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pubmed_125_8811
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Although ring finger protein 2 (RNF2) serves an important role in the occurrence, development and regulation of various types of cancer, RNF2 expression in skin squamous cell carcinoma (SCC) remains unknown. The aim of the present study was to investigate the role of RNF2 expression in SCC and adjacent tissues from patients. The protein and gene expression levels of RNF2 in SCC and adjacent tissues were detected by immunohistochemistry (IHC), western blot analysis and semi-quantitative reverse transcription (RT) PCR. Single factor analysis was used to study the association between RNF2 expression level and the clinicopathological characteristics of patients with SCC. Multifactor Cox survival analysis was used to examine the association between RNF2 expression and the overall survival rate of postoperative patients with SCC. The results from IHC staining demonstrated that the positive expression rate of RNF2 was 84.68% (210/248) and 56.05% (139/248) in SCC and in adjacent tissues, respectively. Furthermore, results from western blot analysis demonstrated that RNF2 protein expression in SCC tissues was significantly higher compared with that in the adjacent tissues (P<0.05). The positive rate of RNF2 mRNA in SCC was 81.05% (201/248), which was significantly higher compared with that in the adjacent tissues 54.44% (135/248; P<0.05). Furthermore, RNF2 protein and gene expression levels were associated with tumor diameter, tumor stage, tumor metastasis and the degree of tumor differentiation in patients with SCC. Patients exhibiting higher RNF2 protein expression in SCC tissues had a significantly shorter disease-specific survival rate compared with patients with low RNF2 expression. In addition, RNF2 protein expression, tumor diameter, tumors site and tumor stage were independent factors affecting the overall survival rate of postoperative patients. High protein and gene expression levels of RNF2 in SCC tissues may be associated with the occurrence and development of SCC and prognosis of patients. The results form this study may serve the development of novel therapeutic options and diagnostic strategies for patients with SCC.
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10.3892/ol.2020.11666
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pubmed_278_18173
|
PURPOSE
Non-white patients are underrepresented in left atrial appendage occlusion (LAAO) trials, and racial disparities in LAAO periprocedural management are unknown.
METHODS
We assessed sociodemographics and comorbidities of consecutive patients at our institution undergoing LAAO between 2015 and 2020, then in adjusted analyses, compared procedural wait time, procedural complications, and post-procedure oral anticoagulation (OAC) use in whites versus non-whites.
RESULTS
Among 109 patients undergoing LAAO (45% white), whites had lower CHA2 DS2 VASc scores, on average, than non-whites (4.0 vs. 4.8, p = .006). There was no difference in median time from index event (IE) or initial outpatient cardiology encounter to LAAO procedure (whites 10.5 vs. non-whites 13.7 months, p = .9; 1.9 vs. 1.8 months, p = .6, respectively), and there was no difference in procedural complications (whites 4% vs. non-whites 5%, p = .33). After adjusting for CHA2 DS2 VASc score, OAC use at discharge tended to be higher in whites (OR 2.4, 95% CI [0.9-6.0], p = .07). When restricting the analysis to those with prior gastrointestinal (GI) bleed, adjusting for CHA2 DS2 VASc score and GI bleed severity, whites had a nearly five-fold odds of being discharged on OAC (OR 4.6, 95% CI [1-21.8], p = 0.05). The association between race and discharge OAC was not mediated through income category (total mediation effect 19% 95% CI [-.04-0.11], p = .38).
CONCLUSION
Despite an increased prevalence of comorbidities amongst non-whites, wait time for LAAO and procedural complications were similar in whites versus non-whites. Among those with prior GI bleed, whites were nearly five-fold more likely to be discharged on OAC than non-whites, independent of income.
|
10.1111/pace.14255
|
pubmed_64_22862
|
A fraction of human Salmonella infections is associated with direct contact with reptiles, yet the number of reptile-associated Salmonellosis cases are believed to be underestimated. Existing data on Salmonella spp. transmission by reptiles in Portugal is extremely scarce. The aim of the present work was to evaluate the prevalence of Salmonella spp. in pet reptiles (snakes, turtles, and lizards), as well as evaluate the isolates' antimicrobial resistance and virulence profiles, including their ability to form biofilm in the air-liquid interface. Additionally, the antimicrobial effect of chlorhexidine gluconate on the isolates was tested. Salmonella was isolated in 41% of the animals sampled and isolates revealed low levels of antimicrobial resistance. Hemolytic and lypolytic phenotypes were detected in all isolates. The majority (90.63%) of the Salmonella isolates were positive for the formation of pellicle in the air-liquid interface. Results indicate chlorhexidine gluconate is an effective antimicrobial agent, against the isolates in both their planktonic and biofilm forms, demonstrating a bactericidal effect in 84.37% of the Salmonella isolates. This study highlights the possible role of pet reptiles in the transmission of non-typhoidal Salmonella to humans, a serious and increasingly relevant route of exposure in the Salmonella public health framework.
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10.3390/antibiotics10030324
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pubmed_372_25498
|
Cells are richly equipped with nuclear receptors, which act as ligand-regulated transcription factors. Peroxisome proliferator activated receptors (PPARs), members of the nuclear receptor family, have been extensively studied for their roles in development, differentiation, and homeostatic processes. In the recent past, there has been substantial interest in understanding and defining the functions of PPARs and their agonists in regulating innate and adaptive immune responses as well as their pharmacologic potential in combating acute and chronic inflammatory disease. In this review, we focus on emerging evidence of the potential roles of the PPAR subtypes in macrophage biology. We also discuss the roles of dual and pan PPAR agonists as modulators of immune cell function, microbial infection, and inflammatory diseases.
|
10.3389/fimmu.2021.783780
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pubmed_666_2791
|
In our previous anatomic study, the authors could pull the platysma effectively in the medial direction, lateral direction, or both the medial and lateral directions. In this paper, the authors analyzed the results of our series of modified medial and lateral platysmaplasties, in which the technique was based on Hamra's platysmaplasty, modified in light of Feldman's corset platysmaplasty and Mendelson's concepts.In medial platysmaplasty, subcutaneous dissection was performed from the mandibular border to 2 or 3 finger breadths above the xiphoid process. Lateral platysmaplasty required only peri-lobular subcutaneous dissection for exposing and anchoring the lateral border of the platysma to the preauricular platysma auricular fascia (PAF). Lateral dissection does not go beyond the occipital hairline. During dissection, the zygomatic retaining ligaments were detached and repositioned and anchored to the lateral side of the PAF using 4-0 sutures. One hundred sixty-eight patients underwent platysmaplasty (87 medial platysmaplasty, 76 lateral platysmaplasty, 3 isolated neck lift).The follow-up period ranged from 1 month to 156 months. In general, medial platysmaplasty was more efficacious than simple lateral pulling back for various conditions involving neck deformities, especially midline bands and severe submental fullness with skin laxity. The complications were 1 case of neuropraxia of the cervical branch (0.6%), 3 cases of hematoma (1.8%), 2 cases of seroma (1.2%), and 2 cases of submental depression (1.2%). All patients had temporary paresthesia around the periauricular area, but fully recovered by 6 months.Using this modified medial and lateral platysmaplasty, we obtained satisfactory results with low complications.
|
10.1097/SCS.0000000000006515
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pubmed_960_203
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We measured the eye movements of a dentist while a pediatric patient walked toward a dental chair. Bilateral eye movements were measured and analyzed three-dimensionally based on the angle of convergence. The frequency of fixation points registered in each test ranged from 2 to 11, with an average of 6.6. No significant differences were observed when the experiments were grouped according to the age of the observed child. In 13 out of 74 experiments, the calculated distances between the observer and the fixation points corresponded to the actual distances. According to the patterns of where the fixation points occurred, 13 experiments had an "inside-outside" pattern and 61 had an "outside-only" pattern. None of the experiments had an "inside-only" pattern. The "outside-only" group was further subclassified into 50 "behind-only" patterns, 5 "in front-only" patterns, and 6 "in-front-and-behind" patterns. As far as depth perception is concerned, the angle of convergence determined by the eye movements would rarely correspond to the actual distance between the observer and the fixation point.
|
10.1007/s10266-004-0031-8
|
pubmed_876_13885
|
In 1985 the (Byar and Blackard, Urology, Vol. X, 556-561, 1978) data set on bladder cancer became available to researchers. Since then, a number of studies have made use of it. However, none of these has fully utilized all of the data nor have they developed a methodology in which it is possible to estimate models of the number of recurrences and durations that are consistent with each other. The purpose of this research is to determine which, if any, of the two drugs used in the trial, pyridoxine and theotepa, were effective and, by example, illustrate procedures that could be useful in the analysis of other clinical trial data sets. First, the number of recurrences is modeled as a count using the Poisson and negative binomial distributions with covariates. Then Poisson models are tested on the durations. Finally, durations and tumor counts per recurrence are fitted to more general autoregressive Wiebull and negative binomial distributions, respectively. Poisson models for durations are rejected in favor of the more general autoregressive models. The data on durations and tumor counts are shown to be more reliable from an inference point of view than the data on the number of recurrences. The data on durations and tumor counts show quite conclusively that both drugs are effective in treating bladder cancer, a result that differs from what others have found.
|
10.1081/BIP-100104198
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pubmed_517_22152
|
Allogeneic islet transplantation has proven difficult because organ shortages are recurrent, several pancreas donors are often needed to treat one diabetic recipient, and the intrahepatic site of islet implantation may not be the most appropriate site. Thus, another source of insulin-producing cells would be beneficial; and pigs represent a possible and viable source for obtaining such cells. Although the use of pig islet grafts appears to be difficult because of the species barrier, recent reports demonstrated that pig islet xenotransplantation can overcome the immunological barrier following strong immunosuppression and function successfully in primates for at least 6 months. Before becoming clinically applicable, however, pig islet xenotransplantation must still overcome the structural and physiological incompatibility between pig donor and human recipient. Researchers agree that it is necessary to produce more preclinical data in the pig-to-primate model before any pig-to-human transplantation of islets can be considered. Therefore, in this review, we provide a summary of the present state of knowledge about pig and human islet compatibility.
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10.1016/j.trre.2011.07.004
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pubmed_635_23900
|
Musical hallucinations are relatively rare auditory percepts which, due to their intrusive nature and the accompanying fear of impending mental decline, tend to cause significant distress and impairment. Although their etiology and pathophysiology appear to be heterogeneous and no evidence-based treatment methods are available, case reports indicate that acetylcholinesterase inhibitors may yield positive results in patients with comorbid hearing loss. We present two female patients (aged 76 and 78 years) both of whom suffered from hearing impairment and practically incessant musical hallucinations. Both patients were successfully treated with the acetylcholinesterase inhibitor rivastigmine. Based on these two case descriptions and an overview of studies describing the use of acetylcholinesterase inhibitors in similar patients, we discuss possible mechanisms and propose further research on the use of acetylcholinesterase inhibitors for musical hallucinations experienced in concordance with hearing loss.
|
10.3389/fpsyt.2015.00046
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pubmed_125_15608
|
Sexual parasitism has evolved as a distinctive mode of reproduction among deep-sea anglerfishes. The permanent attachment of males to host females observed in these species represents a form of anatomical joining, which is otherwise unknown in nature. Pronounced modifications to immune facilities are associated with this reproductive trait. The genomes of species with temporarily attaching males lack functional aicda genes that underpin affinity maturation of antibodies. Permanent attachment is associated with additional alterations, culminating in the loss of functional rag genes in some species, abolishing somatic diversification of antigen receptor genes, the hallmark of canonical adaptive immunity. In anglerfishes, coevolution of innate and adaptive immunity has been disentangled, implying that an alternative form of immunity supported the emergence of this evolutionarily successful group of vertebrates.
|
10.1126/science.aaz9445
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pubmed_740_20073
|
OBJECTIVE
The aim of the present study was to reveal the effect of therapeutic and prophylactic potential of astaxanthin in experimental autoimmune encephalomyelitis (EAE) as an acceptable model for the study of multiple sclerosis (MS).
BACKGROUND
Astaxanthin has powerful antioxidant activities as well as several essential biological functions while multiple sclerosis prevention is highly regarded by researchers.
METHODS
The astaxanthin potential in prevention of multiple sclerosis was examined in the chronic model of experimental autoimmune encephalomyelitis (EAE) by using female C57BL/6 mice induced with oligodendrocyte glycoprotein (MOG). Splenocytes were assessed to measure the levels of proinflammatory and anti-inflammatory cytokines, proliferation rate and FoxP3+Treg cell frequency. Immunohistochemical examinations were performed on spinal cord and brain tissue.
RESULTS
Astaxanthin reduced splenocytes proliferation index and proinflammatory cytokine levels, and vice versa increased the anti-inflammatory cytokine levels. Immunohistochemical studies of the spinal cord and brain showed that the infiltration with inflammatory cells was highly confined in the central nervous system. Protective effects of astaxanthin were visible by assigning low score recording in clinical behavior and disease severity.
CONCLUSION
Astaxanthin is a powerful tool for intervention in EAE on a model of multiple sclerosis, so it can be studied further to prevent and treat MS (Tab. 2, Fig. 3, Ref. 41).
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10.4149/BLL_2018_031
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pubmed_807_18870
|
The tumor suppressor protein, p53 is regarded as a key player in tumor suppression, as it promotes growth arrest, apoptosis and cellular senescence, while also blocking angiogenesis. The plethora of mechanisms underlying the p53 efficient death response involves transcriptional activation or repression of target genes, as well as the recently identified microRNAs, and transcription-independent functions. Pathological conditions such as cancer, neurodegeneration, ischemia, cholestasis or atherosclerosis are all strongly associated with deregulated levels of apoptosis in which p53 dysfunction has a prominent role. The effect of targeting cell death signaling proteins has been established in preclinical models of human diseases. In this regard, therapeutic strategies aimed at reactivation of p53 in tumors emerge as a promising approach for the treatment of cancer patients, as well as chemical inhibitors of p53 that may prove effective in suppressing disorders associated with widespread p53 activation. This review highlights recent developments of p53-induced apoptosis in human diseases. In addition, we will discuss controversies arising from the double-edge sword of targeting p53 in disease. Finally, ursodeoxycholic acid (UDCA), an endogenous bile acid used to treat cholestatic liver diseases, was recently described as a fine modulator of the complex control of p53 by Mdm-2. We will also review recent therapeutic strategies and clinical applications of targeted agents, and their progress in drug lead discovery, with particular emphasis on the potential use of UDCA.
|
10.2174/138161210791959818
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pubmed_468_23492
|
BACKGROUND
Mantle cell lymphoma (MCL) is currently an incurable entity, and new therapeutic approaches are needed. We have applied a high-throughput phospho-proteomic technique to MCL cell lines to identify activated pathways and we have then validated our data in both cell lines and tumor tissues.
METHODS
PhosphoScan analysis was performed on MCL cell lines. Results were validated by flow cytometry and western blotting. Functional validation was performed by blocking the most active pathway in MCL cell lines.
RESULTS
PhosphoScan identified more than 300 tyrosine-phosporylated proteins, among which many protein kinases. The most abundant peptides belonged to proteins connected with B-cell receptor (BCR) signaling. Active BCR signaling was demonstrated by flow cytometry in MCL cells and by western blotting in MCL tumor tissues. Blocking BCR signaling by Syk inhibitor piceatannol induced dose/time-dependent apoptosis in MCL cell lines, as well as several modifications in the phosphorylation status of BCR pathway members and a collapse of cyclin D1 protein levels.
CONCLUSION
Our data support a pro-survival role of BCR signaling in MCL and suggest that this pathway might be a candidate for therapy. Our findings also suggest that Syk activation patterns might be different in MCL compared to other lymphoma subtypes.
|
10.1007/s13402-011-0019-7
|
pubmed_532_7900
|
Fibrosis is a common phenomenon associated with several pathologies, characterized by an excessive extracellular matrix deposition that leads to a progressive organ dysfunction. Thus fibrosis has a relevant role in chronic diseases affecting the kidney, the liver, lung, skin (scleroderma) and joints (arthritis), among others. The pathogenesis of fibrosis in different organs share numerous similarities, being one of them the presence of activated fibroblasts, denominated myofibroblast, which act as the main source of extracellular matrix proteins. Transforming growth factor beta-1 (TGF-β1) is a profibrotic cytokine that plays a pivotal role in fibrosis. The TGF-β1/ALK5/Smad3 signaling pathway has been studied in fibrosis extensively. However, an increasing number of studies involving the ALK1/Smad1 pathway in the fibrotic process exist. In this review we offer a perspective of the function of ALK1/Smad1 pathway in renal fibrosis, liver fibrosis, scleroderma and osteoarthritis, suggesting this pathway as a powerful therapeutical target. We also propose several strategies to modulate the activity of this pathway and its consequences in the fibrotic process.
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pubmed_532_7900
|
pubmed_1103_14037
|
BACKGROUND
Tumour doubling time, a parameter in drug sensitivity testing, reflects both cell proliferation and apoptosis. Variable apoptosis fractions may explain the poor correlation of S-fraction and drug response. DNA aneuploidy (reflecting intrinsic DNA instability) may, by increasing apoptosis, affect drug response.
AIM
To assess the relationship between apoptosis corrected proliferation fraction and DNA ploidy in childhood acute lymphoblastic leukemia (ALL).
METHODS
1.3.1. Study Groups. Thirty two consecutive, unselected diagnostic cases of childhood ALL were included in the study. 1.3.2. Karyotype. A normal karyotype was found in 15 cases (7M, 8F, age 8 m-12 yrs); high hyperdiploid aneuploidy (DNA index > 1.5) was found in 7 patients (1M, 7F, age 3-12 yrs) whereas complex karyotypic anomalies, but with 2n or near 2n DNA were present in 10 patients (7M, 3F, age 1 y 7 m -16 yrs). 1.3.3. Proliferation Fraction Assessment. Immunocytochemical demonstration of S-phase associated nuclear expression of the Ki-67 antigen (MM1, NovaCastra, UK). 1.3.4. Apoptosis Fraction Assessment. Binding of a horse radish peroxidase labelled DNA probe for the 3'-OH ends of apoptosis derived Klenow fragments (Frag-EL, CalBiochem, USA). 1.3.5. Quantitation. Computer assisted image analysis (Quantimet 570C), of 10 systematically random fields of a minimum of 20 nuclei each. A nuclear size bias correcting counting frame and rule were used to correct for cell proliferation associated nuclear volume increase and for the expected nuclear volume reduction resulting from apoptosis.
RESULTS
Corrected for apoptosis, proliferation fraction was highest (mean 57.5%, range 1-100) in poor prognosis, complex karyotype anomalies. Good prognosis, high hyper diploidy showed significantly lower proliferation rates (mean 24.7%, range 12-40) (p < 0.01, t-test).
CONCLUSION
Apoptosis corrected cell proliferation rate in childhood ALL is not independent of karyotype abnormality which may partly explain a relation to therapy response and prognosis.
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10.1007/978-1-4615-4811-9_32
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pubmed_607_7747
|
It has been found that levamisole, an anthelmintic drug, used also as an immunomodulator in human cancer therapy, is a strong inhibitor of tumour aerobic glycolysis. In vitro, in Ehrlich ascites tumour (EAT) cells and supernatants it diminishes glucose uptake and lactate formation. It does not, however, exert a similar inhibitory effect on glycolytic activity in normal liver and muscle supernatants. Metabolic and enzymatic studies have shown that levamisole directly inhibits tumour phosphofructokinase decreasing ATP, as well as 2-phosphoenolpyruvate and pyruvate as further glycolytic intermediates. L-Cysteine used for comparison also as another inhibitor of tumour aerobic glycolysis, decreasing glucose uptake and lactate formation and diminishing pyruvate and ATP levels, differs in the accompanying increase in 2-phosphoenolpyruvate concentration. This crossing-over in metabolite concentration, only seen in tumour material, points to tumour pyruvate kinase as an isoenzyme sensitive to cysteine inhibition. Direct enzymatic studies have confirmed this suggestion. Some similarities in the influence on the metabolism of both compounds studied have been discussed, as well as the role of the effects observed in understanding the mechanisms of levamisole action (also in worms).
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10.1016/0006-2952(86)90750-1
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pubmed_38_709
|
MOTIVATION
Biologically important proteins are often large, multidomain proteins, which are difficult to characterize by high-throughput experimental methods. Efficient domain/boundary predictions are thus increasingly required in diverse area of proteomics research for computationally dissecting proteins into readily analyzable domains.
RESULTS
We constructed a support vector machine (SVM)-based domain linker predictor, DROP (Domain linker pRediction using OPtimal features), which was trained with 25 optimal features. The optimal combination of features was identified from a set of 3000 features using a random forest algorithm complemented with a stepwise feature selection. DROP demonstrated a prediction sensitivity and precision of 41.3 and 49.4%, respectively. These values were over 19.9% higher than those of control SVM predictors trained with non-optimized features, strongly suggesting the efficiency of our feature selection method. In addition, the mean NDO-Score of DROP for predicting novel domains in seven CASP8 FM multidomain proteins was 0.760, which was higher than any of the 12 published CASP8 DP servers. Overall, these results indicate that the SVM prediction of domain linkers can be improved by identifying optimal features that best distinguish linker from non-linker regions.
|
10.1093/bioinformatics/btq700
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pubmed_360_8198
|
Eighty of 103 strains of Aeromonas hydrophila cultured at 100 rev./min produced heat-labile enterotoxins detected using the suckling mouse assay. Results in intestinal perfusion agreed with the suckling mouse test in all strains tested by both methods. Enterotoxic activity correlated with haemolysin and cytotoxin production, but 4% of strains would have been wrongly classified using haemolysin assay in place of the suckling mouse test and 11% misclassified on the basis of cytotoxin assay. There was a significant association between haemolytic and cytotoxic activity, but 15% of strains produced only one of these toxins. Haemolysin, cytotoxin and enterotoxin were not always associated in a given isolate. The time of appearance of exotoxins during bacterial growth and the effects of dialysis, heating and proteolytic enzymes also suggest that haemolysins, cytotoxins and enterotoxins of Aeromonas hydrophila are separate toxins and not different manifestations of the same toxin.
|
10.1038/icb.1981.65
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pubmed_699_14120
|
Metabolic composition can have potential impact on several vital agronomic traits, and metabolomics, which represents the bioactive compounds in plant tissues, is widely considered as a powerful approach for linking phenotype-genotype interactions. However, metabolites related to cane traits such as sugar content, rind color, and texture differences in different sugarcane cultivars using metabolome integrated with transcriptome remain largely inconclusive. In this study, metabolome integrated with transcriptome analyses were performed to identify and quantify metabolites composition, and have better insight into the molecular mechanisms underpinning the different cane traits, namely, brix, rind color, and textures in the stems (S) and leaves (L) of sugarcane varieties FN41 and 165402. We also identified metabolites and associated genes in the phenylpropanoid and flavonoid biosynthesis pathways, starch and sucrose metabolism. A total of 512 metabolites from 11 classes, with the vast majority (122) belonging to flavonoids were identified. Moreover, the relatively high amount of D-fructose 6-p, D-glucose6-p and glucose1-p detected in FN41L may have been transported and distributed by source and sink of the cane, and a majority of them reached the stem of sugarcane FN41L, thereby promoting the high accumulation of sugar in FN41S. Observations also revealed that genes such as C4H, CHS, F3H, F3'H, DFR, and FG2 in phenylpropanoid and flavonoid biosynthesis pathways were the major factors impacting the rind color and contrasting texture of FN41 and 165204. Further analysis revealed that weighted gene co-expression network analysis (WGCNA) hub genes and six transcription factors, namely, Tify and NAC, MYB-related, C2C2-Dof, WRKY, and bHLH play a key role in phenylpropanoid biosynthesis, flavone and flavonol biosynthesis, starch and sucrose metabolism. Additionally, metabolites such as L-phenylalanine, tyrosine, sinapaldehyde, pinobanksin, kaempferin, and nictoflorin were the potential drivers of phenotypic differences. Our finding also demonstrated that genes and metabolites in the starch and sucrose metabolism had a significant effect on cane sugar content. Overall, this study provided valuable insight into the molecular mechanisms underpinning high sugar accumulation and rind color in sugarcane, which we believe is important for future sugarcane breeding programs and the selection of high biomass varieties.
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10.3389/fpls.2022.921536
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pubmed_492_9899
|
In order to identify wild fruits possessing high nutraceutical potential, the antioxidant activities of 56 wild fruits from South China were systematically evaluated. The fat-soluble components were extracted with tetrahydrofuran, and the water-soluble ones were extracted with a 50:3.7:46.3 (v/v) methanol-acetic acid-water mixture. The antioxidant capacities of the extracts were evaluated using the ferric reducing antioxidant power (FRAP) and Trolox equivalent antioxidant capacity (TEAC) assays, and their total phenolic contents were measured by the Folin-Ciocalteu method. Most of these wild fruits were analyzed for the first time for their antioxidant activities. Generally, these fruits had high antioxidant capacities and total phenolic contents. A significant correlation between the FRAP value and the TEAC value suggested that antioxidant components in these wild fruits were capable of reducing oxidants and scavenging free radicals. A high correlation between antioxidant capacity and total phenolic content indicated that phenolic compounds could be the main contributors to the measured antioxidant activity. The results showed that fruits of Eucalyptus robusta, Eurya nitida, Melastoma sanguineum, Melaleuca leucadendron, Lagerstroemia indica, Caryota mitis, Lagerstroemia speciosa and Gordonia axillaris possessed the highest antioxidant capacities and total phenolic contents among those tested, and could be potential rich sources of natural antioxidants and functional foods. The results obtained are very helpful for the full utilization of these wild fruits.
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10.3390/molecules15128602
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pubmed_770_136
|
Isometric exercises raise the mean arterial blood pressure and impose serious stress on left ventricular function. It may be more dangerous for older than for younger people. The effect of aging on blood pressure response was studied in 75 subjects, 25 normal young men aged 25 +/- 4 years, 25 older men aged 51 +/- 3.2 years, and 25 elderly men aged 68 +/- 4 years, during upright isometric dead lift at 30% maximal voluntary effort for 3 min. The heart rate, systolic blood pressure, and diastolic blood pressure were measured during the 3rd min of dead lift contraction. Tension exerted was significantly lower in the older group (33 +/- 4 kg) and lowest in the elderly group (26.9 +/- 6 kg) compared with the young group (43 +/- 8 kg). All groups showed similar and significant increases in heart rate, systolic and diastolic blood pressure during dead lift (p less than 0.01). These data indicate a similar pattern of blood pressure response to acute pressure overload in young, older, and elderly normal men.
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10.1055/s-2007-1024994
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pubmed_414_23129
|
OBJECTIVE
In consideration of the declining use of lithium over the past several decades, this review focuses on three topics to argue for lithium's status as first choice as the maintenance treatment of bipolar disorder.
METHODS
This review (i) describes success rates for patients assigned to lithium and those assigned to placebo in early (1973-1976) and recent (2000-2003) trials, as well as those assigned to alternative mood stabilizers versus placebo; (ii) summarizes the results of studies that compared lithium to alternative mood stabilizers by the degree of weight gain during maintenance therapy; and (iii) reviews evidence that lithium exhibits unique antisuicidal properties.
RESULTS
Differing success rates in early and more recent maintenance trials strongly suggest a cohort effect in which the lithium responders are relatively unavailable for recent maintenance trials. Moreover, among mood stabilizers studied in randomized trials, lithium appears least likely to cause substantial weight gain, and a considerable literature has developed to suggest that lithium has antisuicidal effects that extend beyond its benefits in relapse prevention.
CONCLUSION
The evidence reviewed here strongly supports the consideration of lithium when prophylactic treatment is first begun for a bipolar patient.
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10.1111/j.1399-5618.2009.00712.x
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pubmed_522_17762
|
Radiation dose deposited on a radiochromic film is considered as a dose image. A precise image extraction system with commensurate capabilities is required to measure the transmittance of the image and translate it to radiation dose. This paper describes the development of a spectral microdensitometer which has been designed to achieve this goal under the conditions of (a) the linearity and sensitivity of the dose response curve of the radiochromic film being highly dependent on the wavelength of the analysing light, and (b) the inherent high spatial resolution of the film. The microdensitometer consists of a monochromator which provides an analysing light of variable wavelength, a film tray on a high-precision scanning stage, a transmission microscope coupled to a thermoelectrically cooled CCD camera, a microcomputer and corresponding interfaces. The measurement of the transmittance of the radiochromic film is made at the two absorption peaks with maximum sensitivities. The high spatial resolution of the instrument, of the order of micrometres, is achieved through the use of the microscope combined with a measure-and-step technique to cover the whole film. The performance of the instrument in regard to the positional accuracy, system reproducibility and dual-peak film calibration was evaluated. The results show that the instrument fulfils the design objective of providing a precise image extraction system for radiochromic films with micrometre spatial resolution and sensitive dose response.
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10.1088/0031-9155/49/22/011
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pubmed_633_17453
|
Experiments in captivity have provided evidence for social learning, but it remains challenging to demonstrate social learning in the wild. Recently, we developed network-based diffusion analysis (NBDA; 2009) as a new approach to inferring social learning from observational data. NBDA fits alternative models of asocial and social learning to the diffusion of a behavior through time, where the potential for social learning is related to a social network. Here, we investigate the performance of NBDA in relation to variation in group size, network heterogeneity, observer sampling errors, and duration of trait diffusion. We find that observation errors, when severe enough, can lead to increased Type I error rates in detecting social learning. However, elevated Type I error rates can be prevented by coding the observed times of trait acquisition into larger time units. Collectively, our results provide further guidance to applying NBDA and demonstrate that the method is more robust to sampling error than initially expected. Supplemental materials for this article may be downloaded from http://lb.psychonomic-journals.org/content/supplemental.
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10.3758/LB.38.3.235
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pubmed_364_18634
|
The Federal Reserve is exposed to a greater degree of political influence under its new operating regime. We survey the relevant literature and describe the Fed's new operating regime. Then we explain how the regime change reduced de facto central bank independence. In brief, the regime change increased the appointment power of the President and improved the bargaining power of Congress. We offer some suggestions for bolstering de facto independence at the Fed.
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10.1016/j.qref.2020.10.006
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pubmed_107_11133
|
Epstein-Barr virus (EBV) gene expression in nasopharyngeal carcinoma (NPC) includes abundant rightward transcription of the BamHI A fragment, consisting of mRNAs ranging in size from approximately 4.0 to 8.0 kb. These transcripts include several distinctly spliced forms which are 3'-end coterminal and contain the BamHI A rightward frame 0 (BARF0) open reading frame (ORF) in the final exon. BamHI A transcription is detected at a lower level of expression in EBV-infected lymphoid cells. In this study, cDNA cloning, reverse transcription-based PCR, and Northern (RNA) blotting were used to further define the structures of the BamHI A transcripts and to characterize their expression in different EBV-infected tissues. Three BamHI A cDNAs isolated from a passaged NPC represent previously unidentified mRNAs that contain BARF0 and additional ORFs encoded by multiple exons, including one which extends the size of the BARF0 ORF from 174 to 279 codons. The distinct exons were detected in multiple, differently sized mRNAs, indicating that these transcripts have complex patterns of alternate splicing. In support of this finding, 5'-end analysis confirmed the presence of a previously reported start site and also identified a subset of transcripts of 4.8 kb and larger that initiate further 5' to this site. In addition, 3'-end analysis identified heterogeneous 3'-end processing in all of the BamHI A mRNAs, resulting in transcripts that either contain the entire BARF0 ORF or are cleaved and polyadenylated 5' of the stop codon. Finally, the expression of multiple, distinctly spliced BamHI A transcripts was consistently detected in a wide range of EBV-infected samples, including NPC, Burkitt's lymphoma, and parotid carcinoma biopsy samples, and in type I and type III Burkitt's lymphoma lines and type III lymphoblastoid cell lines. This complex pattern of start site selection, alternate splicing, and heterogeneous 3'-end processing is likely to regulate the expression in vivo of the ORFs encoded by the EBV BamHI A transcripts.
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10.1128/JVI.69.2.1132-1141.1995
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pubmed_1108_6206
|
PURPOSE
We investigated the effect of muscle relaxants (atracurium) on the outcomes of intermittent exotropia surgery under general anesthesia, with a focus on resection procedures.
METHODS
Thirty four patients who underwent recession and resection (R&R) were divided into two groups: atracurium usage (group A, n=18) and no atracurium usage (group B, n=16). Patients were divided into two subgroups according to the amount of resection of the medial rectus (MR): less than 5 mm (group 1, n=13) or 5 mm and greater (group 2, n=21). Deviation angles were compared between groups and subgroups. Surgical outcome was defined as successful if distant deviation angles were equal to or less than 10 prism diopters.
RESULTS
The overall postoperative deviation angles did not show statistically significant differences between groups A and B. However, in patients with larger MR resections (> or = 5 mm), the 1 week postoperative distant deviation was significantly larger in group A (1.8+/-2.6 PD) than in group B (-1.6+/-4.6 PD, p=0.048 by t-test). The overall undercorrection rate at 3 months postoperatively for group A was 16.7%, which was higher than that of group B (6.3%), and the difference was even larger in subgroups with larger MR resections (> or = 5 mm): 18.2% in group A and 0% in group B.
CONCLUSIONS
Patients who underwent R&R procedures under general anesthesia with a muscle relaxant tended to be less corrected than those without muscle relaxant, especially in the early postoperative period and with a larger MR resection equal to or greater than 5 mm. However, there was no significant difference in the later postoperative period.
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10.3341/kjo.2008.22.4.246
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pubmed_6_9921
|
The pathogenesis of colorectal cancer is a multifactorial process. Dysbiosis and the overexpression of COX-2 and LDHA are important effectors in the initiation and development of the disease through chromosomal instability, PGE2 biosynthesis, and induction of the Warburg effect, respectively. Herein, we report the in vitro testing of some new quinoxalinone and quinazolinone Schiff's bases as: antibacterial, COX-2 and LDHA inhibitors, and anticolorectal agents on HCT-116 and LoVo cells. Moreover, molecular docking and SAR analyses were performed to identify the structural features contributing to the biological activities. Among the synthesized molecules, the most active cytotoxic agent, (6d) was also a COX-2 inhibitor. In silico ADMET studies predicted that (6d) would have high Caco-2 permeability, and %HIA (99.58%), with low BBB permeability, zero hepatotoxicity, and zero risk of sudden cardiac arrest, or mutagenicity. Further, (6d) is not a potential P-gp substrate, instead, it is a possible P-gpI and II inhibitor, therefore, it can prevent or reverse the multidrug resistance of the anticancer drugs. Collectively, (6d) can be considered as a promising lead suitable for further optimization to develop anti-CRC agents or glycoproteins inhibitors.
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10.3390/molecules26113121
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pubmed_247_22326
|
The use of intravenous melphalan at higher doses is limited by severe myelosuppression. It was postulated that GM-CSF would permit the use of higher dose melphalan with only moderate myelosuppression easily manageable in an outpatient setting. Therefore, a phase I study of intravenous melphalan utilizing GM-CSF (recombinant granulocyte-macrophage colony-stimulating factor) support was initiated. Intravenous melphalan at doses of 15-45 mg/m2 was administered every 28 days. GM-CSF was utilized at doses of 10-20 micrograms/kg/day subcutaneously Days 2-21 on a 28-day cycle. Twenty-five patients received 53 courses of therapy. The dose-limiting toxicities were severe or life-threatening granulocytopenia and thrombocytopenia. Utilizing 20 micrograms/kg/day GM-CSF, the maximum tolerated dose (MTD) of melphalan is 30 mg/m2 and, with 10 mg/kg/day GM-CSF, the maximum tolerated melphalan dose is only 20 mg/m2. One patient with ovarian cancer achieved a partial response. Because the reported MTD of intravenous melphalan without GM-CSF is 30 mg/m2, GM-CSF has not allowed sufficient escalation of the intravenous melphalan dose for routine outpatient use.
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10.1016/0090-8258(92)90014-a
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pubmed_323_19961
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In this work the thermal and photochemical reactivity of a series of ruthenium complexes [Ru(terpy)(N-N)(L)](X)2 (terpy = 2,2';6',2″-terpyridine, L = 2-(methylthio)ethanol (Hmte) or water, and X is Cl(-) or PF6(-)) with four different bidentate chelates N-N = bpy (2,2'-bipyridine), biq (2,2'-biquinoline), dcbpy (6,6'-dichloro-2,2'-bipyridine), or dmbpy (6,6'-dimethyl-2,2'-bipyridine), is described. For each chelate N-N the thermodynamic constant of the dark equilibrium between the aqua- and Hmte- complexes, the Hmte photosubstitution quantum yield, and the rate constants of the thermal interconversion between the aqua and Hmte complexes were measured at room temperature. By changing the steric hindrance and electronic properties of the spectator N-N ligand along the series bpy, biq, dcbpy, dmbpy the dark reactivity clearly shifts from a nonlabile equilibrium with N-N = bpy to a very labile thermal equilibrium with N-N = dmbpy. According to variable-temperature rate constant measurements in the dark near pH = 7 the activation enthalpies for the thermal substitution of H2O by Hmte are comparable for all ruthenium complexes, whereas the activation entropies are negative for bpy and biq, and positive for dcbpy and dmbpy complexes. These data are indicative of a change in the substitution mechanism, being interchange associative with nonhindered or poorly hindered chelates (bpy, biq), and interchange dissociative for more bulky ligands (dcbpy, dmbpy). For the most labile dmbpy system, the thermal equilibrium is too fast to allow significant modification of the composition of the mixture using light, and for the nonhindered bpy complex the photosubstitution of Hmte by H2O is possible but thermal binding of Hmte to the aqua complex does not occur at room temperature. By contrast, with N-N = biq or dcbpy the thermodynamic and kinetic parameters describing the formation and breakage of the Ru-S bond lie in a range where the bond forms spontaneously in the dark, but is efficiently cleaved under light irradiation. Thus, the ratio between the aqua and Hmte complex in solution can be efficiently controlled at room temperature using visible light irradiation.
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10.1021/ic401105v
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pubmed_1105_19363
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[reaction: see text] A concise method for the preparation of isochromene carboxylates has been developed by the regioselective 1,6-addition of various nucleophiles such as Grignard reagents, alkoxide, and cyanide onto benzopyranylidenetungsten(0) complexes, followed by iodine oxidation of the addition intermediates.
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10.1021/ol052951t
|
pubmed_749_7504
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Cistus genus (Cistaceae) comprises several medicinal plants used in traditional medicines to treat several pathological conditions including hyperglycemia. These include Cistus salviifolius L. (CS) and Cistus monspeliensis L. (CM), still not fully explored as a source of metabolites with therapeutic potential for human diseases. In this study, the antioxidant α-amylase and α-glucosidase enzyme inhibitory effects of aqueous and hydromethanolic extracts from the aerial parts of Moroccan CS and CM were investigated. Antioxidant activity has been assessed using 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS) radicals and ferric reducing/antioxidant power (FRAP) methods. The α-amylase and α-glucosidase inhibitory activity has been assessed using an in vitro model. Moreover, mineral and phenolic contents of CS and CM were analyzed. The extracts of both species exhibited potent antioxidant activity in all used systems and possess strong inhibitory effect towards α-glucosidase (IC50: 0.95 ± 0.14 to 14.58 ± 1.26 μg/mL) and significant inhibitory potential against α-amylase (IC50: 217.10 ± 0.15 to 886.10 ± 0.10 μg/mL). Furthermore, the result showed high levels of phenolic content and unexpectedly some higher levels of mineral content in CS. The results suggest that the phenolic rich extracts of CS and CM may have a therapeutic potential against diseases associated with oxidative stress and may be useful in the management of hyperglycemia in diabetic patients.
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10.1155/2017/2789482
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pubmed_877_5372
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Nurses in the Neonatal Intensive Care Unit (NICU) have an important role in implementing family-centered care (FCC). The aim of the study was to explore the lived experiences of NICU nurses on implementing FCC. An interpretative phenomenological study was conducted and 11 employed nurses were interviewed from April 2015 to February 2016. The data were analyzed through the Diekelmann, Allen, and Tanner approach. Four main themes of "strain to achieve stability," "bewildered by taking multiple roles," "accepting the family," and "reaching bright horizon" were extracted. This study provided deeper understanding about nurses' perceptions of FCC implementation. In Muslim developing countries, FCC implementation is challenging and nurses are under extra pressure because of a shortage in nursing workforce; however, having positive experiences with family participation and valuing theism beliefs allowed them to support family involvement. Support of nurses to take FCC strategies in the NICU is needed by officials overseeing the health care system.
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10.1177/1054773818758171
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pubmed_724_3074
|
Three sections have been studied: the characteristics of the virus (to insist on in their genome, able to produce structural and regulating proteins), and mainly, their biological cycle that allows us to know where the different antiretroviral will act; the resistance phenomena produced by their high answered and mutant capacity; and on third place, it show up some results of the investigations carried out in the Hospital Universitario San Cecilio, Granada, on two aspects: realization and validation of algorithms of interpretation of mutation based on virologic answer, and comparison of the influence according to the adult or smaller number of mutations appeared with the resistances in front of active medicines.
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pubmed_724_3074
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pubmed_30_15874
|
In animal models, severing the chordae tendineae of the mitral valve reduces the maximum global left ventricular elastance (Emax,g), a load-independent measure of left ventricular systolic performance; moreover, chamber geometry is altered with systolic bulging in the region of the papillary muscle insertions. This suggests that forces transmitted by the mitral apparatus increase the regional volume elastance (Emax,r) of segments subtending the insertions of the papillary muscles, and these regions contribute substantially to overall left ventricular systolic function (Emax,g). To test this hypothesis, we developed a method to evaluate changes in the magnitude and uniformity of Emax,r as quantitated by the slopes (E'max,i) of regional left ventricular isovolumetric pressure-dimension relations. Such measurements were obtained before and after all chordal attachments of the mitral valve were surgically divided in seven open-chest swine preparations. Significant declines in E'max,i were limited to the region of the posteromedial papillary muscle insertion. Although the mean E'max,i of all ventricular regions (E'max,ave) was unchanged, regional left ventricular elastances were less uniform after the mitral chordae tendineae were severed, which indicated a less synergistic contraction, and Emax,g fell by 21% from 7.1 +/- 2.0 to 5.6 +/- 1.2 mm Hg/ml (p less than 0.05). These data demonstrate that the mitral apparatus contributes importantly to the magnitude and uniformity of regional left ventricular elastances and suggest that such alterations in regional mechanics underlie the deterioration in global left ventricular systolic performance (Emax,g) after excision of the mitral apparatus.
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pubmed_30_15874
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pubmed_869_9079
|
Excessive soluble P in runoff is a common cause of eutrophication in fresh waters. Evidence indicates that drinking water treatment residuals (WTRs) can reduce soluble P concentrations in P-impacted soils in the short term (days to weeks). The long-term (years) stability of WTR-immobilized P has been inferred, but validating field data are scarce. This research was undertaken at two Michigan field sites with a history of heavy manure applications to study the longevity of alum-based WTR (Al-WTR) effects on P solubility over time (7.5 yr). At both sites, amendment with Al-WTR reduced water-soluble P (WSP) concentration by >or=60% as compared to the control plots, and the Al-WTR-immobilized P (WTR-P) remained stable 7.5 yr after Al-WTR application. Rainfall simulation techniques were utilized to investigate P losses in runoff and leachate from surface soils of the field sites at 7.5 yr after Al-WTR application. At both sites, amendment with Al-WTR reduced dissolved P and bioavailable P (BAP) by >50% as compared to the control plots, showing that WTR-immobilized P remained nonlabile even 7.5 yr after Al-WTR amendment. Thus, WTR-immobilized P would not be expected to dissolve into runoff and leachate to contaminate surface waters or groundwater. Even if WTR-P is lost via erosion to surface waters, the bioavailability of the immobilized P should be minimal and should have negligible effects on water quality. However, if the WTR particles are destroyed by extreme conditions, P loss to water could pose a eutrophication risk.
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10.2134/jeq2006.0162
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pubmed_95_6622
|
Acute lymphoblastic leukemia (ALL) is the most frequent cancer encountered in children. Little is known about the molecular pathology of childhood T cell ALL. Oncogenesis is a multistep process that involves alterations in proto-oncogenes and tumor suppressor genes. Recently, a mutator phenotype detectable by microsatellite instabilities was shown to be associated with predisposition to cancer. This new mechanism for human carcinogenesis is caused by defects in the DNA replication/repair system. To study the involvement of some of these mutational events in the development of T cell ALL, we have initiated a systematic search for losses of heterozygosity (LOH) and microsatellite instabilities in children affected with this disease. These patients were allelotyped by PCR using 56 microsatellite markers located near known or putative tumor suppressor genes. The microsatellite patterns were altered in more than 80% of the patients. LOH were detected in chromosomes 6p, 12p and 9p. Two third of the patients were deleted for chromosome 9p21, suggesting the involvement of a tumor suppressor gene, probably the p16 gene. The only patient refractory to chemotherapy was shown to be associated with a mutator phenotype. This is the first documented case of a childhood neoplasia associated with genomic instabilities. Our results suggest that defects in DNA replication/repair components are involved in the development of a subset of childhood T cell ALL.
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10.1038/sj.leu.2400650
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pubmed_1037_24317
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Many studies have been carried out along mighty rivers with heavily industrialized watersheds to evaluate pollutants and their effects on freshwater organisms. However, their impact on marine organisms is virtually unknown. In order to cover this gap, Solea solea, one of the most important commercial fish species, together with sediments, were sampled during 2013-2015 offshore from the Ebro Delta river mouth. Fish health indicators (condition indices, histological tissue alterations, and parasite descriptors) were used to assess the potential effect of pollutants, an issue of particular interest in the area following the dredging activities taking place in the river upstream in 2013. No major histopathological alterations were detected, but perivascular inflammatory foci (PIF) were frequently observed, especially in 2014. The most prevalent and abundant parasites were acanthocephalans and digeneans within the digestive tract and copepods on the gills. Levels of trace metals from sediments and fish muscle were below the effects range median and reference levels accepted for human consumption, respectively. However, the lower levels of the hepatosomatic index, higher numbers of PIF, and variations in the abundance of parasites in 2014 and 2015 could suggest a pollutant exposure during these years. These results warn signs of toxicity, which could be associated with sediment leaks during the dredging activities.
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10.1007/s11356-021-16408-7
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pubmed_665_20979
|
Infection control professionals have the means to calculate infection rates in their hospitals but not to assess them. They require a practical tool that enables them to compare observed infection rates with external standards. Based on the data obtained from the intensive care unit (ICU) component of the Japanese Nosocomial Infection Surveillance (JANIS) system, a spreadsheet was developed to calculate a standardized infection ratio (SIR) as a risk-adjusted indicator. Out of the factors associated with the development of nosocomial infections in a multi-variate analysis, the following three factors were selected for stratification: APACHE II score (0-10, 11-20, 21+), operation (yes, no) and ventilator use (user, non-user). Infection rates in 2001 were determined (per 1000 patient-days), stratified by the three factors, as a benchmark. The spreadsheet was designed to calculate SIRs on the basis of the Japanese benchmark infection rates using Microsoft Excel software. The user of the spreadsheet should input the number of observed nosocomial infections and patient-days by APACHE II score, operation and ventilator use. When applied to eight Japanese ICUs, the spreadsheet revealed relative differences and temporal changes in the incidence of nosocomial infections within these ICUs.
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10.1016/j.jhin.2005.12.013
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pubmed_467_14291
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This study involved the development of a β-glucosidase-catalyzed hydrolysis method based on a deep eutectic solvent (DES), choline chloride-ethylene glycol 2:1, and continuous feed technique to overcome the difficulty of high-concentration ginsenoside hydrolysis. A productivity of 142 mg·L-1·h-1 was achieved with the following conditions: 30 vol% DES, pH 5.0, 55 °C, and substrate concentration of 12 mM. In the presence of DES, the affinity and catalytic efficiency of β-glucosidase to Rd increased by 49 and 64%, respectively, which promoted the continuation of hydrolysis. Moreover, conformation of β-glucosidase was mostly retained, as confirmed by spectral information. Through a combination of a substrate fed-batch technique to reduce the inhibitory effects of substrates and products, the CK conversion rate increased by 44% compared to traditional single-batch in pure buffer. This report describes a practical method for the continuous conversion of natural compounds through biological processes and solvent engineering.
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10.1016/j.biortech.2020.123039
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pubmed_496_15765
|
Primary angiosarcoma of the lung is a rare disorder with few cases reported in the literature [Patel AM, Ryu JH. Angiosarcoma in the lung. Chest 1993;103:1531-35]. We present a case of primary angiosarcoma of the lung in a 79-year-old woman. Preoperative computed tomographic scan revealed soft tissue nodules surrounded by a halo of ground-glass attenuation, an appearance consistent with hemorrhagic pulmonary nodules [Primack S, Hartman T, Lee KS. Pulmonary nodules and the CT halo sign. Radiology 1994;190:513-15]. Lung biopsy revealed a multifocal malignant neoplasm with areas of hemorrhage. The histologic, cytologic, and immunophenotypic features were characteristic of epithelioid angiosarcoma. This case report contributes to the sparse literature on this disease and provides computed tomographic and pathologic correlation in a patient with hemorrhagic pulmonary nodules.
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10.1016/j.anndiagpath.2005.04.001
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pubmed_989_24910
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Unsafe drinking water is a leading cause of child morbidity, especially among young children in low-income settings. Safe water consumption requires high-quality water available at its source and at point of use. We examined the quality of drinking water at point of collection and point of use in 796 households in three provinces, in Cambodia. Microbiological testing for coliform and Escherichia coli contamination was conducted for samples collected. Bivariable analysis and multivariable logistic regression were used to examine associations between various factors and the deterioration in water quality (increase in the risk according coliform or E. coli concentration) between point of collection and point of use. Contamination with both coliforms and E. coli was higher at point of use than at point of collection, with contamination at point of collection to account for 76.6% (coliforms) and 46.3% (E. coli). Results suggest that child drinking water represents a considerable pathway for the ingestion of pathogens, in Cambodia. Area of residence, seasonality, type of water source, and water chlorination were associated with coliform concentration between the point of collection and point of use, whereas only seasonality was associated with E. coli contamination (OR = 1.46; 95% CI [1.05, 2.02]). Children living in rural settings were two times more likely to drink water with a deteriorating coliform concentration between the two-time points than children living in urban settings (OR = 2.00; 95% CI [1.22, 3.30]). The increase in coliform and E. coli concentrations between point of collection and point of use indicates that water contamination mostly occurs within the household. Strengthening national legislation on water quality standards and promoting safe water management at the household are needed.
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10.1111/mcn.12744
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pubmed_353_13200
|
Mechanical properties of individual living cells are known to be closely related to the health and function of the human body. Here, atomic force microscopy (AFM) indentation using a micro-sized spherical probe was carried out to characterize the elasticity of benign (MCF-10A) and cancerous (MCF-7) human breast epithelial cells. AFM imaging and confocal fluorescence imaging were also used to investigate their corresponding sub-membrane cytoskeletal structures. Malignant (MCF-7) breast cells were found to have an apparent Young's modulus significantly lower (1.4-1.8 times) than that of their non-malignant (MCF-10A) counterparts at physiological temperature (37 degrees C), and their apparent Young's modulus increase with loading rate. Both confocal and AFM images showed a significant difference in the organization of their sub-membrane actin structures which directly contribute to their difference in cell elasticity. This change may have facilitated easy migration and invasion of malignant cells during metastasis.
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10.1016/j.bbrc.2008.07.078
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pubmed_764_12719
|
The fine structure of Leydig and Sertoli cells in Japanese black bears, Ursus thibetanus japonicus, was studied at different stages of reproductive activity in different seasons. Structures of Leydig cells in the testes that were spermatogenically active (May and June), inactive (November and January), and resumptive (March and April) were found to be different. The nucleus and smooth endoplasmic reticulum in Leydig cells had regressed when observed in November and January, and began to develop in March and April. Lipid droplets were numerous in Leydig cells in November and January, but few in March and April. These seasonal variations in the subcellular structures of Leydig cells corresponded to those in the steroidogenic activity of the cells. In Sertoli cells, changes in mitochondria and lipid inclusions with the seasons were detected, but the nuclei and other organelles, including the rough endoplasmic reticulum, did not change throughout the year. Lipid inclusions of both electron-dense and electron-lucent types in Sertoli cells were numerous in November and few in January. This change was reversely proportional to the number of degenerating cell masses in the luminal space, indicating that most of these lipid inclusions might be the end products of germ cells phagocytosed by the Sertoli cells. The results suggest that the seasonal changes in the morphology of Leydig cells are closely associated with their spermatogenic activity
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10.1679/aohc.60.225
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pubmed_51_5609
|
A confocal holography microscope developed at the University of Victoria uniquely combines holography with a scanning confocal microscope to non-intrusively measure fluid temperatures in three-dimensions (Herring, 1997, Abe and Iwasaki, 1999, Jacquemin et al., 2005). The Confocal Scanning Laser Holography (CSLH) microscope was built and tested to verify the concept of 3D temperature reconstruction from scanned holograms. The CSLH microscope used a focused laser to non-intrusively probe a heated fluid specimen. The focused beam probed the specimen instead of a collimated beam in order to obtain different phase-shift data for each scan position. A collimated beam produced the same information for scanning along the optical propagation z-axis. No rotational scanning mechanisms were used in the CSLH microscope which restricted the scan angle to the cone angle of the probe beam. Limited viewing angle scanning from a single view point window produced a challenge for tomographic 3D reconstruction. The reconstruction matrices were either singular or ill-conditioned making reconstruction with significant error or impossible. Establishing boundary conditions with a particular scanning geometry resulted in a method of reconstruction with low error referred to as "wily". The wily reconstruction method can be applied to microscopy situations requiring 3D imaging where there is a single viewpoint window, a probe beam with high numerical aperture, and specified boundary conditions for the specimen. The issues and progress of the wily algorithm for the CSLH microscope are reported herein.
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10.1016/j.ultramic.2012.02.005
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pubmed_620_381
|
A case of self-poisoning with sodium selenate sheep drench, along with blood and urine levels of selenium, is reported. Treatment included gastric lavage, diuresis, vitamin C, and dimercaprol, and the patient recovered without sequelae.
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pubmed_620_381
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pubmed_633_23601
|
The natural or innate immunity is the first-line defense against transformed cells. It guarantees the recognition and removal of malignant cells at an early stage and makes manifest cancers an exceptional event. Natural antibodies, which are predominantly IgM molecules, play a major role in these defense mechanisms and they have some typical features in common. They are coded by specific germline families and equipped mainly with lambda-chains, in contrast to the majority of circulating antibodies. The targets that are recognized by these antibodies are not newly synthesized proteins, but instead post-translationally modified carbohydrate structures on membrane-bound glycoproteins and glycolipids. Another typical feature of these natural IgM antibodies is their ability to induce apoptosis in vitro and in vivo in a death domain-independent manner. These results show that natural IgM antibodies represent a huge reservoir of therapeutic antibodies.
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10.2217/1750743X.1.2.241
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pubmed_890_9309
|
BACKGROUND
Acute esophageal necrosis (AEN) is a rare clinical disorder. Esophageal stenosis or obstruction is one of severe complications, but there are a few reports about surgical treatments. In such a situation, it still remains controversial which to choose, esophagectomy or bypass operation.
CASE PRESENTATION
A 61-year-old woman was admitted to the local hospital for septic shock with diabetic ketoacidosis due to necrotizing fasciitis of the right thigh. Three days later, she had hematemesis, and gastrointestinal endoscopy revealed black mucosal coloration throughout the entire esophagus. She was diagnosed as having AEN. Her general condition improved after intensive care, debridement, and treatment with antibiotics and a proton pump inhibitor; the esophageal mucosal color recovered. However, an esophageal stricture developed after 1 month, and the patient underwent gastrostomy to remove an esophageal obstruction after 3 months. She was referred to our hospital for surgical treatment 1 year and 4 months after the occurrence of AEN because of her strong desire for oral intake. Her medical condition was poor, and she could not walk due to generalized muscle weakness. After rehabilitation for 8 months, we performed an esophageal bypass using a gastric conduit via the percutaneous route rather than esophagectomy because of her multiple severe comorbidities including walking difficulty, chronic hepatitis C, cerebrovascular disease, and chronic renal failure. Minor leakage of the esophagogastrostomy occurred and was resolved with conservative treatment. The patient began oral intake on postoperative day 34 and was discharged on day 52.
CONCLUSION
Esophageal obstruction after AEN was successfully treated by esophageal bypass using a gastric conduit in a high-risk patient. Because the majority of patients with AEN have multiple severe comorbidities, assessing the medical condition of the patient adequately is important prior to choosing either an esophagectomy or bypass surgery.
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10.1186/s40792-016-0277-8
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pubmed_35_11523
|
Recently investigations have shown that the annual flux of lead from shotgun pellets to shooting range soils is significant in some countries. This paper presents the data of chemical and mineralogical analyses of soils and Pb-pellet crusts from five shooting ranges in Sweden and, based on these results, evaluates the retention of lead in these shooting range soils. In the soils, Pb-pellets and bullets are readily decomposed and transformed to crust materials composed of Pb-bearing minerals. The transformation products in the crust materials, identified by X-ray diffraction, are predominantly hydrocerussite [Pb(3)(CO(3))(2) (OH)(2)], associated with cerussite (PbCO(3)) and anglesite (PbSO(4)). In a period of 20-25 years, an average of 4.8% metallic lead in the pellets has been transformed to lead carbonate and lead sulphate, where the former is the more stable mineral in the surface environment. However, in soils relatively rich in humus an average of 15.6% metallic lead in the pellets was transformed to secondary lead compounds in the same period. The results of the chemical analyses indicate that Pb is rather immobile in the soil profile. The surficial horizon contains higher concentrations of lead (52-3400 mg kg(-1)), while lower concentrations of lead were found in the E and B horizons where the total Pb concentrations (8-37 mg kg(-1)) are within about one standard deviation of the mean reference sample concentration. An inverse relationship is revealed between the aluminium hydroxide content of the soil fraction and EDTA-extractable Pb, which suggests that these compounds have affected the retention of lead.
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10.1016/0269-7491(94)00068-o
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pubmed_857_19876
|
Flow and pressure dynamics in minute human lymphatics are unexplored. Lymphatic capillary pressure was measured by the servo-nulling technique at the foot dorsum of 14 patients with primary lymphedema and 15 healthy controls. Glass micropipettes (7-9 microns) were inserted under microscopic control into lymphatic microvessels previously stained by fluorescence microlymphography (FITC-Dextran 150,000). Mean lymphatic capillary pressure was 7.9 +/- 3.4 mm Hg in the controls and 15.0 +/- 5.1 mm Hg in the patients. The difference was significant at the P < 0.001 level. In about half of the patients and control subjects studied pressure fluctuated by more than 3 mm Hg. The mean intralymphatic pressure of lymphedema patients was slightly below mean interstitial pressure measured by J. T. Christensen, N. J. Shaw, M. M. Hamas and H. K. Al Hassan (1985, Microcirc., Endothelium, Lymphatics 2, 267-384) (17.9 mm Hg) in lower leg lymphedema. Microlymphatic hypertension present in patients with primary lymphedema is probably an important factor for edema formation.
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10.1006/mvre.1993.1041
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pubmed_1093_10037
|
OBJECTIVE
Glandular cell abnormality (GCA) in Pap smears is uncommon. Detection is important as the possibility of underlying high-grade lesions is greater in this entity than in atypical squamous cells of undetermined significance. This study was undertaken with an aim to correlate GCA cases with histology, scrutinize its mimics and identify cytologic features to segregate significant lesions from benign.
STUDY DESIGN
A total of 22,618 conventional Pap smears were retrospectively analyzed. In all, 74 GCA cases were identified, correlated with histology and reevaluated using parameters based on architectural pattern, cellular features and background.
RESULTS
This study revealed 15 false positives. On review, 11 cases [1 adenocarcinoma, 5 atypical glandular cells (AGC), not otherwise specified, 5 AGC, favor neoplasia (FN)] were recategorized as reactive. Of 9 cases reported as cervical intraepithelial neoplasia on histology, cytodiagnosis in 5 was revised from AGC-FN to high-grade squamous intraepithelial lesion involving glands. Initial overall cytohistology concordance was 79.7%. Reevaluation of the smears, based on stringent cytomorphological criteria, enhanced overall agreement to 94.59%.
CONCLUSIONS
A diagnosis of AGC has considerable clinical implications. Dissociated atypical cells, nuclear membrane, architecture and chromatin pattern are the key distinguishing features between neoplastic and benign lesions.
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10.1159/000342744
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pubmed_258_13278
|
Background
JinGuanLan (JGL) formula is a traditional Chinese medicine (TCM) developed by the Department of Pharmacology at the First Hospital of Lanzhou University. The network pharmacology approach was applied to determine the potential active compounds, therapeutic targets, and main pathways of the JGL formula to evaluate its application value in acne vulgaris.
Methods
Data on the active compounds and their related targets were obtained from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). Acne vulgaris-related targets were searched from the Online Mendelian Inheritance in Man (OMIM) database, GeneCards Database, Comparative Toxicogenomics Database (CTD), Therapeutic Target Database (TTD), and DisGeNET Database. Targets intersecting between JGL- and acne vulgaris-related targets were chosen as potential therapeutic targets. The protein-protein interaction (PPI) network of potential therapeutic targets was visualized using Cytoscape software based on the PPI data collected from the STRING database. Three topological features, namely, "Degree," "MCC," and "EPC" of each node in the PPI network were calculated using the cytoHubba plugin of Cytoscape to excavate the core targets. R program was used for the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the potential therapeutic targets. Finally, the compound-target-pathway network was constructed.
Result
Among the 148 active compounds that were identified, quercetin and kaempferol showed the highest degree of target interaction and thus may play essential roles in the pharmacological effect of the JGL formula for acne treatment. Among the 97 potential therapeutic targets that were screened out, the 6 core targets were TNF, JUN, IL6, STAT3, MAPK1, and MAPK3. A total of 2260 terms of GO enrichment analysis were obtained, including 2090 for biological processes (BP), 37 for cellular components (CC), and 133 for molecular function (MF). A total of 156 enriched KEGG pathways were identified, including TNF, IL-17, Th17 cell differentiation, MAPK, PI3K-Akt, T cell receptor, and Toll-like receptor signalling pathways.
Conclusion
This work showed that the JGL formula might reverse the pathological changes associated with acne vulgaris through its antiinflammatory effect and regulate the excessive lipogenesis in sebaceous glands via different signalling pathways. This new drug has application value and is worthy of further research and development.
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10.1155/2022/6944792
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pubmed_1001_11732
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Here we present a basic concept and several examples of methods of analysis for chemicals that disrupt cellular signaling pathways, in view of risk assessment for potential endocrine disrupting chemicals (EDCs). The key cellular signaling pathways include 1) ER/coactivator interaction, 2) AR translocation into the nucleus, 3) ER/NO/sGC/cGMP, 4) ER/Akt, 5) ER/Src, 6)ER/Src/Grb2, and 7) ER/Ca2+/CaM/CaMK pathways. These were visualized in relevant live cells using newly developed fluorescent and bioluminescent probes. Changes in cellular signals were thereby observed in nongenomic pathways of steroid hormones upon treatment of the target cells with steroid hormones and related chemicals. This method of analysis appears to be a rational approach to high-throughput prescreening (HTPS) of biohazardous chemicals, EDCs, in particular. Also described was the screening of gene expression by serial analysis of gene expression and gene chips upon applying EDCs to breast cancer cells, mouse livers, and human neuroblastoma NB-1 cells.
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pubmed_1001_11732
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pubmed_20_13103
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Gamma oscillations are a robust component of sensory responses but are also part of the background spontaneous activity of the brain. To determine whether the properties of gamma oscillations in cortex are specific to their mechanism of generation, we compared in mouse visual cortex in vivo the laminar geometry and single-neuron rhythmicity of oscillations produced during sensory representation with those occurring spontaneously in the absence of stimulation. In mouse visual cortex under anesthesia (isoflurane and xylazine), visual stimulation triggered oscillations mainly between 20 and 50 Hz, which, because of their similar functional significance to gamma oscillations in higher mammals, we define here as gamma range. Sensory representation in visual cortex specifically increased gamma oscillation amplitude in the supragranular (L2/3) and granular (L4) layers and strongly entrained putative excitatory and inhibitory neurons in infragranular layers, while spontaneous gamma oscillations were distributed evenly through the cortical depth and primarily entrained putative inhibitory neurons in the infragranular (L5/6) cortical layers. The difference in laminar distribution of gamma oscillations during the two different conditions may result from differences in the source of excitatory input to the cortex. In addition, modulation of superficial gamma oscillation amplitude did not result in a corresponding change in deep-layer oscillations, suggesting that superficial and deep layers of cortex may utilize independent but related networks for gamma generation. These results demonstrate that stimulus-driven gamma oscillations engage cortical circuitry in a manner distinct from spontaneous oscillations and suggest multiple networks for the generation of gamma oscillations in cortex.
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10.1152/jn.00137.2015
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pubmed_316_14400
|
Researchers and clinicians have tended to minimize the role of psychological characteristics of male spouse abusers, which has restricted the selection of potentially appropriate treatment interventions. A review of clinical literature on psychological characteristics of male batterers, including some studies incorporating psychometric testing, suggests that many of the characteristics of batterers are consistent with DSM-III criteria for personality disorders. Several authors have defined subtypes of batterers, which can be associated with specific types of personality disorders. Treatment programs for male spouse abusers should address the specific problems presented by patients with personality disorders, including alcohol-abusing batterers, a particularly difficult group to treat.
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10.1176/ps.39.7.763
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pubmed_1100_15461
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Intrathoracic extramedullary hematopoiesis (IEH) is a rare condition, usually asymptomatic, which accompanies a chronic hematologic disease. A 72-year-old woman with IEH is presented. The patient had no past medical history of anemia and was completely asymptomatic. Open biopsy showed extramedullary hematopoiesis (EH) due to heterozygous sickle cell anemia.
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10.1016/1010-7940(94)90119-8
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pubmed_859_18810
|
BACKGROUND/AIM
This study aimed to evaluate the prognostic value of modified geriatric nutritional risk index (mGNRI) in patients with unresectable/recurrent esophageal cancer (EC).
PATIENTS AND METHODS
We included 143 patients aged >65 years with unresectable/recurrent EC. The mGNRI was calculated as (1.489/CRP in mg/dl) + (41.7 × body mass index/22). Participants were divided into two groups: low-mGNRI (mGNRI <80, n=90) and high-mGNRI (mGNRI ≥80, n=53). We retrospectively examined the relationship between mGNRI and the prognosis of EC.
RESULTS
Median survival time in the low-mGNRI group was significantly lower than that in the high-mGNRI group (5.1 vs. 16.9 months, p<0.001). Multivariate analysis revealed that low mGNRI [hazard ratio (HR)=3.85, p<0.001] and absence of chemotherapy or chemoradiotherapy (HR=2.69, p<0.001) were independent and unfavorable prognostic factors of overall survival. Among patients who received chemotherapy or chemoradiotherapy, the mGNRI-low group had a significantly poorer prognosis than the mGNRI-high group (p<0.001). The mGNRI was the most appropriate prognostic index compared with other immune-inflammatory markers by the Akaike and Bayesian information criteria.
CONCLUSION
In patients with unresectable/recurrent EC, low mGNRI was correlated with unfavorable prognosis and was a useful independent prognostic factor.
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10.21873/anticanres.16111
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pubmed_353_3944
|
Complete duplication of the bladder and urethra is a rare entity. It may occur in the coronal and sagittal planes, and is often associated with other organ system anomalies, in particular of the gastrointestinal tract. We report an unusual variant of sagittal duplication of the bladder, in a male, associated with rudimentary hindgut duplication, and review the literature pertaining to this unusual anomaly.
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10.1016/j.jpurol.2008.02.001
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pubmed_219_24736
|
PURPOSE
To evaluate whether PDSC, an L-carnitine ester derivative of prednisolone and OCTN2 substrate, could provide a targeted delivery of the corticosteroid into the lung tissues of an asthmatic guinea pig model.
METHODS
PRED (prednisolone) and PDC (an L-carnitine prodrug of prednisolone not recognized by OCTN2) served as controls. Water solubility and logP values were determined, and PDSC and PDC in vivo were quantified by LC-MS/MS.
RESULTS
Unlike PRED, the intra-tracheal instillation of PDSC resulted in effective and prolonged accumulation of prednisolone in the lung tissues, leading to 3.8-fold higher reduction in inflammatory cell count in the bronchoalveolar fluid, and less severe lung and bronchial lesions in the asthmatic guinea pig. PDC showed similar pharmacokinetic profile to PRED, but exhibited higher efficiency (1.7-fold higher) at reducing the inflammatory cell count and the severity of lung histopathology, possibly due to the release of L-carnitine in vivo.
CONCLUSIONS
The collective data suggest that PDSC has the potential to be an effective prodrug for the treatment of asthma with concomitant reduction in systemic side effects, and that novel prodrugs produced by L-carnitine conjugation can have useful applications in the targeted accumulation of drugs in the lungs.
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pubmed_219_24736
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pubmed_1089_4852
|
Long noncoding RNAs (lncRNAs) represent a sub-group of noncoding RNAs that are longer than 200 nucleotides. The characterization of lncRNAs and their acceptance as crucial regulators of numerous developmental and biological pathways have suggested that the lncRNA study has gradually become one of the hot topics in the field of RNA biology. Many lncRNAs show spatially and temporally restricted expression patterns during embryogenesis and organogenesis. This study aimed to characterize the lncRNA profile of the fetal mouse heart at three key time points (embryonic day E11.5, E14.5, and E18.5) in its development, by performing a microarray lncRNAs screen. Gene Ontology analysis and ingenuity pathway analysis showed some significant gene functions and pathways were altered in heart development process. We compared lncRNAs profile between the three points (E14.5 vs. E11.5 [early development]; E18.5 vs. E14.5 [later development]). A total of 1,237 lncRNAs were found to have consistent fold changes (>2.0) between the three time points. Among them, 20 dysregulated lncRNAs were randomly selected and confirmed by real-time qRT-PCR. Additionally, bioinformatics analysis of AK011347 suggested it may be involved in heart development through the target gene Map3k7. In summary, this study identified differentially expressed lncRNAs in the three time points studied, and these lncRNAs may provide a new clue of mechanism of normal heart development.
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10.1002/jcb.24733
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pubmed_661_9787
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In order to predict remission in Graves' disease, it is important to recognize abnormalities of thyroid function in euthyroid subjects who are prone to be thyrotoxic as well as in those who are untreated thyrotoxic patients. Changes in thyroid function during thionamide therapy and in remission are also very important to understand the remission and the relapse in Graves' disease. From the careful analysis of thyroid-related abnormalities in each stage of the clinical course of Graves' disease, it is suggested that to bring patients into remission by thionamide therapy is merely to return them to a thyroid functional status prior to the development of clinical active Graves' disease. Various methods employed to predict remission are useful in differentiating active patients from those in remission but none of them can predict the duration of remission.
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pubmed_661_9787
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pubmed_794_23413
|
BACKGROUND
Inadequate adherence to hypertension (HT) clinical standards by healthcare providers is one of the major barriers for HT management. We examined the effectiveness of four short instructional training videos on HT management.
METHODS
Eighteen primary health care facilities were randomly selected using systematic sampling from five districts in the Dar es Salaam region, Tanzania. Pre-post provider knowledge assessments were conducted six months after training and provider performance was measured using patient observations on 8-10 consecutive adult patients per facility. A Screening Quality Index (SQI), comprised of ten HT screening standards, was used to measure adherence.
RESULTS
Pre-post knowledge scores improved significantly, for, time between blood pressure (BP) readings (28.1% to 72.7%, p=0.01), BP threshold for patients with complications (21.2% to 97.0%, p<0.001), and lifestyle/dietary counseling (from 36.4% to 97.0%, p<0.001). SQI was significantly higher following the training for all provider groups; Nurses (3.0±3.5 to 8.4±1.0, p<0.001), Assistant Medical Officers and Medical Officers (3.5±4.1 to 7.6±2.4, p<0.001), and Assistant Clinical Officers and Clinical Officers (5.4±3.8 to 8.4±2.0, p<0.001). After training, significantly higher adherence was evident for key aspects of managing patients with HT: e.g., counseling on medication (62.1% to 92.7%, p=0.002), side effects (41.4% to 56.1%, p=0.009), reducing caloric intake (69.0 % to 95.1%, p=0.003), reducing cooking salt (65.5% to 97.6%, p<0.01), increasing physical activity (55.2% to 92.7% p<0.001), stopping/reducing cigarette smoking (24.1% to 63.4%, p=0.001), and reducing alcohol consumption (24.1% to 68.3%, p<0.001). SQI was significantly associated with number of years of provider experience (more than 2 years), type of primary healthcare facility (public facility), and exposure to the training intervention.
CONCLUSION
Training with short instructional videos can improve provider competency and clinical performance for HT management. The strategy has the potential to enhance effective implementation of HT control strategies in primary care clinics in Tanzania and elsewhere.
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10.1186/s12913-022-08064-5
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pubmed_724_10945
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All-trans retinoic acid (atRA), a metabolite of vitamin A, is essential for embryonic development. Thus the spatial and temporal dispersal of RA must be tightly controlled. Previous studies show that excessive atRA led to growth inhibition and p21 accumulation in mouse embryonic palatal mesenchymal (MEPM) cells. We reported here the identification of p21 as a required mediator during atRA-induced growth inhibition. atRA caused a G1 arrest in the cell cycle with an increase in the proportion of cells in G0/G1 and a decrease in the proportion of cells in S phase. In addition to a marked effect on cell cycling, atRA also triggered DNA fragmentation, reflected by an increase of the fraction of cells in the sub-G(1) population. Western blot analysis revealed that atRA treatment led to an increase in p21 level and a decrease in cyclin D1 protein and Rb phosphorylation. Using luciferase assay with reporter gene regulated by p21 promoter, we showed that atRA increased the reporter activity in a dose-dependent manner; and p21 siRNA blocked the growth inhibition by atRA, suggesting that p21 is required for atRA-mediated growth inhibition. Moreover, the induction of p21 by atRA was partially attenuated when RAR was silenced with specific siRNA. atRA stimulated RARE-driven reporter gene activity dose-dependently. Using chromatin immunoprecipitation, we demonstrated that RAR protein could bind to the p21 promoter. Taken together, our results indicate p21 is responsible for atRA-induced growth inhibition of MEPM cells and RAR plays a role during this process.
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10.1002/jcb.21773
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pubmed_715_19635
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Wheat alpha-amylase inhibitors represent an important tool in engineering crop plants against bean bruchids. Because Acanthoscelides obtectus is a devastating storage bean insect-pest, we attempted to purify and characterize its gut alpha-amylases, to study their interaction with active proteinaceous inhibitors. Two digestives alpha-amylases (AoA1 and AoA2) were purified from gut larvae, showing molecular masses of 30 and 45 kDa for each one, respectively. The stoichiometry interaction between these alpha-amylases with two wheat inhibitors (0.19 and 0.53) showed a binding complex of 1:1 enzyme:inhibitor. In vivo activities of these inhibitors against A. obtectus were also evaluated using a rich ammonium sulfate inhibitor fraction (F(20)(-)(40)) and purified inhibitors after reversed phase high-performance liquid chromatography columns. Incorporation of three different inhibitor concentrations (0.25, 0.5, and 1.0% w/w) into artificial seeds showed that addition of the purified 0.19 inhibitor at the highest concentration (1.0%) reduced the larval weight by 80%. Similar data were observed when 0.53 inhibitor was incorporated at 0.5%. When the concentration of purified 0.53 was enhanced to 1.0%, no larvae or adult emergence were observed. Our data suggest that these alpha-amylase inhibitors present great potential for use in Phaseolus genetic improvement programs.
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10.1021/jf049343x
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pubmed_691_3150
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We evaluated the presence of thromboxane B2, the stable metabolite of thromboxane A2, early in the course of acute myocardial infarction (AMI) in both animal and patient studies. In an open-chest model, the left anterior descending artery (LAD) was isolated and the great cardiac vein was cannulated in nine dogs. Following occlusion of the LAD, there was an increase in thromboxane B2 concentration from 0.77 +/- 0.0093 to 1.79 +/- 0.46 pmol/ml (p less than 0.05) and 1.96 +/- 0.48 pmol/ml (p less than 0.05) at 1 and 5 minutes, respectively, following coronary occlusion. At 30 and 60 minutes after occlusion there was no significant increase compared to the baseline. In 17 patients with AMI the mean thromboxane B2 concentration was 0.96 +/- 0.13 pmol/ml at 4.88 +/- 0.40 hours after the onset of chest pain. In 12 patients with sequential samples before and after restoration of patency of the occluded vessel, the initial concentration was 0.71 +/- 0.058 pmol/ml. At 5 minutes after restoration of patency thromboxane B2 concentration was 1.1 +/- 0.17 pmol/ml (p = 0.05). One hour later a return to baseline was noted (0.82 +/- 0.75 pmol/ml). Two patients with the highest thromboxane B2 concentrations (2.0 and 2.6 pmol/ml) were unable to have successful recanalization. We conclude that generation of thromboxane A2 occurs during the early stages of AMI and may be an important pathophysiologic phenomenon in AMI.
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10.1016/0002-8703(84)90447-2
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pubmed_202_8714
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To test the hypothesis that rapid eye movement (REM) sleep in schizophrenic patients is associated with cognitive function, we studied 18 schizophrenic inpatients by means of electroencephalograms taken during sleep in their own hospital beds after a minimum 2-wk medication withdrawal period. Patients underwent neuropsychological tests to measure memory function and other aspects of cognitive performance. REM sleep measures demonstrated positive and negative correlations with cognition and memory measures, depending on when REM occurred after sleep onset. Minutes of REM sleep and REM density in the first period correlated negatively with performance, while REM minutes occurring after the first REM period correlated positively with neuropsychological performance. Further work should test whether phasic REM sleep regulation at the beginning of the night plays a compensatory role for neuropsychological dysfunction in schizophrenics.
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10.1016/0006-3223(92)90221-k
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pubmed_195_17174
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Implants are widely used for orthopaedic applications such as fixing fractures, repairing non-unions, obtaining a joint arthrodesis, total joint arthroplasty, spinal reconstruction, and soft tissue anchorage. Previously, orthopaedic implants were designed simply as mechanical devices; the biological aspects of the implant were a byproduct of stable internal/external fixation of the device to the surrounding bone or soft tissue. More recently, biologic coatings have been incorporated into orthopaedic implants in order to modulate the surrounding biological environment. This opinion article reviews current and potential future use of biologic coatings for orthopaedic implants to facilitate osseointegration and mitigate possible adverse tissue responses including the foreign body reaction and implant infection. While many of these coatings are still in the preclinical testing stage, bioengineers, material scientists and surgeons continue to explore surface coatings as a means of improving clinical outcome of patients undergoing orthopaedic surgery.
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pubmed_195_17174
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pubmed_1123_24346
|
Roy pioneers the concept and practice of risk management of disastrous events via his safety-first principle for portfolio selection. More specifically, his safety-first principle advocates an optimal portfolio strategy generated from minimizing the disaster probability, while subject to the budget constraint and the mean constraint that the expected final wealth is not less than a preselected disaster level. This article studies the dynamic safety-first principle in continuous time and its application in asset and liability management. We reveal that the distortion resulting from dropping the mean constraint, as a common practice to approximate the original Roy's setting, either leads to a trivial case or changes the problem nature completely to a target-reaching problem, which produces a highly leveraged trading strategy. Recognizing the ill-posed nature of the corresponding Lagrangian method when retaining the mean constraint, we invoke a wisdom observed from a limited funding-level regulation of pension funds and modify the original safety-first formulation accordingly by imposing an upper bound on the funding level. This model revision enables us to solve completely the safety-first asset-liability problem by a martingale approach and to derive an optimal policy that follows faithfully the spirit of the safety-first principle and demonstrates a prominent nature of fighting for the best and preventing disaster from happening.
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10.1111/j.1539-6924.2011.01751.x
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pubmed_671_2707
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A technique is described which couples the aqueous aldehyde fluorescence (Faglu) method [5,6] with polyethylene glycol (PEG) embedding to obtain sections of brain as thin as 2 microns for light microscopic examination. Blocks from rat brains perfused with Faglu solution were embedded in PEG, sectioned on a rotary microtome and examined for amine fluorescence. Both catecholaminergic perikarya and their terminal arborizations were observed with high resolution in 2 micron sections. Single neurons could be traced in serial sections and varicosities as well as intervaricose segments were visible in terminal regions. This technique offers the further advantage of fixation compatible with electron microscopy, immunohistochemistry and other neuroanatomical methods. PEG-embedding of Faglu-fixed tissue thus provides a useful addition to existing fluorescence histochemical techniques for the visualization of catecholamines.
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10.1016/0361-9230(82)90117-4
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pubmed_1097_4936
|
UNLABELLED
Removal of airborne particles in airborne infection isolation rooms is important for infection control of airborne diseases. Previous studies showed that the downward ventilation recommended by Centers for Disease Control and Prevention (CDC) could not produce the expected 'laminar' flow for pushing down respiratory gaseous contaminants and removing them via floor-level exhausts. Instead, upper-level exhausts were more efficient in removing gaseous contaminants because of upward body plumes. The conventional wisdom in the current CDC-recommended design is that floor-level exhausts may efficiently remove large droplets/particles, but such a hypothesis has not been proven. We investigated the fate of respiratory particles in a full-scale six-bed isolation room with exhausts at different locations by both experimental and computational studies. Breathing thermal manikins were used to simulate patients, and both gaseous and large particles were used to simulate the expelled fine droplet nuclei and large droplets. Gaseous and fine particles were found to be removed more efficiently by ceiling-level exhausts than by floor-level exhausts. Large particles were mainly removed by deposition rather than by ventilation. Our results show that the existing isolation room ventilation design is not effective in removing both fine and large respiratory particles. An improved ventilation design is hence recommended.
PRACTICAL IMPLICATIONS
Our findings of the relatively poor performance of fine-particle removal by the existing CDC design of isolation room ventilation suggests a need for improvement, and the findings of the removal of large particles by deposition, not by ventilation, suggest that floor-level exhausts are unnecessary, and that regular surface cleaning and disinfection is necessary, thus providing evidence for maintaining isolation room surface hygiene.
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10.1111/j.1600-0668.2010.00653.x
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pubmed_898_25899
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Accurate identification of compound-protein interactions (CPIs) in silico may deepen our understanding of the underlying mechanisms of drug action and thus remarkably facilitate drug discovery and development. Conventional similarity- or docking-based computational methods for predicting CPIs rarely exploit latent features from currently available large-scale unlabeled compound and protein data and often limit their usage to relatively small-scale datasets. In the present study, we propose DeepCPI, a novel general and scalable computational framework that combines effective feature embedding (a technique of representation learning) with powerful deep learning methods to accurately predict CPIs at a large scale. DeepCPI automatically learns the implicit yet expressive low-dimensional features of compounds and proteins from a massive amount of unlabeled data. Evaluations of the measured CPIs in large-scale databases, such as ChEMBL and BindingDB, as well as of the known drug-target interactions from DrugBank, demonstrated the superior predictive performance of DeepCPI. Furthermore, several interactions among small-molecule compounds and three G protein-coupled receptor targets (glucagon-like peptide-1 receptor, glucagon receptor, and vasoactive intestinal peptide receptor) predicted using DeepCPI were experimentally validated. The present study suggests that DeepCPI is a useful and powerful tool for drug discovery and repositioning. The source code of DeepCPI can be downloaded from https://github.com/FangpingWan/DeepCPI.
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10.1016/j.gpb.2019.04.003
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pubmed_949_9099
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The authors present 25 patients ranging in age from 8 to 16 years who had malignant supratentorial astrocytomas. This type of lesion represents one of the most important and statistically significant causes of morbidity and mortality in late childhood. Compared to adult malignant supratentorial astrocytomas, these lesions seem to show a better survival rate. The reason is unknown. The authors present their experience regarding the importance of radical removal and histology for a better prognosis.
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10.1007/s003810050093
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pubmed_316_4937
|
Membrane-bound (H+ + K+)-ATPase purified from hog gastric mucosa was exposed to limited papain digestion. Such treatment resulted in a rapid inhibition of the K+-stimulated adenosine triphosphatase and p-nitrophenyl phosphatase activities, with about 90% of these activities lost after 3 min incubation at 37 degrees C with 0.1 units of papain per mg of enzyme protein. Parallel to the inhibition of the enzyme activities, there was a production of a 77 kDa membrane-bound fragment containing the aspartyl phosphate residue of the phospho-intermediate. This fragment accounted for about 45% of the total enzyme protein after the 3 min papain treatment. The digestion barely affected the steady-state level of phosphorylation, allowed the aspartyl phosphate of the 77 kDa fragment to undergo the transition to the E2P form, and did not significantly alter the fraction of ADP-sensitive phosphoenzyme. The presence of KCl, however, depressed the steady-state level of phosphoenzyme formed from [gamma-32P]ATP considerably less than that of the control enzyme. With further exposure to papain the 77 kDa peptide became fragmented into a 28 kDa soluble peptide that retained the phosphorylating site. Binding of fluorescein 5'-isothiocyanate (FITC) to the native enzyme did not affect the sites of papain hydrolysis because the same peptide fragments were obtained. The FITC reaction site was also in the 28 kDa soluble peptide fragment.
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10.1016/0167-4838(87)90248-2
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pubmed_821_19431
|
Forty three patients with severely resorbed maxillae who had been referred for implant treatment were assigned to 1 of 3 treatment options: bone grafting and implant placement (graft group), modified implant placement with no bone grafting (trial group), or optimized complete dentures (no-implant group). Sixteen, 20, and 7 patients, respectively, were assigned to the 3 groups. The patients have been examined annually, and at the time of this report they had been followed for 3 to 5 years after treatment. At the 1-year follow-up, 10% (22 of 221) of the implants had been lost, and at the 2-year follow-up, 18% of the implants had been lost (40 of 221; 25% in the graft and 13% in the trial group); after that time, no further losses occurred. Life table analysis showed cumulative success rates of 82% in the graft group and 96% in the trial group after 1 year, and 74% and 87%, respectively, at the final examination after 3 to 5 years. The failure rate was higher in smokers than in non-smokers. A substantial reduction of the grafted bone, especially of onlay grafts, occurred early after grafting surgery in many patients. Mean marginal peri-implant bone loss was 0.6 mm during the period from prosthesis connection to the 1-year follow-up, and from the 1-year to the 3-year follow-up, average peri-implant bone loss was 0.3 mm in the graft group and 0.5 mm in the trial group. The results corroborated previous findings that patients with severely resorbed maxillae have an increased risk of implant failure in comparison to patients with good bone quantity and quality. However, in this investigation, practically all implant losses occurred during the first 2 years, whereupon a steady state seemed to follow for up to 5 years after loading.
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pubmed_821_19431
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pubmed_737_13261
|
Endoplasmic reticulum (ER) stress and the activation of the unfolded protein response (UPR) have been implicated in a number of complications associated with diabetes mellitus including micro- and macrovascular dysfunction. In this study we examine ER stress levels in blood cells isolated from human subjects with metabolic syndrome and in healthy controls. Total RNA and protein were isolated from leukocytes and the levels of specific ER stress markers were quantified by real-time-PCR and immunoblot analysis. Our results indicate that, compared to healthy controls, individuals with metabolic syndrome have elevated mRNA levels of genes indicative of ER stress; including spliced XBP-1 (sXBP-1), Grp78, and CHOP. Induced ER stress levels correlate with blood glucose but not plasma lipid concentration. Furthermore, in healthy individuals, a standard 75 g oral glucose challenge produced a significant elevation in spliced XBP-1 (1.3 fold), Grp78 (2.0 fold), and calreticulin (3.5 fold) mRNA 60 min post challenge and a significant increase in Grp78 (2.0 fold), calreticulin (2.7 fold) protein levels 2 h postchallenge, relative to fasting levels. The UPR was also activated ex vivo, in human leukocytes cultured in the presence of 15 mmol/l glucose, supporting a specific role for glucose. The oral glucose challenge was associated with a significant increase in the expression of inflammatory cytokines, including interleukin (IL)-1α/β, IL-6, and IL-8, that may result from ER stress. These findings suggest that there is an association between both acute and chronic dysglycemia and ER stress in humans.
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10.1038/oby.2011.144
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pubmed_295_8457
|
The human proteome contains approximately 20,000 proteins, and it is estimated that more than 600 of them are functionally important for various types of cancers, including nearly 400 non-enzyme proteins that are challenging to target by traditional occupancy-driven pharmacology. Recent advances in the development of small-molecule degraders, including molecular glues and heterobifunctional degraders such as proteolysis-targeting chimeras (PROTACs), have made it possible to target many proteins that were previously considered undruggable. In particular, PROTACs form a ternary complex with a hijacked E3 ubiquitin ligase and a target protein, leading to polyubiquitination and degradation of the target protein. The broad applicability of this approach is facilitated by the flexibility of individual E3 ligases to recognize different substrates. The vast majority of the approximately 600 human E3 ligases have not been explored, thus presenting enormous opportunities to develop degraders that target oncoproteins with tissue, tumour and subcellular selectivity. In this Review, we first discuss the molecular basis of targeted protein degradation. We then offer a comprehensive account of the most promising degraders in development as cancer therapies to date. Lastly, we provide an overview of opportunities and challenges in this exciting field.
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10.1038/s41568-021-00365-x
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pubmed_106_8737
|
Percutaneous transluminal angioplasty (PTA) of infrainguinal arteries has been frequently reported in the literature. Independent of the technical feasibility, the results, in short-and long-term follow-up differ among published series. The objective of this article was to assess the long-term results of angioplasty in small, (<3 cm) segmental lesions of the superficial femoral artery treated with primary stenting. Eighteen patients (12 men, 6 women) with lesions of the superficial femoral artery smaller than 3 cm were selected for endovascular treatment and follow-up. The median patient age was 65 years (range, 54 to 84). The indication for treatment was intermittent claudication in 7 patients and critical ischemia (ischemic pain associated with trophic lesions) in 11 patients (62%). Of these, 13 lesions were stenoses and 5 total occlusions. The run-off was good in 15 patients who had more than 2 distal arteries and 3 had only 1 patent artery. During follow-up, all patients were observed with physical examination, progressive exercise treadmill test; pulse volume was measured with Doppler and duplex scan after 1, 3, and 6 months, and then twice a year. There was only 1 primary failure; the initial success rate was 94%. During follow-up of 40 months (6 to 70 months), only 1 patient presented with thrombosis of the stent 6 months after the procedure. There was no symptomatic restenosis in our study. One patient suffered an acute myocardial infraction after 45 months and died. The primary patency after 1 and 3 years was 88%. No patient was lost to follow-up. Primary stenting of segmental lesions (less than 3 cm) of the superficial femoral artery produced satisfactory results immediately and during long-term follow-up.
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10.1177/153857440303700406
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pubmed_397_62
|
The comparison of the adolescent boxer Hagesidamus and his trainer Ilas to Patroclus and Achilles in Pindar's Olympian 10.16-21 and the subsequent comparison of Hagesidamus to Ganymede in Olympian 10.99-105 suggest that the relationship was in some sense pederastic, particularly in the wake of Aeschylus' treatment of Achilles and Patroclus in these terms in Myrmidons. This possibility motivates a broader examination of the evidence for such relationships in fifth-century Greece. There is no doubt that the palaestra was a central locus for the formation of pederastic liaisons and that athletic nudity was integral to the esthetic construction of adolescent beauty. There is also no doubt that the trainer's position afforded him regular intimacy and close physical contact with boys; several Hellenistic texts take for granted the erotic opportunities connected with the position. The Solonian law presuming to protect pupils from such relationships, attested in Aeschines, was probably a late fifth-century development in reaction to their common occurrence in earlier generations. Evidence also exists for lovers acting as financial backers to boy athletes or as informal trainers. Some of the most intriguing evidence for the conflation of the trainer's and lover's roles can be found in red-figure vase painting of the late sixth and fifth centuries.
|
10.1300/j082v49n03_05
|
pubmed_200_20391
|
BACKGROUND
Substance abuse worsens the course of schizophrenia, but it is not known whether or not there are differences between specific substances concerning their association with the hospitalizations of patients with schizophrenia.
AIMS
The primary aims of this study were to examine the possible associations between amphetamine, cannabis, and opioid abuse, and the risk of hospitalizations among patients with schizophrenia.
METHODS
The study population consisted of 146 patients with ICD-defined schizophrenia from two different geographical sites in Finland, and it included both inpatients and outpatients. Data were collected retrospectively from the patients' medical files. Substance abuse was defined as either harmful use or dependence according to ICD-10.
RESULTS
The cumulative prevalence of substance abuse was 10.9% (16/146) for cannabis, 8.9% (13/146) for amphetamine, and 4.1% (6/146) for opioids. Among patients with schizophrenia and abuse of any substance, the number of hospitalizations was about 1.5-fold when compared to those without substance abuse. The incidence rate ratio for hospitalizations was 2.9 (95% CI 2.47-3.63) for opioids, 2.0 (1.71-2.41) for amphetamine, and 1.6 (1.33-1.84) for cannabis, when compared with no abuse of each substance. The risk of hospitalizations was significantly higher for opioids when compared with amphetamine (p < 0.001) or cannabis (p < 0.001).
CONCLUSIONS
Harmful use or dependence of opioids among patients with schizophrenia is associated with significantly higher risk of hospitalizations than either harmful use or dependence of amphetamine or cannabis.
|
10.3109/08039488.2015.1059884
|
pubmed_504_12066
|
Water confined on metal oxide surface plays significant roles in heterogeneous catalysis. Heteropolyacid, a 1.2 nm-metal oxide cluster with well-defined structure, is applied as a model to understand the dynamics of water on its surface. The surface water strongly associates with heteropolyacid cluster and form the so-called 'pseudoliquid phase' where catalytic reactions are conducted. Broadband dielectric spectroscopy and differential scanning calorimetry have been applied to probe the dynamics of water in this pseudoliquid phase. A supercooling phase transition of water below its normal melting temperature and a dipolar glassy relaxation behaviour due to the hindered dynamics of water have been observed. The rich dynamic behavior on the surface of such well-defined metal clusters provide new perspectives to understand the properties of surface water and their relation to catalytic performance of heteropolyacid.
|
10.1002/cphc.202000832
|
pubmed_515_18681
|
As important analysis tools, microscopes with high spatial resolution are indispensable for scientific research and clinical diagnosis. We report a proof-of-principle experimental demonstration of a two-arm microscope scheme and show that, by measuring the second-order correlation of light fields, more details of an object can be obtained through recording more information about the initial illumination field. The effects arising from the transverse coherence length and the axial correlation depth of the illumination field are also discussed.
|
10.1364/ol.34.001222
|
pubmed_929_16821
|
Radiation resistant bacteria genus Deinococcus species were well studied on DNA repair and anti-oxidative stress response mechanisms. There are many protection factors as enzymatic and nonenzymatic involved. One of them is intracellular redox potential as like thiol compounds including cysteine acts as primary protectant against oxidation stress. A gene cluster consisting of the genes Dgeo_1986 and Dgeo_1987 of Deinococcus geothermalis was identified as a cystine importer. The expression levels of dgeo_1986 and dgeo_1987 were up-regulated by over 60-fold and 4-fold during the late exponential (L) growth phase, respectively. The double-knockout mutant of dgeo_1986 and dgeo_1987 was reduced in cystine and thiol concentrations and leading to enhanced sensitivity against H2O2 stress. The expression of catalase (Dgeo_2728) as an enzymatic anti-oxidant is more induced in the wild-type strain than the Δdgeo_1986-87 strain at the late growth phase. The expression level of the oxidative stress response regulator OxyR (Dgeo_1888) is dependent on the intracellular redox balance. That is, when the intracellular thiol content was reduced in the wild-type strain during the L phase, OxyR was clearly induced. Interestingly, the expression level of OxyR was higher in the Δdgeo_1986-87 strain than in the wild-type strain upon H2O2 treatment. Although OxyR was induced by H2O2 treatment in Δdgeo_1986-87 strain, where intracellular redox potential of cystine was reduced as a thiol compound due to reduced cystine import, the relative level of expression of catalase was unexpectedly down-regulated. Therefore, the catalase induction system as an enzymatic antioxidant protection should be affected via the cystine importer but not rely on the OxyR controlled manner.
|
10.1007/s10482-020-01388-4
|
pubmed_648_21639
|
The present study was carried out to gain consumer insights on the use of tempeh (a fermented soy bean product) to improve the healthiness of beef patties and to determine the acceptable level of tempeh (10%, 20%, or 30%) in the patty. The study consisted of conducting two focus groups (n = 15), a pilot sensory evaluation, and a full consumer sensory study. The focus groups were asked about their consumption of beef patties, attitudes towards processed meat, attitudes towards negative aspects of red meat consumption, and attitudes towards tempeh consumption, as well as sensory perceptions of the cooked patties and their visual acceptance of raw patties. Focus group discussions suggested that there was a market for the product if consumers were informed of tempeh health benefits. Participants seemed more willing to choose how to balance their diet with an antioxidant source than buy a beef patty with added antioxidants. The focus group participants rated the visual attributes of raw patties from all treatments and it was found that the 20% tempeh and 30% tempeh patties were ranked lower (p < 0.05) than the others. Overall, the sensory experiments showed that the inclusion of 10% tempeh was the most acceptable level of addition. There were no significant (p > 0.05) differences between the control and 10% tempeh patties for overall acceptability or acceptance of flavor. However, 10% tempeh patties were found to be more tender and juicier than the control (p < 0.05). A proper knowledge and awareness of consumers about the benefits of tempeh could allow the development of beef containing tempeh products.
|
10.3390/foods9010063
|
pubmed_815_4787
|
Activation of the Saccharomyces cerevisiae PHO5 gene by phosphate starvation is accompanied by the disappearance of two pairs of positioned nucleosomes that flank a short hypersensitive region in the promoter. The transcription factor Pho4 is the key regulator of this transition. By in vitro footprinting it was previously shown that there is a low affinity site (UASp1) which is contained in the short hypersensitive region in the inactive promoter, and a high affinity site (UASp2) which is located in the adjacent nucleosome. To investigate the interplay between nucleosomes and Pho4, we have performed in vivo footprinting experiments with dimethylsulfate. Pho4 was found to bind to both sites in the active promoter. In contrast, it binds to neither site in the repressed promoter. Lack of binding under repressing conditions is largely due to the low affinity of Pho4 for its binding sites under these conditions. Despite the increased affinity of Pho4 for its target sites under activating conditions, binding to UASp2 is prevented by the presence of the nucleosome and can only occur after prior disruption of this nucleosome in a process that requires UASp1. Protection of the PHO5 UASp2 by the nucleosome is not absolute, however, since overexpression of Pho4 can disrupt this nucleosome even when UASp1 is deleted. Also under these conditions, with only UASp2 present, all four nucleosomes at the PHO5 promoter are disrupted, whereas no chromatin change at all is observed when both UAS elements are destroyed.
|
10.1002/j.1460-2075.1994.tb06811.x
|
pubmed_148_8267
|
The sea catfish is a relatively abundant teleost fish. Its placement on the phylogenetic scale remains in question, although its brain resembles grossly those of some of the other teleosts which also possess pedunculated olfactory bulbs. The forebrain of Galeichthys felis consists of two hemispheres which lack lateral ventricles. They are joined at the midline by a thin membrane ventromedially and by the hippocampal and anterior commissures. The telencephalic hemispheres are overlaid by a single, ventrolaterally attached membrane which is continuous rostrally with the roofs of the olfactory ventricles. Six basic nuclear regions are evident in the telencephalon of the sea catfish: a dorsomedial, a ventromedial, a ventral, a lateral, a dorsal and a central. Dorsomedially, the primordial hippocampal formation is divided into an anterior continuation, a primordial dentate gyrus, a primordial cornu ammonis and a primordial subiculum. Ventromedially, the precommissural septum consists of the medial septal nucleus (pars dorsalis and pars ventralis), the lateral septal nucleus and the nuclei of the hippocampal and anterior commissure. Ventrally, the medial and the lateral zones and the medial island constitute the tuberculum olfactorium. The primordial general pallium comprises the dorsal area. Laterally, the primordial piriform cortex and the prepiriform region overlie the relatively large primordial amygdaloid complex, which includes an anterior anygdaloid nucleus, a primordial corticomedial amygdaloid nucleus and a primordial basolateral amygdaloid nucleus. The hyperstriatum, the neostriatum, and paleostriatum augmentatum and the paleostriatum primitivum constitute the central region. Basic fiber systems in Galeichthys felis which are homologous to those of higher vertebrates include the medial and the lateral olfactory tracts, the fornix, the medial and the lateral forebrain bundles, the stria medullaris pathways and the stria terminalis. In spite of the lack of lateral telencephalic ventricles in this form, nuclear areas were defined which, on the basis of topography, cellular morphology and fiber pathways, were homologized with the six basic regions found in the forebrain of higher vertebrates. The basic pattern of the fiber pathways present in the sea catfish corresponds to that found in the other submammalian vertebrates.
|
pubmed_148_8267
|
pubmed_257_17838
|
47 hydrocephalic children (mean age 10.4 years) were examined on average 7.9 years after initial shunting. The etiology of hydrocephalus was classified into 5 groups as follows: perinatal intraventricular hemorrhage 19, congenital obstructive hydrocephalus 15, intracranial cysts 5, severe intracranial anomalies 4 and central nervous system infections 4 children. Audiological examination included pure-tone audiometry, tympanometry, registration of stapedius reflex thresholds and adaptation. A sensorineural high-frequency hearing loss was found in 18 (38%) of 47 examined shunt-treated hydrocephalic children, and 11 of the losses could be classified as the retrocochlear type. The differences of the mean hearing thresholds between the etiological groups of childhood hydrocephalus were minimal.
|
10.1016/0165-5876(89)90227-9
|
pubmed_1123_25154
|
Cholesterol plays an important role in determining the biophysical properties of biological membranes, and its concentration is tightly controlled by homeostatic processes. The intracellular transport of cholesterol among organelles is a key part of the homeostatic mechanism, but sterol transport processes are not well understood. Fluorescence microscopy is a valuable tool for studying intracellular transport processes, but this method can be challenging for lipid molecules because addition of a fluorophore may alter the properties of the molecule greatly. We discuss the use of fluorescent molecules that can bind to cholesterol to reveal its distribution in cells. We also discuss the use of intrinsically fluorescent sterols that closely mimic cholesterol, as well as some minimally modified fluorophore-labeled sterols. Methods for imaging these sterols by conventional fluorescence microscopy and by multiphoton microscopy are described. Some label-free methods for imaging cholesterol itself are also discussed briefly.
|
10.1016/B978-0-12-386487-1.00017-1
|
pubmed_939_10349
|
BACKGROUND
Early diagnosis is crucial for the treatment of childhood cancer as it in some cases can prevent progression of disease and improve prognoses. However, childhood cancer can be difficult to diagnose and barriers to early diagnosis are multifactorial. New knowledge about factors influencing the pathway to diagnosis contribute to a deeper understanding of the mechanisms that influence this time span. Qualitative research in the field is sparse but can be expected to lead to additional useful insights that could contribute to efforts shorten time to diagnosis. The purpose of this study was to explore parents' experiences of the pathway to diagnosis in the time between their noticing bodily or behavioural changes and their child's diagnosis.
METHODS
The study is a qualitative interview study carried out in large Danish hospital. Thirty-two interviews with a total of 46 parents of children with cancer were included for analysis. The children were diagnosed with haematological cancers (n = 17), solid tumours (n = 9) or brain tumours (n = 6). Data were analysed applying the theoretical model of pathways to treatment and an inductive-deductive approach. A revised 'diagnostic triage' model was developed and validated by member checking.
RESULTS
The pathway to diagnosis was influenced by various factors which we present as consistent parts of a new diagnostic triage model. Each factor impacts the level of urgency assigned to bodily and behavioural changes by parents, general practitioners and specialists. The model of diagnostic triage was developed and validated to understand mechanisms influencing time from the point parents notice changes in their child to diagnosis. The model identifies dynamic movement between parental triage in everyday life and professional triage in a healthcare system, both affecting appraisal and case escalation according to: 1) the nature of bodily and behavioural changes, 2) parental intuition, 3) social relations, 4) professional-child-parent interaction, and 5) specialist-child-parent interaction.
CONCLUSIONS
Diagnostic triage is a model which explains mechanisms that shape the pathway to diagnosis. It is a contribution aimed at supporting the clinical diagnostic process, that ultimately could ensure more timely testing, referral and diagnosis, and also a novel theoretical framework for future research on diagnostic pathways.
|
10.1186/s12913-020-05821-2
|
pubmed_50_357
|
BACKGROUND/AIMS
The best treatment for an avulsed tooth is immediate replantation. If this is not possible, a proper transport medium is required for the maintenance of viability of the periodontal ligament cells (PDL). The aim was to systematically review the efficacy of different storage media used for the survival of PDL cells of avulsed teeth in the in vitro setting.
METHODS
The search strategy was based on the MeSH keywords in PubMed/MEDLINE: "Transport media for avulsed teeth," "Storage media for avulsed teeth," "Knocked out teeth," "Tooth avulsion," "Biological transport of avulsed tooth," "Cell survival of avulsed tooth," "Cell viability of avulsed tooth," "Tooth replantation," and "Periodontal ligament in avulsed teeth." The "AND" and "OR" Boolean operators were applied to combine keywords. Each study was evaluated for eight criteria, including use of human PDL, in vitro cell culture models, the number of passages, types of storage media, percentages of surviving PDL cells, pH and osmolality of storage media, and the type of test used to asses PDL viability.
RESULTS
In 15 selected studies, nine storage media (HBSS, tap water, DMEM, milk, saliva, 10% and 20% propolis, Gatorade, and Viaspan) were analyzed at six time points. For storage up to 2 hours, HBSS, DMEM, milk, 10% propolis, 20% propolis, and Viaspan conserved more than 80% of PDL viability. For storage at 24 hours, Viaspan showed best cell survival at 88.4%, followed by DMEM (70.9%) and 10% propolis (68.3%). Milk and HBSS showed similar PDL survival at 24 hours (57.2% and 57.3%, respectively).
CONCLUSIONS
Milk remains the most convenient, cheapest, and readily available solution in most situations while also being capable of keeping PDL cells alive. Further studies are required to evaluate the efficacy of more commonly found storage media besides milk.
|
10.1111/edt.12437
|
pubmed_892_18346
|
We have demonstrated previously that the activity of schedule-induced polydipsia (SIP) was persistently depressed after successive lesions of the bilateral symmetrical locus coeruleus and the ventral tegmental area. The hypothesis that central catecholaminergic neurons mediate animal behaviors in arousal or coping processes, e.g., SIP, was tested by the demonstration of concomitant changes of transmissions in regions of appropriate nerve terminals. By using the high performance liquid chromatography coupled with electrochemical detection methods, the current experiments were designed to examine the regional turnover of monoamines in the performance of SIP of the control rats by measurements of the biochemical derivatives including dopamine (DA), norepinephrine (NE), serotonin (5-HT), 3,4-dihydroxyphenylacetic acid (DOPAC), dihydroxyphenylalanine (DOPA), 4-hydroxy-3-methoxyphenylglycol-4-sulfate (MHPG-SO4) and 5-hydroxyindoleacetic acid (5-HIAA). It was found that rats in the performance of SIP, the DA levels and DA synthesis and utilization in the limbic area were increased and that the NE level and NE synthesis in the several pontine NE projected areas, e.g., limbic area, hippocampus, cortex and pons were also increased. Conversely, both NE and 5-HT metabolism in the hippocampus and the cortex were decreased. We concluded that the enhanced actions of the DA-limbic system and NE-pontine system in the rats are both important for the maintenance of SIP performance.
|
pubmed_892_18346
|
pubmed_245_10921
|
INTRODUCTION
A debate can be a pedagogical method used to instill essential functions in pharmacy students. This non-traditional teaching method may help to further develop a number of skills that are highlighted in the current Accreditation Council for Pharmacy Education Standards 2016 and Center for the Advancement of Pharmacy Education Educational Outcomes 2013.
COMMENTARY
Debates have also been used as an educational tool in other health disciplines. Current pharmacy literature does illustrate the use of debates in various areas within the pharmacy curriculum in both required and elective courses; however, the current body of literature would suggest that debates are an underutilized teaching tool in pharmacy experiential education.
IMPLICATIONS
With all potential benefits of debates as a teaching tool, pharmacy experiential preceptors should further explore their use in the experiential setting.
|
10.1016/j.cptl.2017.09.016
|
pubmed_957_24507
|
The self-assembly of colloidal diamond (CD) crystals is considered as one of the most coveted goals of nanotechnology, both from the technological and fundamental points of view. For applications, colloidal diamond is a photonic crystal which can open new possibilities of manipulating light for information processing. From a fundamental point of view, its unique symmetry exacerbates a series of problems that are commonly faced during the self-assembly of target structures, such as the presence of kinetic traps and the formation of crystalline defects and alternative structures (polymorphs). Here we demonstrate that all these problems can be systematically addressed via SAT-assembly, a design framework that converts self-assembly into a Boolean satisfiability problem (SAT). Contrary to previous solutions (requiring four or more components), we prove that the assembly of the CD crystal only requires a binary mixture. Moreover, we use molecular dynamics simulations of a system composed by nearly a million nucleotides to test a DNA nanotechnology design that constitutes a promising candidate for experimental realization.
|
10.1039/d2nr03533b
|
pubmed_326_17376
|
The primary theme emerging from molecular genetic work conducted with Mycobacterium tuberculosis and several other mycobacterial species is that resistance is commonly associated with simple nucleotide alterations in target chromosomal genes rather than with acquisition of new genetic elements encoding antibiotic-altering enzymes. Mutations in an 81-bp region of the gene (rpoB) encoding the beta subunit of RNA polymerase account for rifampin resistance in 96% of M. tuberculosis and many Mycobacterium leprae isolates. Streptomycin resistance in about one-half of M. tuberculosis isolates is associated with missense mutations in the rpsL gene coding for ribosomal protein S12 or nucleotide substitutions in the 16S rRNA gene (rrs). Mutations in the katG gene resulting in catalase-peroxidase amino acid alterations nad nucleotide substitutions in the presumed regulatory region of the inhA locus are repeatedly associated with isoniazid-resistant M. tuberculosis isolates. A majority of fluoroquinolone-resistant M. tuberculosis isolates have amino acid substitutions in a region of the DNA gyrase A subunit homologous to a conserved fluoroquinolone resistance-determining region. Multidrug-resistant isolates of M. tuberculosis arise as a consequence of sequential accumulation of mutations conferring resistance to single therapeutic agents. Molecular strategies show considerable promise for rapid detection of mutations associated with antimicrobial resistance. These approaches are now amenable to utilization in an appropriately equipped clinical microbiology laboratory.
|
10.1128/CMR.8.4.496
|
pubmed_788_16684
|
OBJECTIVE
The purpose of this study was to investigate the effects of orally administered over-the-counter omega-3 (n-3) fatty acid supplements on primary patency of polytetrafluoroethylene (PTFE) grafts.
DESIGN
This study was conducted with a triple-blind, permuted-block, randomized, placebo-controlled experimental design.
SETTING
Dialysis clinics with patients who, in accordance with physician diagnosis, needed a new PTFE graft.
PATIENTS AND OTHER PARTICIPANTS
Patients on long-term hemodialysis with newly placed PTFE grafts who were unable to receive a native arteriovenous fistula.
INTERVENTION
Patients were followed prospectively for 8 months after they had been placed into an n-3 fatty acid or control group and were monitored for primary patency.
MAIN OUTCOME VARIABLE
Primary patency of the PTFE graft.
RESULTS
The n-3 fatty acid group had a mean PTFE graft primary patency rate of 254.2 days (SEM = 51.8), and the control group had a mean PTFE graft primary patency rate of 254.1 days (SEM = 34.6), revealing no significant difference in survival time between groups.
CONCLUSIONS
No significant differences in primary patency rates were noted in the experimental and control groups.
|
10.1053/j.jrn.2006.07.009
|
pubmed_854_18129
|
Phosphorylation of the TNF-alpha receptor TNF-R1 has been shown to differentially regulate receptor signaling and function and promote changes in its subcellular localization. Previous studies have shown that p42(mapk/erk2) phosphorylates Ser and Thr residues (T236, S240, S244, and S270) in the membrane proximal region of TNF-R1 and that mutation of these residues to Glu and Asp residues (TNF-R1.4D/E) mimics the effect of phosphorylation on receptor signaling and localization. In the present study, we investigated whether the initial phosphorylation of these residues by p42(mapk/erk2) promotes hierarchical phosphorylation of additional sites within the cytoplasmic domain of TNF-R1. This question was addressed by investigating the ability of the TNF-R1.4D/E mutant receptor to be phosphorylated in in vitro kinase assays using GST-mutant cytoplasmic domain fusion proteins as substrates and in intact cells following mutant receptor expression. In addition, we determined the location of the additional phosphorylation sites. Incubation of Sepharose bead-bound GST-TNF-R1(207)(-)(425).4D/E fusion protein with lysates containing activated p42(mapk/erk2) led to the phosphorylation of Ser and Thr residues in addition to the previously defined sites at T236, S240, S244, and S270. Deletional mutagenesis localized these residues to a stretch of 14 amino acids that encompasses three basic Pro-directed ([S/T]P) kinase consensus sequences located between residues S256 and T267. Point mutagenesis of T257, S262, and T267 to Ala residues indicated that these sites are targets of phosphorylation by p42(mapk/)(erk2). These findings support the conclusion that p42(mapk/erk2) promotes extensive phosphorylation of the membrane proximal region in a hierarchical fashion at both consensus and nonconsensus ERK-phosphorylation sites.
|
10.1021/bi050058w
|
pubmed_1013_4163
|
Background
Obesity has been considered as a leading cause of multiple metabolic syndromes, such as type 2 diabetes and hypertension cardiovascular diseases. Jian Pi Tiao Gan Yin (JPTGY), a Chinese herb preparation, is used to treat obesity of liver qi stagnation and spleen deficiency. The mechanism of action of JPTGY in obesity remains unclear. This study evaluated the effect of JPTGY on obesity.
Methods
The mechanism of action of JPTGY on obesity was investigated in high-fat diet (HFD)-induced obese mice and palmitic acid-treated 3T3-L1 cells. Lipid droplet accumulation was detected using oil red O staining. Factors associated with lipid accumulation were detected by western blotting.
Results
Treatment with JPTGY reduced HFD-induced adiposity and body weight gain. JPTGY increased the levels of brown adipose tissue biomarkers in obese mice and palmitic acid-treated 3T3-L1 cells, including peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC-1α) and uncoupling protein-1 (UCP-1). Meanwhile, the protein expression of white adipose tissue biomarkers, such as AGT, primary subtalar arthrodesis (PSTA), and endothelin receptor type A (EDNRA), was decreased in obese mice and palmitic acid-treated 3T3-L1 cells. JPTGY affects browning of 3T3-L1 cells through mechanistic target of rapamycin complex 1 (mTORC1) signaling. JPTGY decreased the expression levels of key adipogenic-specific proteins and lipogenic enzymes, including peroxisome proliferator-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), sterol regulatory element binding protein (SREBP), and FAS. Treatment with the mTOR activator MHY reversed JPTGY-mediated protein expression.
Conclusions
We concluded that JPTGY relieved obesity phenotypes through mTORC1/SREBP1 signaling in vitro and in vivo. JPTGY may benefit the attenuation of obesity.
|
10.21037/atm-22-685
|
pubmed_874_15808
|
This brief considers the attitude coordination control problem for spacecraft formation flying when only a subset of the group members has access to the common reference attitude. A quaternion-based distributed attitude coordination control scheme is proposed with consideration of the input saturation and with the aid of the sliding-mode observer, separation principle theorem, Chebyshev neural networks, smooth projection algorithm, and robust control technique. Using graph theory and a Lyapunov-based approach, it is shown that the distributed controller can guarantee the attitude of all spacecraft to converge to a common time-varying reference attitude when the reference attitude is available only to a portion of the group of spacecraft. Numerical simulations are presented to demonstrate the performance of the proposed distributed controller.
|
10.1109/TNNLS.2012.2196710
|
pubmed_669_14200
|
BACKGROUND
Using a population-based database, this study investigates the risk factors, epidemiology, and outcomes of basal cell adenocarcinoma (BCAC) of the head and neck.
METHODS
The Surveillance, Epidemiology, and End Results database was analyzed for all patients with BCAC of the head and neck from 1973 to 2015.
RESULTS
Three hundred and twenty-two cases of BCAC of the head and neck were identified. Mean age of diagnosis was 64.1 years. 52.5% were male and 77.3% were white. The most common primary site was the parotid gland (71.7%). Most patients underwent surgery alone (51.9%). Five-year disease-specific survival (5Y-DSS) was 95.6%, and 10Y-DSS was 90.3%. Highest survival was seen with surgery alone followed by combined surgery and radiation (10Y-DSS: 93.9% vs. 88.9%, p = 0.001). Age, primary site, T-classification, grade, and treatment type significantly affected survival.
CONCLUSIONS
BCAC of the head and neck presents most frequently in the parotid glands. Surgery alone is associated with highest survival.
|
10.1002/hed.26955
|
pubmed_303_6723
|
Scientific communications have two main forms, oral presentation at scientific meetings, accompanied by audio-visual aids, and manuscripts prepared for publication in scientific journals. In an oral presentation, the author should be prepared to speak for ten minutes, without depending on notes, and have prepared answers to anticipated questions. Slides are standard aids to summarize and reinforce the material. Preparation of manuscripts follows well-established guidelines available from scientific journals. Manuscripts should proceed from introduction to methods, results, discussion, and conclusion. Prior to writing, the author should answer the following: 1) What is the purpose of this communication? 2) How is this communication different from other data already in the literature? What is its unique contribution? 3) Who is the audience? Manuscripts will go through as many as seven drafts.
|
10.1016/s0361-1124(78)80358-x
|
pubmed_321_5178
|
There has been increasing interest in the development of small molecules that can selectively bind to G-quadruplex DNA structures. The latter have been associated with a number of key biological processes and therefore are proposed to be potential targets for drug development. Herein, we report the first example of a reduction-activated G-quadruplex DNA binder. We show that a new octahedral platinum(IV)-salphen complex does not interact with DNA in aqueous media at pH 7.4; however, upon addition of bioreductants such as ascorbic acid or glutathione, the compound is readily reduced to the corresponding square planar platinum(II) complex. In contrast to the parent platinum(IV) complex, the in situ generated platinum(II) complex has good affinity for G-quadruplex DNA.
|
10.1002/anie.201709968
|
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