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pubmed_596_653
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The objectives of the current study were to investigate (i) the phase behavior of a PEGylated recombinant human growth hormone (PEG-rhGH, ∼60 kDa) during freeze-drying and (ii) its storage stability. The phase transitions during freeze-thawing of an aqueous solution containing PEG-rhGH and sucrose were characterized by differential scanning calorimetry. Finally, PEG-rhGH and sucrose formulations containing low, medium, and high polyethylene glycol (PEG) to sucrose ratios were freeze-dried in dual-chamber syringes and stored at 4°C and 25°C. Chemical decomposition (methionine oxidation and deamidation) and irreversible aggregation were characterized by size-exclusion and ion-exchange chromatography, and tryptic mapping. PEG crystallization was facilitated when it was covalently linked with rhGH. When the solutions were frozen, phase separation into PEG-rich and sucrose-rich phases facilitated PEG crystallization and the freeze-dried cake contained crystalline PEG. Annealing caused PEG crystallization and when coupled with higher drying temperatures, the primary drying time decreased by up to 51%. When the freeze-dried cakes were stored at 4°C, while there was no change in the purity of the PEG-rhGH monomer, deamidation was highest in the formulations with the lowest PEG to sucrose ratio. When stored at 25°C, this composition also showed the most pronounced decrease in monomer purity, the highest level of aggregation, and deamidation. Furthermore, an increase in PEG crystallinity during storage was accompanied by a decrease in PEG-rhGH stability. Interestingly, during storage, there was no change in PEG crystallinity in formulations with medium and high PEG to sucrose ratios. Although PEG crystallization during freeze-drying did not cause protein degradation, crystallization during storage might have influenced protein stability.
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10.1002/jps.22562
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pubmed_608_25445
|
Triatomines (Heteroptera: Reduviidae) include around 139 species, widely known as vectors of Chagas disease. Our aim is to review the existing knowledge of the genital morphology and sexual behavior and provide some functional analysis of these traits in triatomines. A complex set of traits comprise genitalia and these are highly variable among species. The components of the phallus and seminal products (secreted by action of testes and two accessory glands) interact to allow successful sperm transfer to the female spermathecae (usually a pair of blind tubes that emerge from the common oviduct). Seminal products may inhibit female physiology and extend mating duration. Mating behavior in triatomines is best characterized as scramble competition. We suggest that males may evaluate female condition prior to copulation, given that female fitness is largely affected by food (blood) source. Although rearing several triatomine species may be difficult and discourage from undertaking studies on this group, any further investigation on sexual behavior and mating interactions may provide data for applicative studies including Chagas disease vectors control.
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10.1016/j.asd.2018.11.012
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pubmed_482_244
|
Partial agonists for G protein-coupled receptors (GPCRs) provide opportunities for novel pharmacotherapies with enhanced on-target safety compared to full agonists. For the human adenosine A1 receptor (hA1AR) this has led to the discovery of capadenoson, which has been in phase IIa clinical trials for heart failure. Accordingly, the design and profiling of novel hA1AR partial agonists has become an important research focus. In this study, we report on LUF7746, a capadenoson derivative bearing an electrophilic fluorosulfonyl moiety, as an irreversibly binding hA1AR modulator. Meanwhile, a nonreactive ligand bearing a methylsulfonyl moiety, LUF7747, was designed as a control probe in our study. In a radioligand binding assay, LUF7746's apparent affinity increased to nanomolar range with longer pre-incubation time, suggesting an increasing level of covalent binding over time. Moreover, compared to the reference full agonist CPA, LUF7746 was a partial agonist in a hA1AR-mediated G protein activation assay and resistant to blockade with an antagonist/inverse agonist. An in silico structure-based docking study combined with site-directed mutagenesis of the hA1AR demonstrated that amino acid Y2717.36 was the primary anchor point for the covalent interaction. Additionally, a label-free whole-cell assay was set up to identify LUF7746's irreversible activation of an A1 receptor-mediated cell morphological response. These results led us to conclude that LUF7746 is a novel covalent hA1AR partial agonist and a valuable chemical probe for further mapping the receptor activation process. It may also serve as a prototype for a therapeutic approach in which a covalent partial agonist may cause less on-target side effects, conferring enhanced safety compared to a full agonist.
|
10.1016/j.bcp.2020.114144
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pubmed_97_16042
|
Eleven patients with prospectively documented premenstrual depression were given 100 mg atenolol or placebo daily to suppress melatonin secretion during the symptomatic premenstrual phase of the menstrual cycle. There was no significant improvement in mood following treatment with atenolol vs. placebo. These findings suggest that bright light may exert antidepressant effects in patients with premenstrual syndrome through mechanisms other than melatonin suppression and that atenolol does not appear to be a viable treatment modality for the majority of patients with premenstrual depression.
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10.1016/0165-1781(91)90070-6
|
pubmed_623_12025
|
BACKGROUND
Age-associated decline in central cholinergic activity makes older adults susceptible to the harmful effects of anticholinergic (AC) medications; however, there is an inadequate understanding of the association and possible effects of AC drugs on cognition. This cross-sectional study examines the associations of AC medications on cognition among older adults with questionable cognitive impairment (QCI).
METHODS
For this cross-sectional study, we used a multicenter database of community-dwelling older adults (N = 7351) aged 60+ years with QCI, from September 2005 to March 2014, as the baseline data. The Anticholinergic Drug Scale was used to categorize AC drug load into no, low, or moderate/high groups. Individuals with a Clinical Dementia Rating-Sum of Boxes score between 0.5 and 2.5 were identified as having QCI, while cognitive performance was evaluated using the Neuropsychological Test Battery. The mean z-scores of neuropsychological tests were grouped into a global cognition score.
RESULTS
Participants who took AC medications were older, largely female, and had a higher prevalence of incontinence than those without AC exposure. Global cognition was significantly greater in the moderate/high-AC group than the no-AC group (-0.23 ± 0.53 vs. -0.32 ± 0.53). Multivariable linear regression showed that the global cognition score among the low- and moderate/high-AC groups, compared with the no-AC group, was 0.064 higher (p = 0.006 and p = 0.12, respectively).
CONCLUSIONS
This cross-sectional study indicates that older adults with QCI who were exposed to AC medications might have higher global cognitive scores than those without AC exposure. The observed associations indicate that older adults might experience some beneficial cognitive effects from AC drugs, possibly due to the therapeutic effects of these medications in controlling comorbidities, thus outweighing their adverse effects on cognition.
|
10.1007/s40266-016-0400-3
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pubmed_347_25318
|
Following kidney injury, repair can result in functional tissue becoming a patch of cells and disorganized extracellular matrix--a scar--or it can recapitulate the original tissue architecture through the process of regeneration. Regeneration can potentially occur in all animal species and humans. Indeed, the repair of portions of the existing nephron after tubular damage, a response that has been designated classically as cellular regeneration, is conserved in all animal species from the ancestral phases of evolution. By contrast, another type of regenerative response--nephron neogenesis--has been described in lower branches of the animal kingdom, but does not occur in adult mammals. Converging evidence suggests that a renal progenitor system is present in the adult kidney across different stages of evolution, with renal progenitors having been identified as the main drivers of kidney regenerative responses in fish, insects, rodents and humans. In this Review, we describe similarities and differences between the renal progenitor systems through evolution, and propose explanations for how progressive kidney adaptation to environmental changes both required and permitted neonephrogenesis to be given up and for cellular regeneration to be retained as the main regenerative strategy. Understanding the mechanisms that drive renal progenitor growth and differentiation represent the key step for modulating this potential for therapeutic purposes.
|
10.1038/nrneph.2012.290
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pubmed_132_24978
|
Approximately 5300 hybrid sturgeons with an average body weight of 600-800 g were farmed in 3 round tankers measuring 3m in diameter each containing 28,000 L of aerated groundwater. According to the owner's description, the diseased fish had anorexia, pale body color, and reddish spots on the abdomen. The morbidity and lethality rates in this outbreak were about 70% (3706/5300) and 100% (3706/3706), respectively. The clinical examination revealed enteritis, enlarged abdomen, and rapid respiration rate. The gross findings revealed a volume of about 4 mL of ascites. The histopathological examination showed multiple massive, hemorrhagic or coagulative necrotic foci in the liver and spleen. Furthermore, there was diffuse infiltration of glycogen in hepatic cells, and a few polymorphonuclear and mononuclear leucocytes were observed surrounding the spleen. Some bacterial clumps were noted around the necrotic foci. We also observed that there was moderate to severe, acute, multifocal, coagulative necrosis in the renal parenchyma, with some necrotic foci present beneath the margin of the kidney. Additionally, multifocal, coagulative necrosis was found in the pancreas. Results of microbiologic examinations, including biochemical characteristics, PCR amplification of 16S rRNA gene, sequencing and comparison, and phylogenetic analysis, revealed the pathogen of this infection was Lactococcus lactis subsp. lactis, and based on the results of an antimicrobial agent sensitivity test the bacterium was only sensitive to ampicillin and florfenicol. Additionally, results of in vivo experimental infections in hybrid tilapia showed that 1×10(8) and 1×10(9) CFU/mL of our isolate caused death in all fish and LD(50) values ranged from 10(2) to 10(5) CFU/mL. To the best of the authors' knowledge, this is the first reported case of Lactococcus lactis subsp. lactis infection in hybrid sturgeon.
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10.1016/j.rvsc.2011.10.007
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pubmed_739_5964
|
Cell anchorage strongly affects the signal transduction cascade initiated by peptide mitogens. For both epidermal growth factor and platelet-derived growth factor, activation of the consensus mitogen-activated protein kinase cascade is impaired when cells are held in suspension as compared with cells anchored to a fibronectin substratum. Upstream events in the signaling cascade, including tyrosine phosphorylation of the mitogen receptor and GTP loading of Ras, are similar in anchored and suspended cells. However, propagation of the signal to Raf and subsequently to the downstream kinases MEK and mitogen-activated protein kinase is markedly attenuated in suspended cells. Thus, there seems to be a distinct anchorage-dependent step between Ras and Raf in the signaling cascade initiated by peptide mitogens. These observations may have important implications for understanding the anchorage dependence of cell growth.
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pubmed_739_5964
|
pubmed_876_20865
|
Five cases of renal cell carcinoma metastatic to the testis or its adnexa are described, including 3 that represented the initial presentation and mimicked primary testicular neoplasms. The patients ranged from 46 to 85 years of age. Three presented with self-identified testicular masses. One patient was investigated because of fever of unknown origin and was found to have a left rib metastasis. Further work-up led to the discovery of a testicular mass. The final patient had a tumor of the spermatic cord that was examined without knowledge that he had a prior renal neoplasm. All the tumors were unilateral. They ranged from 1.8 to 5.0 cm; multiple tumor nodules were present in one of them but the others were discrete solitary masses. Four tumors were yellow/yellow-tan, and one was gray. On microscopic examination all the tumors were of the clear cell type. Patterns included solid sheets, acini, cysts, alveoli, and trabeculae. Two had prominent vascular invasion. Diagnoses initially entertained in these cases included Sertoli cell tumor, Sertoli-Leydig cell tumor, and clear cell cystadenoma of the epididymis. In 3 cases a kidney tumor was discovered 2 to 4 weeks after the diagnosis of renal cell carcinoma metastatic to the testis was rendered. On follow-up two patients died of tumor, and two were alive (5 months and 1 year) after orchiectomy. The diagnosis of renal cell carcinoma metastatic to the testis should be considered in evaluating a clear cell tumor of the testis, particularly in an older male or if the appearance suggests a Sertoli cell tumor. The differences in survival between metastatic renal cell carcinoma and sex cord-stromal tumors indicate the importance of considering the former in the differential.
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10.1177/106689690100900108
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pubmed_675_10417
|
OBJECTIVE
The Protective Behavioral Strategies for Marijuana Scale (PBSM), a 17-item scale targeting strategies for mitigating the negative consequences of cannabis use, highlights a range of behaviors that can reduce harm beyond straightforward decreases in quantity or frequency. The 17-item scale's factor structure remains under-examined but could reveal meaningful distinctions among strategies. This study aimed to confirm the factor structure of the short form of the PBSM.
METHODS
This study recruited cannabis-using undergraduates (N = 454,Mage = 19.6, 68.8% female, 39% White), who reported using cannabis approximately 2.3 days per week with mild cannabis-related consequences (CAPQ; M = 9.74).
RESULTS
A confirmatory factor analysis demonstrated poor fit for the one-factor model of the PBSM, prompting an exploratory factor analysis. Analyses revealed two internally reliable factors: a "Quantity" factor, strategies specific to mitigating overuse and limiting amounts consumed and an "Context" factor loosely related to troubles with others. This two-factor model accounted for over half of the total variance; invariance testing indicated reduced fit as models became more restrictive. Though each of the factors covaried negatively with both days of use and problems, Context had a stronger relation to both variables compared to Quantity. Only Context predicted fewer cannabis problems and use.
CONCLUSIONS
The two-factor solution suggests further work on the psychometric properties of the scale could provide heuristic information to allow for more nuanced approaches in clinical and research settings. Theoretically, each factor might have novel links to some constructs but not others in ways that could assist harm-reduction strategies and treatment.
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10.1016/j.addbeh.2021.106852
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pubmed_337_17249
|
Ticks are responsible for the transmission of viral, bacterial, and protozoal diseases of man and animals and also produce significant economic losses to cattle industry. The use of acaricides constitutes a major component of integrated tick control strategies. However, this is accompanied by the selection of acaricide-resistant ticks and contamination of environment and milk and meat products with drug residues. These issues highlight the need for alternative approaches to control tick infestations and have triggered the search for tick protective antigens for vaccine development. Vaccination as a tick control method has been practiced since the introduction of TickGARD and Gavac that were developed using the midgut glycoprotein Bm86 as antigen. Gavac within integrated tick management systems has proven to reduce the number of acaricidal applications per year that are required to control some strains of R. microplus ticks in different geographical regions. Nevertheless, it has limited or no efficacy against other tick species. These issues have stimulated research for additional tick protective antigens with critical functions in the tick. This chapter presents methodologies for the design and test of molecules as antigens against ticks. Considerations about different methods for the tick control compared to the immunological methods, the desirable characteristics for an anti-tick vaccine and the obstacles encountered for developing this kind of vaccines are discussed. Detailed methodologies for the establishment of a biological model to test new molecules as immunogens against ticks and to perform challenge trials with this model are presented. General considerations in the efficacy calculation for any anti-tick vaccine are also discussed.
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10.1007/978-1-4939-3389-1_17
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pubmed_792_4030
|
A total of 143 samples of Ugandan mothers' breast milk were analysed by gas chromatography for the presence and levels of DDT residues. The relationship between the level of DDT in the milk and the mother's age, parity, dietary habits, and place of usual residence were studied. DDT levels in the milk were not significantly related to the mother's age. Mothers nursing their first child had a significantly higher mean DDT level in their milk than those nursing their second child. Furthermore, mothers who resided in the urban area had a significantly higher mean-DDT level in their milk than those who resided in the rural area. No statistically significant differences were observed in the mean levels of DDT in the milk samples of vegetarian and non-vegetarian mothers. From the present findings, it could be concluded that milk from mothers nursing the first child and residing in an urban area is a good bioindicator for assessing exposure of lactacting mothers to DDT in Uganda.
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pubmed_792_4030
|
pubmed_1014_10855
|
OBJECTIVES
To establish the inter- and intra-rater reliability of the Netball Movement Screening Tool, for screening adolescent female netball players.
DESIGN
Inter- and intra-rater reliability study.
METHODS
Forty secondary school netball players were recruited to take part in the study. Twenty subjects were screened simultaneously and independently by two raters to ascertain inter-rater agreement. Twenty subjects were scored by rater one on two occasions, separated by a week, to ascertain intra-rater agreement. Inter and intra-rater agreement was assessed utilising the two-way mixed inter class correlation coefficient and weighted kappa statistics.
RESULTS
No significant demographic differences were found between the inter and intra-rater groups of subjects. Inter class correlation coefficients' demonstrated excellent inter-rater (two-way mixed inter class correlation coefficients 0.84, standard error of measurement 0.25) and intra-rater (two-way mixed inter class correlation coefficients 0.96, standard error of measurement 0.13) reliability for the overall Netball Movement Screening Tool score and substantial-excellent (two-way mixed inter class correlation coefficients 1.0-0.65) inter-rater and substantial-excellent intra-rater (two-way mixed inter class correlation coefficients 0.96-0.79) reliability for the component scores of the Netball Movement Screening Tool. Kappa statistic showed substantial to poor inter-rater (k=0.75-0.32) and intra-rater (k=0.77-0.27) agreement for individual tests of the NMST.
CONCLUSIONS
The Netball Movement Screening Tool may be a reliable screening tool for adolescent netball players; however the individual test scores have low reliability. The screening tool can be administered reliably by raters with similar levels of training in the tool but variable clinical experience. On-going research needs to be undertaken to ascertain whether the Netball Movement Screening Tool is a valid tool in ascertaining increased injury risk for netball players.
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pubmed_1014_10855
|
pubmed_94_14170
|
Cold atmospheric plasma (CAP) has been recognized as a potential alternative or supplementary cancer treatment tool, which is attributed by its selective antiproliferation effect on cancer cells over normal cells. Standardization of the CAP treatment in terms of biological outputs such as cell growth inhibition and gene expression change is essential for its clinical application. This study aims at identifying genes that show consistent expression profiles at a specific CAP condition, which could be used to monitor whether CAP is an appropriate treatment to biological targets. To do this, genes showing differential expression by two different CAP treatment conditions were screened in the MCF-7 breast cancer cells. As a result, ZNRD1 was identified as a potential marker with being consistently upregulated by 600 s but downregulated by the 10 × 30 s CAP treatment scheme. Expression of ZNRD1 was increased in breast cancer tissues compared to normal tissues, judged by cancer tissue database analysis, and supported by the antiproliferation after siRNA-induced downregulation in MCF-7. Interestingly, the antisense long noncoding RNA (lncRNA) of ZNRD1, ZNRD1-AS1, was regulated to the opposite direction of ZNRD1 by CAP. The siRNA-based qPCR analysis indicates that ZNRD1 downregulates ZNRD1-AS1, but not vice versa. ZNRD1-AS1 was shown to increase a few cis-genes such as HLA-A, HCG9, and PPP1R11 that were also regulated by CAP. Altogether, this study identified a pair of gene and its antisense lncRNA of which expression is precisely controlled by CAP in a dose-dependent manner. These genes could help elucidate the molecular mechanism how CAP regulates lncRNAs in cancer cells.
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10.1155/2020/9490567
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pubmed_485_12672
|
Hydrotherapy is based on several important bioengineering principles that permit the design and development of aquatic exercise devices, techniques and programs. These principles involve several forces (buoyancy, drag, inertia), hydrostatic pressure and the specific heat of water. By acquiring a knowledge of these bioengineering principles, an individualized exercise program can be prescribed that will enhance physical fitness which is associated with desirable psychological changes.
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pubmed_485_12672
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pubmed_132_18331
|
The influence of the autonomic nervous system (ANS) on triggering and perpetuation of atrial fibrillation (AF) is well established. Ganglionated plexi (GP) ablation achieves autonomic denervation by affecting both the parasympathetic and sympathetic components of the ANS. An anatomic approach for GP ablation at relevant atrial sites appears to be safe, and improves the results of PV isolation in patients with paroxysmal and persistent AF. GP ablation can be accomplished endocardially or epicardially, ie, during the maze procedure or thoracoscopic approaches. Further experience is needed to assess the clinical value of this promising technique.
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pubmed_132_18331
|
pubmed_1135_16734
|
In this paper, three representative varieties of peanut seeds were selected for the experiment based on visible/near-infrared reflectance spectroscopy living in the wavelength rang from 600 to 1 100 nm. Firstly, spectral datas ware collected by the near-infrared fiber optic spectrometer, and the spectral features of the original spectral dates were extracted by the wavelet analysis. Then the principal component analysis (PCA) was used for cluster analysis of spectral features. Finally, the four principal components were applied as the inputs, the varieties category as the output and the Mahalanobis distance as the discriminant function of the recognition model, so a linear discriminant analysis model was established. In the 50 samples of each varieties, 30 samples were randomly selected as the training set, and the remaining 20 samples as the predictor set. The recognition model for three peanut varieties have a recognition rate of 95% on average. As the experimental results show that this method is reliable and effectively, and a new method to distinguish and discriminate the quality of peanut seeds was put forword.
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pubmed_1135_16734
|
pubmed_968_2692
|
The study aimed to investigate the effect of erdosteine on middle ear effusion in rats through mediating the Toll-like receptor 4 (TLR4) signaling pathway. Rats were injected with endotoxin to prepare the model of acute secretory otitis media (SOM). Then, they were divided into an acute SOM model group (model group, n = 15) and erdosteine treatment group (18 mg/kg, gavage, treatment group, n = 15). Besides, a normal group (n = 15) was set up. Two weeks later, routine biochemical indicators such as aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were detected. The inflammatory effusion due to otitis media was scored. The content of myeloperoxidase (MPO), matrix metalloproteinase (MMP), and tumor necrosis factor-beta (TNF-β) in middle ear lavage fluid was detected via enzyme-linked immunosorbent assay (ELISA). Additionally, histomorphological changes were observed with the help of hematoxylin-eosin (HE) staining, and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting assays were carried out to measure the expression levels of TLR4 pathway genes and proteins as well as the messenger ribonucleic acid (mRNA) expression levels of key factors for otitis media (mucin 2 (MUC2) and MUC5A). In the model group, the levels of AST, ALP, and glutamic-pyruvic transaminase (GPT) were significantly increased (p < 0.05). Besides, the content of MPO, MMP, and TNF-β was overtly raised in the model group (p < 0.05), while it was notably lowered in the treatment group (p < 0.05). In the treatment group, the cilia were slightly swollen, and inflammatory cells were fewer. The mRNA levels of MUC2, MUC5A, and pathway genes TLR4 and c-Jun N-terminal kinase (JNK) were elevated in the model group. In addition, the protein assay results revealed that the protein levels of TLR4 and JNK were evidently increased in the model group. Erdosteine can treat the middle ear effusion in rats by repressing the activation of the TLR4 signaling pathway.
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10.1155/2021/9968907
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pubmed_472_8701
|
BACKGROUND
Agricultural biotechnology, including the generation of genetically modified food crops, has been the subject of much controversy over the last few years. Initially serving the basic needs of farmers, Ag Biotech has more recently gained much appeal for its opportunities with respect to both the nutritional and pharmaceutical sciences.
METHODS
The following review describes a number of recently approved patents that could have direct implications for the field of medicine. Topics range from the development of pharmaceuticals in plants using hairy roots or virus expression vectors, to the role of epigenetics for improving the nutritional value of food crops.
RESULTS
Many of these patents were developed by smaller companies or publically funded research institutes, disproving the perception that intellectual property in Ag Biotech is restricted to only large multinational corporations.
CONCLUSION
The review concludes with a discussion of the future of these technologies in the face of the current negative political climate.
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10.2174/2212798408666161101102236
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pubmed_621_10136
|
OBJECTIVE
The objective of this study was to evaluate the efficacy of a hydrogel patch containing capsaicin 0.1% compared with a placebo hydrogel patch without capsaicin to treat chronic myofascial neck pain.
DESIGN
The study was designed as a double-blinded randomized controlled trial. Setting. The study was set at Kyung-hee University Hospital at Gangdong, Korea.
SUBJECTS
Sixty-one participants between 18 and 65 years with at least 3 months duration of neck pain and a clinical presentation of myofascial pain syndrome were enrolled in the study from September 1 to November 20, 2010. Interventions. Participants received capsaicin 0.1% hydrogel patches or control hydrogel patches without capsaicin according to the randomization scheme. All participants were instructed to apply one patch to each side of the neck and shoulder girdle overlying the point of maximal pain for 12 hours daily during the duration of the 4-week study.
OUTCOME MEASURES
Each participant completed five surveys at baseline, at 2 weeks after the start of treatments, and at the conclusion of the 4-week study. The primary outcome measure was visual analog scale (VAS). Other outcome measures included the Neck Disability Index (NDI), Beck's Depression inventory (BDI), Short Form 36 Korean version, and Euroqol 5-D.
RESULTS
Fifty-seven patients completed the study. The mean VAS, NDI, and BDI scores were significantly decreased at 2 and 4 weeks after the start of the intervention in both groups. There was no significant difference between the two groups in any of the outcome measures.
CONCLUSIONS
Future research may help to discern specific effects of capsaicin, trigger point stimulation by application of the patch, and the placebo effect.
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10.1111/j.1526-4637.2012.01413.x
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pubmed_448_5674
|
Introduction: Neighborhood environment factors are relevant for dietary behaviors, but associations between home neighborhood context and disease prevention behaviors vary depending on the definition of neighborhood. The present study uses a publicly available dataset to examine whether associations between neighborhood socioeconomic status (NSES) and fruit/vegetable (FV) consumption vary when NSES is defined by different neighborhood sizes and shapes. Methods: We analyzed data from 1,736 adults with data in GeoFLASHE, a geospatial extension of the National Cancer Institute's Family Life, Activity, Sun, Health, and Eating Study (FLASHE). We examined correlations of NSES values across neighborhood buffer shapes (circular or street network) and sizes (ranging from 400 to 1,200 m) and ran weighted simple and multivariable regressions modeling frequency of FV consumption by NSES for each neighborhood definition. Regressions were also stratified by gender. Results: NSES measures were highly correlated across various neighborhood buffer definitions. In models adjusted for socio-demographics, circular buffers of all sizes and street buffers 750 m and larger were significantly associated with FV consumption frequency for women only. Conclusion: NSES may be particularly relevant for women's FV consumption, and further research can examine whether these associations are explained by access to food stores, food shopping behavior, and/or psychosocial variables. Although different NSES buffers are highly correlated, researchers should conceptually determine spatial areas a priori.
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10.3389/fpubh.2021.706151
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pubmed_801_15061
|
A series of bimetallic ruthenium complexes [{Ru(dppe)Cp*}(2)(μ-C≡CArC≡C)] featuring diethynylaromatic bridging ligands (Ar = 1,4-phenylene, 1,4-naphthylene, 9,10-anthrylene) have been prepared and some representative molecular structures determined. A combination of UV-vis-NIR and IR spectroelectrochemical methods and density functional theory (DFT) have been used to demonstrate that one-electron oxidation of compounds [{Ru(dppe)Cp*}(2)(μ-C≡CArC≡C)](HC≡CArC≡CH = 1,4-diethynylbenzene; 1,4-diethynyl-2,5-dimethoxybenzene; 1,4-diethynylnaphthalene; 9,10-diethynylanthracene) yields solutions containing radical cations that exhibit characteristics of both oxidation of the diethynylaromatic portion of the bridge, and a mixed-valence state. The simultaneous population of bridge-oxidized and mixed-valence states is likely related to a number of factors, including orientation of the plane of the aromatic portion of the bridging ligand with respect to the metal d-orbitals of appropriate π-symmetry.
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10.1021/ja207827m
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pubmed_738_14509
|
The recently published article by P. Tsimaris et al. (2019) gave great prospective insight into non-traditional clinical applications of probiotic use as alternative and/or complementary therapeutics to traditional antibiotics for treatment of vulvovaginitis. However, these findings are too broad to be generalised as a treatment option for all women. The study design includes a cohort of Caucasian women and does not represent women of other ethnic groups.
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10.3920/BM2020.0034
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pubmed_594_1112
|
Percutaneous nucleotomy is a relatively new technique for treating lumbar disc herniation. There is no agreement as to the volume of disc material to be removed. A long-term study of clinical and radiological data from patients treated by percutaneous nucleotomy was designed to identify the factors associated with favourable and unfavourable outcomes. We studied 42 patients for at least ten years; the mean follow-up was 10.9 years. They were divided into two subgroups to assess the value of preserving the nucleus pulposus in the central area of the disc. The overall success rate for both subgroups was 50%. A decrease in disc height on plain radiography and a decrease in signal intensity on MRI were observed more infrequently in patients in whom the nucleus pulposus in the central area of the disc had been preserved, than in those in whom it had been extensively removed. These adverse radiological findings correlated closely with increased low back pain during the first one to two years after operation and a poorer overall outcome. We conclude that percutaneous nucleotomy is most likely to be successful when the central area of the disc is preserved.
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10.1302/0301-620x.83b4.11508
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pubmed_48_13979
|
A large number of susceptibility genes have been implicated in psychiatric disorders with a developmental origin, yet their biological roles and signaling mechanisms in neurodevelopment are largely unknown. Disrupted-In-Schizophrenia 1 (DISC1), a susceptibility gene for several major psychiatric disorders, regulates the development of newborn neurons in the adult hippocampus. Systemic pharmacological inhibition of mTOR signaling with rapamycin has been shown to rescue DISC1 deficiency-induced neurodevelopmental defects, as well as cognitive and affective deficits. Whether mTOR signaling plays a cell-autonomous and/or non-cell-autonomous role in DISC1-dependent regulation of neuronal development is not clear. Here we provide genetic evidence that hyper-activation of mTOR activator Rheb1 (Ras homolog enriched in brain 1) in newborn neurons recapitulates DISC1 deficiency-induced neurodevelopmental defects, including neuronal morphogenesis and migration. We further show that genetic deletion of Rheb1 rescues those defects in a cell-autonomous fashion in developing newborn neurons in the adult hippocampus. Our genetic and functional studies demonstrate that Rheb1 acts as a key mediator of DISC1-dependent regulation of mTOR signaling and neuronal development during adult hippocampal neurogenesis.
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10.1080/23262133.2015.1081715
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pubmed_278_20728
|
High neuroticism is related to cardiovascular morbidity. Early detection of metabolic and cardiovascular risk is important in high-risk groups to enable preventive measures. The aim of this study was therefore to explore if neuroticism is associated with early biomarkers for cardiovascular and metabolic disease in young adults from a psychiatry cohort. Blood samples and self-ratings on neuroticism with the Swedish universities Scales of Personality (SSP) questionnaire were collected from 172 psychiatric outpatients and 46 healthy controls. The blood samples were analysed for plasma leptin, adiponectin, CRP, IL-6 and TNF-α. Associations between neuroticism and biomarkers were assessed using Spearman's correlation coefficients and generalized linear models adjusting for confounders. In the adjusted generalized linear models, neuroticism predicted the leptin/adiponectin ratio (p = 0.003), leptin (p = 0.004) and IL-6 (p = 0.001). These associations were not better explained by current major depressive disorder and/or anxiety disorder. Adiponectin, CRP and TNF-α were not associated with neuroticism. In conclusion, the findings suggest that high neuroticism is related to elevated levels of plasma leptin/adiponectin ratio, leptin and IL-6 in young adults. Young adults with high neuroticism may therefore benefit from preventive interventions to decrease the risk for future metabolic and cardiovascular morbidity, but more research is required to test this hypothesis.
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10.1038/s41598-021-89251-y
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pubmed_731_22499
|
Neurodegenerative disorders and osteoporosis share some common underlying pathological features including calcium overload, accumulation of toxic chemicals, inflammation and impaired protein prenylation by isoprenoids (farnesyl pyrophosphate and geranylgeranyl pyrophosphate) appear later stage of life. Substantial number of pre-clinical and clinical reports as well as in vitro data univocally acknowledged the negative impact of altered post-translational modification (prenylation) of proteins like small GTPases (Rffhes, Rho, Rac etc.) and cholesterol levels in both serum and brain on CNS integrity. Bisphosphonates (BPs), referred to as gold standard for osteoporosis treatment, have well established role in attenuation of bone resorption and osteoclast apoptosis by inhibition of farnesyl pyrophosphate synthase enzyme (FPPS) in mevalonate pathway. BPs mainly nitrogen containing BPs (NBPs) have potential to offer new therapeutic targets for neurological disorders and received increasing attention in recent years. A year back clinical and pre-clinical studies revealed that NBPs have the potential to alleviate the symptoms of neurological disorders like brain calcification, Alzheimer's disease and Huntington's disease by targeting mevalonate pathway. Though these drugs have well developed role in inhibition of isoprenoids synthesis, these were demonstrated to inhibit acetyl cholinesterase enzyme and cholesterol synthesis in brain that are considered as the critical factors for impairment of cognitive functions which is the hallmark of several neurological disorders. Still the current understanding of BPs' effect in CNS is limited due to lack of studies focusing the molecular and cellular mechanism. The present review aims to reveal the updated discussion on the mechanism contributing BPs' effect in CNS disorders.
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10.1016/j.pharep.2018.03.011
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pubmed_1005_16700
|
Interest in muscle biomechanics is growing with availabilities of patient biopsies and animal models related to muscle diseases, muscle wasting (sarcopenia, cachexia), exercise and drug effects. However, development of technologies or facilitated systems required to measure biomechanical and contractile properties of single fibres has not kept pace with this demand. Most studies use manual mechatronics systems that have not changed in decades and are confined to a few labs worldwide. Available commercial systems are expensive and limited in versatility, throughput and user-friendliness. We review major standard systems available from research labs and commercial sources, and benchmark those to our recently developed automated MyoRobot biomechatronics platform that provides versatility to cover multiple organ scales, is flexible in programming for active/passive muscle biomechanics using custom-made graphics user interfaces, employs on-the-fly data analyses and does not rely on external research microscopes. With higher throughput, this system blends Industry 4.0 automation principles into myology.
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10.1016/j.biocel.2019.105563
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pubmed_980_11634
|
BACKGROUND
With the expansion of the donkey industry, timed artificial insemination (TAI) is becoming increasingly important in the reproductive management of jennies, however, TAI has not been widely investigated in donkeys.
OBJECTIVES
To develop efficient TAI protocols for cooled or frozen semen in jennies, based around ovulation induction with a GnRH analogue.
STUDY DESIGN
Experimental exploratory study.
METHODS AND RESULTS
In experiment 1, the effects of different GnRH analogue (deslorelin) doses, follicle diameter (FD) at induction, repeated use of a GnRH analogue, and the influence of season on induction efficiency, as well as distribution of ovulations over time after induction were investigated. Induction efficiency was sufficient with 2.2 mg deslorelin (≥90% ovulation within 48 hours of treatment). Ovulation rate between 24 and 48 hours was highest when the FD at treatment was 31-35 mm, as compared to 25-30 mm or 36-40 mm. Repeated use of deslorelin or treatment during different seasons had no effect on induction efficiency. About 70% of ovulations occurred between 32 and 48 hours, and highest incidence of ovulation was at 36-38 hours after induction. In experiment 2, TAI using cooled semen (1 × 109 motile sperm in a 10 mL volume) was performed once at 8 hours after induction (n = 59). Pregnancy rate after TAI with cooled semen was 49.2% (29/59). In experiment 3, jennies were inseminated twice with 10 (n = 23), 5 (n = 31), 3 (n = 32), 2 (n = 82) and 1 (n = 66) straws (more than 50 × 106 motile spermatozoa in each 0.5 mL straw) of frozen semen at 34 and 42 hours after induction. The pregnancy rates were 30.4%, 35.5%, 34.4%, 29.3% and 28.8%, respectively (P > 0.05).
MAIN LIMITATIONS
In the frozen semen trial, 22.5% (68/302) jennies were excluded after failure to ovulate during the appropriate time interval. In addition, there were no control groups for the AI trials.
CONCLUSION
When FD reaches 31-35 mm, a donkey jenny can be inseminated once using cooled semen at 8 hours or twice using frozen semen at 34 and 42 hours after deslorelin treatment. The frozen semen TAI protocol resulted in acceptable pregnancy rates using 1 × 108 motile spermatozoa per cycle.
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10.1111/evj.13412
|
pubmed_279_451
|
The aim was to study the humoral response to Pneumocystis carinii and its diagnostic use in patients with P. carinii pneumonia (PCP). The antibody response was measured by indirect immunofluorescence in AIDS patients versus other immunosuppressed patients with 122 episodes of confirmed PCP. During the early acute stage of the pneumonia, anti-P. carinii antibodies were found in 17% of AIDS and 24% of other immunosuppressed patients. In the second serum sample, antibodies were still found in 17% of the AIDS patients but in as many as 56% of the otherwise immunosuppressed patients. Antibodies were also found in 17% of HIV-positive and 15% of other immunosuppressed control patients, but only in 3% of immunocompetent controls (p < 0.001). Paired sera were available from 55 patients during 58 PCP episodes. Seroconversion or a fourfold rise in titre was detected in only 1/36 (3%) AIDS patients but in 10/22 (45%), (95% c.i.: 24-66%) other immunosuppressed patients (p < 0.001). We conclude that AIDS patients seem to have lost their ability to develop a humoral response to P. carinii during pneumonia, whereas many other immunosuppressed patients do respond. In these patients the serological test against P. carinii was of no diagnostic value in the acute phase of the infection, whereas when analysing paired sera it was a useful complement to the clinical diagnosis.
|
10.3109/00365549409008588
|
pubmed_275_8107
|
BACKGROUND AND OBJECTIVES
Imatinib induces complete cytogenetic responses (CCR) in the majority of patients with chronic myeloid leukemia (CML) in chronic phase (CP). However, a subgroup of patients is refractory at the cytogenetic level. Clinically, it would be advantageous to identify such patients a priori, since they may benefit from more aggressive therapy.
DESIGN AND METHODS
To elucidate mechanisms underlying cytogenetic refractoriness, we used Affymetrix oligonucleotide arrays to determine the transcriptional signature associated with cytogenetic refractoriness in unselected white blood or bone marrow cells from 29 patients with CML in first CP prior to treatment with imatinib. Patients with CCR within 9 months were defined as responders (n = 16) and patients lacking a major cytogenetic response (> 35% Philadelphia-positive metaphases) after 1 year were defined as non-responders (n = 13).
RESULTS
Differences in gene expression between responders and non-responders were subtle. Stringent statistical analysis with multiple comparison adjustments revealed very few differentially expressed genes. Differentially expressed genes could not be confirmed in an independent test set.
INTERPRETATION AND CONCLUSIONS
We conclude that transcriptional profiling of unselected white cells is of limited value for identifying genes consistently associated with cytogenetic refractoriness to imatinib.
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pubmed_275_8107
|
pubmed_691_3820
|
From a series of 129 neonates, well defined with regard to weight and gestational age, the authors established that serum concentration of prealbumin (PA) in an aseptic neonate depends on its gestational age on the first day of extrauterine life (p less than 0.001). Serum concentrations of PA are significantly different in appropriate for gestational age (AGA) and small for gestational age (SGA) neonates; this may be the consequence of insufficient materno-foetal transfers in the majority of SGA children. The study of the ratio maternal PA/neonatal PA at the time of delivery helps to establish the cause of SGA. On and after the 12th day of life, serum concentrations of PA are closely correlated with the usual data of anthropometry (weight, height, skull circumference) (p less than 0.001), when correlation is less close with gestational age at the time of sample taking: it may be used as a marker of the appropriateness of gestational age rather than of maturity. However, the ratio PA/weight varies from one child to another and from one week to another for a same child, giving PA a value different from ordinary anthropometry for the evaluation of the appropriateness of gestational size in neonates.
|
pubmed_691_3820
|
pubmed_1084_4213
|
OBJECTIVE
To determine the best method for anterior internal fixation by comparing the biomechanical characteristics of various anterior fixation methods for vertically unstable sacroiliac dislocations.
METHODS
Eight pelves with Tile C fracture with vertical loading were measured separately. Three- and two-hole anterior double plates were fixed at different angles and compared with sacroiliac screws.
RESULTS
For two-hole anterior double plates, with increasing angle, axial stability increases while lateral stability decreases. For three-hole plates with an angle of 60°, axial stability is clearly better when placed horizontally, while lateral stability shows no obvious differences.
CONCLUSION
For fixing sacroiliac dislocations, three-hole anterior double plates placed at about 60° produce excellent stability, which would be greatly increased if screws were added on the iliac side.
|
10.1111/j.1757-7861.2009.00017.x
|
pubmed_904_20686
|
BACKGROUND
The prognostic role of neutrophil-to-lymphocyte ratio (NLR) has been proposed in head and neck squamous cell carcinoma (HNSCC). However, it is currently unclear which cutoff values of NLR could consistently and independently differentiate HNSCC patients to better and worse prognosis groups.
METHODS
We performed a meta-analysis of prognostic significance of pretreatment NLR values, using data extracted from 24 relevant articles. Main outcomes were overall survival (OS) and disease-free survival (DFS) in HNSCC patients. Pooled hazard ratio (HR) and 95% confidence intervals (95%CI) were calculated using the random effect model for outcomes. Impacts of NLR cutoff values across the studies were assessed with a meta-regression analysis. Results were validated using an independent data set of patients (n = 540).
RESULTS
Pretreatment high NLR values above the cutoff were significantly associated with shorter OS (HR = 1.96, 95%CI = 1.66-2.31) and DFS (HR = 1.90, 95%CI = 1.41-2.54). Of note, NLR cutoffs ranging from 1.9 to 6.0 did not affect HR of OS or DFS in meta-regression analyses. In an independent cohort, any NLR cutoff between 2 and 6 produced significant HR of OS, similarly. Instead of binary cutoffs, three subgroups of NLR (< 2, 2 to 6, and ≥ 6) showed significant differences of OS in survival analyses.
CONCLUSIONS
Meta-analyses confirmed that pretreatment NLR values above the cutoff were associated with shorter survival in HNSCC patients. However, the binary cutoffs of NLR values were variable across studies. Rather, pretreatment NLR values below 2 and above 6 using a three-tier classification (< 2, 2 to 6, and ≥ 6) could consistently imply better and worse prognosis in HNSCC patients, which could be readily translated to clinics.
|
10.1186/s12885-018-4876-6
|
pubmed_82_12912
|
General transcription factor TFIID consists of TATA box-binding protein (TBP) and TBP-associated factors (TAF(II)s), which together play a central role in both positive and negative regulation of transcription. The N-terminal region of the 230 kDa Drosophila TAF(II) (dTAF(II)230) binds directly to TBP and inhibits TBP binding to the TATA box. We report here the solution structure of the complex formed by dTAF(II)230 N-terminal region (residues 11-77) and TBP. dTAF(II)230(11-77) comprises three alpha helices and a beta hairpin, forming a core that occupies the concave DNA-binding surface of TBP. The TBP-binding surface of dTAF(II)230 markedly resembles the minor groove surface of the partially unwound TATA box in the TBP-TATA complex. This protein mimicry of the TATA element surface provides the structural basis of the mechanism by which dTAF(II)230 negatively controls the TATA box-binding activity within the TFIID complex.
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10.1016/s0092-8674(00)81599-8
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pubmed_407_15042
|
BACKGROUND AND PURPOSE
The colon-derived peptide hormone, peptide YY (PYY), regulates colonic motility, secretion and postprandial satiety; but little is known about the influence of endogenous PYY on 5-HT release from colonic mucosa. Tachykinin NK(2) receptor-selective agonist, βAla-NKA-(4-10) induces 5-HT release from guinea pig colonic mucosa via NK(2) receptors on the mucosal layer. The present study was designed to determine the influence of endogenous PYY on 5-HT release from guinea pig colonic mucosa, evoked by the NK(2) receptor agonist, βAla-NKA-(4-10).
EXPERIMENTAL APPROACH
Muscle layer-free mucosal preparations of guinea pig colon were incubated in vitro and the outflow of PYY or 5-HT and its metabolite, 5-HIAA, from these preparations were determined by enzyme immunoassays or HPLC with electrochemical detection respectively.
KEY RESULTS
βAla-NKA-(4-10) produced a tetrodotoxin-resistant sustained increase in the outflow of PYY and 5-HT from the mucosal preparations. The βAla-NKA-(4-10)-evoked 5-HT outflow was partially inhibited by Y(1) receptor antagonist, BIBO3304, and Y(2) receptor antagonist, BIIE0246, but with less potency. Exogenously-applied PYY also produced a sustained increase in the outflow of 5-HT that was inhibited by Y(1) blockade but not Y(2) blockade.
CONCLUSION AND IMPLICATIONS
Our findings support the view that the NK(2) receptor-selective agonist, βAla-NKA-(4-10) produces a long-lasting PYY release from guinea pig colonic mucosa via NK(2) receptors on L cells and βAla-NKA-(4-10)-evoked 5-HT release is in part mediated by endogenously released PYY, acting mainly on Y(1) receptors on EC cells. The PYY-containing L cells appear to play a role in controlling the release of 5-HT from colonic EC cells.
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10.1111/j.1476-5381.2012.02094.x
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pubmed_733_608
|
Educational theory can and should form the basis for teaching in veterinary medicine. Nevertheless, formal training for teachers in veterinary medicine is uncommon and rarely includes study of different educational theories or perspectives, leaving educators to rely on informal or "hidden" educational constructs to guide them in their everyday teaching. Using a modified case-based format, we present critiques of a hypothetical teaching scenario from four different educational viewpoints: behaviorist, cognitive, social learning, and inspired teaching approaches. The importance and utility of formal educational theory in faculty development is discussed.
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10.3138/jvme.29.2.117
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pubmed_1009_12940
|
The formal teaching of medical ethics is a recent addition to the curricula of U.S. medical schools. In this paper, the author examines the evolution and goals of teaching medical ethics, the nature of medical ethics, and integrating such teaching into the curriculum. The author concludes that teachers of medical ethics must impart knowledge that can be applied to the problems medical students face. Because moral considerations are as much a part of medical decisions as technical considerations, this teaching is best done in the context of real cases with which the student is involved and in which ethical considerations can be shown to make a critical difference. A brief description of such a teaching program is included.
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10.1097/00001888-198608000-00005
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pubmed_926_294
|
Widespread flooding in south-eastern Australia in 2010 resulted in a hypoxic (low dissolved oxygen, DO) blackwater (high dissolved carbon) event affecting 1800 kilometres of the Murray-Darling Basin. There was concern that prolonged low DO would result in death of aquatic biota. Australian federal and state governments and local stakeholders collaborated to create refuge areas by releasing water with higher DO from irrigation canals via regulating structures (known as 'irrigation canal escapes') into rivers in the Edward-Wakool system. To determine if these environmental flows resulted in good environmental outcomes in rivers affected by hypoxic blackwater, we evaluated (1) water chemistry data collected before, during and after the intervention, from river reaches upstream and downstream of the three irrigation canal escapes used to deliver the environmental flows, (2) fish assemblage surveys undertaken before and after the blackwater event, and (3) reports of fish kills from fisheries officers and local citizens. The environmental flows had positive outcomes; mean DO increased by 1-2 mg L-1 for at least 40 km downstream of two escapes, and there were fewer days when DO was below the sub-lethal threshold of 4 mg L-1 and the lethal threshold of 2 mg L-1 at which fish are known to become stressed or die, respectively. There were no fish deaths in reaches receiving environmental flows, whereas fish deaths were reported elsewhere throughout the system. This study demonstrates that adaptive management of environmental flows can occur through collaboration and the timely provision of monitoring results and local knowledge.
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10.1007/s00267-017-0941-1
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pubmed_321_9405
|
The aim of this study is to investigate the dynamic gut microbial diversity in weaning swine after administering feed supplemented with probiotic bacteria that specifically inhibit the activity of quorum molecules. Initially, the universal quorum molecule autoinducer-2 (AI-2) bioassay results indicated that AI-2 activity was profoundly inhibited in enterohemorrhagic Escherichia coli (EHEC) O157:H7 in the presence of Lactobacillus acidophilus strain 30SC cell extract, although the growth of EHEC was not affected. Based on plate counting results, bacterial community analysis revealed a specific reduction in coliforms compared to the control, whereas the population of lactobacilli increased in weaning swine in in vivo trials. Supplementation with L. acidophilus strain 30SC did not affect the counts of other communities, such as total aerobes and yeast/mold. In addition, PCR-denaturing gradient gel electrophoresis analysis showed a significant difference in the 16S rRNA gene products after administering L. acidophilus strain 30SC. Selected bands were sequenced, and most of them were identified as uncultured bacterium clones or a Lactobacillus- and Bifidobacterium-specific community. Therefore, our results indicate that quorum-quenching probiotic bacteria can significantly modulate the gut microbiota of swine and these beneficial effects can contribute to the improvement of performance and health in the gastrointestinal tract of weaning pigs.
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10.1111/asj.12954
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pubmed_214_22844
|
Effective information management promotes safe patient care. Lack of human resources can cause failures when managing patient information. The aim of this study was to analyse the nature of reported patient safety incidents and their location in Choo's information management process model phases when the contributing factor of the incidents was related to human resources and the consequence of the incident was related to harm to the organization's corporate image. Data consisted of the information management related patient safety incident reports (n = 475) from 49 health and social care organizations from 2007-2016 in Finland. Deductive analysis and descriptive statistics were used to analyse the data. The results of the study indicated that the shortage of human resources contributed to incomplete documentation, insufficient information sharing between professionals and documenting of information in the wrong place. The majority of the incidents occurred during the information organizing and storage and information distribution phases of the information management process model. Despite the use of electronic health records and electronic patient data, a lack of human resources can lead to breaches in information management processes and harm an organization's corporate image in health and social care contexts.
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10.3233/SHTI220429
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pubmed_355_20995
|
The developmental control of expression of the human epsilon-globin gene appears to be mediated, at least in part, by a transcriptional silencer in the DNA 5' to the cap site of this gene. We have used site-directed mutagenesis and DNA-protein binding assays to define the active motifs of this epsilon-globin silencer. DNase I foot-printing of the silencer region with K562 cell nuclear extracts defined a sequence, which we designate as the epsilon-globin silencer motif or epsilon GSM (epsilon -278 to -258 base pairs (bp)) containing a region (epsilon -270 to -258) with 90% homology to the yeast mating type silencer, ABF-1 (autonomous replicating sequence binding factor one) and which also overlaps at (epsilon -269 to -262) with the human YY1 consensus sequence, an element which mediates transcription repression and activation of viral, mouse, and human genes. The DNase I footprint extended 5' in the silencer region to include an inverted repeat of a six-nucleotide motif (epsilon -267 to -278 bp) which shares 5 of 6 bases with the GATA-1 consensus sequence. In gel mobility shift assays, two specific proteins (A and B) in nuclear extracts from erythroleukemia K562 cells bound to the DNase I-footprinted region. Protein B, associated with epsilon-globin silencer activity in vitro, required an intact epsilon GSM sequence for binding. Mutation of 5 bases within the epsilon GSM in an epsilon-globin promoter-containing fragment extending upstream to 1400 bp in transient transfection assays increased activity by 3.0-fold compared with the native sequence, suggesting that the silencer activity was mediated by the epsilon GSM sequence. We found that protein A could be displaced by a competitor containing the GATA-1 consensus sequence, suggesting that protein A is a GATA-like protein. The region from -267 to -271 within the epsilon GSM and GATA-1 homology region was important for binding of both proteins A and B. These data suggest that protein binding to the epsilon GSM and GATA motifs mediate the negative effect of the silencer on transcription, possibly via direct competition for binding to this DNA region. Recombinant yeast ABF-1 and human YY1 bound to the epsilon GSM. Mutating three bases (epsilon -259, -262, -264) in the epsilon GSM decreased the binding affinity of protein B and recombinant human YY1 but increased the binding affinity of recombinant yeast ABF-1. Furthermore, competitor containing the YY1 consensus sequence competed for protein B binding, whereas competitor containing a perfect yeast ABF-1 consensus sequence did not.(ABSTRACT TRUNCATED AT 400 WORDS)
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pubmed_355_20995
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pubmed_506_10864
|
Prenatal attachment can be described as the parents' emotions, perceptions and behaviors that are related to the fetus. This relationship has been described as the most basic form of the human intimacy and represents the earlier internalized representation of the fetus that both parents typically acquire and elaborate during pregnancy. The quality of the relationship between an infant and his or her parent is an important factor influencing the child's later development, both cognitive and emotional. There is evidence - even though yet unclear - that demographic, perinatal and psychological variables may correlate with attachment. In this perspective, it is essential to recognize the factors influencing attachment of parents towards their fetus and to planning psychosocial interventions in antepartum units or in obstetric clinics, in order to preserve a positive physical and emotional development of the infant and to provide family-centered prenatal care. Particular attention should be paid to women hospitalized for a high-risk pregnancy, since this condition involves a high distress that often results in feelings of anxiety and depression, that can hinder an adequate mother-fetus attachment.
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pubmed_506_10864
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pubmed_403_6
|
Recently, a great deal of research has been started on generating fairly strong photoluminescence from organic molecules without having any conjugated π-system or fluorophore. Discrete chromophores or auxochromophores termed as "subfluorophores" may undergo "space conjugation" via co-operative intramolecular conformation followed by intermolecular aggregation to generate fluorescence or sometimes phosphorescence emission. Polymeric materials are important in this regard as nonconjugated polymers self-assemble/aggregate in a moderately concentrated solution and also in the solid state, producing membranes, films, and so forth with good physical and mechanical properties. Therefore, promoting fluorescence in these commodity polymers is very much useful for sensing, organic light emitting diodes (OLED), and biological applications. In this perspective, we have discussed the aggregation-induced emission from four different types of architectures, for example, (i) dendrimers or hyperbranched polymers, (ii) entrapped polymeric micellar self-assembly, (iii) cluster formation, and (iv) stretching-induced aggregation, begining with the genesis of fluorescence from aggregation of propeller-shaped small organic molecules. The mechanism of induced fluorescence of polymers with subfluorophoric groups is also discussed from the theoretical calculations of the energy bands in the aggregated state. Also, an attempt has been made to highlight some useful applications in the sensing of surfactants, bacteria, cell imaging, drug delivery, gene delivery, OLED, and so forth.
|
10.1021/acsomega.0c04700
|
pubmed_271_21150
|
While the literature is rich with data for the electrical behavior of nanotransistors based on semiconductor nanowires and carbon nanotubes, few data are available for ultrascaled metal interconnects that will be demanded by these devices. Atomic layer deposition (ALD), which uses a sequence of self-limiting surface reactions to achieve high-quality nanolayers, provides an unique opportunity to study the limits of electrical and thermal conduction in metal interconnects. This work measures and interprets the electrical and thermal conductivities of free-standing platinum films of thickness 7.3, 9.8, and 12.1 nm in the temperature range from 50 to 320 K. Conductivity data for the 7.3 nm bridge are reduced by 77.8% (electrical) and 66.3% (thermal) compared to bulk values due to electron scattering at material and grain boundaries. The measurement results indicate that the contribution of phonon conduction is significant in the total thermal conductivity of the ALD films.
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10.1021/nl203548w
|
pubmed_911_1837
|
OBJECTIVE
To identify human spermatogenesis-related proteins.
DESIGN
Prospective study.
SETTING
University research laboratory.
PATIENT(S)
Three fertile men with normal spermatogenesis, 3 azoospermic patients with sloughing and disorganization of germ cells.
INTERVENTION(S)
Testicular tissue samples were collected by biopsy after informed consent.
MAIN OUTCOME MEASURE(S)
The protein expressional profiles of human testes of fertile men and azoospermic patients were compared using a proteomic approach by combining two-dimensional gel electrophoresis analyses and mass spectrometry. Bioinformatic analysis helped to reveal the regulation pathway. Expression of some selected proteins in normal and pathological testes was analyzed by immunohistochemistry.
RESULT(S)
Ten protein spots were identified as expressing differentially between the normal testes and pathological testes with sloughing and disorganization of germ cells; these included the phospholipid hydroperoxide glutathione peroxidase, peroxiredoxin 4 (Prx4), heat shock protein beta-1 (HSP27), and cathepsin D (CTSD). Bioinformatic analysis revealed that many differentially expressed proteins participate in cellular proliferation, apoptosis, and cell death and helped us to focus on a few of them. Immunohistochemical analysis of Prx4, HSP27, and CTSD confirmed the results obtained by proteomic analysis.
CONCLUSION(S)
These 10 proteins may help in elucidating the pathways involved in human spermatogenesis.
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10.1016/j.fertnstert.2007.07.1342
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pubmed_969_7501
|
Intravital microscopic studies of the mesenteric microcirculation have demonstrated that leukocyte adherence and emigration in postcapillary venules are a characteristic feature of tissues exposed to ischemia-reperfusion. The objectives of this study were to determine whether: (1) neutrophils are the predominant leukocytes that adhere and emigrate in postischemic mesenteric venules, and (2) leukocyte adherence and/or emigration are a prerequisite for reperfusion-induced increases in venular permeability. Leukocyte kinetics in cat mesenteric venules (25-35 microns diameter) were evaluated using both intravital microscopy and quantitative morphometry. The intestine and mesentery were exposed to 60 min of ischemia, followed by 60 min reperfusion. Some animals were pretreated with a monoclonal antibody (MoAb IB4) against the leukocyte adhesion glycoprotein, CD11/CD18. Vessels observed by intravital microscopy and adjacent venules of similar diameter were excised and processed for light (LM) and electron microscopy (EM). Horseradish peroxidase (HRP), administered intravenously, was used to assess vascular permeability by EM. By LM, the control (nonischemic) mesentery is sparsely populated by plasma cells, mast cells, and leukocytes; 30-50% of the resident population is neutrophils. Ischemia-reperfusion led to a significant increase in the number of extravascular cells, with neutrophils accounting for greater than 80% of the total cell population. Control and ischemic venules demonstrated no leakage of HRP into the interstitium. However, venules exposed to ischemia and reperfusion demonstrated HRP leakage between endothelial cells and into the surrounding interstitium; neutrophils were adherent to the luminal surface of the endothelium, transmigrating the vessel wall, and in the surrounding interstitium. Animals pretreated with MoAb IB4 presented the same cell profile as nonischemic controls, with no adherent or transmigrating neutrophils. However, some HRP leakage was noted following reperfusion in venules treated with MoAb IB4. The results of this study indicate that: (1) neutrophils are the predominate leukocytes that adhere and emigrate in postischemic venules, and (2) inhibition of leukocyte adhesion does not completely prevent the venular dysfunction associated with ischemia-reperfusion.
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10.1007/BF00917350
|
pubmed_245_1645
|
PURPOSE
Analyze and compare the mean tongue contours and articulatory gestures in the production of the sound [j] in adults and children with typical and atypical speech development. The children with atypical development presented speech sound disorders.
METHODS
The diagnosis was determined by speech assessments. The study sample was composed of 90 individuals divided into three groups: 30 adults with typical speech development aged 19-44 years (AT), 30 children with typical speech development (CT), and 30 children with speech sound disorders, named as atypical in this study, aged four years to eight years and eleven months (CA). Ultrasonography assessment of tongue movements was performed for all groups. Mean tongue contours were compared between three groups in different vocalic contexts following the sound [j]. The maximum elevation of the tongue tip was considered for delimitation of gestures using the Articulate Assistant Advanced (AAA) software and images in sagittal plane/Mode B. The points that intercepted the language curves were analyzed by the statistical tool R. The graphs of tongue contours were obtained adopting a 95% confidence interval. After that, the regions with significant statistical differences (p<0.05) between the CT and CA groups were obtained.
RESULTS
The mean tongue contours demonstrated the gesture for the sound [j] in the comparison between typical and atypical children. For the semivowel [j], there is an articulatory gesture of tongue and dorsum towards the center of the hard palate, with significant differences observed between the children.
CONCLUSION
The results showed differences between the groups of children regarding the ability to refine articulatory gestures.
|
10.1590/2317-1782/20172016214
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pubmed_1065_20565
|
Investigations on platelets are essential to understanding the regulation of hemostasis and thrombosis. Activated platelets undergo dramatic conformational and morphological changes mediated by numerous plasma proteins. AFM techniques can combine high spatial resolution with measurements of the mechanical properties of platelet surfaces. Here, we demonstrate two-dimensional force mapping over a human platelet adsorbed on glass under physiological buffer. The best resolution of platelet membrane elasticity we obtained was at 15.6x15.6 nm(2) pixel(-1). In addition, quantitative information on platelet surface charge density was extracted from individual force curves with the aid of DLVO theory.
|
10.1016/s0927-7765(00)00144-2
|
pubmed_19_15644
|
Suppression of distortion induced by nonlinearity in a dynamical system (such as an analog optical link) is very challenging, particularly for a wide-bandwidth signal. Conventional compensation techniques are computationally intensive, significantly limiting their realization in real-time applications. Here, we propose and demonstrate an efficient digital postprocessing technique to suppress distortions added to a wideband signal by a nonlinear system with memory effect. Experimentally, digital broadband linearization of the photonic time-stretch analog-to-digital converter (TSADC) is demonstrated. In case of TSADC, a dynamic range improvement of >15 dB compared to conventional memory-less correction method is achieved.
|
10.1364/OL.36.001077
|
pubmed_1057_10621
|
OBJECTIVE
Develop and evaluate a framework for quality improvement which will provide a common approach, terminology and greater likelihood of success in achieving demonstrable and sustained improvement.
DESIGN
Descriptive with mixed methods evaluation.
SETTING
Tertiary care academic hospital in Ottawa, Canada.
PARTICIPANTS
Students enrolled in the Quality and Patient Safety Leadership Executive Program at the local university.
METHODS
The quality improvement (QI) framework was developed though comparison and coding of key strengths across four commonly applied quality improvement frameworks. Effectiveness of the framework was evaluated through a satisfaction survey of students who were taught the framework, and independent assessment of student improvement initiatives that followed the QI Framework versus initiatives from a prior year who did not.
MAIN OUTCOME MEASURES
Acceptability and effectiveness of the QI Framework.
RESULTS
All participants found the QI Framework to be useful and easy to follow. Independent evaluation of improvement initiatives following the QI Framework, as compared to those that did not, scored higher (95% CI: 3.0 ± 0.49) than the projects completed without the QI Framework (95% CI: 2.2 ± 0.30), P value < 0.01. Scores were higher for cohort 2017/18 in all criteria except scaling and spreading, in which there was no change (2015/16 95% CI: 1.2 ± 0.24, 2017/18 95% CI: 1.2 ± 0.38).
CONCLUSIONS
The method we have developed is acceptable and helpful to users, and overall application resulted in higher quality initiatives. We believe this method, which we have branded as The Ottawa Hospital Innovation Framework, can be beneficial in healthcare settings for a variety of change initiatives.
|
10.1093/intqhc/mzaa075
|
pubmed_149_19799
|
Fecal microbiota transplant (FMT) is a safe and effective treatment for recurrent or refractory Clostridioides (Clostridium) difficile infection (RCDI) in the short term. However, there are a paucity of data on long-term durability and safety of FMT. The aim of this study is to determine the long-term efficacy and safety of FMT for RCDI. Ninety-four patients underwent FMT via retention enema for RCDI between 2008 and 2012 and completed a follow-up questionnaire 4 to 8 years following the last FMT. Of these, 32 were unreachable and 37 were deceased; 23 of the remaining 25 participants completed the survey. No CDI recurrences were reported in patients treated with FMT; 12 of the 23 participants (52.2%) received at least one course of non-CDI antibiotic(s). Nine participants (40.9%) received probiotics and 4 (17.4%) received both non-CDI antibiotics and probiotics. All 23 participants rated their overall health compared with pre-FMT. Current health was considered "much better" in 17 patients (73.9%); "somewhat better" in 3 patients (13.0%); and "about the same" in 3 patients (13.0%). A total of 11 participants (47.8%) reported an increase in weight of more than 5 kg (kg) post-FMT and 9 participants (39.1%) reported no change in weight (± 5 kg). Four of the 23 participants (17.4%) reported improvement or resolution (undifferentiated colitis, n = 1; Crohn's disease, n = 2; ulcerative colitis, n = 1) of pre-existing gastrointestinal condition following FMT. Eight of 23 participants (34.8%) experienced new medical condition(s) post-FMT. The long-term efficacy (48-96 months) of FMT for RCDI appears to be durable even after non-CDI antibiotic use. Thirty percent had improvement of their pre-existing medical conditions following FMT; 73.9% reported "much better" overall health following FMT.
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10.1007/s10096-019-03602-2
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pubmed_787_820
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RNA-directed DNA methylation (RdDM) is a conserved mechanism for epigenetic silencing of transposons and other repetitive elements. We report that the rdm4 (RNA-directed DNA Methylation4) mutation not only impairs RdDM, but also causes pleiotropic developmental defects in Arabidopsis. Both RNA polymerase II (Pol II)- and Pol V-dependent transcripts are affected in the rdm4 mutant. RDM4 encodes a novel protein that is conserved from yeast to humans and interacts with Pol II and Pol V in plants. Our results suggest that RDM4 functions in epigenetic regulation and plant development by serving as a transcriptional regulator for RNA Pol V and Pol II, respectively.
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10.1101/gad.1851809
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pubmed_1020_22246
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Parthenium hysterophorus L. (Asteraceae) is an invasive alien weed with detrimental effects on agricultural production, biodiversity, human and animal health, threating rural livelihoods in Asia and Africa. The problem emerged recently in the Kenyan Rift Valley, where it began to affect the landholdings of both agro-pastoralists and crop farmers. These vulnerable smallholders depend heavily on natural resources for their livelihoods. In this study, we assessed the severity of parthenium invasion and farmers' management responses using a sample of 530 agro-pastoralists in Baringo County, Kenya, in 2019. We hypothesise that the implementation of existing management strategies depends on the state of parthenium invasion and household socio-economic characteristics. The prevalence and severity of parthenium invasion differed greatly among field plots. To control weeds, farmers resort to either hand weeding, the use of synthetic herbicides, or intensive tillage, sometimes in combination with mulching. A multivariate probit regression model shows that households' characteristics determine the type of control strategies used as well as their complementarity and substitutability. Hand weeding is the most common option, adopted by almost 40% of farmers. The use of agrochemicals or soil-based control strategies appears to be related to knowledge and information characteristics such as access to extension services, membership in organisations and the educational level of household heads. While hand weeding and the use of synthetic herbicides depict significant substitutability, the latter strategy is limited to a few larger farms with market-oriented production. As parthenium invasion continues, policies need to improve farmer awareness and access to knowledge to enable pro-poor and environmentally sustainable control of parthenium on smallholder farms.
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10.1007/s00267-021-01577-5
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pubmed_262_14440
|
UNLABELLED
Although genitourinary complications of Crohn's are well recognized, available information regarding their clinical course and management is sparse especially in the paediatric population. We report a myriad of urological complications in five paediatric cases, our experience from a tertiary paediatric urological and gastroenterological centre. All children with urological complications had severe Crohn's disease which necessitated the use of immuno-suppressants including Infliximab. Three of four children healed and closed their fistulas after treatment, although failed to avoid future surgery, albeit for other reasons.
CONCLUSION
We suggest Infliximab should be considered as a treatment option but in the absence of a common consensus, treatment be tailored to individual cases.
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10.1111/j.1651-2227.2010.01731.x
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pubmed_80_20377
|
BACKGROUND
Although smartphone apps have shown promise for smoking cessation, there is a need to enhance their low engagement rates. This study evaluated the application of the growth mindset theory, which has demonstrated the potential to improve persistence in behavior change in other domains, as a means to improve engagement and cessation.
OBJECTIVE
This study aimed to explore the feasibility, utility, and efficacy of a Web-based growth mindset intervention for addiction when used alongside a smoking cessation app.
METHODS
Daily smokers (N=398) were all recruited on the Web and randomly assigned to receive either a cessation app alone or the app plus a Web-delivered growth mindset intervention. The primary outcome was engagement, that is, the number of log-ins to the smoking cessation app. The secondary outcome was 30-day point prevalence abstinence at 2-month follow-up collected through a Web-based survey.
RESULTS
The 2-month outcome data retention rate was 91.5% (364/398). In addition, 77.9% (310/398) of the participants in the experimental arm viewed at least 1 page of their growth mindset intervention, and 21.1% (84/398) of the group viewed all the growth mindset intervention. The intention-to-treat analysis did not show statistically significant differences between the experimental and comparison arms on log-ins to the app (19.46 vs 21.61; P=.38). The experimental arm had cessation rates, which trended higher than the comparison arm (17% vs 13%; P=.10). The modified intent-to-treat analysis, including only participants who used their assigned intervention at least once (n=115 in experimental group and n=151 in the control group), showed that the experimental arm had a similar number of log-ins (32.31 vs 28.48; P=.55) but significantly higher cessation rates (21% vs 13%; P=.03) than the comparison arm.
CONCLUSIONS
A growth mindset intervention for addiction did not increase engagement rates, although it may increase cessation rates when used alongside a smartphone app for smoking cessation. Future research is required to refine the intervention and assess efficacy with long-term follow-up to evaluate the efficacy of the mindset intervention.
TRIAL REGISTRATION
ClinicalTrials.gov NCT03174730; https://clinicaltrials.gov/ct2/show/NCT03174730.
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10.2196/14602
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pubmed_481_1655
|
In this paper, we present a cDNA sequence encoding a full-length precursor form of a new member (ACLD) of the metalloproteinase-disintegrin-like protein family from the venom glands of Agkistrodon contortrix laticinctus (broad-banded copperhead) snake. Comparison of the deduced amino acid sequence of ACLD with those of other members of the metalloproteinase-disintegrin protein family from both mammalian and snake venom origin suggests that some conserved residues may be involved in processing of the disintegrin domain.
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10.1016/s0167-4838(97)00111-8
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pubmed_64_14416
|
Gossypol is a key anti-nutritional factor which limits the feeding application of cottonseed by-products in animal production. A 2 × 4 factorial in vitro experiment was conducted to determine the effect of gossypol addition levels of 0, 0.25, 0.5, and 0.75 mg/g on ruminal fermentation of a high-forage feed (HF, Chinese wildrye hay/corn meal = 3:2) in comparison with a low-forage feed (LF, Chinese wildrye hay/corn meal = 2:3). After 48 h of incubation, in vitro dry matter disappearance was greater in the LF than the HF group, while the cumulative gas production and asymptotic gas production were greater in the HF than the LF group (p < 0.05). Regardless of whatever ration type was incubated, the increasing gossypol addition did not alter in vitro dry matter disappearance. The asymptotic gas production, cumulative gas production, molar percentage of CO2 and H2 in fermentation gases, and microbial protein in cultural fluids decreased with the increase in the gossypol addition. Conversely, the gossypol addition increased the molar percentage of CH4, ammonia N, and total volatile fatty acid production. More than 95% of the gossypol addition disappeared after 48 h of in vitro incubation. Regardless of whatever ration type was incubated, the real-time PCR analysis showed that the gossypol addition decreased the populations of Fibrobactersuccinogenes, Ruminococcus albus, Butyrivibrio fibrisolvens, Prevotella ruminicola, Selenomonas ruminantium, and fungi but increased Ruminococcus flavefaciens, protozoa, and total bacteria in culture fluids in comparison with the control (p < 0.01). Additionally, the tendency of a smaller population was observed for R. albus, B. fibrisolvens, and fungi with greater inclusion of gossypol, but a greater population was observed for F. succinogenes, R. flavefaciens, S. ruminantium, protozoa, and total bacteria. In summary, the present results suggest that rumen microorganisms indeed presented a high ability to degrade gossypol, but there was an obvious detrimental effect of the gossypol addition on rumen fermentation by decreasing microbial activity when the gossypol inclusion exceeded 0.5 mg/g, and such inhibitory effect was more pronounced in the low-forage than the high-forage group.
|
10.3390/toxics9030051
|
pubmed_292_17969
|
Neoadjuvant treatment in terms of preoperative radiotherapy reduces local recurrence in rectal cancer, but this improvement has little if any impact on overall survival. Currently performed optimal quality-controlled total mesorectal excision (TME) surgery for patients in the trial setting can be associated with very low local recurrence rates of less than 10% whether the patients receive radiotherapy or not. Hence metastatic disease is now the predominant issue. The concept of neoadjuvant chemotherapy (NACT) is a potentially attractive additional or alternative strategy to radiotherapy to deal with metastases. However, randomised phase III trials, evaluating the addition of oxaliplatin at low doses plus preoperative fluoropyrimidine-based chemoradiotherapy (CRT), have in the main failed to show a significant improvement on early pathological response, with the exception of the German CAO/ARO/AIO-04 study. The integration of biologically targeted agents into preoperative CRT has also not fulfilled expectations. The addition of cetuximab appears to achieve relatively low rates of pathological complete responses, and the addition of bevacizumab has raised concerns for excess surgical morbidity. As an alternative to concurrent chemoradiation (which delivers only 5-6 weeks of chemotherapy), potential options include an induction component of 6-12 weeks of NACT prior to radiotherapy or chemoradiation, or the addition of chemotherapy after short-course preoperative radiotherapy (SCPRT) or chemoradiation (defined as consolidation chemotherapy) which utilises the "dead space" of the interval between the end of chemoradiation and surgery, or delivering chemotherapy alone without any radiotherapy.
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10.1016/j.ejcsup.2013.07.032
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pubmed_1081_2100
|
Remote ischemic pre-conditioning (rIPC) has emerged as a potential mechanism to reduce ischemia-reperfusion injury. Clinical data, however, have been mixed, and its physiological basis remains unclear, although it appears to involve release of circulating factor(s) and/or neural pathways. Here, the authors demonstrate that adenosine receptor activation is an important step in initiating human pre-conditioning; that pre-conditioning liberates circulating cardioprotective factor(s); and that exogenous adenosine infusion is able to recapitulate release of this factor. However, blockade of adenosine receptors in ischemic tissue does not block the protection afforded by pre-conditioning. These data have important implications for defining the physiology of human pre-conditioning and its translation to future clinical trials.
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10.1016/j.jacbts.2016.06.002
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pubmed_533_2017
|
Astrocytes are highly complex cells with many emerging putative roles in brain function. Of these, gliotransmission (active information transfer from glia to neurons) has probably the widest implications on our understanding of how the brain works: do astrocytes really contribute to information processing within the neural circuitry? "Positive evidence" for this stems from work of multiple laboratories reporting many examples of modulatory chemical signaling from astrocytes to neurons in the timeframe of hundreds of milliseconds to several minutes. This signaling involves, but is not limited to, Ca2+-dependent vesicular transmitter release, and results in a variety of regulatory effects at synapses in many circuits that are abolished by preventing Ca2+ elevations or blocking exocytosis selectively in astrocytes. In striking contradiction, methodologically advanced studies by a few laboratories produced "negative evidence," triggering a heated debate on the actual existence and properties of gliotransmission. In this context, a skeptics' camp arose, eager to dismiss the whole positive evidence based on a number of assumptions behind the negative data, such as the following: (1) deleting a single Ca2+ release pathway (IP3R2) removes all the sources for Ca2+-dependent gliotransmission; (2) stimulating a transgenically expressed Gq-GPCR (MrgA1) mimics the physiological Ca2+ signaling underlying gliotransmitter release; (3) age-dependent downregulation of an endogenous GPCR (mGluR5) questions gliotransmitter release in adulthood; and (4) failure by transcriptome analysis to detect vGluts or canonical synaptic SNAREs in astrocytes proves inexistence/functional irrelevance of vesicular gliotransmitter release. We here discuss how the above assumptions are likely wrong and oversimplistic. In light of the most recent literature, we argue that gliotransmission is a more complex phenomenon than originally thought, possibly consisting of multiple forms and signaling processes, whose correct study and understanding require more sophisticated tools and finer scientific experiments than done until today. Under this perspective, the opposing camps can be reconciled and the field moved forward. Along the path, a more cautious mindset and an attitude to open discussion and mutual respect between opponent laboratories will be good companions.Dual Perspectives Companion Paper: Multiple Lines of Evidence Indicate That Gliotransmission Does Not Occur under Physiological Conditions, by Todd A. Fiacco and Ken D. McCarthy.
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10.1523/JNEUROSCI.0017-17.2017
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pubmed_14_6503
|
BACKGROUND
The aim of this study was to retrospectively evaluate the short-and long-term effectiveness of different methods of endoscopic treatment for bleeding Dieulafoy's lesions.
METHODS
Patients were allocated into 2 groups according to the hemostatic method applied: (1) injection group (epinephrine and/or ethanolamine oleate), and (2) thermal coagulation group (heat probe), either alone or combined with epinephrine injection. The combination of epinephrine and ethanolamine oleate was used in 5 patients, epinephrine alone in 3, ethanolamine oleate alone in one, heat probe and epinephrine in 8, and heat probe alone in 1 patient.
RESULTS
Dieulafoy's lesions were found in 18 (1%) of 1750 patients with acute nonvariceal upper GI bleeding. Comorbid conditions were present in 5 (28%) patients. Initial hemostasis was achieved endoscopically in 13 patients (72%) and permanent hemostasis in 17 patients (94%). Bleeding recurred in 5 patients (2 with concomitant disease) in the injection group; 3 were successfully retreated by heat probe coagulation and epinephrine injection, 1 with hemoclip application and 1 by surgery. There was no recurrent bleeding in thermal treatment group. Thermal treatment was significantly superior to injection (p = 0.0029).
CONCLUSIONS
Endoscopic thermal coagulation with or without epinephrine injection should be the initial treatment of choice for Dieulafoy's lesions. Mortality is lowest in patients with no significant comorbidity and an unremarkable medical history.
|
10.1067/mge.2002.122652
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pubmed_652_16863
|
We compared the gut prokaryotic communities in wild, organically-, and conventionally reared sea bream (Sparus aurata) individuals. Gut microbial communities were identified using tag pyrosequencing of the 16S rRNA genes. There were distinct prokaryotic communities in the three different fish nutritional treatments, with the bacteria dominating over the Archaea. Most of the Bacteria belonged to the Proteobacteria, Firmicutes, Actinobacteria, and Bacteroidetes. The number of bacterial operational taxonomic units (OTUs) was reduced from the wild to the conventionally reared fish, implying a response of the gut microorganisms to the supplied food and possibly alterations in food assimilation. The dominant bacterial OTU in all examined fish was closely related to the genus Diaphorobacter. This is the first time that a member of the β-Proteobacteria, which dominate in freshwaters, are so important in a marine fish gut. In total the majority of the few Archaea OTUs found, were related to methane metabolism. The inferred physiological roles of the dominant prokaryotes are related to the metabolism of carbohydrates and nitrogenous compounds. This study showed the responsive feature of the sea bream gut prokaryotic communities to their diets and also the differences of the conventional in comparison to the organic and wild sea bream gut microbiota.
|
10.1002/mbo3.202
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pubmed_1021_722
|
To examine whether GTP-binding proteins (G proteins) mediate the ability of neurotensin to lower the affinity of dopamine D2 agonist binding, the modulation by neurotensin in vitro of N-[3H]propylnorapomorphine [( 3H]-NPA) binding was investigated following pretreatment with pertussis toxin and N-ethylmaleimide in rat neostriatal membranes. Preincubation with N-ethylmaleimide (100 microM) markedly inhibited pertussis toxin-induced back-ADP ribosylation of three proteins with apparent molecular masses of 41, 40, and 39 kDa, respectively. This inhibition was prevented by adding dithiothreitol (250 microM) during the preincubation. N-Ethylmaleimide increased the KD (180 +/- 30%) and decreased the Bmax (-31 +/- 9%) of [3H]NPA binding sites but did not affect the binding properties of the selective D2 antagonist [3H]raclopride. N-Ethylmaleimide pretreatment did not affect the neurotensin (3 nM)-induced increase in the KD of [3H]NPA binding sites. Pertussin toxin treatment in vivo and in vitro was similarly ineffective. In conclusion, the present study indicates that neurotensin modulation of D2 agonist binding in neostriatal membranes is not mediated by G proteins.
|
10.1111/j.1471-4159.1991.tb02578.x
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pubmed_560_22432
|
N-Methyl-D-aspartate (NMDA)-gated ion channels are known to play a critical role in motoneuron depolarization, but the molecular mechanisms modulating NMDA activation in the spinal cord are not well understood. This study demonstrates that activated 5HT2C receptors enhance NMDA depolarizations recorded electrophysiologically from motoneurons. Pharmacological studies indicate involvement of Src tyrosine kinase mediates 5HT2C facilitation of NMDA. RT-PCR analysis revealed edited forms of 5HT2C were present in mammalian spinal cord, indicating the availability of G-protein-independent isoforms. Spinal cord neurons treated with the 5HT2C agonist MK 212 showed increased Src(Tyr-416) phosphorylation in a dose-dependent manner thus verifying that Src is activated after treatment. In addition, 5HT2C antagonists and tyrosine kinase inhibitors blocked 5HT2C-mediated Src(Tyr-416) phosphorylation and also enhanced NMDA-induced motoneuron depolarization. Co-immunoprecipitation of synaptosomal fractions showed that GluN2A, 5HT2C receptors, and Src tyrosine kinase form protein associations in synaptosomes. Moreover, immunohistochemical analysis demonstrated GluN2A and 5HT2C receptors co-localize on the processes of spinal neurons. These findings reveal that a distinct multiprotein complex links 5-hydroxytryptamine-activated intracellular signaling events with NMDA-mediated functional activity.
|
10.1074/jbc.M111.277806
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pubmed_509_3402
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Neuropathic pain (NeuP) is challenging to diagnose and manage, despite ongoing improved understanding of the underlying mechanisms. Many patients do not respond satisfactorily to existing treatments. There are no published guidelines for diagnosis or management of NeuP in South Africa. A multidisciplinary expert panel critically reviewed available evidence to provide consensus recommendations for diagnosis and management of NeuP in South Africa. Following accurate diagnosis of NeuP, pregabalin, gabapentin, low-dose tricyclic antidepressants (e.g. amitriptyline) and serotonin norepinephrine reuptake inhibitors (duloxetine and venlafaxine) are all recommended as first-line options for the treatment of peripheral NeuP. If the response is insufficient after 2 - 4 weeks, the recommended next step is to switch to a different class, or combine different classes of agent. Opioids should be reserved for use later in the treatment pathway, if switching drugs and combination therapy fails. For central NeuP, pregabalin or amitriptyline are recommended as first-line agents. Companion treatments (cognitive behavioural therapy and physical therapy) should be administered as part of a multidisciplinary approach. Dorsal root entry zone rhizotomy (DREZ) is not recommended to treat NeuP. Given the large population of HIV/AIDS patients in South Africa, and the paucity of positive efficacy data for its management, research in the form of randomised controlled trials in painful HIV-associated sensory neuropathy (HIV-SN) must be prioritised in this country.
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10.7196/samj.5472
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pubmed_301_7778
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Synapses that rise quickly but have long persistence are shown to have certain computational advantages. They have some unique mathematical properties as well and in some instances can make neurons behave as if they are weakly coupled oscillators. This property allows us to determine their synchronization properties. Furthermore, slowly decaying synapses allow recurrent networks to maintain excitation in the absence of inputs, whereas faster decaying synapses do not. There is an interaction between the synaptic strength and the persistence that allows recurrent networks to fire at low rates if the synapses are sufficiently slow. Waves and localized structures are constructed in spatially extended networks with slowly decaying synapses.
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10.1162/089976603322385054
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pubmed_415_16054
|
PURPOSE
To assess the accuracy of contour deformation and feasibility of dose summation applying deformable image coregistration in adaptive dose painting by numbers (DPBN) for head and neck cancer.
METHODS AND MATERIALS
Data of 12 head-and-neck-cancer patients treated within a Phase I trial on adaptive (18)F-FDG positron emission tomography (PET)-guided DPBN were used. Each patient had two DPBN treatment plans: the initial plan was based on a pretreatment PET/CT scan; the second adapted plan was based on a PET/CT scan acquired after 8 fractions. The median prescription dose to the dose-painted volume was 30 Gy for both DPBN plans. To obtain deformed contours and dose distributions, pretreatment CT was deformed to per-treatment CT using deformable image coregistration. Deformed contours of regions of interest (ROI(def)) were visually inspected and, if necessary, adjusted (ROI(def_ad)) and both compared with manually redrawn ROIs (ROI(m)) using Jaccard (JI) and overlap indices (OI). Dose summation was done on the ROI(m), ROI(def_ad), or their unions with the ROI(def).
RESULTS
Almost all deformed ROIs were adjusted. The largest adjustment was made in patients with substantially regressing tumors: ROI(def) = 11.8 ± 10.9 cm(3) vs. ROI(def_ad) = 5.9 ± 7.8 cm(3) vs. ROI(m) = 7.7 ± 7.2 cm(3) (p = 0.57). The swallowing structures were the most frequently adjusted ROIs with the lowest indices for the upper esophageal sphincter: JI = 0.3 (ROI(def)) and 0.4 (ROI(def_ad)); OI = 0.5 (both ROIs). The mandible needed the least adjustment with the highest indices: JI = 0.8 (both ROIs), OI = 0.9 (ROI(def)), and 1.0 (ROI(def_ad)). Summed doses differed non-significantly. There was a trend of higher doses in the targets and lower doses in the spinal cord when doses were summed on unions.
CONCLUSION
Visual inspection and adjustment were necessary for most ROIs. Fast automatic ROI propagation followed by user-driven adjustment appears to be more efficient than labor-intensive de novo drawing. Dose summation using deformable image coregistration was feasible. Biological uncertainties of dose summation strategies warrant further investigation.
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10.1016/j.ijrobp.2011.07.037
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pubmed_912_18415
|
Saturated hydrocarbon mineral oils in vacuum pumps used in ³H handling facilities often contain significant amounts of ³H (as much as several hundred GBq L⁻¹), and during maintenance the air around an open pump may contain MBq L of volatile and aerosol species. It follows that H-contaminated pump oils pose a workplace hazard-especially if inhaled deposits are retained in the lung. A long-term study (1-y duration) was undertaken to establish the retention time of ³H-pump oil in the lungs of rats. Excretion data was collected to establish the mechanism of oil clearance from the lung. Finally, liver data was collected both to indicate the levels of H in the rat body and to indicate either the presence or absence of the transfer of unmetabolized pump oil within cells from the lungs to liver. Within 1 d following intubation into the trachea, ∼16.5% of the emulsified pump oil had been rapidly mechanically cleared to feces, and 1.1%, present as HTO, or exchangeable H, was excreted in urine. 69.4% of the instilled dose remained in the lungs as the initial alveolar burden. Subsequently, H cleared from the lungs with a retention half-time of of 223 d. The lung burden was mostly cleared to feces-indicating that the pump oil droplets remaining in the lungs were behaving like insoluble particles, but the kinetics of clearance of particles and oil droplets may be different. Overall, it is concluded that inhaled H-pump oil should most likely be regarded as an insoluble particulate (ICRP Inhalation Type S) for the purposes of radiological protection dosimetry, but the possibility of Type M behavior cannot be excluded.
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10.1097/HP.0b013e31827a7d48
|
pubmed_861_17789
|
BACKGROUND
To systematically assess the efficacy and safety between flow diversion and coiling for patients with unruptured intracranial aneurysms.
METHODS
Potential academic articles were identified from Cochrane Library, Medline, PubMed, EMBASE, ScienceDirect, and other databases. The time range we retrieved from was the inception of electronic databases to February 2019. Gray studies were identified from the references of included literature reports. STATA version 11.0 was used to analyze the pooled data.
RESULTS
A total of 11 articles (10 retrospective studies and 1 prospective study) were involved in our study. The overall participants of the coiling group were 611, whereas 576 were in the flow diversion group. Our meta-analysis showed that flow diversion was preferable for unruptured intracranial aneurysms as its lower value of total cost per case (weighted mean difference, 5705.906; 95% confidence interval [CI], [4938.536, 6473236]; P < 0.001), fluoroscopy time per case (weighted mean difference, 25.786; 95% CI, 17.169-34.377; P < 0.001), and retreatment rates (odds ratio [OR], 7.127; 95% CI, [3.525, 14.410]; P < 0.001), at the same time, a higher rate of immediate completed occlusion (OR, 0.390; 95% CI, [0.224, 0.680]; P = 0.001) and follow-up completed occlusion (OR, 0.173; 95% CI, [0.080, 0.375]; P < 0.001) was demonstrated in the flow diversion group. There was no difference on intraoperative complication rates (P = 0.070), procedure-related mortality (P = 0.609) and rupture rates (P = 0.408), modified Rankin Scale (mRS) 0-2 at discharge (P = 0.077), and mRS 0-2 at follow-up (P = 0.484).
CONCLUSIONS
The use of flow diversion for the treatment of unruptured intracranial aneurysms may reduce total cost per case, fluoroscopy time per case, retreatment rates, and increases immediate completed occlusion and follow-up completed occlusion rates without affecting the results of mRS and intraoperative complication.
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10.1016/j.wneu.2019.05.149
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pubmed_667_9812
|
Isolated microperfused rabbit renal proximal tubule S2 segments, if incubated in conventional substrate containing HCO3- Ringer solution, exhibit lower cell membrane potentials (Vb) and elevated intracellular Na+ concentrations ([Na]i) compared to rat tubules in vivo. Assuming that these and other differences reflect insufficient metabolic and/or hormonal stimulation of the cells, we have used microelectrode techniques to test whether improving substrate supply and applying norepinephrine (NE, to compensate for the missing nerve supply) reverts Vb and [Na]i to values observed in vivo. Application of D-glucose (5.5 mmol/l) and additional application of pyruvate, lactate, or L-alanine (each 10 mmol/l), or bathing the tubules in Dulbecco's modified Eagle's tissue culture medium (DMEM) significantly increased Vb and, whenever tested, reduced [Na]i as compared to substrate-free or D-glucose-containing control solution and these effects could be prevented - as tested in the case of pyruvate - by inhibition of the Na/K pump with ouabain. However, high concentrations of acetate, beta-hydroxybutyrate, or L-glutamine had no significant effect. The largest effect was obtained with joint application of DMEM and NE (10 micromol/l) which increased Vb from -42.8 +/- 1.3 mV (SEM) to -55.3 +/- 2.5 mV (n = 11). Interestingly we noticed that under the latter conditions the Vb response to bath application of 1 mmol/l amiloride virtually disappeared, i.e. it changed from a depolarization of +14.6 +/- 1.4 mV (in D-glucose Ringer solution) to +0.6 +/- 0.7 mV (in DMEM plus NE) (n = 8), with some tubules showing even a small hyperpolarization. The latter implies partial restoration of the in vivo behaviour, since in experiments on rat proximal tubules in vivo amiloride regularly hyperpolarized the cells (by -3.4 +/- 0.76 mV, n = 5). Obviously under conventional in vitro conditions an amiloride-inhibitable K+ conductance is activated which is inactive in vivo and also inactivates under improved conditions in vitro. In agreement with observations reported in the subsequent publication our results demonstrate that isolated proximal tubules undergo functional alterations which may be largely prevented by improved metabolic and stimulatory incubation conditions.
|
10.1007/s004240050410
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pubmed_344_17636
|
Jawless vertebrates such as lamprey and hagfish lack T-cell and B-cell receptors; instead, they have unique antigen receptors known as variable lymphocyte receptors (VLRs). VLRs generate diversity by recombining highly diverse leucine-rich repeat modules and are expressed clonally on lymphocyte-like cells (LLCs). Thus far, two types of receptors, VLRA and VLRB, have been identified in lampreys and hagfish. Recent evidence indicates that VLRA and VLRB are expressed on distinct populations of LLCs that resemble T cells and B cells of jawed vertebrates, respectively. Here we identified a third VLR, designated VLRC, in the lamprey. None of the approximately 100 VLRC cDNA clones subjected to sequencing had an identical sequence, indicating that VLRC can generate sufficient diversity to function as antigen receptors. Notably, the C-terminal cap of VLRC exhibits only limited diversity and has important structural differences relative to VLRA and VLRB. Single-cell PCR analysis identified LLCs that rearranged VLRC but not VLRA or VLRB, suggesting the presence of a unique population of LLCs that express only VLRC.
|
10.1073/pnas.1001910107
|
pubmed_612_13065
|
Supplemental activated biochar pellet fertilizers (ABPFs) were evaluated as a method to sequester carbon and reduce greenhouse gas (GHG) emissions, and improve rice production. The evaluated treatments were a control (standard cultivation method, no additives applied), activated rice hull biochar pellets with 40% of N (ARHBP-40%), and activated palm biochar pellets with 40% of N (APBP-40%). The N supplied by the ARHBP-40% and APBP-40% treatments reduced the need for supplemental inorganic nitrogen (N) fertilizer by 60 percent. The ARHBP-40% treatment sequestered as much as 1.23 tonne ha-1 compared to 0.89 tonne ha-1 in the control during the rice-growing season. In terms of greenhouse gas (GHG) emissions, CH4 emissions were not significantly different (p > 0.05) between the control and the ARHBP-40%, while the lowest N2O emissions (0.002 kg ha-1) were observed in the ARHBP-40% during the crop season. Additionally, GHG (CO2-equiv.) emissions from the ARHBP-40% application were reduced by 10 kg ha-1 compared to the control. Plant height in the control was relatively high compared to others, but grain yield was not significantly different among the treatments. The application of the ARHBP-40% can mitigate greenhouse gas emissions and enhance carbon sequestration in crop fields, and ABPFs can increase N use efficiency and contribute to sustainable agriculture.
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10.1016/j.envpol.2021.117457
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pubmed_410_960
|
Immunohistochemistry (IHC) plays an important role in the evaluation of breast pathology specimens to provide both diagnostic and prognostic/therapeutic information. Although most IHCs used in breast pathology can be easily interpreted, pitfalls do exist, especially in some uncommon scenarios. This review intends to focus on the challenging areas such as the interpretation of myoepithelial cell markers in differentiating benign proliferation and in situ carcinoma from invasive carcinoma, lobular cell markers in differentiating lobular from ductal carcinoma, cytokeratin and other markers in diagnosing metaplastic carcinoma, and breast tissue origin markers in diagnosing breast primary carcinoma. The challenges in interpreting prognostic and predictive markers will be also discussed.
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10.1159/000521682
|
pubmed_214_8945
|
SIGNIFICANCE
Full-field optical coherence tomography (FF-OCT) enables en face views of scattering samples at a given depth with subcellular resolution, similar to biopsy without the need of sample slicing or other complex preparation. This noninvasive, high-resolution, three-dimensional (3D) imaging method has the potential to become a powerful tool in biomedical research, clinical applications, and other microscopic detection.
AIM
Our review provides an overview of the disruptive innovations and key technologies to further improve FF-OCT performance, promoting FF-OCT technology in biomedical and other application scenarios.
APPROACH
A comprehensive review of state-of-the-art accomplishments in OCT has been performed. Methods to improve performance of FF-OCT systems are reviewed, including advanced phase-shift approaches for imaging speed improvement, methods of denoising, artifact reduction, and aberration correction for imaging quality optimization, innovations for imaging flux expansion (field-of-view enlargement and imaging-depth-limit extension), new implementations for multimodality systems, and deep learning enhanced FF-OCT for information mining, etc. Finally, we summarize the application status and prospects of FF-OCT in the fields of biomedicine, materials science, security, and identification.
RESULTS
The most worth-expecting FF-OCT innovations include combining the technique of spatial modulation of optical field and computational optical imaging technology to obtain greater penetration depth, as well as exploiting endogenous contrast for functional imaging, e.g., dynamic FF-OCT, which enables noninvasive visualization of tissue dynamic properties or intracellular motility. Different dynamic imaging algorithms are compared using the same OCT data of the colorectal cancer organoid, which helps to understand the disadvantages and advantages of each. In addition, deep learning enhanced FF-OCT provides more valuable characteristic information, which is of great significance for auxiliary diagnosis and organoid detection.
CONCLUSIONS
FF-OCT has not been completely exploited and has substantial growth potential. By elaborating the key technologies, performance optimization methods, and application status of FF-OCT, we expect to accelerate the development of FF-OCT in both academic and industry fields. This renewed perspective on FF-OCT may also serve as a road map for future development of invasive 3D super-resolution imaging techniques to solve the problems of microscopic visualization detection.
|
10.1117/1.JBO.27.5.050901
|
pubmed_902_14364
|
This work presents a retrospective analysis of long-term trends in loading of forms of nitrogen (N) from the Metropolitan Syracuse Wastewater Treatment Plant (Metro), N concentrations in the receiving urban lake (Onondaga Lake, New York), and related water quality status for the period from 1972 to 2007. The history of the evolution of treatment and discharge at Metro, as it affected N loading, is reviewed and forms the basis for identification of five regimes during which unifying conditions of loading and in-lake conditions prevailed. Changes in industrial waste inputs have complicated the effects of upgrades in treatment at Metro from primary (until 1978) to advanced (starting in 2004). Current N loading from Metro is approximately 35% lower than the peak levels observed in the late 1980s to late 1990s, but the areal rate to the lake remains extremely high (approximately 97 g/m(2).y), representing approximately 75% of the overall N load. Implementation of year-round nitrification treatment has resulted in transformation of the composition of the N load from Metro from ammonia (T-NH3) to nitrate (NO3(-)) dominance. High N concentrations have prevailed in the upper waters of the lake throughout the study period with averages of total N ranging from 2.6 to 4.3 mg/L for the five regimes. Total N levels and partitioning among the forms in the lake generally have tracked Metro loading conditions for the five regimes. The effects of Metro loading on seasonal in-lake patterns are demonstrated to be modified by both hydrologic inputs from tributaries and in-lake operation of biochemical processes. Resolution of these effects is supported by application of both empirical and dynamic mass balance models. Water quality problems related to high concentrations of forms of N are documented, including (1) augmentation of dissolved oxygen depletion during fall mixing from in-lake nitrification events, enabled by high T-NH3 levels; (2) violations of ammonia toxicity limits; and (3) violations of nitrite toxicity standards. These problems were either greatly ameliorated or eliminated by Metro's most recent treatment upgrades. Prevailing conditions are considered in a management context, including (1) likelihood of exceedances of toxicity limits in the future and (2) potential role of elevated nitrate levels in preventing mobilization of methyl mercury from the lake's sediments.
|
10.2175/106143009x407384
|
pubmed_789_18310
|
An analysis is presented of the behavior of muons in the low-temperature state in spin ice. It is shown in detail how the behavior observed in some previous muon experiments on spin ice in a weak transverse field may result from the macroscopic stray field of magnetized spin ice. A model is presented which allows these macroscopic field effects to be simulated and the results agree with experiment. The persistent spin dynamics at low temperature originate from the sample and could be a muon-induced implantation effect that is operative in out-of-equilibrium systems with long relaxation times.
|
10.1103/PhysRevLett.108.147601
|
pubmed_496_5916
|
UNLABELLED
Hepatic hydatid disease is an uncommon surgical emergency. We report an observation and its diagnosis and treatment.
CASE REPORT
An algerian child consulted in emergency unit for appendicitis syndrome. The surgeon discovered an opened hydatid liver cyst. He performed a cystectomy associated with post-operative chemotherapy.
DISCUSSION
Hepatic hydatid disease is frequent in endemic zone. If not complicated, it is often revealed by hepatomegaly. The diagnosis is radiological and mainly serological. Management is medicosurgical.
CONCLUSION
Prognosis depends on early surgical management. Long-time serological and echographic follow-up is required.
|
10.1016/j.arcped.2005.06.026
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pubmed_644_21520
|
The highly organized structure of the Golgi apparatus becomes compromised during mitosis. The Golgi cisternae unstack and form vesicles, which are then partitioned into the daughter cells. Here, we analyzed the fate of the SREBP and ATF6, two key transcription factors of sterol biogenesis and the unfolded protein response, respectively. During interphase the precursors of both transcription factors are silent in the ER, but upon activation signals SREBP and ATF6 move to the Golgi where they are activated by proteolytic cleavage by S1P and S2P. Since the spatial separation between the ER and the Golgi is the basis for the regulated activation, we investigated whether mitosis is sufficient to trigger activation. We found that the strict compartmentalization of the ER and the Golgi is maintained during mitosis to inhibit the activation of SREBP and ATF6.
|
10.4161/cc.7.14.6327
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pubmed_536_2354
|
New approaches for control of the dengue vector Aedes aegypti (L.) are being developed, including the potential introduction of life-shortening symbiont bacteria into field populations and the release of transgenic strains with reduced vector competency. With these new approaches comes the need for rapid estimations of existing field population size. Here, we describe the use of simulation modeling with container-inhabiting mosquito simulation (CIMSiM) for estimation of Ae. aegypti pupal crop size in north Queensland, Australia. CIMSiM was calibrated for local conditions by deploying "sentinel key containers" (tire, 2-liter plastic bucket, 0.6-liter pot plant base, and tarpaulin indentation) in which water flux and pupal productivity were studied for 72 d. Iterative adjustment of CIMSiM parameters was used to fit model outputs to match that of sentinel key containers. This calibrated model was then used in a blind field validation, in which breeding container and local meteorological data were used to populate CIMSiM, and model outputs were compared with a field pupal survey. Actual pupae per ha during two 10-d periods in 2007 fell within 95% confidence intervals of simulated pupal crop estimates made by 10 replicate simulations in CIMSiM, thus providing a successful field validation. Although the stochasticity of the field environment can never be wholly simulated, CIMSiM can provide field-validated estimates of pupal crop in a timely manner by using simple container surveys.
|
10.1603/0022-2585(2008)45[1173:reoaap]2.0.co;2
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pubmed_94_602
|
As a small fruit rich in anthocyanins, blueberry (Vaccinium corymbosum × angustifolium) has become a focus of research in recent years for identifying genes related to anthocyanin transport and stress resistance mechanisms based on transcriptome sequencing. However, the lack of validated, stably expressed reference genes greatly limits the functional study of blueberry genes. Therefore, in this study, we selected 14 candidate reference genes from a blueberry transcriptome database and used three algorithms (geNorm, NormFinder and BestKeeper) to evaluate the expression stability of these genes in various organs at different fruit developmental stages under five abiotic stress conditions. EF1α, EIF and TBP were observed to be the most stable and were thus chosen as reference genes for quantitative real-time PCR. Measurement of the relative expression of VcMATE1 (European Nucleotide Archive accession number KF875433) in blueberry further verified the reliability of these reference genes, which may have great utility for determining the accuracy of gene expression analyses in future research on blueberry.
|
10.1002/2211-5463.12903
|
pubmed_987_6148
|
This review of the familial tumor syndromes involving the endocrine organs is focused on discussing the main updates on the upcoming fifth edition of the WHO Classification of Endocrine and Neuroendocrine Tumors. This review emphasizes updates on histopathological and molecular genetics aspects of the most important syndromes involving the endocrine organs. We describe the newly defined Familial Cancer Syndromes as MAFA-related, MEN4, and MEN5 as well as the newly reported pathological findings in DICER1 syndrome. We also describe the updates done at the new WHO on the syndromic and non-syndromic familial thyroid diseases. We emphasize the problem of diagnostic criteria, mention the new genes that are possibly involved in this group, and at the same time, touching upon the role of some immunohistochemical studies that could support the diagnosis of some of these conditions. As pathologists play an important role in identifying tumors within a familial cancer syndrome, we highlight the most important clues for raising the suspicious of a syndrome. Finally, we highlight the challenges in defining these entities as well as determining their clinical outcome in comparison with sporadic tumors. Instead of the usual subject review, we present the highlights of the updates on familial cancer syndromes by answering select questions relevant to practicing pathologists.
|
10.1007/s12022-022-09705-5
|
pubmed_877_23954
|
PURPOSE OF REVIEW
To describe the pathology, impact of comorbidities, functional limitations, symptoms, and quality of life (QOL) related to treatment of acute myeloid leukemia (AML) in older adults.
RECENT FINDINGS
AML is a rare aggressive hematologic disease that occurs most often in older adults. The prognosis for older patients with AML is markedly worse due to genetic mutations and patient characteristics such as comorbidities and functional limitations. Patient characteristics may influence treatment decisions, as well as impact symptoms, functional ability, health-related outcomes and (QOL).
SUMMARY
As the population continues to age, the number of people diagnosed with AML is expected to increase. Better management of comorbidities is imperative to improving QOL and other treatment related outcomes. Prospective, longitudinal and multi-site studies are warranted to further understand the interaction between these characteristics on symptoms, outcomes and QOL.
|
10.1007/s13670-017-0227-8
|
pubmed_701_7694
|
Fifteen patients with the incomplete form of congenital stationary night blindness (iCSNB) were reviewed to better characterize their electroretinographic (ERG) findings in view of differential diagnosis with other retinal conditions also presenting with negative bright-flash ERG responses. In all 15 patients, in dark-adapted conditions, the bright-flash ERG response had a normal a-wave followed by a subnormal b-wave. Oscillatory potentials (OPs) observed on the ascending limb of the b-wave, although delayed in implicit time, were of large amplitude. The response to a long-wavelength stimulus showed cone-related components and some well-delineated OPs. On the other hand, the photopically elicited cone responses were strongly abnormal, with a subnormal a-wave followed by a barely recordable b-wave. No OPs could be elicited under photopic conditions. The cone related components and the OP characteristics clearly distinguish iCSNB from the complete form of CSNB and other retinal conditions presenting with minimal fundus abnormalities but with negative bright-flash ERG responses, such as found in Duchenne muscular dystrophy and Aland Island eye disease. The severely abnormal post-synaptic components in the photopic recordings contrast with the well-differentiated cone activity evoked in scotopic conditions. We propose a cone system that does not respond optimally under the normal operating range (photopic) but rather under mesopic or scotopic conditions. In spite of the severe cone-ERG deficits, visual acuity was only slightly reduced. We propose that the defect, which interferes marginally with the neuronal flow of information, lies in the structures responsible for the building of the b-wave.
|
10.1016/0042-6989(95)00006-l
|
pubmed_302_10160
|
BACKGROUND
Patients with type 2 diabetes mellitus are usually treated with oral antidiabetic agents but it is still not known whether these drugs have antioxidant effects in humans.
METHODS
We studied 60 patients with type 2 diabetes mellitus, divided into three groups on the basis of hypoglycaemic treatment (Group A: metformin, Group B: glibenclamide, Group C: diet). All patients were followed for at least 1 year. The three subgroups had similar clinical characteristics. Twenty healthy subjects, of comparable sex and age, were enrolled as controls. In each subject, platelet production of superoxide anion (O(2)(-)) elicited by collagen, was determined by lucigenin assay.
RESULTS
Patients with diabetes had higher platelet O(2)(-) production than controls; no correlation was observed between blood glucose and platelet O(2)(-) production. Group A patients had platelet O(2)(-) production similar to that of healthy subjects but lower than Group B and Group C patients.
CONCLUSION
The present findings suggest an in vivo antioxidant activity of metformin and warrant prospective studies to further explore this hypothesis.
|
10.1002/dmrr.282
|
pubmed_32_21567
|
Acute abdominal pain is one of the most widely studied applications of computer-aided diagnosis. The usual approach is to apply Bayes' theorem with the assumption of conditional independence ("independence Bayes"). We compared various approaches to designing diagnostic programs for abdominal pain of suspected gynaecological origin. The methods range from statistical to knowledge-based. All programs were evaluated using a database of 1,270 cases collected retrospectively. Our results suggest that in this application no significant improvement in accuracy can be made by taking interactions into account, either by statistical or by knowledge-based means; independence Bayes is near-optimal. As far as accuracy is concerned, there appears to be little point in pursuing knowledge-based approaches. However, the "nearest neighbours" method using a new metric appears to be at least as accurate as independence Bayes. We argue that the nearest neighbours method is more suitable than independence Bayes for clinical use because of greater accountability.
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pubmed_32_21567
|
pubmed_401_9808
|
The complexity of biaxial tests and analysis of their results makes it difficult to study the interlaminar shear properties of fibre-reinforced composites, particularly under through-thickness compression, which occurs in thick-walled composite elements. The improvements in experimental methods to study the features of the nonlinear behaviour of composites under biaxial loading is now an important and relevant task in the development aircraft structural elements made of carbon fibre-reinforced polymers. This study aimed to develop a new experimental approach for the reliable determination of the interlaminar shear properties of laminates under through-thickness compression using a standard testing machine. An appropriate V-notched specimen was developed based on the configuration of well-known Iosipescu and butterfly-shaped specimens. The approach is demonstrated using woven carbon/epoxy laminates. Both the preliminary assessment of the stress fields under combined compression/shear loading and the analysis of fracture mechanisms were performed with finite-element modelling in a three-dimensional formulation. The digital image correlation (DIC) method was used to obtain experimental, full-field deformations of the specimens and to estimate the uniformity of the strain distribution in the gauge section. The stress-strain curves were obtained under biaxial loading, and the corresponding features of the composite failure behaviour were analysed in detail. It was found that the maximum compression strain on the stress-strain curves, in some cases, corresponded to the discontinuity in the composite structure. In these cases, the disproportionate changes in through-thickness strains in the gauge section of the specimens were recorded at the maximum load. With the increase in through-thickness compression stresses, the difference between the shear strength values, determined by the maximum load and the maximum compressive strain, increased by up to 20%. It was shown that the assessment of the composite strength at maximum load at the design stage significantly increased the risk of premature failure of the composite elements during exploitation.
|
10.3390/polym14132575
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pubmed_212_2156
|
A report of a patient with a Bartholin gland cancer is presented. Although this desease is rare, it should be born in mind when treating common Bartholin gland enlargements. Bartholin gland carcinomas are misdiagnosed as common cysts or abscesses in half of the cases, leading to considerable delay in diagnosis. From a review of the literature concerning this disease some recommendations are made.
|
10.3109/00016348009160092
|
pubmed_126_2033
|
To assess the neurophysiologic properties and molecular mechanisms of the bladder acellular matrix graft (BAMG), we performed cystometric and neurophysiologic studies in male Sprague-Dawley rats (n = 46) at varying intervals. The animals were assigned to 3 groups: 1) normal, 2) partial cystectomy (>50%), and 3) partial cystectomy (>50%) and grafting with a BAMG of equal size. Additionally, matrix-grafted and host bladders were processed for analysis of mRNA expression of transforming growth factor (TGF)-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 by reverse transcriptase polymerase chain reaction. Matrix-grafted bladders showed a significantly higher bladder capacity at 3 and 6 weeks and 4 months than those with partial cystectomy alone, and a significantly higher bladder capacity at 4 months than in normal controls (P < or = 0.01). Residual urine volume was significantly increased at 4 months. Electrostimulation of the pelvic nerve provoked generalized bladder contractions, a response that was reduced by atropine and hexamethonium. Variable induction of TGF-alpha, TGF-beta1, TGF-beta2, and TGF-beta3 gene transcription was evident in the BAMG, with prominent mRNA expression of TGF-alpha and TGF-beta1 6 months after surgery. These cystometric results and detrusor responses to stimulation provide further evidence that graft components do not interfere with host components. Matrix-grafted rat bladders generate, although not increased over time, adequate intravesical pressure responses to produce sustained voiding. Gene expression of different growth factors may be significant in understanding their role in the development and differentiation of the BAMG for partial bladder replacement.
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10.1002/(sici)1520-6777(1998)17:1<37::aid-nau7>3.0.co;2-e
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pubmed_466_10404
|
The purpose of this study was to subject groups of newborn male and female Sprague-Dawley rats each to a specific 10% simulated increase in body weight, to a maximum of a doubling of body weight, to study the effects of quantified, increased, intermittent, compressive forces on limb bone growth. Chronic centrifugation was employed. After 90 days of centrifugation the rats were sacrificed. The humerus, radius, ulna, femur, and tibia were removed from each animal, cleared of all soft tissues, measured and weighed. Tukey's Studentized multiple range test was performed to identify aggregations (sets) of force groups between which there are significant differences. The data suggest that newborn male and female rats subjected to simulated increases in body weight, within the range used for this study, undergo enhanced general body growth and limb bone growth.
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10.1159/000145934
|
pubmed_1091_20023
|
Trade-offs are central to the cannabis policy debate. Prohibition and strict regulation may help reduce the physical, mental and social harms of cannabis consumption, but at the cost of increasing the harms from illegal markets and reducing consumption benefits. An economic model clarifies how these costs and benefits relate to policy and connects them to observable prices and tax-levels given the assumptions of the analysis. These model- based arguments are related to the ongoing academic policy debate. While some arguments from this literature modify the interpretation of the model (e.g., due to dependence, cognitive biases and market structure), the literature often fails to appropriately account for the magnitude of the policy costs and benefits identified. Taking various caveats into account, the framework indicates that a strict regulation would likely be preferable to prohibition given current estimates of excess harms (externalities and internalities) from cannabis use. While cannabis prohibition appears difficult to justify within an economic regulatory framework, risks from industry influence, policy ratchet effects, and human "decision-making flaws" speak to the need for caution and strong regulation when implementing legal regimes.
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10.1016/j.drugpo.2018.03.024
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pubmed_698_15547
|
The emergency department (ED) nurse plays a major role both in recognizing and in the management of the patients affected by alcohol related problems, such-as acute alcohol intoxication (AAI), alcohol withdrawal (AW), traumatic or spontaneous illness due to acute or chronic effects of alcohol abuse. Here are described both the clinical problems and the diagnostic instruments that nurse can use in ED to increase diagnostic sensibility. Furthermore both clinical features of AAI in relation with blood alcohol concentration (BAC), diagnostic criteria and test to evaluate AW severity are reported in this review. Even diagnostic instruments to identify alcohol abuse also in trauma are reported: the alcohol breath test, BAC and laboratory test. Even the Alcohol Use Disorders Identification Test (A.U.D.I.T.) questionnaire is reported to recognize the alcohol abuser. In conclusion acquiring a specific training, nurse can play a major role in the complex intervention net of alcoholics rehabilitation.
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pubmed_698_15547
|
pubmed_83_9577
|
Prior studies have suggested that for leukemia patients with high-risk features, haplo-identical-hematopoietic stem cell transplantation (HID-HSCT) has a stronger anti-leukemia effect compared with HSCT using an identical sibling donor (ISD-HSCT). However, it is unclear whether an HID-HSC transplant also augments the graft-versus-leukemia (GVL) effect among refractory/relapsed (R/R) acute myeloid leukemia (AML) patients who are not in remission (NR). We conducted a retrospective analysis of 124 R/R AML patients with NR status who underwent HID-HSCT between April 2012 and December 2016 and compared these to 27 R/R AML patients who underwent an ISD-HSCT within the same timeframe. Among all of the patients, 68 (45.0%) had primary induction failure (PIF) and 83 (54.9%) were relapsed and had failed to respond to at least one cycle of salvage combination chemotherapy. Myeloablative conditioning regimens were administered to all patients. Here, we present a retrospective multivariate analysis of pre-transplantation risk factors and characteristics of all 151 patients and developed a predictive scoring system to predict patient survival. The median period of follow-up was 46 months for all patients. The HID cohort had a higher 5-year overall survival (OS) compared with the ISD cohort (48.6% ± 4.6% vs 25.9% ± 8.4, respectively; P = 0.017) and higher LFS (leukemia-free survival) (41.6% ± 7.5% vs 25.9% ± 8.4%, respectively; P = 0.019). There was no difference in the 5-year cumulative incidence of non-relapse mortality (NRM) (18.0% ± 3.8% and 34.9% ± 12.6%, respectively; P = 0.212) between the two group. However, the 5-year cumulative incidence of relapse (CIRs) was lower in the HID group compared with the ISD group (55.4% ± 8.9% vs 67.3% ± 9.9%, respectively; P = 0.021). Multivariate analysis showed three risk factors associated with OS and LFS: (1) ISD-HSCT, (2) use of a standardized conditioning regimen, and (3) less than 50% proportional reduction of blast cells in the bone marrow (BM). Based on these three risk factors, we developed a predictive scoring system for R/R AML patients undergoing HSCT. Patients who had a predictive score of 0 and 1 had a 66.6% ± 4.5% and 44.1% ± 3.6% OS rate at 5 years, respectively. Patients with a score ≥ 2 had only a 4.4 ± 0.2% OS rate at 5 years. An HID-HSCT had a better anti-leukemia effect among R/R AML patients with an NR status compared with an ISD-HSCT. We also identified pre-transplantation risk factors to delineate subgroups that could derive maximal benefit from HSCT.
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10.1007/s00277-020-04283-0
|
pubmed_390_7679
|
Natural and synthetic glycosphingolipids containing neutral sugars have been analyzed by positive and negative ion fast atom bombardment mass spectrometry. Basic structural characterization including saccharide size and sequence and ceramide composition is possible on the basis of the fragment ions observed. The degree of fragmentation could be increased by using higher sample concentrations and lower fast atom beam energies. Commercially available synthetic compounds that had been presumed to be pure were shown to contain homologous fatty acids. Mixtures of glycosphingolipids such as those obtained from Gaucher's spleen and from human erythrocytes can be characterized and quantitated.
|
10.1021/bi00319a008
|
pubmed_1071_20270
|
We observe a resonant transition in the microwave absorption of thin thermally deposited Au nanoparticle films near the geometrical percolation transition pc where the films exhibit a 'fractal' heterogeneous geometry. Absorption of incident microwave radiation increases sharply near pc, consistent with effective medium theory predictions. Both the theory and our experiments indicate that the hierarchical structure of these films makes their absorption insensitive to the microwave radiation wavelength λ, so that this singular absorption of microwave radiation is observed over a broad frequency range between 100 MHz and 20 GHz. The interaction of electromagnetic radiation with randomly distributed conductive scattering particles gives rise to localized resonant modes, and our measurements indicate that this adsorption process is significantly enhanced for microwaves in comparison to ordinary light. In particular, above the percolation transition a portion of the injected microwave power is stored within the film until dissipated. Finally, we find that the measured surface conductivity can be quantitatively described at all Au concentrations by generalized effective medium theory, where the fitted conductivity percolation exponents and pc itself are consistent with known two-dimensional estimates. Our results demonstrate that microwave measurements provide a powerful means of remotely measuring the electromagnetic properties of highly heterogeneous conducting films, enabling purposeful engineering of the electromagnetic properties of thin films in the microwave frequency range through fabrication of 'disordered' films of conducting particles such as metal nanoparticles or carbon nanotubes.
|
10.1021/la401753y
|
pubmed_266_13313
|
OBJECTIVE
The goals were twofold: To estimate the depression and anxiety levels among caregivers of patients with eating disorders (ED) in China during the COVID-19 pandemic when compared with a control group, and to assess whether an online education program was effective in decreasing the anxiety and depression of the caregivers of patients with ED, and associated factors.
METHOD
Caregivers of patients with ED (n = 254) and a comparison group of non-ED caregivers (N = 254) were recruited at baseline. Additionally, caregivers of patients with ED were invited into a free 4-week online education program, with an additional online group as support. Depression and anxiety levels were assessed at baseline and after the intervention.
RESULTS
Caregivers of patients with ED showed significantly higher levels of depression and anxiety than the comparison group of non-ED caregivers. The online education program showed no significant effect on decreasing depression and anxiety levels of caregivers of patients with ED overall. Caregivers who had older loved ones and not living with them were more likely to decrease their depression levels. Caregivers of patients with longer illness duration were less likely to decrease their anxiety levels.
DISCUSSION
These results showed that caregivers of ED patients suffered more serious psychological distress during the pandemic. A more structured and intensive online intervention with a limited number of participants might be required to address caregivers' distress in post-COVID-19 China.
|
10.1002/erv.2783
|
pubmed_618_8802
|
In this study we mixed low concentrations of graphene oxide (GO) with microgel (MG) particles and formed composite doubly cross-linked microgels (DX MG/GO) gels. The MG particles comprised poly(ethyl acrylate-co-methacrylic acid-co-1,4-butanediol diacrylate) with pendant glycidyl methacrylate units. The MG/GO mixed dispersions formed physical gels of singly cross-linked MGs (termed SX MG/GO), which were subsequently heated to produce DX MG/GO gels by free-radical reaction. The influence of the GO concentration on the mechanical properties of the SX MG/GO and DX MG/GO gels was investigated using dynamic rheology and static compression measurements. The SX MG/GO physical gels were injectable and moldable. The moduli for the DX MG/GO gels increased by a factor of 4-6 when only ca. 1.0 wt % of GO was included. The isostrain model was used to describe the variation of modulus with DX MG/GO composition. Inclusion of GO dramatically altered the stress dissipation and yielding mechanisms for the gels. GO acted as a high surface area, high modulus filler and played an increasing role in load distribution as the GO concentration increased. It is proposed that MG domains were dispersed within a percolated GO network. Comparison of the modulus data with those published for GO-free DX MGs showed that inclusion of GO provided an unprecedented rate of modulus increase with network volume fraction for this family of colloid gels. Furthermore, the DX MG/GO gels were biocompatible and the results imply that there may be future applications of these new systems as injectable load supporting gels for soft tissue repair.
|
10.1021/la5032015
|
pubmed_1020_19205
|
Both disturbed sleep and lack of exercise can disrupt metabolism in pregnancy. Accelerometery was used to objectively assess movement during waking (physical activity) and movement during sleeping (sleep disturbance) periods and evaluated relationships with continuous blood glucose variation during pregnancy. Data was analysed prospectively. 15-women without pre-existing diabetes mellitus wore continuous glucose monitors and triaxial accelerometers from February through June 2018 in Sweden. The relationships between physical activity and sleep disturbance with blood glucose rate of change were assessed. An interaction term was fitted to determine difference in the relationship between movement and glucose variation, conditional on waking/sleeping. Total movement was inversely related to glucose rate of change (p < 0.001, 95% CI (- 0.037, - 0.026)). Stratified analyses showed total physical activity was inversely related to glucose rate of change (p < 0.001, 95% CI (- 0.040, - 0.028)), whereas sleep disturbance was not related to glucose rate of change (p = 0.07, 95% CI (< - 0.001, 0.013)). The interaction term was positively related to glucose rate of change (p < 0.001, 95% CI (0.029, 0.047)). This study provides temporal evidence of a relationship between total movement and glycemic control in pregnancy, which is conditional on time of day. Movement is beneficially related with glycemic control while awake, but not during sleep.
|
10.1038/s41598-021-03257-0
|
pubmed_963_9175
|
Thrombin activatable fibrinolysis inhibitor (TAFI) is a carboxypeptidase B-like proenzyme, that after activation down regulates fibrinolysis. TAFI is activated by thrombin in the presence of the cofactor thrombomodulin (TM). By stimulation of TAFI activation TM down regulates fibrinolysis, however TM is also a cofactor in the activation of protein C. Activated protein C (APC) can up regulate fibrinolysis by limitine the activation of TAFI via the attenuation of thrombin production. We studied these counteracting fibrinolytic properties of TM in plasma by measuring the activation of TAFI during tissue factor induced coagulation. TAFI activation was stimulated at low concentrations of TM but decreased at higher concentrations of TM. Similarly, the clot lysis times increased at low concentrations of TM but decreased at higher concentrations of TM. The reduction of TAFI activation at high TM concentrations was found to be dependent on a functional protein C pathway. The concentration of TM is therefore an important factor in the regulation of TAFI activation and in the regulation of fibrinolysis. High concentrations of TM result in up regulation of fibrinolysis, whereas low concentrations of TM have a down regulatory effect on fibrinolysis. These results suggest that fibrinolysis might be differentially regulated by TM in different parts of the body depending on the local TM concentration in the vasculature.
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pubmed_963_9175
|
pubmed_560_2270
|
INTRODUCTION
In France, more than 4 million people benefit from the universal complementary health insurance coverage (CMUc). Approved by many doctors, CMUc remains discussed by a part of the medical profession. What is the perception of general medical practice students regarding patients receiving CMUc and what are the determinants influencing it?
METHODS
A cross-sectional study was carried out by providing final year interns in general medicine with a self-administered questionnaire. The primary assessment criterion was the perception of the interns regarding patients receiving CMUc, classified into three categories: positive, negative or neutral. After a description of the sample, statistical analysis included multivariate logistic polytomous regression models developed with the SAS 9.1 software.
RESULTS
A total of 57.1% (200) of the third year interns of Île-de-France in 2009-2010 responded to the questionnaire. Forty-two percent of students had a "neutral" perception of the patients receiving CMUc, 41% a "positive" one and 17% a "negative" one. Influencing factors were: the perception of the first encounter, the gender of the intern, the type of practice that he intended to take up and the experience he had of patients receiving CMUc. In multivariate analysis, a positive impression of the first encounter significantly increased the probability of having a positive future perception compared to a negative impression of the first encounter (OR=16,19 [2,37-110,48]).
DISCUSSION
To improve these perceptions, the main proposals are increased contacts with underprivileged populations and the close supervision of the students by their course tutors.
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10.1016/j.lpm.2011.09.033
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