed through a small bone opening and a minimal cortical incision. | 10.1016/0090-3019(87)90056-5 |
others_189_11189 | The flora of the grassland surrounding Okanj oxbow lake, located in the vicinity of the village of Elemir (the Vojvodina Province, Serbia), was found to comprise 182 plant taxa. Of these 182 taxa (166 species, 7 subspecies and 2 varieties, 6 forms and 1 lusus naturae), 174 were used for ecological analysis, i.e., 166 species, 7 subspecies and, because of its plant geographic and ecological importance, one variety (the Pontic-Pannonian element Aster tripolium var. pannonicus). Based on mean values of the ecological indices developed according to Landolt's criteria, it was concluded that the grassland flora in the riparian zone around Okanj oxbow lake was composed of taxa adapted to a habitat having the following average values: medium humid to moderately dry (F-2.65), moderately basic (R-3.28), moderately poor in the biogenic mineral N (N-3.20) and organo-mineral substances (H-2.99), with a moderately adequate aeration (D-3.97), and considerably saline (S + - 26.44 %). The flora is predominated by heliophilous (L-3.80) and thermophilous (T-4.01) plants adapted to the moderately continental climatic conditions of the studied habitat (K-3.18) | others_189_11189 |
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