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pubmed_836_10350
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Despite the demonstrated efficacy of implantable cardioverter defibrillators (ICDs) in reducing sudden and total mortality in selected patients, their implantation rates vary greatly between countries. In the United States, implantation rate is 228 implants per million inhabitants compared to only 45 implants per million in Western Europe. The differences in the ICD use may be explained by following factors: manner in which sudden cardiac death is perceived by politicians and physicians (sudden cardiac death is perceived as a "nice way of dying"); differences in indications; physicians' information; prevalence of coronary artery disease; sudden cardiac death survival rates; perceived reliability of alternative treatment (namely antiarrhythmics including amiodarone); economic backgrounds; and health care politics. Furthermore, the cost of this treatment strategy must be considered. This issue has been raised because generalization of ICD use in patients matching clinical characteristics of patients enrolled in the primary prevention trials may represent a significant economic burden to be added to the already overloaded health care system. This low acceptance may not be entirely related to budget constraint but also to the perceived efficacy of ICDs by physicians and health authorities.
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10.1023/a:1023603118860
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pubmed_99_12089
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Unactivated, molybdate-stabilized, [3H]triamcinolone acetonide-labeled, glucocorticoid receptors from mouse whole brain were activated by removal of the molybdate and incubation at 22 degrees C for 1.5 to 24 min and then rapidly quenched at 0 degrees C with molybdate. The loss of the 9.2 S (unactivated) form of the [3H]TA-receptor complex and the concomitant formation of the 3.8 S (activated) form displayed first-order kinetics with a half-time of less than two min. The increase in the 3.8 S form correlated nearly perfectly with an increased binding to DNA-cellulose, and with a decreased and increased adsorption to DEAE-cellulose and glass fiber filters, respectively. The changes in adsorption to these filters, which occurred at a faster rate than did the changes in binding to DNA-C, are thought to reflect an increase in the relative number of positive charges and hydrophobic groups on the surface of the activated complex.
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10.1007/BF00964175
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pubmed_1026_14580
|
PURPOSE
To compare oral health [dental caries, periodontal status, and erosive tooth wear (ETW)], diet and oral hygiene habits between obese and normal weight adolescents, and to explore possible risk associations.
METHODS
In this case-control study, a convenience sample of 71 obese adolescents (age range 11-18) from a rehabilitation centre, and 54 age-sex-matched normal weight adolescents were selected for this study. Groups were defined using the Body Mass Index and growth curves for Flemish adolescents. Oral health was measured using DMFT, gingival, plaque and BEWE index. A validated questionnaire was utilized to assess diet and oral hygiene habits. Mann-Whitney U test was used to compare oral health between groups. Multivariate Firth's logistic regression analysis, conditional regression analysis and classification trees were used to detect associations between oral health and potential risk factors.
RESULTS
Prevalence of ETW did not differ significantly between groups, although obese adolescents presented a significantly higher caries experience, gingivitis, presence of plaque and periodontal problems, compared to normal weight adolescents. After adjusting for age and sex, obesity was associated only with the presence of dental plaque (p ≤ 0.001). Obese participants reported a significantly higher intake of sugar-rich and caloric food items than normal weight group. The consumption of acidic drinks, however, was similar.
CONCLUSION
Obese adolescents presented significantly higher caries experience, gingivitis and plaque, although after adjusting, obesity became significantly associated only with the presence of dental plaque.
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10.1007/s40368-020-00534-w
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pubmed_1094_16536
|
BACKGROUND
Colorectal cancer (CRC) develops through the alteration of several critical pathways. This study was aimed at evaluating the influence of critical pathways on survival outcomes for patients with CRC.
METHODS
Targeted next-generation sequencing of 40 genes included in the 5 critical pathways of CRC (WNT, P53, RTK-RAS, phosphatidylinositol-4,5-bisphosphate 3-kinase [PI3K], and transforming growth factor β [TGF-β]) was performed for 516 patients with stage III or high-risk stage II CRC treated with surgery followed by adjuvant fluoropyrimidine and oxaliplatin chemotherapy. The associations between critical pathway mutations and relapse-free survival (RFS) and overall survival were analyzed. The associations were further analyzed according to the tumor location.
RESULTS
The mutation rates for the WNT, P53, RTK-RAS, PI3K, and TGF-β pathways were 84.5%, 69.0%, 60.7%, 30.0%, and 28.9%, respectively. A mutation in the PI3K pathway was associated with longer RFS (adjusted hazard ratio [HR], 0.59; 95% confidence interval [CI], 0.36-0.99), whereas a mutation in the RTK-RAS pathway was associated with shorter RFS (adjusted HR, 1.60; 95% CI, 1.01-2.52). Proximal tumors showed a higher mutation rate than distal tumors, and the mutation profile was different according to the tumor location. The mutation rates of Kirsten rat sarcoma viral oncogene homolog (KRAS), phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit α (PIK3CA), and B-Raf proto-oncogene serine/threonine kinase (BRAF) were higher in proximal tumors, and the mutation rates of adenomatous polyposis coli (APC), tumor protein 53 (TP53), and neuroblastoma RAS viral oncogene homolog (NRAS) were higher in distal tumors. The better RFS with the PI3K pathway mutation was significant only for proximal tumors, and the worse RFS with the RTK-RAS pathway mutation was significant only for distal tumors.
CONCLUSIONS
A PI3K pathway mutation was associated with better RFS for CRC patients treated with adjuvant chemotherapy, and an RTK-RAS pathway mutation was associated with worse RFS. The significance of the prognostic impact differed according to the tumor location. Cancer 2017;123:3513-23. © 2017 American Cancer Society.
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10.1002/cncr.30760
|
pubmed_946_5048
|
Based on the results of an ergometric stress testing performed in 22 patients with mitral replacement, the author concludes that this method is a highly reproductive and safe to evaluate the functional improvement of patients undergoing a mitral replacement. The results are similar for Bjork-Shiley (11 patients) and Starr-Edwards prothesis (11 patients), slurring that the only parameter that can affect functional results can be a controlled rehabilitation program.
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pubmed_946_5048
|
pubmed_768_9629
|
Overcoming cellular senescence is strictly required for virus-driven tumors, including those associated with Epstein-Barr virus (EBV). This critical step is successfully accomplished by EBV through TERT expression and telomerase activation in infected cells. We herein review the complex interplay between EBV and TERT/telomerase in EBV-driven tumorigenesis. Evidence accumulated so far clearly indicates that elucidation of this issue may offer promising opportunities for the design of innovative treatment modalities for EBV-associated malignancies. Indeed, several therapeutic strategies for telomerase inhibition have been developed and are being investigated in clinical trials. In this respect, our recent finding that TERT inhibition sensitizes EBV+ lymphoma cells to antivirals through activation of EBV lytic replication is particularly promising and provides a rationale for the activation of clinical studies aimed at assessing the effects of combination therapies with TERT inhibitors and antivirals for the treatment of EBV-associated malignancies.
|
10.1186/1750-9378-9-8
|
pubmed_64_19584
|
Tamoxifen is an endocrine treatment for hormone receptor positive breast cancer. The effectiveness of tamoxifen may be compromised in patients with metabolic resistance, who have insufficient metabolic generation of the active metabolites endoxifen and 4-hydroxy-tamoxifen. This has been challenging to validate due to the lack of measured metabolite concentrations in tamoxifen clinical trials. CYP2D6 activity is the primary determinant of endoxifen concentration. Inconclusive results from studies investigating whether CYP2D6 genotype is associated with tamoxifen efficacy may be due to the imprecision in using CYP2D6 genotype as a surrogate of endoxifen concentration without incorporating the influence of other genetic and clinical variables. This review summarizes the evidence that active metabolite concentrations determine tamoxifen efficacy. We then introduce a novel approach to validate this relationship by generating a precision endoxifen prediction algorithm and comprehensively review the factors that must be incorporated into the algorithm, including genetics of CYP2D6 and other pharmacogenes. A precision endoxifen algorithm could be used to validate metabolic resistance in existing tamoxifen clinical trial cohorts and could then be used to select personalized tamoxifen doses to ensure all patients achieve adequate endoxifen concentrations and maximum benefit from tamoxifen treatment.
|
10.3390/jpm11030201
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pubmed_333_8552
|
This paper reports the findings in a study involving 1537 patients with 'acute abdominal pain' presenting over a 13-month period to the Accident and Emergency Department of the General Infirmary at Leeds. Of these, 341 patients who proved to have pain of greater duration than a week, pain incidental to some other identifiable condition or no pain at the time of their attendance were excluded. The remaining 1196 were diagnosed clinically (using a structured case sheet) and subsequently by a Bayesian computer system. Feedback of the results of clinical and computer systems was given to clinicians at regular intervals. Clinical diagnostic accuracy in patients with surgical disorders rose from 40 per cent before the study to 61 per cent. Computer accuracy in these patients was 69-9 per cent. The proportion of patients sent home without ill effects rose from 20 per cent to 39 per cent. In other areas (e.g. gynaecology) the effects were less marked. It is suggested that the introduction of a simple postgraduate educational service, aided by a small computer, might prove of practical benefit in this clinical situation.
|
10.1002/bjs.1800640407
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pubmed_520_13163
|
BACKGROUND
Encystation is one of the two processes comprising the life cycle of Giardia lamblia, a protozoan pathogen with tetraploid genome. Giardia lamblia Myb2 (GlMyb2) is a distinct encystation-induced transcription factor whose binding sites are found in the promoter regions of many encystation-induced genes, including its own.
METHODS
Two sequential CRISPR/Cas9 experiments were performed to remove four glmyb2 alleles. The expression level of G. lamblia cyst wall protein 1 (GlCWP1), a well-known target gene of GlMyb2, was measured via western blotting and immunofluorescence assays. Chromatin immunoprecipitation experiments using anti-GlMyb2 antibodies were performed on the encysting G. lamblia cells. Quantitative real-time PCR was performed to confirm an expression of candidate GlMyb2-regulated genes by comparing the transcript level for each target candidate in wild-type and knockout mutant Giardia. The promoter region of glcwp1 was analyzed via deletion and point mutagenesis of the putative GlMyb2 binding sites in luciferase reporters.
RESULTS
Characterization of the null glmyb2 mutant indicated loss of functions related to encystation, i.e. cyst formation, and expression of GlCWP1. The addition of the wild-type glmyb2 gene to the null mutant restored the defects in encystation. Chromatin immunoprecipitation experiments revealed dozens of target genes. Nineteen genes were confirmed as GlMyb2 regulons, which include the glmyb2 gene, six for cyst wall proteins, five for signal transduction, two for transporter, two for metabolic enzymes, and three with unknown functions. Detailed analysis on the promoter region of glcwp1 defined three GlMyb2 binding sites important in its encystation-induced expression.
CONCLUSIONS
Our data confirm that GlMyb2 acts as a transcription activator especially during encystation by comparing the glmyb2 knockout mutant with the wild type. Further investigation using glmyb2 null mutant will provide knowledge regarding transcriptional apparatus required for the encystation process of G. lamblia.
|
10.1186/s13071-022-05489-z
|
pubmed_727_8970
|
Cancers of the head and neck are accessible to both inspection and palpation in the majority of patients. This accessibility allows for improvements in detection, through education of the medical profession and also of the allied health personnel. Some of the new advances in detection and diagnosis have been associated with development of new instruments. A new lens system developed by Hopkins allows a brighter endoscopic image and a significantly greater breadth of field. Needle aspiration biopsy techniques have also improved both in facility of performance and in accuracy of diagnosis. Asteriography aids in the detection of carotid body tumors. Selective parathormone studies have considerably improved the preoperative accuracy of evaluating parathyroid disease. Scans, both using ultrasound and a fluorescent iodine scan have also improved the preoperative evaluation of thyroid tumors. A challenge of detection is the realization that there is an increased risk of the development of thyroid cancer in childhood and in adults in those patients who received radiation therapy to the head and neck during infancy or childhood. A national campaign to alert potential individuals at risk should be a prime objective of the American Cancer Society.
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10.1002/1097-0142(197601)37:1+<604::aid-cncr2820370727>3.0.co;2-g
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pubmed_885_19698
|
BACKGROUND
Good bone and joint health is essential for the physical tasks of daily living and poorer indicators of physical capability in older adults have been associated with increased mortality rates. Genetic variants of indicators of bone and joint health may be associated with measures of physical capability.
METHODS
As part of the Healthy Ageing across the Life Course (HALCyon) programme, men and women aged between 52 and 90+ years from six UK cohorts were genotyped for a polymorphism associated with serum calcium (rs1801725, CASR), two polymorphisms associated with bone mineral density (BMD) (rs2941740, ESR1 and rs9594759, RANKL) and one associated with osteoarthritis risk rs3815148 (COG5). Meta-analysis was used to pool within-study effects of the associations between each of the polymorphisms and measures of physical capability: grip strength, timed walk or get up and go, chair rises and standing balance.
RESULTS
Few important associations were observed among the several tests. We found that carriers of the serum calcium-raising allele had poorer grip strength compared with non-carriers (pooled p=0.05, n=11,239) after adjusting for age and sex. Inconsistent results were observed for the two variants associated with BMD and we found no evidence for an association between rs3815148 (COG5) and any of the physical capability measures.
CONCLUSION
Our findings suggest elevated serum calcium levels may lead to lower grip strength, though this requires further replication. Our results do not provide evidence for a substantial influence of these variants in ESR1, RANKL and COG5 on physical capability in older adults.
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pubmed_885_19698
|
pubmed_1071_23489
|
AIM
To retrospectively analyze the efficacy and safety of sildenafil (Sf) in patients with systemic sclerosis (SS).
SUBJECTS AND RESULTS
Sf was used in 16 patients (including 14 women) aged 20-66 years (mean 48.6 +/- 14.6 years; median 51.5 years) with SS of a duration of 2 months to 27 years (mean 8.8 +/- 7.3 years; median 6.5 years). The indications for Sf treatment were significant Raynaud's phenomenon (RP) in 3 patients, digital ulcers (DU) and/or necroses (N) in 9, pulmonary hypertension (PH) in 5 (2 patients had PH concurrent with DU/N), and critical ischemia of the left fingers in 1 patient. RP was seen in all the patients and so the effect of Sf on the course of RP was evaluated in the whole patient group.
RESULTS
There was a significant decrease in the frequency and intensity of Raynaud's attacks in 11 (73%) of the 15 patients treated with Sf. This effect was obvious just in the first days of Sf treatment and remained stable throughout the treatment. No RP changes were seen in 3 patients. All 7 patients with DUs showed a decrease in their sizes just within the first two weeks of treatment. Complete DU healing was observed within 4-12 weeks of treatment. During a month, the necrotic area reduced and the signs of reparation appeared in 4 of the 6 patients. Pain ceased just within the first 5-7 days of treatment. Sf resulted in a rapid reduction in systolic pulmonary artery pressure (sPAP); in one case the latter diminished from 60 to 40 mm Hg just 90 min after the first intake of Sf 50 mg and remained unchanged during all 6 months during which the female patient was taking the drug. Doppler echocardiography showed that sPAP decreased from 103 to 85 mm Hg in another female taking Sf 100 mg for a month. The two cases showed clinical improvement as alleviated dyspnea and increased physical activity. In another case, Sf was discontinued because of dizziness after its first intake in a dose of 12.5 mg. The initial drug intake of the drug was not followed by adverse reactions in 12 (75%) of the 16 patients. Four patients had Sf-induced complaints, including headache (1), dizziness (2), and more severe angina pectoris (1). In different periods after treatment initiation, four more patients developed complications, such as fatal myocardial infarction after 6-week treatment, atrial fibrillation at 8 weeks, more severe angina at 6 months, and congestive heart failure after 5-year treatment. These complications were observed in patients with severe ECG changes, such as myocardial focal fibrosis or blood supply impairment.
CONCLUSION
Sf is an effective drug to treat the manifestations of scleroderma vasculopathy, such as RP, DU/N, and PH. Sf is well tolerated in most cases. The SS patients with pronounced ECG changes have an increased risk of severe cardiac events and they need careful ECG monitoring.
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pubmed_1071_23489
|
pubmed_177_10527
|
Differential scanning calorimetry (DSC) is a commonly employed analytical technique for the analysis and characterization of amorphous solid dispersions. However, steps typical of standard temperature programs can alter the material in situ. Data for two active pharmaceutical ingredients are detailed, wherein isothermal hold times, traditionally employed to remove thermal history and/or residual solvent, were observed to impact the observed dispersability of the compounds in polyvinylpyrrolidone vinyl-acetate copolymer (PVPva). Re-crystallized tolbutamide was observed to re-dissolve in PVPva, while terfenadine was observed to crystallize during the isothermal hold period. Exposing co-solidified drug-polymer mixtures to temperature changes and experimental hold times can potentially confound correct categorization of dispersability, particularly when DSC is used as the lone characterization technique. This work illustrates the importance of using a combination of techniques to improve the certainty of conclusions made with respect to the true, initial physical state of a co-solidified mixture.
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10.1016/j.jpba.2017.12.001
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pubmed_1031_18190
|
BACKGROUND
Management of asthma can be complicated by both medical and psychiatric conditions, such as gastroesophageal reflux, chronic sinusitis, and anxiety. When symptoms of asthma are interpreted without regard to such conditions treatment may yield a suboptimal outcome. For example, anxiety-associated dyspnea, tachypnea, and chest tightness can be mistakenly interpreted as resulting from an exacerbation of asthma. Medical treatment directed only for asthma may thus lead to overuse of asthma medications and increased hospitalizations.
CASE PRESENTATION
The described case illustrates how a systemic steroid-dependent patient with asthma benefited from receiving care from a pediatric pulmonologist who also was well versed in the diagnosis and treatment of anxiety. By using self-hypnosis, the patient was able to reduce her dependence on bronchodilators. Following modification of her medical therapy under supervision of the pulmonologist, and regular use of hypnosis, the patient ultimately was weaned off her systemic steroid therapy.
CONCLUSIONS
This report emphasizes that anxiety must be considered as a comorbid condition in the treatment of asthma. Self-hypnosis can be a useful skill in the treatment of a patient with anxiety and asthma.
|
10.1186/1471-2431-3-7
|
pubmed_174_3582
|
A model is presented which enables radiation doses following the administration of technetium-99m diethylenetriaminepentaacetic acid ([99mTc]DTPA) aerosol to be calculated. The organ with potentially the highest radiation dose is shown to be the bladder wall. Radiation doses to the lungs, kidneys, and bladder wall and the effective whole-body dose are discussed in terms of the lung clearance rate of [99mTc]DTPA aerosol and the pattern of bladder voiding. The model indicated the influence of urine flow rate on bladder dose assuming a critical volume at which bladder voiding occurs. It is concluded that significant reductions in radiation doses may be achieved by encouraging patients or subjects undergoing investigations using [99mTc]DTPA aerosols to drink freely following the study.
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pubmed_174_3582
|
pubmed_121_294
|
β-adrenergic receptor (β-AR) signaling plays predominant roles in modulating energy expenditure by triggering lipolysis and thermogenesis in adipose tissue, thereby conferring obesity resistance. Obesity is associated with diminished β3-adrenergic receptor (β3-AR) expression and decreased β-adrenergic responses, but the molecular mechanism coupling nutrient overload to catecholamine resistance remains poorly defined. Ten-eleven translocation (TET) proteins are dioxygenases that alter the methylation status of DNA by oxidizing 5-methylcytosine to 5-hydroxymethylcytosine and further oxidized derivatives. Here, we show that TET proteins are pivotal epigenetic suppressors of β3-AR expression in adipocytes, thereby attenuating the responsiveness to β-adrenergic stimulation. Deletion of all three Tet genes in adipocytes led to increased β3-AR expression and thereby enhanced the downstream β-adrenergic responses, including lipolysis, thermogenic gene induction, oxidative metabolism, and fat browning in vitro and in vivo. In mouse adipose tissues, Tet expression was elevated after mice ate a high-fat diet. Mice with adipose-specific ablation of all TET proteins maintained higher levels of β3-AR in both white and brown adipose tissues and remained sensitive to β-AR stimuli under high-fat diet challenge, leading to augmented energy expenditure and decreased fat accumulation. Consequently, they exhibited improved cold tolerance and were substantially protected from diet-induced obesity, inflammation, and metabolic complications, including insulin resistance and hyperlipidemia. Mechanistically, TET proteins directly repressed β3-AR transcription, mainly in an enzymatic activity-independent manner, and involved the recruitment of histone deacetylases to increase deacetylation of its promoter. Thus, the TET-histone deacetylase-β3-AR axis could be targeted to treat obesity and related metabolic diseases.
|
10.1073/pnas.2205626119
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pubmed_955_5347
|
The initial replication of lactate dehydrogenase-elevating virus (LDV) in mice, its invasion of the central nervous system (CNS) and infection of anterior horn neurons in C58 and AKXD-16 mice were investigated by Northern and in situ hybridization analyses. Upon intraperitoneal injection, LDV replication in cells in the peritoneum was maximal at 8 h post-infection (p.i.). Next, LDV infection was detected in bone marrow cells and then in macrophage-rich regions of all tissues investigated (12 to 24 h p.i.). By 2 to 3 days p.i., LDV RNA-containing cells had largely disappeared from all non-neuronal tissues due to the cytocidal nature of the LDV infection of macrophages. In the CNS at 24 h p.i. LDV replication was very limited and confined to cells in the leptomeninges. LDV replication in the cells of the leptomeninges should result in the release of progeny LDV into the cerebrospinal fluid and thus its dissemination throughout the CNS. However, in C58 and AKXD-16 mice, which are susceptible to paralytic LDV infection, only little LDV RNA and few LDV-infected cells were detectable in the spinal cord until at least 10 days p.i. Extensive cytocidal infection of anterior horn neurons occurred only shortly before the development of paralytic symptoms between 2 and 3 weeks p.i. The reason for the relatively long delay in LDV infection of anterior horn neurons is not known. No LDV RNA or LDV RNA-containing cells were detected in the brain, except in the leptomeninges at early times after infection.
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10.1099/0022-1317-76-3-581
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pubmed_314_4184
|
Inflammatory bowel disease is characterized by chronic inflammation which predisposes to colorectal cancer. The mechanisms by which inflammation promotes tumorigenesis are not fully known. We aimed to investigate the links between colonic inflammation and tumorigenesis via epigenetic gene silencing. Colon cancer specimens were assessed for the expression of DNA methyltransferase-1 (DNMT-1) using immunohistochemistry. Colorectal carcinoma cell lines were assessed for DNMT1 expression, methylcytosine content, promoter methylation, gene expression, and tumorigenesis in response to interleukin (IL)-6. DNMT1 was expressed at higher levels in both the peritumoral stroma and tumor in inflammatory bowel disease-associated cancers compared with sporadic colon cancers. IL-6 treatment of colon cancer cells resulted in an increase in DNMT1 expression, independent of de novo gene expression. IL-6 increased the methylation of promoter regions of genes associated with tumor suppression, adhesion, and apoptosis resistance. Expression of a subset of these genes was downregulated by IL-6, an effect that was prevented by preincubation with 5-azadeoxycytidine, a DNMT1 inhibitor. Anchorage-independent growth and migration of colon cancer cells was also increased by IL-6 in a 5-azadeoxycytidine-sensitive manner. Our results indicate that DNMT-mediated gene silencing may play a role in inflammation-associated colon tumorigenesis.
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10.1158/1541-7786.MCR-09-0496
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pubmed_1135_13242
|
OBJECTIVES
Autophagy has recently been shown to regulate osteoclast activity and osteoclast differentiation. Here, we aim to investigate the impact of autophagy inhibition as a potential therapeutic approach for the treatment of osteoporosis in preclinical models.
METHODS
Systemic bone loss was induced in mice by glucocorticoids and by ovariectomy (OVX). Autophagy was targeted by conditional inactivation of autophagy-related gene 7 (Atg7) and by treatment with chloroquine (CQ). Bone density was evaluated by microCT. The role of autophagy on osteoclastogenesis was analysed by osteoclastogenesis and bone resorption assays. The quantification of receptor activator of nuclear factor κ B ligand and osteoprotegerin proteins in cocultures was performed using ELISA whereas that of osteoclast and osteoblast differentiation markers was by qPCR.
RESULTS
Selective deletion of Atg7 in monocytes from Atg7(fl/fl)_x_LysM-Cre mice mitigated glucocorticoid-induced and OVX-induced osteoclast differentiation and bone loss compared with Atg7(fl/fl) littermates. Pharmacological inhibition of autophagy by treatment with CQ suppressed glucocorticoid-induced osteoclastogenesis and protected mice from bone loss. Similarly, inactivation of autophagy shielded mice from OVX-induced bone loss. Inhibition of autophagy led to decreased osteoclast differentiation with lower expression of osteoclast markers such as NFATc1, tartrate-resistant acid phosphatase, OSCAR and cathepsin K and attenuated bone resorption in vitro. In contrast, osteoblast differentiation was not affected by inhibition of autophagy.
CONCLUSIONS
Pharmacological or genetic inactivation of autophagy ameliorated glucocorticoid-induced and OVX-induced bone loss by inhibiting osteoclastogenesis. These findings may have direct translational implications for the treatment of osteoporosis, since inhibitors of autophagy such as CQ are already in clinical use.
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10.1136/annrheumdis-2015-207240
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pubmed_697_2300
|
Interfacial waters are increasingly appreciated as playing a key role in protein-protein interactions. We report on a study of the prediction of interfacial water positions by both Molecular Dynamics and explicit solvent-continuum electrostatics based on the Dipolar Poisson-Boltzmann Langevin (DPBL) model, for three test cases: (i) the barnase/barstar complex (ii) the complex between the DNase domain of colicin E2 and its cognate Im2 immunity protein and (iii) the highly unusual anti-freeze protein Maxi which contains a large number of waters in its interior. We characterize the waters at the interface and in the core of the Maxi protein by the statistics of correctly predicted positions with respect to crystallographic water positions in the PDB files as well as the dynamic measures of diffusion constants and position lifetimes. Our approach provides a methodology for the evaluation of predicted interfacial water positions through an investigation of water-mediated inter-chain contacts. While our results show satisfactory behaviour for molecular dynamics simulation, they also highlight the need for improvement of continuum methods.
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10.1038/srep38259
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pubmed_565_19466
|
[reaction: see text]. Beta-thioacetal-substituted aldehydes, which are conveniently prepared from the corresponding ynals, can be combined with a range of alkynes or electron-poor alkenes to deliver intermolecular hydroacylation adducts. The reactions employ [Rh(dppe)]ClO4 as a catalyst and are proposed to proceed via a chelated rhodium acyl intermediate. The thioacetal-containing products can be deprotected to the corresponding ketones or reduced to alkanes in good yields.
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10.1021/ol050638l
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pubmed_402_7469
|
The subclass antibodies against IgG1, IgG3 and IgG4 in sera of the patients with chronic Schistosomiasis japonica were detected before treatment, and after treatment--6 and 12 months respectively, using Biotin-Avidin-ELISA (BA-ELISA) established by purified 31/32 KD antigen from the adult worms. At the same time IgG1 and IgM were examined by the standard ELISA. False positive reaction with normal control and cross reaction with other parasitic diseases have not been observed. The IgG1 and IgG3 subclasses showed high sensitivity and specificity and reduced quickly 6 months after treatment. These results indicate that the level of specific IgG1 and IgG4 to the 31/32 KD adult worm protein has high value for diagnosis of Schistosomiasis japonica and evaluation of the curative efficiency of the disease.
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pubmed_402_7469
|
pubmed_897_21100
|
The berries of Lycium barbarum, a perennial plant native to Asia and southeastern Europe, have been used for centuries in traditional Chinese medicine to treat poor vision, anemia, inflammation, and cough. They are also consumed as food and used in soup recipes. Lycium has gained immense popularity in the United States over the past decade because of its antioxidant properties. It is available in health food stores and is marketed via the Internet in juice form, typically blended with the juices of other berries and fruits. A wide range of health benefits, including cancer prevention and treatment, have been claimed for lycium.
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pubmed_897_21100
|
pubmed_200_18825
|
BACKGROUND
Peritoneal carcinomatosis is life-threatening without cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC). Only a few studies in the literature addressed the relationship between age and outcomes of peritonectomy. This study was designed to review the clinical outcomes in elderly patients who underwent CRS and PIC.
METHODS
This is a retrospective study of prospectively collected data of 611 consecutive patients with peritoneal carcinomatosis who underwent CRS and PIC by the same surgical team at St George Hospital in Sydney, Australia, between January 1996 and December 2013. Patients were divided into two groups; group 1 (<65 years old, n = 487) and group 2 (≥ 65 years old, n = 124). Subgroup analysis was performed in patients who were ≥75 years old (n = 20). A significant difference was defined as p < 0.05.
RESULTS
There was no significant statistical difference in terms of mean total hospital stay, intensive care unit stay, high dependency unit stay and complication rates. Postoperative mortality was 2 and 3 % in groups 1 and 2, respectively. Overall survival did not reach a statistical significance between the two groups. In subgroup analysis, patients showed similar morbidity results to patients who were <65 years old.
CONCLUSIONS
CRS and PIC can be safely done in the elderly. Age alone should not be the single exclusion criterion but rather taken into consideration along with other factors to determine the suitability of elderly patients.
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10.1186/s12957-015-0682-7
|
pubmed_799_18586
|
Virus removal experiments using river water spiked with bacteriophages were conducted by an in-line coagulation-ceramic microfiltration hybrid system to investigate the effects of filtration flux (62.5 and 125 L/(m2 x h)) and type of virus (Qbeta and MS2) on virus removal. In addition, the mass balance of viruses through the hybrid system was analysed by quantifying the infectious and inactive viruses by a combination of the polymerase chain reaction (PCR) method and the plaque forming units (PFU) method. Even when the system was operated at high filtration flux (125 L/(m2 x h)), high virus removal (> 6 log) with short coagulation time (2.4 s) was successfully achieved by dosing polyaluminium chloride (PACI) at more than 1.08 mg-Al/L. Removal performances were different between Qbeta and MS2, although their diameters are almost the same: greater virus removal was achieved for MS2 at PACI dosing of 0.54 mg-Al/L, and for Qbeta at PACI dosing of more than 1.08 mg-Al/L. The combination of the PCR and PFU methods revealed that two phenomena, adsorption to/entrapment in aluminium floc and virucidal activity of PACI, partially account for the high virus removal in the coagulation-MF hybrid system.
|
10.2166/wst.2006.225
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pubmed_590_7714
|
This study examined the potential of two-step fermentation to preserve TPs in functional soy-tea beverage. Fermented soymilk-tea (FST) was produced by culturing Streptococcus thermophilus, Lactobacillus delbrueckii ssp. bulgaricus and Bifidobacterium longum in soymilk supplemented with tea extract (TE). Total phenolic content (TPC) and anti-radical activities were determined for FSTs and fermented soymilk (FS). A HPLC method was employed to quantify nine major tea phenolics in FST products. TPC was significantly higher (p<0.05) in FST than FS, in the order of green tea>oolong tea>black tea>soymilk. The FSTs were effective at scavenging DPPH-radical rather than hydroxyl radical. Optimal pH to stabilize TPs in SMT was ca. 5.7, which reduced total TP loss by ca. 40% compared with that obtained from products with TE supplemented at the beginning of fermentation. A gradual decrease in TPs was observed during storage (4 °C), with more than half of total TPs remained in FST after 8 weeks.
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pubmed_590_7714
|
pubmed_844_20573
|
Both oximes and hydroxylamine (HYAM) are compounds with known oxidative capacity. We tested in vitro whether acetaldoxime (AAO), cyclohexanone oxime (CHO), methyl ethyl ketoxime (MEKO) or HYAM affect haemoglobin oxidation (into HbFe3+), formation of thiobarbituric acid reactive substances (TBARS), and glutathione (GT) depletion in human haemolysate, erythrocytes or blood. All these parameters are known to be related to oxidative stress. Glutathione S-transferase (GST) activity was measured as it may be affected by oxygen radicals. All three oximes caused a low degree of HbFe3+ accumulation in erythrocytes. This was higher in haemolysates indicating that membrane transport may be limiting or that protective mechanisms within erythrocytes are more effective. HbFe3+ accumulation was lower for the oximes than for HYAM. AAO and HYAM caused TBARS formation in blood. For HYAM this was expected as free radicals are known to be generated during HbFe3+ formation. Free radical generation by AAO and HYAM in erythrocytes was confirmed by the inhibition of GST. For the other two oximes (CHO and MEKO) some special effects were found. CHO did inhibit erythrocyte GST while it did not cause TBARS formation. MEKO was the least potent oxime as it caused no TBARS formation, little HbFe3+ accumulation and little GST inhibition in erythrocytes. However, GT depletion was more pronounced for MEKO than for the other oximes, indicating that glutathione conjugation occurs. TBARS formation, GT depletion and GST modulation caused by the oximes and HYAM were also tested in rat hepatocytes. However, no effects were found in hepatocytes. This suggests that a factor present in erythrocytes is necessary for free radical formation. Studies with proposed metabolites of the oximes (i.e. cyclohexanone, acetaldehyde or methylethyl ketone) and addition of rat liver preparations to the erythrocyte incubations with oximes, suggest that metabolism is not a limiting factor in erythrocyte toxicity.
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10.1007/s002040050501
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pubmed_199_12978
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This study examined renin release and renal function of the nonclipped kidney of 2K-1C rats (HYPER) with hypertension of 3 to 4 weeks duration. Kidneys from uninephrectomized rats (UN) served as controls. The kidneys were removed and perfused in vitro and renin release was compared under basal conditions and then under stimulated conditions using (a) a 50 mm Hg reduction in perfusion pressure (LP), (b) beta-receptor stimulation with isoproterenol (ISOP), or (c) perfusion with a low calcium solution (LCa). Basal perfusate flow, glomerular filtration rate, urine flow, sodium excretion, and basal renin release were all lower in HYPER kidneys than UN kidneys. UN kidneys showed striking increases in renin release with all three stimuli employed. HYPER kidneys showed a significant but attenuated response to ISOP and showed no detectable response to LP or LCa. Renin content of HYPER kidneys was found to be 28% of the renin content of UN kidneys. The results show that chronic hypertension leads to increased renal vascular resistance, reduced glomerular filtration, and reduced solute excretion in the nonclipped kidney. The results suggest that a reduction in renin content plays a major role in the reduced rates of basal renin release and the attenuated renin responses to a number of stimuli observed in this experimental model.
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10.3181/00379727-179-42076
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pubmed_365_18803
|
The findings on an adult patient with mandibular asymmetry and temporomandibular dysfunction are presented. The patient had four first premolars extracted earlier, followed by a short treatment attempt. Control of tongue function and jaw posture before, during, and after active treatment helped achieve a functional occlusion and a relief of the symptoms of the temporomandibular dysfunction. Specific diagnostic (assessment of occlusion and jaw movements) as well as therapeutic means (lower removable appliance and crown reshaping) are described.
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10.1016/s0889-5406(98)70175-1
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pubmed_198_5824
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This paper gives the results of an intercomparison exercise on the determination of plutonium-238 in urine. The urine, containing metabolised plutonium, was analysed by 6 laboratories in the United Kingdom and 5 in France. Three solutions were provided, a high and low level solution and a blank solution comprising the diluent urine. Several different methods were used by the various laboratories and the results showed good agreement between them.
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10.1016/0048-9697(88)90332-4
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pubmed_226_10233
|
BACKGROUND
Over the last 30 years, South Africa has experienced four 'colliding epidemics' of HIV and tuberculosis, chronic illness and mental health, injury and violence, and maternal, neonatal, and child mortality, which have had substantial effects on health and well-being. Using data from the 2019 Global Burden of Diseases, Injuries and Risk Factors Study (GBD 2019), we evaluated national and provincial health trends and progress towards important Sustainable Development Goal targets from 1990 to 2019.
METHODS
We analysed GBD 2019 estimates of mortality, non-fatal health loss, summary health measures and risk factor burden, comparing trends over 1990-2007 and 2007-2019. Additionally, we decomposed changes in life expectancy by cause of death and assessed healthcare system performance.
RESULTS
Across the nine provinces, inequalities in mortality and life expectancy increased over 1990-2007, largely due to differences in HIV/AIDS, then decreased over 2007-2019. Demographic change and increases in non-communicable diseases nearly doubled the number of years lived with disability between 1990 and 2019. From 1990 to 2019, risk factor burdens generally shifted from communicable and nutritional disease risks to non-communicable disease and injury risks; unsafe sex remained the top risk factor. Despite widespread improvements in healthcare system performance, the greatest gains were generally in economically advantaged provinces.
CONCLUSIONS
Reductions in HIV/AIDS and related conditions have led to improved health since 2007, though most provinces still lag in key areas. To achieve health targets, provincial governments should enhance health investments and exchange of knowledge, resources and best practices alongside populations that have been left behind, especially following the COVID-19 pandemic.
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10.1136/jech-2021-217480
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pubmed_1112_21979
|
The B chromosomes are accessory elements that are widely distributed among eukaryotic genomes and often show non-Mendelian inheritance. They are considered dispensable for the growth, development, and reproduction of organisms. Some studies have suggested that these elements may affect sex determination. Harttia is a small armored catfish genus that shows sexual dimorphism, including hypertrophied odontodes on the pectoral fin spines and along the margins of the snout in mature males. They exhibit considerable karyotypic diversity with diploid number (2n) variation and heteromorphic sex system in H. carvalhoi. To date, no occurrences of B chromosomes in the Harttia genus were detected and no relation to sexual differentiation in Neotropical fish has been determined. To determine the validity of this claim, the present paper characterized specimens of Harttia longipinna by classical and molecular cytogenetic methods. The 2n found was 58 (16m + 12sm + 16st + 14a), but of the 50 specimens analyzed (30 male and 20 female), 23 specimens (16 males and seven females) show an intra-individual from 0 to 2 micro B chromosomes. The B chromosomes were completely heterochromatic. The single NORs were shown in the first acrocentric pair with silver staining and 18S rDNA probing. FISH performed with 5S rDNA probe showed a single cistron in the proximal region of the short arm of a small metacentric pair. Thus, the cytogenetic data obtained in this study of H. longipinna highlight the karyotypic diversity found within the genus Harttia, and represent the first description of B chromosomes for this genus.
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10.2108/zsj.29.604
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pubmed_6_10661
|
BACKGROUND
There is a broad range of potential differential diagnoses for chorea. Besides rare, inherited neurodegenerative diseases such as Huntington's disease (HD) chorea can accompany basal ganglia disorders due to vasculitis or infections, e.g., with the human immunodeficiency virus (HIV). The clinical picture is complicated by the rare occurrence of HIV infection and HD.
METHODS
First, we present a case suffering simultaneously from HIV and HD (HIV/HD) focusing on clinical manifestation and disease onset. We investigated cross-sectional data regarding molecular genetic, motoric, cognitive, functional, and psychiatric disease manifestation of HIV/HD in comparison to motor-manifest HD patients without HIV infection (nonHIV/HD) in the largest cohort of HD patients worldwide using the registry study ENROLL-HD. Data were analyzed using ANCOVA analyses controlling for covariates of age and CAG repeat length between groups in IBM SPSS Statistics V.25.
RESULTS
The HD diagnosis in our case report was delayed by approximately nine years due to the false assumption that the HIV infection might have been the cause of chorea. Out of n = 21,116 participants in ENROLL-HD, we identified n = 10,125 motor-manifest HD patients. n = 23 male participants were classified as suffering from HIV infection as a comorbidity, compared to n = 4898 male non-HIV/HD patients. Except for age, with HIV/HD being significantly younger (p < 0.050), we observed no group differences regarding sociodemographic, genetic, educational, motoric, functional, and cognitive parameters. Male HIV/HD patients reported about a 5.3-year-earlier onset of HD symptoms noticed by themselves compared to non-HIV/HD (p < 0.050). Moreover, patients in the HIV/HD group had a longer diagnostic delay of 1.8 years between onset of symptoms and HD diagnosis and a longer time regarding assessment of first symptoms by the rater and judgement of the patient (all p < 0.050). Unexpectedly, HIV/HD patients showed less irritability in the Hospital Anxiety and Depression Scale (all p < 0.05).
CONCLUSIONS
The HD diagnosis in HIV-infected male patients is secured with a diagnostic delay between first symptoms noticed by the patient and final diagnosis. Treating physicians therefore should be sensitized to think of potential alternative diagnoses in HIV-infected patients also afflicted by movement disorders, especially if there is evidence of subcortical atrophy and a history of hyperkinesia, even without a clear HD-family history. Those patients should be transferred for early genetic testing to avoid further unnecessary diagnostics and improve sociomedical care.
|
10.3390/brainsci11060710
|
pubmed_314_19859
|
We assessed the clinical course and biochemical profile of symptomatic children with viral hepatitis A who had atypical manifestations. Of 229 children with hepatitis A, atypical manifestations were found in 32 (14%) subjects. Prolonged cholestasis (n = 14), acute liver failure (9), relapse (9), ascites (8), and hematological problems (8) were the common presentations. Liver histology was suggestive of chronic liver disease in six children with protracted jaundice. Patients with atypical presentations were older (7.7 [1.6] years vs. 6.5 [2.6] years; p=0.012) and had higher total serum bilirubin (13.7 [8.1] mg/dL vs. 7.2 [4.0] mg/dL; p=<0.001) than those with typical presentation. Approximately 15% of children with acute hepatitis A infection have atypical presentation which is associated with increase in morbidity.
|
10.1007/s12664-010-0006-3
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pubmed_866_23245
|
BACKGROUND
Cocaine use disorder (CUD) remains a substantial public health problem with no clearly effective pharmacotherapy available. In a prior trial, combined amphetamine and topiramate treatment significantly reduced cocaine use among individuals demonstrating the most frequent use at baseline. This trial targeted such frequent users.
METHODS
A double-blind, randomized placebo-controlled trial, testing the combination of mixed amphetamine salts extended-release (MAS-ER) and topiramate or placebo over a 12-week medication phase was conducted. The two-site outpatient trial included 127 adults (96 males) with CUD using at least 9 days in the prior month. MAS-ER was titrated to a maximum dose of 60 mg/day and topiramate to a maximum dose of 100 mg twice/day. The primary outcome was the proportion of individuals who achieved three consecutive abstinent weeks at the end of the study (EOS) as measured by urine toxicology and self-report.
RESULTS
The proportion of participants achieving three abstinent weeks at the EOS was significantly (P = .03) larger in the treatment (14.1%) compared to the placebo group (0.0%), while controlling for baseline cocaine use, sex, current alcohol use disorder, and site. Of note, due to conservative cardiac safety-parameters a considerable number of individuals in the treatment group were discontinued from study medication (20.3%).
CONCLUSIONS
While these findings provide further evidence that the combination of MAS-ER and topiramate is efficacious in promoting abstinence in CUD adults with frequent use it remains possible that the combination treatment is no more effective than either treatment alone. Despite this, the study provides a valuable "proof of concept."
|
10.1016/j.drugalcdep.2019.107700
|
pubmed_124_5334
|
The solubility of methylparaben was determined at 25 degrees in a series of amide-water cosolvent systems. The data were used to demonstrate the possibility of an amide excess at or near the ester solute over that in the bulk solvent. The analysis, stemming from an interfacial tension-solute area solubility model proposed by earlier workers, involved data obtained as a function of amide concentration and as a function of amide alkylation. Both sets of data support the basic contention of the paper.
|
10.1002/jps.2600680922
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pubmed_338_141
|
Skin from bullfrog tadpoles does not show the potential difference characteristic of adult frog skin until several days after the emergence of the forelimbs, presumably because the mechanism for active sodium transport is absent or nonfunctional. Exposure to low concentrations of thyroxine accelerates appearance of the transepidermal potential difference at rates which are related to the dosage. This system may provide a new basis for evaluating the importance of specific biochemical mechanisms in active sodium transport.
|
10.1126/science.148.3677.1612
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pubmed_295_17607
|
Starting in January 2020, the novel coronavirus, now known as acute respiratory syndrome coronavirus (SARS-CoV-2) and the disease that it causes (COVID-19) has had significant impacts on human health, the environment, and the economy globally. The rapid lockdown that occurred as well as its well documented timing allows for an unprecedented opportunity to examine the impact of air pollution from densely populated regions has on adjacent and pristine environments. Here, we use in situ and satellite observations to show that there was a step function decrease in two key indicators of air quality, nitrogen dioxide and airborne particulates, in locations within the Indo-Gangetic Plan (IGP) as a result of the Spring 2020 lockdown. Based on anomaly patterns, we find a dipole response with a statistically significant reduction in air pollution along the western IGP and Himalaya and an increase in air pollution in the eastern IGP and Himalaya. We show that spatial variability in the reductions in economic activity across northern India and the adjoining countries of Nepal, Pakistan, and Bangladesh contributed to this dipole as did a persistent atmospheric circulation anomaly across the region during the lockdown.
|
10.1029/2020GH000351
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pubmed_267_12422
|
Riboflavin status in 270 free-living and healthy elderly was determined from dietary intake (3-day food records) and erythrocyte glutathione reductase activity coefficients (EGR-AC). High EGR-ACs (greater than 1.35) indicate poor riboflavin nutriture. Mean dietary intakes of riboflavin were 1.86 +/- 0.64 (SD) for males and 1.58 +/- 0.69 mg/day for females. Approximately 45% of the population were taking some supplemental riboflavin and total riboflavin intakes ranged from 0.65 to 165 mg/day. The mean EGR-AC for those taking supplemental riboflavin was significantly lower than that of the nonsupplemented group (1.06 and 1.16, respectively). Only three subjects had EGR-ACs greater than 1.35. A significant correlation was found between total riboflavin intake and EGR-AC (r = 0.53). In a separate population of 667 volunteers between the ages of 20 and 87 yr, a significant decrease in mean EGR-AC with age was found. The mean EGR-AC for those over 60 yr and not taking a supplement was 1.16 +/ 0.10 compared to 1.23 +/- 0.11 for those from 20 to 29 yr old. Inadequate riboflavin nutriture appears to be more of a problem for younger than older adults.
|
10.1093/ajcn/36.5.902
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pubmed_14_18242
|
OBJECTIVES
To evaluate the safety and short-term efficacy of stent revascularization as treatment for renal artery stenosis.
METHODS
Percutaneous transluminal renal angioplasty with stent (PTRAS) was performed on 30 consecutive patients with severe renal artery stenosis for poorly controlled hypertension or preservation of renal function. They subsequently underwent 3-month clinical follow-up for the effect of the procedure on renal function, blood pressure control and the number of antihypertensive medications used.
RESULTS
Angiographic success was obtained in 29 (96.7%) of the 30 patients after PTRAS. 3 months after the procedure systolic and diastolic blood pressures significantly decreased (from 173.5 to 135.8 mm Hg and from 95.8 to 75.6 mm Hg, respectively; P < 0.001) and less antihypertensive medications were taken (from 2.5 to 1.5). Blood pressure in 5 (16.7%) of the 30 patients became normal without taking any antihypertensive medication and blood pressure control was more facile in 22 (73.3%) of the patients. However, there was no improvement in 3 (10.0%) of the patients. Creatinine slightly decreased in 2 (6.7%) of the 30 patients and remained stable in 28 (93.3%) of the 30 patients. There was no statistical significance in this respect.
CONCLUSIONS
Renal artery stent revascularization has a short-term beneficial effect on blood pressure control and a nondeleterious effect on renal function. The long-term efficacy should be investigated. The procedure is safe in usual.
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pubmed_14_18242
|
pubmed_247_4366
|
35 intracranial tumours, 18 gliomas, 12 meningiomas, one neurilemmoma (neurinoma), one malignant melanoma and two metastases were successfully grown in-vitro and were submitted to immunocytochemical reactions, including cytokeratin, glial fibrillary acid protein (GFAP), vimentin, fibronectin, S-100 protein, neurofilament proteins, neuron-specific enolase (NSE) and basic myelin protein (MBP). Cytokeratin in metastases, GFAP and vimentin in gliomas, vimentin in meningiomas were consistently positive. S-100 protein was weakly and partially positive in gliomas, meningiomas, the neurilemmoma and malignant melanoma. Positive demonstration of fibronectin within cells was interpreted as a consequence of phagocytosis, except in meningiomas where fibronectin expression next to cell membranes seemed genuine. All other tested markers proved negative. The most important result seems to be that cells expressed markers irrespective of cellular shape and cytological morphology. It can be concluded that the cellular population as a whole consisted of tumour cells during the short time under observation and that supportive cell contamination during this early growth period was negligible.
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pubmed_247_4366
|
pubmed_264_768
|
Threonine deaminase (l-threonine dehydratase EC 4.2.1.16) has been partially purified from a new extreme thermophilic bacterium, Thermus X-1, which is similar to T. aquaticus YT-1. The threonine deaminase of strain X-1 has a maximal rate of reaction at 85 to 90 C and is more thermostable than the threonine deaminase from mesophilic bacteria. The enzyme has an apparent molecular weight of 100,000 to 115,000, a K(m) for l-threonine of 14 mM, a pH optimum of 8.0, and like other threonine deaminases also catalyzes the deamination of serine. However the Thermus X-1 threonine deaminase does not show a strong feedback inhibition by isoleucine. It is suggested that the regulation of the biosynthesis of isoleucine in this extreme theromophile may resemble that reported in Rodospirillum rubrum.
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10.1128/jb.114.2.556-562.1973
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pubmed_859_6973
|
OBJECTIVE
Sex disparities in out-of-hospital cardiac arrest (OHCA) care processes have been reported. This study aimed to investigate the association between sex and prehospital advanced cardiac life support (ACLS) interventions provided by emergency medical services in Japan.
METHODS
We analyzed data from January 1, 2013, to December 31, 2020, from the All-Japan Utstein Registry of patients with OHCA aged ≥18 years who were resuscitated by bystanders. The primary outcomes were prehospital ACLS interventions, including advanced airway management (AAM) and epinephrine administration. Sex-based disparities in receiving prehospital ACLS interventions were assessed via multivariable logistic regression analyses.
RESULTS
Among 314,460 eligible patients, females with OHCA received fewer prehospital ACLS interventions than males: 83,571/187,834 (44.5%) males vs. 55,086/126,626 (43.5%) females (adjusted odds ratio [AOR] = 0.94, 95% confidence interval [CI] = 0.93-0.96) for AAM and 60,097/187,834 (32.0%) males vs. 35,501/126,626 (28.0%) females (AOR = 0.84, 95% CI = 0.83-0.85) for epinephrine administration. Similar results were also obtained in the subgroup analysis (groups included patients aged 18-74 years and ≥75 years and those with cardiac origin, ventricular fibrillation (VF), non-VF, non-family member witnessed, and family member witnessed).
CONCLUSION
Compared with males, females were less likely to receive prehospital ACLS. Emergency medical service staff must be made aware of this disparity, and off-the-job training on intravenous cannulation or AAM replacement must be conducted. Investigation of the impact of sex disparity on OHCA care processes can facilitate planning of future public health policies to improve survival outcomes.
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10.1016/j.ajem.2022.11.025
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pubmed_95_20822
|
Synthesis of melatonin in the mammalian pineal gland is regulated by the rhythmic expression of acetyl-CoA: serotonin N-acetyltransferase (SNAT) and other unknown factors. To screen for pineal-specific mRNAs potentially involved in melatonin synthesis and/or regulation, differential display PCR (DDPCR) was employed. We used 80 primer pairs and examined 40 bands of interest. One of the pineal specific clones (relative to brain and eye), PG25, was studied further. Hybridization histochemical and Northern analyses confirmed its tissue specificity. The size of the corresponding mRNA is 2.4 kb. A cDNA (2 kb) containing the coding region was obtained using a long-template PCR-based RACE technique. A data base search indicates that PG25 is highly homologous to a recently identified human lung endothelial cell-specific gene, ESM-1. Interestingly, not only the amino acid sequences but also the cDNA sequences, including the long 3' untranslated regions, are highly similar. This suggests that the conserved 3' untranslated region may carry information to regulate its own expression. Northern analysis revealed that PG25 is also expressed in the rat lung, but at a much lower (10%) level compared to the pineal. Finally, our work shows the feasibility of a fast, integrated PCR-based cloning method for obtaining long, potentially full-length cDNAs with restricted expression in anatomically complex regions of the brain. This protocol combining several existing methodologies is suitable for use with limited tissue sources and uses minimal amounts of isotopes.
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10.1016/s0165-0270(97)02237-1
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pubmed_518_9740
|
In 1998, the authors studied the effect of residential exposure to electric and magnetic fields from high-power lines on female urinary excretion of 6-sulfatoxymelatonin (6-OHMS) in the Quebec city, Canada, metropolitan area. A sample of 221 women living near a 735-kV line was compared with 195 women the same age living away from any power lines. Participants provided morning urine samples on 2 consecutive days and wore a magnetic dosimeter for 36 consecutive hours to measure personal magnetic exposure. The indoor electric field was assessed by spot measurements. After adjustment for other factors associated with low melatonin secretion, such as medication use or light exposure, nighttime concentration of 6-OHMS was similar in the two groups. When either 24-hour or sleep-time exposure to magnetic field or electric field measurements was used, no exposure-effect relation was evident. However, the trend of decreasing 6-OHMS concentration with age was more pronounced for women living near the lines, as was a lower 6-OHMS concentration in women with high body mass index. Chronic residential exposure to magnetic fields from high-power lines may accentuate the decrease in melatonin secretion observed in some vulnerable subgroups of the population.
|
10.1093/aje/154.7.601
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pubmed_968_25832
|
A novel and efficient rearrangement of N-tosylhydrazones bearing allyl ethers into trans-olefin-substituted sulfonylhydrazones is proposed. The reaction involves breakage of the C-O bond and formation of the C-N bond. The reaction can be extended to a wide range of substrates, and the target products can be synthesized smoothly, regardless of the presence of electron-donating and electron-withdrawing groups. The proposed strategy is a new direction in the field of rearrangement reactions.
|
10.3389/fchem.2021.782641
|
pubmed_200_11964
|
Doping quantum dots (QDs) with lanthanide (Ln) ions is promising to modify the optical properties of QDs, but incorporating Ln(3+) ions into QD hosts remains a challenge. In this work, we adopt the trapped-dopant model for fabricating Eu-doped ZnS QDs via direct wet chemical synthesis. Sharp Eu dopant photoluminescence (PL) was observed in the PL spectra of the as-prepared Eu-doped ZnS QDs and the bands at ~590, ~618 and ~695 nm were assigned to transitions from (5)D0 to (7)F1, (7)F2 and (7)F4, respectively. Quenching of the ZnS bandgap PL and enhancement of the Eu dopant PL were observed with increasing Eu(3+) doping concentration, and also, the excitation spectra for Eu emission (618 nm) were similar to the typical excitonic features of the ZnS host. These spectroscopic results, as well as the XRD and EDS data, demonstrated that Eu(3+) ions were incorporated in the ZnS host rather than just on the surface, and the Eu dopant PL was derived from energy transfer from the QD host to Eu(3+) rather than direct excitation of Eu(3+). By surface passivation, the sharp Eu emission was well-separated from the ZnS bandgap emission, which led to a good signal-to-noise ratio for more sensitive detection.
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10.1088/0957-4484/26/37/375601
|
pubmed_763_9286
|
BACKGROUND
Intensity modulated radiotherapy (IMRT) is routinely utilized in the treatment of locally advanced non-small cell lung cancer (NSCLC). RTOG 0617 found that overall survival was impacted by increased low (5 Gy) and intermediate (30 Gy) cardiac doses. We evaluated the impact of esophageal-sparing IMRT on cardiac doses with and without the heart considered in the planning process and predicted toxicity compared to 3D-conventional radiotherapy (3DCRT).
METHODS
Ten consecutive patients with N2 Stage III NSCLC treated to 60 Gy in 30 fractions, between February 2012 and September 2014, were evaluated. For each patient, 3DCRT and esophageal-sparing IMRT plans were generated. IMRT plans were then created with and without the heart considered in the optimization process. To compare plans, the dose delivered to 95% and 99% of the target (D95% and D99%), and doses to the esophagus, lung and heart were compared by determining the volume receiving X dose (VXGy) and the normal tissue complication probability (NTCP) calculated.
RESULTS
IMRT reduced maximum esophagus dose to below 60 Gy in all patients and produced significant reductions to V50Gy, V40Gy and esophageal NTCP. The cost of this reduction was a non-statistically, non-clinically significant increase in low dose (5 Gy) lung exposure that did not worsen lung NTCP. IMRT plans produced significant cardiac sparing, with the amount of improvement correlating to the amount of heart overlapping with the target. When included in plan optimization, for selected patients further sparing of the heart and improvement in heart NTCP was possible.
CONCLUSIONS
Esophageal-sparing IMRT can significantly spare the heart even if it is not considered in the optimization process. Further sparing can be achieved if plan optimization constrains low and intermediate heart doses, without compromising lung doses.
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10.21037/jtd.2016.03.64
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pubmed_1026_1060
|
The mitogen activated protein kinases (MAPKs) form part of a signaling cascade through phosphorylation reactions conserved in all eukaryotic organisms. The MAPK cascades are mainly composed by three proteins, MAPKKKs, MAPKKs and MAPKs. Some signals induce MAPKKK-mediated phosphorylation and activation of MAPKK that phosphorylate and activate MAPK. Afterward, MAPKs can act either in the cytoplasm or be imported into the nucleus to activate other proteins or transcription factors. In the green microalga Chlamydomonas reinhardtii the pathway for nitrogen (N) assimilation is well characterized, yet its regulation still has many unknown features. Nitric oxide (NO) is a fundamental signal molecule for N regulation, where nitrate reductase (NR) plays a central role in its synthesis. The MAPK cascades could be regulating N assimilation, since it has been described that the phosphorylation of NR by MAPK6 promotes NO production in Arabidopsis thaliana. We have identified the proteins involved in the MAPK cascades in Chlamydomonas reinhardtii, finding 17 MAPKs, 2 MAPKKs and 108 MAPKKKs (11 MEKK-, 94 RAF- and 3 ZIK-type) that have been structurally and phylogenetically characterized. The genetic expressions of MAPKs and the MAPKK were slightly regulated by N. However, the genetic expressions of MAPKKKs RAF14 and RAF79 showed a very strong repression by ammonium, which suggests that they may have a key role in the regulation of N assimilation, encouraging to further analyze in detail the role of MAPK cascades in the regulation of N metabolism.
|
10.3390/ijms21103417
|
pubmed_132_13487
|
Tryptophan metabolism has been extensively studied in humans as well as in soil. Its metabolism takes place mainly through kynurenine pathway yielding hydroxylated, deaminated and many other products of physiological significance. However, tryptophan metabolism has not been studied in an isolated thermophilic bacterium. Geobacillus stearothermophilus is a local thermophile isolated from Kuwait desert soil contaminated with petroleum hydrocarbons. The bacterium grows well at 65 °C in 0.05 M phosphate buffer (pH 7), when supplied with organic compounds as a carbon source and has a good potential for transformation of steroids and related molecules. In the present study, we used tryptophan ethyl ester as a carbon source for the bacterium to study the catabolism of the amino acid at pH 5 and pH 7. In this endeavor, we have resolved twenty one transformation products of tryptophan by GC/LC and have identified them through their mass spectral fragmentation.
|
10.4137/IJTR.S6457
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pubmed_1122_9964
|
The issue of how neurons communicate with each other through patterns of action potentials, that is, of what is the neural code, is one of the major problems in modern science. Because complex stimuli can be easily and rapidly presented to the visual system, and because vision is both behaviorally important to and occupies a large amount of neural tissue in humans, a great deal of the research on the neuronal code has been done in the primate visual system. One of the more challenging aspects of this research concerns how the time-varying nature of neuronal responses might be used by the nervous system. This review addresses some of the major lines of investigation as to how the temporal variation of a neural response might function in transferring information in the primate visual system.
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10.1615/critrevneurobiol.v13.i1.40
|
pubmed_173_18029
|
BACKGROUND
imbalances in metabolic, inflammatory and redox homeostasis play an important role in the leading theories of age-related morbidity, but no large-scale epidemiological study has been conducted so far assessing their associations with total morbidity and multi-morbidity in the same model.
METHODS
analyses were conducted in 2,547 participants of an established population-based cohort study from Germany. The participants' median age was 70 years (range: 57-84) and 51.9% were women. End points were total somatic morbidity and multi-morbidity, assessed by the Cumulative Illness Rating Scale-Geriatric version.
RESULTS
overall, 251 study participants had multi-morbidity (9.9%). Except for the redox marker 'total thiol levels of proteins', all other assessed metabolic (obesity, diabetes, dyslipidaemia and hypertension), inflammatory (C-reactive protein) and oxidative stress markers (derivatives of reactive oxygen metabolites) were significantly associated with total somatic morbidity and multi-morbidity if assessed individually. If modelled jointly, effect estimates were attenuated but remained statistically significant for the outcome 'total morbidity' and for low weight, obesity, insufficiently controlled diabetes and derivatives of reactive oxygen metabolites with respect to the outcome 'multi-morbidity'.
CONCLUSIONS
results from this large sample of older adults support hypotheses that relate imbalances in metabolic, inflammatory and redox homeostasis to age-related morbidity. Despite over adjustment for closely related metabolic, inflammatory and oxidative stress conditions in the full model, independent associations of the markers with total morbidity and/or multi-morbidity were observed. Therefore, adverse metabolic, inflammatory and oxidative stress conditions may all play important roles in the pathogenesis of age-related morbidity, which should be investigated further in future longitudinal studies.
|
10.1093/ageing/afv159
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pubmed_72_1353
|
The functional diversity and molecular adaptations of reactive microglia in the chronically inflamed central nervous system (CNS) are poorly understood. We previously showed that mice lacking multifunctional protein 2 (MFP2), a pivotal enzyme in peroxisomal β-oxidation, persistently accumulate reactive myeloid cells in the gray matter of the CNS. Here, we show that the increased numbers of myeloid cells solely derive from the proliferation of resident microglia and not from infiltrating monocytes. We defined the signature of Mfp2(-/-) microglia by gene expression profiling after acute isolation, which was validated by quantitative polymerase reaction (qPCR), immunohistochemical, and flow cytometric analysis. The features of Mfp2(-/-) microglia were compared with those from SOD1(G93A) mice, an amyotrophic lateral sclerosis model. In contrast to the neurodegenerative milieu of SOD1(G93A) spinal cord, neurons were intact in Mfp2(-/-) brain and Mfp2(-/-) microglia lacked signs of phagocytic and neurotoxic activity. The chronically reactive state of Mfp2(-/-) microglia was accompanied by the downregulation of markers that specify the unique microglial signature in homeostatic conditions. In contrast, mammalian target of rapamycin (mTOR) and downstream glycolytic and protein translation pathways were induced, indicative of metabolic adaptations. Mfp2(-/-) microglia were immunologically activated but not polarized to a pro- or anti-inflammatory phenotype. A peripheral lipopolysaccharide challenge provoked an exaggerated inflammatory response in Mfp2(-/-) brain, consistent with a primed state. Taken together, we demonstrate that chronic activation of resident microglia does not necessarily lead to phagocytosis nor overt neurotoxicity.
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10.1002/glia.22831
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pubmed_866_3675
|
A total maximum daily load (TMDL) is required for water bodies in the U.S. that do not meet applicable water quality standards. Computational watershed models are often used to develop TMDL pollutant reduction scenarios. Uncertainty is inherent in the modeling process. An explicit uncertainty analysis would improve model performance and result in more robust decision making when comparing alternative pollutant reduction scenarios. This paper presents a risk-based framework for evaluating alternative pollutant allocation scenarios considering reliability in achieving water quality goals. We demonstrate a generic routine for the application of Generalized Likelihood Uncertainty Estimation (GLUE) to Hydrological Simulation Program-FORTRAN (HSPF) using existing softwares to evaluate two bacteria reduction scenarios from a recently developed TMDL that addressed a bacterial impairment in a mixed land use watershed in Virginia, U.S. Our probabilistic analysis showed that for reliability levels <25%, the recommended TMDL bacterial load reduction scenario had the same exceedance rate as the full reduction scenario (fully reducing all bacterial loads except wildlife), while for reliability levels between 25% and 50%, the exceedance rates for the two pollutant reduction scenarios were similar, with the TMDL recommended scenario violating the water quality criteria only slightly more often. The full reduction scenario performed better in higher reliability levels, although it could not meet the water quality criteria. Our results indicated that, in this case, achieving water quality goals with very high reliability was not possible, even with extreme levels of pollutant reduction. The risk-based framework presented here illustrates a method to propagate watershed model uncertainty and assess performance of alternative pollutant reduction scenarios using existing tools, thereby enabling decision makers to understand the reliability of a given scenario in achieving water quality goals.
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10.1016/j.scitotenv.2019.135022
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pubmed_1006_10230
|
This clinical study describes two combined modalities of treatment, orthodontic and porcelain laminate placement, to facilitate diastema closure. Geristore, a dual-cure fluoride-releasing composite was mixed to bond orthodontic brackets in place. H6 elastic bands were used with the orthodontic brackets to close the diastemas sufficiently and to allow the placement of Cerinate porcelain laminates to produce a beneficial cosmetic effect.
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10.1111/j.1708-8240.1992.tb00709.x
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pubmed_1070_3845
|
BACKGROUND
Several factors influence ischemic/reperfusion injury in simultaneous pancreas-kidney transplantation (SPKT). Per-operative period is full of intense changes in systemic parameters related to pancreatic reperfusion (PR). This work aims to study these changes evaluating fluid reposition, need of vasopressors and other related factors.
MATERIAL/METHODS
Sixteen SPKT enduring patients mean age 32.4+/-4.76 had metabolic, electrolyte and hemodynamic data evaluated and compared at three times. Arterial blood gases, glucose, hematocrit; Na, K; MAP, HR and PAP were monitored after skin incision (T1), before and after PR (T2-T3). Fluid reposition, vasopressors, endocrine graft recovery and other related factors as donors, grafts, surgery team and receptors were also considered.
RESULTS
Glucose, PaO2, PaCO2 and electrolytes didn't vary along the times. From T1v.T2 there was significant metabolic acidosis; T2v.T3 identified tachycardia and pulmonary hypertension; T1v.T3 confirmed metabolic acidosis, hemodilution and arterial hypotension. Use of crystalloids (8500+/-2909.75 mL), colloids (647.05+/-492.59 mL), human albumin (8.57+/-2.44 U), fresh frozen plasma (1.06+/-1.91 U), platelets (1.86+/-4.16 U) and red packed cells (5.75+/-3.25 U), needs of noradrenalin and dobutamin: 37,5% and 6,25%. Endocrine graft recovery median was 4.15 h. Related factors to donor's: 25.43+/-8.14 years, BMI 23.24+/-1.66, serum creatinine 1.1+/-0.47mg/dl, hemodynamically stable and trauma as cause of 50% donors brain death; graft storage: cold ischemia time (CIT) median of 12.5 h; surgery team: warm ischemia time (WIT) median of 60min; receptors: ASA4, type 1 diabetes mellitus and end stage renal disease medias of 18.87+/-5.64 and 2+/-1.3 years.
CONCLUSIONS
Our experience confirmed the intense instability related in literature caused by PR in SPKT.
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pubmed_1070_3845
|
pubmed_786_16238
|
A new technique is sweeping the world, and changing the course of human work and life. It is impacting upon models, methods and the development of medical research. In the development of this new technique, a huge quantity of experimental research and clinical practice has proved that many human diseases have a close relationship to pathological changes that take place in the microvascular system. It has been proven that the microvascular system is the target for studying disease development and the treatment of disease. Many studies have shown that successful pathogenesis and pathological research must be aimed at understanding the key proteins in cells, organs and systems, as well as investigating their interaction, and finding out how these proteins change under disease conditions. This paper reviews the current status of microvascular medicine and proteomics.
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pubmed_786_16238
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pubmed_588_3772
|
UNLABELLED
The purpose of this paper is to appreciate the Acrysof Natural IOL comportment during the implantation after phacoemulsification, and to evaluate the visual acuity at 2 months and 2 years postoperative.
MATERIAL AND METHODS
Prospective clinical study which comprises 48 patients( 48 eyes) with cataract operated on with phacoemulsification and implantation of Acrysof Natural IOL with the Monarch II injector and the implantation forceps.
RESULTS
The patients' age was between 4- 82 years; The IOLs were introduced with the Monarch II injector in 47 cases and with the implantation forceps in 1 case; No IOL was damaged during the implantation; The unfolding and the rotation of the IOL were possible in all cases, without incidents; The visual acuity appreciated 2 months and 2 years postoperative was good in the most of the cases; the chromophore pigment did not influence the quality of vision and the color perception.
CONCLUSIONS
The implantation of the Acrysof Natural IOL is identical with the implantation of the Acrysof single piece IOL, is easy to perform and completely atraumatic.
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pubmed_588_3772
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pubmed_225_9233
|
The osteoclast is known to be derived from the hemopoietic stem cell, but its lineage and the mechanisms by which its differentiation is regulated are largely unknown. There is evidence that osteoclastic differentiation is induced through a contact-dependent interaction between bone marrow stromal cells and hemopoietic precursors. To analyze osteoclastic lineage, colonies were generated in semi-solid medium from mouse spleen cells in the presence of erythropoietin with either Wehi 3B-conditioned medium or interleukin 3 (IL3). After 7 days, individual colonies were picked. Half of each colony was phenotyped by the morphology of cells in cytospin preparations; the second half of each was incubated for 7 days with a bone marrow-derived cell line (ts8) that induces osteoclastic differentiation from hemopoietic cells, on bone slices in the presence of 1,25-dihydroxyvitamin D3. After incubation, bone resorption was assessed by scanning electron microscopy. No resorption was induced in cells derived from single-lineage colonies, but resorptive cells differentiated in 17% of granulocyte-macrophage (GM) colonies and 38% of multilineage colonies. Since only a minority of GM colonies contained osteoclastic precursors, this suggests that the GM colonies that contained osteoclasts were not typical GM colonies but may have been a form of multilineage colony analagous to other multilineage colonies that contain granulocytes, macrophages, and a third cell type. No resorptive cells were formed when IL3-derived colonies were incubated on bone slices without ts8 cells. The results suggest that osteoclasts are derived from a multilineage precursor, upon which IL3 acts to generate cells capable of osteoclastic differentiation, which form resorptive cells upon incubation with bone marrow stromal cells in the presence of 1,25-dihydroxyvitamin D3.
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10.1210/endo-128-1-259
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pubmed_57_4529
|
OBJECTIVE
Direct rigid laryngoscopy (DRL) is a relatively simple and well-tolerated procedure that can provide both diagnostic and therapeutic benefits. There are no data regarding the risk of acquiring bacteremia after DRL. The purpose of this prospective study was to assess the frequency of bacteremia and nosocomial colonization following DRL and to identify possible risk factors for the development of these complications.
METHODS
In this study, 55 consecutive patients with benign or malignant laryngeal pathologies undergoing DRL were included between January 2010 and January 2011. The patients have benign laryngeal lesions and suspicious malignancy. In appropriate circumstances of each patient before intubation and at postoperative 24 hours of throat swab, samples were taken in the transport medium of the patients who underwent planned DRL and underwent surgery. The samples were evaluated in our Microbiology Department. Blood cultures were performed using automated system at postoperative 5 and 24 hours. For each patient at preoperative and postoperative period, C-reactive protein levels in blood samples were measured. SPPS 16 package program was used for statistical analysis.
RESULTS
The distribution of sex was 45 males and 10 females with average age of 51.4 (between 23 and 99 years). Patients who had malignant lesions (n = 17) accounted for 30.9% of all patients. Preoperative Candida colonization was recovered from the cultures obtained from 9 oropharyngeal specimens (16.4%). Postoperative oropharyngeal nosocomial bacteria colonization was observed in 14 patients (25.5%). Nosocomial colonization was found related to malignancy (P = 0.014). C-reactive protein levels of patients before and after surgery were not statistically significant (P > 0.05). At postoperative 5 and 24 hours, blood cultures of all patients were negative. Postsurgical bacteremia was not observed.
CONCLUSIONS
Although there is no association between DRL and bacteremia, nosocomial colonization may be significant. Nosocomial colonization possesses a risk of development of infection especially in patients with malignancy.
|
10.1097/SCS.0000000000000429
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pubmed_1038_13480
|
An approach to constructing a severity index for emergency medical services patients with cardiac-related problems is developed. The procedure is based on two linear programming models and produces a set of weights which can be added to estimate the severity of a patient's condition. A set of patients independent of the set used to derive the weights was ranked with respect to severity by a set of physicians who were also independent of the model development process. The average value for Spearman's rank order correlation coefficient (rho) between a ranking based on the severity weights and the physicians was 0.6897. The average value of rho calculated over all possible pairs of the physician rankings was 0.6859. Thus, the ranking based on the severity weights correlated as well with the physicians ranking as did the physician rankings among themselves.
|
10.1016/0010-4825(92)90057-t
|
pubmed_975_15854
|
Since the 1950's a number of methods have been developed whose aims is to provide enhanced mapping tools, which allow the depiction of the distribution of disease, and thereafter, to assess risks due to environmental factors (or other spatial-defined factors). Our review of statistical-epidemiological methodology for spatial analysis of diseases shall outline the distinction between global tests for clustering (detection of non casual distribution of events in an area) and cluster detection's techniques for the identification and location of abnormal aggregation of disease's cases. In this paper we evaluate each-one of the proposed methods, on general grounds, with regard to whether they meet the aims of the analysis and how successful they are in overcoming problems.
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pubmed_975_15854
|
pubmed_17_7429
|
BACKGROUND
In arteries, agonists such as acetylcholine release an endothelium-derived hyperpolarizing factor (EDHF) that is neither nitric oxide nor prostacyclin.
OBJECTIVES
To examine the responses to acetylcholine in segments of forearm veins from patients with chronic renal failure who either had never received dialysis or had undergone long-term dialysis, and to determine the contribution of nitric oxide and EDHF to endothelium-dependent relaxation in veins from patients with chronic renal failure.
METHODS
Isometric tension was recorded in rings of forearm vein from 34 non-dialysed patients, 27 dialysed patients and 14 multiorgan donors (controls).
RESULTS
Relaxation in response to acetylcholine was reduced in veins of non-dialysed and dialysed patients. The inhibitors of nitric oxide synthase NG-monomethyl-l-arginine (l-NMMA) and NG,NG-dimethyl-l-arginine (ADMA) reduced by 50% the maximum relaxation in response to acetylcholine in veins from controls and non-dialysed patients; the remaining relaxation was inhibited by 20 mmol/l KCl or by the K+ channel blockers tetraethylammonium chloride, iberiotoxin, charybdotoxin and the combination of barium plus ouabain, but not by apamin or glibenclamide. Relaxation in veins from dialysed patients was inhibited by K+ channel blockade but not by l-NMMA or ADMA.
CONCLUSIONS
The results demonstrate that the endothelium-dependent relaxation in forearm veins from controls and non-dialysed patients is mediated by release of nitric oxide and EDHF. In contrast, the relaxation in veins from dialysed patients is mediated mainly by EDHF. EDHF-induced relaxation involves activation of large-conductance Ca2+-activated K+ channels.
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10.1097/00004872-200310000-00021
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pubmed_759_8098
|
Covalent light chain dimers (L2) and cysteine-blocked L chain monomers readily react with partially reduced heavy (H) chains. A rapid disappearance of these blocked L chain species is followed by the appearance of covalent intermediates-HL, H2, and H2L-leading to fully assembled H2L2. The mechanism of initial disulfide bond formation between heavy and light chains is disulfide interchange.
|
10.1126/science.415360
|
pubmed_946_1953
|
Serological and biochemical studies were performed on M components isolated from 3 patients with transitional cell carcinoma of the urinary bladder (TCC). All were IgG1(K) proteins. 2 of the 3 belonged to the VKI subgroup, and these 2 also possessed cross-reactive idiotypic determinants. These findings are consistent with the ideas that M components in patients with a given kind of cancer may have restricted heterogeneity, and that the synthesis of an M component and the manifestation of a solid tumor may be related events in some patients who exhibit both abnormalities.
|
10.1159/000206983
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pubmed_882_19571
|
Pt-Cu bimetallic alloys, as a key component in many heterogeneous catalysts, have the potential to be used in a range of industrially important reactions. The stability of platinum-modified Cu(1 1 0) and Cu(1 1 1) surfaces in the absence/presence of CO, NO and O has been investigated based on density-functional theory. We find that Pt alloyed in the second layer of the Cu (1 1 0) surface, rather than in the bulk, is the most favorable configuration. To relieve the strain, platinum tends to stay in the surface layer of close-packed Cu(1 1 1). Adsorbates can affect the stability of Pt-modified surfaces. Upon the adsorption of CO and NO, Pt segregation to the (1 1 0) surface becomes favorable, while on oxygen adsorption, no segregation occurs. Platinum only prefers to segregate on the Cu (1 1 1) surface when it is exposed to carbon monoxide, it tends to locate in the second layer for the other two adsorbates. Combining the position of d-band center, the d-bandwidth, and the separation between the bonding and antibonding states of the adsorbates, we interpret the results and correlate the relationship between the electronic properties of the substrate and the adsorption energy of the adsorbates, which could shed light on the prediction of bimetallic structures with desirable chemical properties.
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10.1088/0953-8984/28/8/085001
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pubmed_641_14548
|
Gastric lipase activity in aspirates from premature human infants was tested for fatty acid and positional selectivity using racemic diacid triacylglycerols (TG) as substrates. The resulting free fatty acids and monoacylglycerols (MG) were recovered and analyzed. Octanoic acid (8:0) and decanoic acid (10:0) were hydrolyzed with a preference of 61.5:1 and 2.4:1 compared to palmitic acid (16:0) from rac-16:0-8:0-8:0 and rac-16:0-10:0-10:0, respectively. The ratio of lauric acid (12:0) to oleic acid (18:1) hydrolyzed from rac-18:1-12:0-12:0 was 13:1. Myristic acid (14:0), 18:1 and linoleic acid (18:2) were released at similar rates. These data and the composition of the MG suggest that, in vitro, the lipase is selective for shorter chain fatty acids and for fatty acids on the primary positions of the TG backbone.
|
10.1007/BF02537313
|
pubmed_921_4422
|
Many problem situations arising between patients and medical officers have their source in the psyche of the persons involved. The aim of this study is to analyse psychological factors which may cone in these situations, and an attempt to describe, interpret and categorize them. We took as our starting point an analysis of protests submitted by patients (or their relatives) which were discussed by the management of the Faculty Hospital in Pilsen during the period of one year. We dealt with finished cases where the issue of the protest was of a psychological nature. Problem situations often arise under the influence of the following factors: personality features, the handling of information, maladaptation to a disease or situational factors. Majority of problem situations can be understood, prevented, and--if they arise--can be effectively handled. Pre-graduation and continuous education in this areas should provide a significant aid.
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pubmed_921_4422
|
pubmed_368_24674
|
Artemisinin has been demonstrated to exert beneficial effects on ventricular remodeling. The present study investigated whether artemisinin was able to decrease the ventricular fibrillation threshold (VFT) in rats following myocardial infarction (MI) and aimed to determine the possible underlying mechanisms. The rats were subjected to surgery to induce MI by ligation of the left anterior descending artery and were randomly allocated to receive vehicle or artemisinin (75 mg/kg/day) treatment for four weeks. Programmed electrical stimulation demonstrated a significantly increased VFT in the artemisinin-treated group compared with the vehicle-treated group. The electrophysiological improvement of the VFT was accompanied by increased immunofluorescence-stained connexin 43 (Cx43), myocardial Cx43 protein and mRNA levels in artemisinin-treated rats. The present study also demonstrated that artemisinin significantly decreased tissue tumor necrosis factor (TNF)-α levels at the infarcted border zone. Thus, artemisinin demonstrated a protective effect on ventricular arrhythmias following MI. Although the precise mechanism by which artemisinin modulates the dephosphorylation of Cx43 is unknown, it is likely that artemisinin increased the expression of Cx43 via the inhibition of TNF-α.
|
10.3892/mmr.2014.2431
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pubmed_12_6498
|
The internal consistency reliabilities of 5 subscales of the Family Environment Scale were re-examined in a study of 311 stressed and 74 control families. The reliability coefficients generated were lower than those originally reported for this instrument; most coefficients generated were below the acceptable level for practical or research use, and there was considerable variation in the reliabilities across type of stressed family. An attempt to generate more reliable scales using the original items was unsuccessful, and questions about the validity of the subscales were raised. Our results illustrate the importance of examining reliabilities of instruments, even well-known and widely used instruments, for each sample studied.
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10.1111/j.1545-5300.1990.00191.x
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pubmed_686_20703
|
Three greenhouse experiments were conducted to evaluate western corn rootworm, Diabrotica virgifera virgifera LeConte, beetle emergence from individual pots containing glyphosate-tolerant transgenic corn, Zea mays L., expressing the Cry3Bbl endotoxin from the soil bacterium Bacillus thuringiensis Berliner (MON863), nontransgenic glyphosate-tolerant isoline corn, grassy weeds (giant foxtail, Setariafaberi R.A.W. Herrm; and large crabgrass, Digitaria sanguinalis (L.) Scop.), and combinations thereof infested with 40 neonate larvae. In the first two experiments, pots with corn and weed combinations were treated with glyphosate 5 d after larval infestation to kill the weeds. The third experiment was similar to the first two except that untreated corn-weed combinations were added. In all three experiments beetle emergence varied significantly. Beetle recovery generally did not vary between the nontransgenic, nontransgenic + weeds, and MON863 + weeds. Significantly more beetles were recovered from MON863 + weeds than MON863 alone or weeds alone. Beetle emergence from MON863 + weeds was likely enhanced by larvae that initially survived on weeds before application of glyphosate. Preliminary data indicated that fecundity was highest from beetles reared on nontransgenic isoline corn and fewer eggs were laid by beetles reared on MON863 alone. Egg viability was generally lowest from beetles reared on MON863. The implications of these results in relation to insect resistant management are discussed.
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10.1603/0022-0493-98.5.1679
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pubmed_1006_18379
|
Human monoamine oxidase A that had been synthesized in a reticulocyte lysate translation system was capable of binding to and inserting into either rat liver mitochondria or isolated mitochondrial outer membranes. The inserted form was as resistant to proteinase K as endogenous mitochondrial monoamine oxidase A. The insertion, but not the binding, of monoamine oxidase A was prevented by depleting the reaction mixture of either ATP (with apyrase) or ubiquitin (with purified antibodies against this polypeptide). Addition of ATP or ubiquitin, respectively, to these depleted mixtures restored the insertion of the enzyme. In the absence of mitochondria, in vitro synthesized monoamine oxidase A did not catalyze its own alkylation by the mechanism-based inhibitor, [3H]clorgyline. However, both monoamine oxidase A that had been membrane-inserted in vitro and monoamine oxidase A that had been bound to the mitochondria under conditions of ATP depletion catalyzed adduct formation. Furthermore, reaction of either clorgyline or another mechanism-based inhibitor, pargyline, with the membrane-bound enzyme during ATP depletion inhibited the insertion of monoamine oxidase A when ATP was restored. These observations indicate that monoamine oxidase A acquired a catalytically active conformation on interaction with the mitochondrial outer membranes prior to its ATP and ubiquitin-dependent insertion into the membrane.
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pubmed_1006_18379
|
pubmed_490_6210
|
Two sandwich-type polyoxomolybdates Na₈[MO₂{Mo₂O₅(O₃PCH₃C(O)PO₃)}₂] (M = Ni2+ (1); Co2+ (2)) were synthesized by one-pot reaction of Na₂HPMo12O40·14H₂O, 1-hydroxy ethidene diphosphonic acid (HEDP=HOC(CH₃)(PO₃H₂)₂), and (1) NiCl₂/CoCl₂ (2). Compounds 1 and 2 were characterized by single crystal X-ray analysis, X-ray powder diffraction (XRPD), IR spectroscopy, 31P NMR spectra, UV-vis spectroscopy, and thermogravimetric analyses (TGA). Structural analysis reveals that 1 and 2 exhibit similar centrosymmetric structure, which consists of one transition metal (TM) ion sandwiched by two same subunits {Mo₂O₅(O₃PCH₃C(O)PO₃)}. The clusters 1 and 2 show efficient catalytic activities for oxidation of thioanisole. Moreover, they are catalytically selective for oxidizing thioanisole. Both resuable polyoxomolybdates 1 and 2 catalysts show good thermo- and hydrolytic stability. It is noted that compound 1 shows outstanding catalytic activity for oxidation of various sulfides to corresponding sulfones with 93-100% selectivity at 97-100% conversion in one hour under mild conditions, which is potentially valuable to the removal of organic sulfides.
|
10.3390/ma10101173
|
pubmed_911_11131
|
We report what is believed to be the first observation of a nonlinear mode in a cylindrical nonlinear Fabry-Perot cavity. The field enhancement from cavity buildup, as well as the large chi((3)) optical nonlinearity that is due to resonantly excited (85)Rb vapor, allows the nonlinear mode to form at low incident optical powers of less than 1 mW. The mode is observed to occur for both self-focusing and self-defocusing nonlinearity.
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10.1364/ol.24.001850
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pubmed_1096_6597
|
Biocatalysis of curcumenol (1) was performed by Mucor polymorphosporus AS 3.3443. Six metabolites including five new compounds were obtained, and their structures were elucidated as 10β-hydroxy-9,10-dihydrocurcumenol (2), 2β-hydroxycurcumenol (3), 15-hydroxycurcumenol (4), 12-hydroxycurcumenol (5), 1-hydroxy-4αH-guai-1,6,9-triene-2,8-dione (6), and 5-hydroxycarbonyl-1-oxo-3,7-dimethylindane (7) by spectroscopic analysis. M. polymorphosporus catalyzed unusual degradation and rearrangement reactions to generate a ring-contracted metabolite (7) of curcumenol (1). Curcumenol (1) and metabolites 4-7 exhibited inhibitory activities against lipopolysaccharide-induced nitric oxide production in RAW 264.7 macrophages, with 7 exhibiting more potent activity than curcumenol.
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10.1021/np500845z
|
pubmed_227_8590
|
Gli3 is a zinc finger transcription factor proteolytically processed into a truncated repressor lacking C-terminal activation domains. Gli3 processing is stimulated by protein kinase A (PKA) and inhibited by Hedgehog signaling, a major signaling pathway in vertebrate development and disease. We show here that multisite glycogen synthase kinase 3beta (GSK3beta) phosphorylation and ubiquitination by SCFbetaTrCP are required for Gli3 processing. We identified multiple betaTrCP-binding sites related to the DSGX2-4S motif in Gli3, which are intertwined with PKA and GSK3beta sites, and SCFbetaTrCP target lysines that are essential for processing. Our results support a simple model whereby PKA triggers a cascade of Gli3 phosphorylation by GSK3beta and CK1 that leads to direct betaTrCP binding and ubiquitination by SCFbetaTrCP. Binding of betaTrCP to Gli3 N- and C-terminal domains lacking DSGX2-4S-related motifs was also observed, which could reflect indirect interaction via other components of Hedgehog signaling, such as the tumor suppressor Sufu. Gli3 therefore joins a small set of transcription factors whose processing is regulated by the ubiquitin-proteasome pathway. Our study sheds light on the role of PKA phosphorylation in Gli3 processing and will help to analyze how dose-dependent tuning of Gli3 processing is achieved by Hedgehog signaling.
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10.1128/MCB.02183-05
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pubmed_658_8371
|
Cardiac complications such as myocardial infarction and congestive heart failure are the primary source of perioperative morbidity and mortality in elderly surgical patients. This is the result of structural and functional age-related changes in the heart and the vasculature and an increasing incidence of cardiovascular disorders. Appropriate perioperative management of the elderly patient should be based on the extent of functional compromise, the type and severity of pre-existing disease, and the invasiveness of the surgical procedure. Current studies suggest that appropriately administered medical therapy, particularly beta-adrenergic blockade, may reduce perioperative cardiovascular morbidity and mortality in these patients. In this article, we review changes in cardiovascular structure and function that occur with advancing age and describe perioperative medical interventions that may improve cardiac outcome in the elderly critically ill patient.
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10.1097/00075198-200210000-00004
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pubmed_130_2457
|
INTRODUCTION
The most common cause of deep neck infections is dental infection. They are diagnosed with physical examination, imaging studies, ultrasound, or computed tomography. Surgical drainage of collections should always be performed early in a classical or percutaneous way, depending on the case. The aim of the study was to compare ultrasound-guided percutaneous drainage techniques vs. surgical drainage in deep cervical abscesses of odontogenic origin in a controlled and randomized trial.
METHODS
A randomized controlled clinical trial was performed from January 2015 to December 2019. Hospital stay was evaluated as an efficiency variable. Epidemiological and secondary variable data (tumour, trismus, fever, pain), leukocytosis, cosmetic result comparing both techniques were analysed. Statistical analysis was carried out with STATA v 14.0.
RESULTS
128 patients were analysed, 51 women and 77 men. Average age 27.3 (SD = 10.13). The percutaneous group had a mean hospital stay of 3.03 (SD = 2.86) days and the surgical group 5.46 (SD = 2.96). The P-value was <.001. Cosmetic results showed differences favouring the percutaneous drainage group. None of the other variables showed statistically significant results.
DISCUSSION
Surgical treatment (cervicotomy and debridement) should be undertaken early with evidence of extensive collection in deep spaces. Minimally invasive image-guided procedures are an alternative. These can be performed in well-located, unilocular collections, without compromising of the patient's airway. Percutaneous drainage and suction techniques if necessary, serially, or drainage placement may be performed.
CONCLUSIONS
Ultrasound-guided and serially guided percutaneous drainage is the best therapeutic option in patients with mild and/or moderate dental infections.
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10.1016/j.otoeng.2020.08.008
|
pubmed_142_13704
|
BACKGROUND
Resistance to thyroid hormone (RTH) is a rare syndrome characterized by elevated thyroid hormone (TH) along with nonsuppressed thyroid-stimulating hormone (TSH). The clinical symptoms can vary considerably, and no definite treatment has been established thus far.
METHODS
A family with RTH harboring a TH receptor (THR)-β gene mutation (A234T) is described, the therapeutic strategies for RTH are reviewed, and optimization of the treatment strategies was attempted.
RESULTS
Gene sequencing revealed a point mutation (A234T) in the THR-β gene of the proposita, her elder brother and her mother. During the 20-month follow-up period, it was found that the proposita experienced apparently higher TSH level and normal TH level on taking antithyroid medication. However, on discontinuing the medication, her thyroid function returned to the baseline of elevated FT3, FT4 level along with inappropriately normal TSH. Thus far, there is no guideline regarding the treatment strategies for the RTH. Antithyroid drugs are effective for patients with thyrotoxic symptoms but pose an increased risk of thyrotroph hyperplasia. The efficacy and safety of D-T4 and bromocriptine still remains debatable, TRIAC may be the most promising drug, as it is effective and can reduce both TH and TSH level. However, L-T3 or L-T4 may be necessary for some RTH patients who exhibit massive goiter or hypothyroid symptoms.
CONCLUSIONS
It is demonstrated in this article that the A234T mutation in the THR-β gene can cause the RTH. Treatment of this condition is challenging, and individualized therapy is required because of the variable clinical features.
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10.1097/MAJ.0000000000000538
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pubmed_688_7318
|
Controversy exists over the nature of the abnormality in cardiac sympathetic nerves in heart failure. In the cardiomyopathy of the Syrian hamster, reduction in tissue stores and increased turnover of norepinephrine is clearly associated with excessive sympathetic stimulation but in animal models and humans with heart failure secondary to mechanical overload there is evidence for depression of neuronal uptake. Because norepinephrine is both released and taken up by sympathetic fibers it is impossible to assess norepinephrine kinetics in an intact heart without separating these two functions. A technique for doing so has recently been developed in normal dogs and we therefore acquired similar data in humans with heart failure secondary to chronic pressure and volume overload. The technique involves the combination of transient norepinephrine tracer coronary sinus outflow in relation to intravascular and interstitial references after simultaneous injection into the left coronary artery and the measurement of endogenous norepinephrine concentrations in artery and coronary sinus. We found a marked reduction in cardiac norepinephrine release and uptake in a group of patients with clinical left ventricular failure secondary to mechanical overload, relative to a group of patients with no failure. Norepinephrine balance and overflow across the heart were not significantly different. We conclude that there is hypofunction of the cardiac sympathetic nerves in heart failure secondary to mechanical overload and that traditional methods are inadequate in assessing cardiac norepinephrine kinetics when there are simultaneous changes in neuronal uptake and release.
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10.1172/JCI112164
|
pubmed_583_1180
|
It is shown how the photon-number amplifier may be used to make, for either novel or conventional sources, an efficient direct-detection receiver and transceiver in a local-area network environment and how the parametric amplifier may be used similarly for a homodyne-detection receiver.
|
10.1364/ol.12.000789
|
pubmed_851_23194
|
The objective of this study is to assess the effect of orientation, glazing proportion and aspect ratio of building zones on heat fluxes through their surfaces, under specific environmental conditions. The investigation is carried out for thermally-insulated building zones with a varying facade orientation corresponding to each cardinal point, during the winter period in the northern Greek region. For this purpose, three glazing-to-facade ratios (GR) are taken into account; along with the glazing ratio the influence of the glazing U value is also considered. Regarding the impact of the fenestration layout geometry, five different building aspect ratio profiles are examined. Thermal fluxes are assessed for two different indoor temperature settings, while the operation of the heating unit is assumed to be continuous. The transient thermal analysis with its mathematical formulation and solution are based on the thermal-network modelling approach, while the solar heat gain through glazing relies on the sunlit-pattern approach; in this way, the stricken by the solar rays glazing area is projected onto any interior surfaces to form the so called "sunlit" areas. As the orientation, glazing proportion and aspect ratio of the building zone vary, so do the sizes and shapes of the illuminated "sunlit" areas. Accordingly, the delivered into the zone direct solar energy and its diffused and ground reflected components can be determined. The adopted methodology provides a more accurate determination of solar heat gain with respect to glazing proportion and orientation as well as zone aspect ratio. With regard to surface orientation, glazing proportion and aspect ratio, computer results demonstrate the improvement of the thermal performance for a building zone with a south oriented glazing surface, as well as the deterioration for the other surface orientations; relative increases/decreases in the energy fluxes of a rectangular shaped building zone compared to a square-shaped building zone can reach up to 50%/100%.
|
10.1007/s11356-017-9700-3
|
pubmed_573_5927
|
Previous research has shown an inconsistent effect of hypoxia on dynamic cerebral autoregulation (dCA), which may be explained by concurrent CO2 control. To test the hypothesis that hypoxic dCA is mediated by CO2, we assessed dCA (transcranial Doppler) during and following acute normobaric isocapnic and poikilocapnic hypoxic exposures. On 2 separate days, the squat-stand maneuver was used to determine dCA in healthy subjects (n = 8; 3 women) in isocapnic and poikilocapnic hypoxia exposures (end-tidal oxygen pressure 50 Torr for 20 min). In isocapnic hypoxia, the amplitude of the cerebral blood flow response to increases and decreases in mean arterial blood pressure were elevated (i.e., increases in gain of +35 and +28%, respectively; P < 0.05). However, dCA gain to increases in pressure was reduced compared with baseline (-32%, P < 0.05) following the isocapnic hypoxia exposure. Similarly, intravenous bolus injections of sodium nitroprusside and phenylephrine in a separate group of subjects (n = 8; 4 women) also demonstrated a reduction in dCA gain to hypertension following isocapnic hypoxia. In contrast, dCA gain with the squat-stand maneuver did not significantly change from baseline during or following poikilocapnic hypoxia (P > 0.05). Our results demonstrate that dCA impairment in isocapnic hypoxia can be prevented with hypocapnia, and highlight the integrated nature of hypoxic cerebrovascular control, which is under strong CO2 influence.
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10.1152/japplphysiol.00024.2013
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pubmed_156_12975
|
BACKGROUND
Osteoarthritis is the most common degenerative disease in humans. It usually begins in middle age and is progressive. Chronic pain in older people presents a significant obstacle in maintaining function and independence. Previous studies have shown that music can improve motivation, elevate mood, and increase feelings of control in older people.
PURPOSE
The purpose of this randomized clinical trial was to examine the influence of music as a nursing intervention on osteoarthritis pain in elders.
METHOD
Data were collected using the short form of the McGill Pain Questionnaire with 66 elders suffering from chronic osteoarthritis pain. Differences in perceptions of pain were measured over 14 days in an experimental group who listened to music for 20 minutes daily and a control group who sat quietly for 20 minutes daily. All participants completed the Short Form McGill Pain Questionnaire (SF-MPQ) on day 1, 7, and 14 of the study.
RESULTS
Results of t-tests indicated that those who listened to music had less pain on both the Pain Rating Index on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001) and on the Visual Analogue Scale on day 1 (P = 0.001), day 7 (P = 0.001) and day 14 (P = 0.001), when compared with those who sat quietly and did not listen to music. A repeated measure analysis of variance controlling for pretest measures demonstrated a significant decrease in pain among experimental group participants when compared with the control group on the pain descriptor section of the SF-MPQ (P = 0.001) and the visual analogue portion of the SF-MPQ (P = 0.001).
CONCLUSION
Listening to music was an effective nursing intervention for the reduction of chronic osteoarthritis pain in the community-dwelling elders in this study.
|
10.1046/j.0309-2402.2003.02835.x
|
pubmed_987_10317
|
Inhalation of beryllium and its compounds can cause lung injuries, resulting from inflammation and oxidative stress. Multivesicular bodies (MVB), such as exosomes, are membrane vesicles produced by early and late endosomes that mediate intercellular communications. However, the role of exosomes in beryllium toxicity has not been elucidated. This current study aimed to investigate the functional role of exosomes in lung injury resulting from beryllium sulfate (BeSO<sub>4</sub> ). Here, Sprague-Dawley (SD) rats were exposed to 4, 8, and 12 mg/kg BeSO<sub>4</sub> by nonexposed intratracheal instillation. Murine macrophage (RAW 264.7) cells were pretreated with 50 nmol/L rapamycin (an mTOR signaling pathway inhibitor) for 30 min and then cultured for 24 h with 100 μg/mL exosomes, which had been previously isolated from the serum of 12 mg/kg BeSO<sub>4</sub> -treated SD rats. Compared with those of the controls, exposure to BeSO<sub>4</sub> in vivo increased LDH activity, elevated levels of inflammatory cytokines (IL-10, TNF-α, and IFN-γ) alongside inflammation-related proteins expression (COX-2 and iNOS), and enhanced secretion of exosomes from the SD rat's serum. Moreover, the BeSO<sub>4</sub> -Exos-induced upregulation of LDH activity and inflammatory responses in RAW 264.7 cells can be alleviated following pretreatment with rapamycin. Collectively, these results suggest that serum exosomes play an important role in pulmonary inflammation induced by BeSO<sub>4</sub> in RAW 264.7 cells via the mTOR pathway.
|
10.1002/jat.4321
|
pubmed_836_4171
|
BACKGROUND
Food atopy patch tests (APTs) are considered a useful tool for the diagnosis of food allergy. Hypersensitivity to peanuts has not been investigated by means of APTs so far.
METHODS
APTs and skin prick tests (SPTs) with peanuts were performed in 136 atopic dermatitis (AD) patients. Relevance of positive and negative responses to these tests was assessed by repeated open challenges with peanuts.
RESULTS
Nine percent of our AD patients reacted to the challenge. Positive responses to APTs were recorded in 19% of the patients, whereas in 12% positive SPTs were observed. APTs were more frequently positive in subjects with eczematous responses after challenge with respect to those with urticarial reactions. SPT reactivity proved to be higher in patients above 12 years of age, whereas APT positivity was more frequent in children under 6 years. APT sensitivity proved significantly higher than SPT sensitivity, in particular in children under 12 years of age. On the contrary, SPT specificity and positive predictive value were significantly higher with respect to those of APT in the age group of subjects under 6 years of age.
CONCLUSIONS
Our data suggest that APTs with peanuts may represent a useful integration to standard testing modalities employed for the diagnosis of peanut allergy in AD patients.
|
10.1034/j.1398-9995.2003.00153.x
|
pubmed_931_18768
|
The catalytic and structural characteristics of two new self-phosphorylating deoxyribozymes (referred to as deoxyribozyme kinases), denoted "Dk3" and "Dk4", are compared to those of Dk2, a previously reported deoxyribozyme kinase. All three deoxyribozymes not only utilize GTP as the source of activated phosphate and Mn(II) as the divalent metal cofactor but also share a common secondary structure with significant sequence variations. Multiple Watson-Crick helices are identified within the secondary structure, and these helical interactions confine three extremely conserved sequence elements of 8, 5, and 14 nucleotides in length, presumably for the formation of the catalytic core for GTP binding and the self-phosphorylating reaction. The locations of the conserved regions suggest that these three deoxyribozymes arose independently from in vitro selection. The existence of three sequence variants of the same deoxyribozyme from the same in vitro selection experiment implies that these catalytic DNAs may represent the simplest structural solution for the DNA self-phosphorylation reaction when GTP is used as the substrate.
|
10.1021/bi061613c
|
pubmed_38_17995
|
In times of globalisation, the future of bio-medicolegal sciences in Europe depends on the scientific community's ability to develop new strategies for research, to introduce new and generally accepted standards, to develop new analytical methods, all in order to draw up inter-site, multidisciplinary and interdisciplinary long-term research projects, eligible for European Union (EU) funding. To analyse the scientific output and to identify the topics of greatest interest and appeal in these sciences, an innovative method has been developed to select and analyse publications. This method has been applied to analyse a total of 21,176 records from PubMed out of which 5,826 papers were suitable for further analysis because they were published in national and international journals in the time between January 1, 2005 and June 1, 2010 by European authors in the field of interest. In 69% of all manuscripts, authors presented results of systematic research (original articles); 84% of the papers were written in English language. The cumulative impact factor increased from 1,670 points in 2005 to 1,878 in 2009, and extrapolated 2,812 points in 2010. The most frequent topics were the description of new analytical methods in forensic toxicology (5.7% of all papers), the analysis of short tandem repeat systems (STR, 5.6%) as well as the analysis of injury mechanisms in forensic pathology and clinical forensic medicine (4.9%). If the impact factor related potential of different topics is calculated (ratio of frequency of papers and frequency of impact points achieved), SIDS research reaches 1.64 points, followed by studies on mtDNA (1.59) and the development of new analytical methods in forensic toxicology (1.49). The findings made in the present bibliometric analysis reveal a clear and interesting overall picture of the European scientific production and productivity and could be used to identify the most innovative research lines.
|
10.1007/s00414-010-0538-1
|
pubmed_501_1148
|
Recent studies have demonstrated a negative correlation between the cholesterol content of the HDL fraction of serum lipoproteins and the incidence of arteriosclerosis. In this study the limits of normality of HDL-cholesterol have been determined in a male and female population, followed by an analysis of the HDL-cholesterol in patients with myocardial infarction. Normal values for total cholesterol in males and females were, respectively, 194.7 +/- 61.8 mg/dl and 188 +/- 62.8 mg/dl, and those of HDL-cholesterol, 63.1 +/- 14.6 mg/dl and 70.3 +/- 24.4 mg/dl. Total cholesterol in the patients with myocardial infarction was not significantly different from that of the control group, but HDL-cholesterol was significantly lower (p < 0.05).
|
pubmed_501_1148
|
pubmed_1138_2407
|
We investigated whether the distribution (concentration) of morphine in the central nervous system (CNS) after systemic administration could be an index for the in vivo binding of morphine. Neither the morphine concentration nor its decline correlated with the density of opiate receptors. Naloxone decreased the morphine concentration in some CNS regions and plasma after a high dose of morphine, but not after a small dose of morphine. The CNS regions in which naloxone decreased the morphine concentration did not correlate with the density of opiate receptors, and the concentration ratios (CNS regions versus plasma) of morphine were not affected by naloxone. These results suggested that the morphine concentration in the CNS did not reflect the in vivo binding of morphine and that the naloxone-induced decrease in morphine concentration was not due to a displacement of morphine from its receptor sites but due to a change in morphine kinetics. Pharmacokinetic studies suggested that naloxone decreased the morphine concentration through an increased volume of morphine distribution. This naloxone-induced decrease in morphine concentration may contribute to the naloxone-induced inhibition of morphine action in addition to the competitive antagonism at opiate receptors.
|
10.1254/jjp.63.235
|
pubmed_368_541
|
BACKGROUND
The aim of this study was to examine the phonological functioning (reading speed and accuracy) of hospital patients under general anaesthesia administered during colonoscopy.
METHODS
In this study the 'Łatysz' non-word reading test was used to measure the impact of selected anaesthetics on the phonological aspect of language processing (defined as decoding without referring to the meaning) in a group of 22 anaesthetised patients compared to 23 non-anaesthetised patients from university clinics.
RESULTS
Compared to the preoperative performance, a decrease in reading accuracy and reading speed was observed only in the Anaesthesia Group - AG (in the subjects aged ≥ 35 years) 1.5 h after the administration of anaesthetics. Postoperatively, the AG were significantly slower and less accurate than the Control Group - CG - after 1.5 h. After 3 h, the AG had regained their baseline values both in reading accuracy and reading speed. During the last assessment session, the AG pronounced 82% of the words correctly, while the CG pronounced 74% correctly. Moreover, subjects aged ≥ 35 years performed worse than younger subjects in their reading accuracy and speed.
CONCLUSIONS
The patients who underwent colonoscopy under general anaesthesia manifested impaired phonological functioning shortly after the procedure, both in the speed and accuracy of reading non-words. However, the accuracy problems subsided relatively quickly.
|
10.5603/AIT.2014.0026
|
pubmed_194_9840
|
Six ewes were immunized against a prostaglandin F-2alpha-protein conjugate. Between 24 and 82 days after immunization the regular cyclic occurrence of oestrus was abolished in all six ewes. Further investigations of the immunized animals revealed that the blockade of oestrus was due to a persistence of the CL and the constantly elevated (greater than 2 ng/ml) blood levels of progesterone. Surgical enucleation of the persistent CL was promptly followed by a fall in progesterone concentrations (less than 0-5 ng/ml), normal oestrus and a subsequent return to a state of constantly elevated blood progesterone levels. These results show that neutralization of the biological activity of PGF by active immunization against PGF-2alpha results in a failure of luteal regression and provide evidence that endogenous PGF is involved in normal luteal regression in this species.
|
10.1530/jrf.0.0460039
|
pubmed_302_20017
|
We designed a new computer program (MIMETIC), which generates a series of peptides for interaction with a target peptide sequence. The genetic algorithm employed ranks the sequences obtained from one generation to the next by "goodness of fit" to the target. MIMETIC designed recognition peptides to various regions of HIV-1 reverse transcriptase. Among ten peptide candidates synthesized, three inhibited reverse transcription in vitro. TLMA2993 and PSTW1594 both targeted the connection domain of reverse transcriptase and ESLA2340 targeted the thumb domain.
|
10.1111/j.1348-0421.2002.tb02688.x
|
pubmed_580_18252
|
We investigated rheological adaptation of leukocytes and platelets for their adhesive functions in inflammation and hemostasis, respectively. Adhesion and margination of leukocytes or platelets were quantified for blood perfused through capillaries coated with P-selectin or collagen, when flow rate, suspending phase viscosity, red cell aggregation, or rigidity was modified. Independent variation of shear rate and shear stress indicated that the ability of platelets to attach at higher levels than leukocytes was largely attributable to their smaller size, reducing their velocity before attachment, and, especially, drag after attachment. Increasing red cell aggregation increased the number of marginated and adhering leukocytes but inhibited platelet adhesion without effect on the number marginated. Increasing red cell rigidity tended to inhibit leukocyte adhesion but promote platelet adhesion. The effects on platelets may be explained by changes in the depth of the near-wall, red cell-depleted layer; broadening (or narrowing) this layer to greater (or less) than the platelet diameter would decrease (or increase) the normal force applied by red blood cells and make attachment less (or more) efficient. Thus different adhesive capabilities of leukocytes and platelets may arise from their differences in size, both directly because of influence on cell velocity and force experienced at the wall and indirectly through effects of size on margination in the bloodstream and interaction with the cell-free layer. In addition, red cell aggregation (of hitherto uncertain physiological significance) may be useful in promoting leukocyte adhesion in inflamed venules but inhibiting unwanted platelet deposition in veins.
|
10.1152/ajpheart.00881.2012
|
pubmed_625_3719
|
As pharmaceutical and biotech markets continue to globalize, there are increasing concerns for ensuring the safety and legitimacy of pharmaceutical products. An efficient network in which the supply chain is secure and patients are safe is of great importance to the reputation of the industry in today's global marketplace. Consequently, systems and processes for identifying products through the supply chain are being put into place to meet new regulations. These same systems and processes offer the industry an opportunity to move beyond compliance and reap additional benefits affecting overall performance and patient adherence.
|
10.1177/2168479014553034
|
pubmed_335_25791
|
PURPOSE OF REVIEW
Copy number variation (CNV) disorders arise from the dosage imbalance of one or more gene(s), resulting from deletions, duplications or other genomic rearrangements that lead to the loss or gain of genetic material. Several disorders, characterized by multiple birth defects and neurodevelopmental abnormalities, have been associated with relatively large (>1 Mb) and often recurrent CNVs. CNVs have also been implicated in the etiology of neuropsychiatric disorders including autism and schizophrenia as well as other common complex diseases. Thus, CNVs have a significant impact on human health and disease.
RECENT FINDINGS
The use of increasingly higher resolution, genomewide analysis has greatly enhanced the detection of genetic variation, including CNVs. Furthermore, the availability of comprehensive genetic variation data from large cohorts of healthy controls has the potential to greatly improve the identification of disease associated genetic variants in patient samples.
SUMMARY
This review discusses the current knowledge about CNV disorders, including the mechanisms underlying their formation and phenotypic outcomes, and the advantages and limitations of current methods of detection and disease association.
|
10.1007/s40142-017-0129-2
|
pubmed_617_18232
|
BACKGROUND
Exosomes, derived from endocytic membrane vesicles are thought to participate in cell-cell communication and protein and RNA delivery. They are ubiquitous in most body fluids (breast milk, saliva, blood, urine, malignant ascites, amniotic, bronchoalveolar lavage, and synovial fluids). In particular, exosomes secreted in human saliva contain proteins and nucleic acids that could be exploited for diagnostic purposes. To investigate this potential use, we isolated exosomes from human saliva and characterized their structural and transcriptome contents.
METHODOLOGY
Exosomes were purified by differential ultracentrifugation and identified by immunoelectron microscopy (EM), flow cytometry, and Western blot with CD63 and Alix antibodies. We then described the morphology, shape, size distribution, and density using atomic force microscopy (AFM). Microarray analysis revealed that 509 mRNA core transcripts are relatively stable and present in the exosomes. Exosomal mRNA stability was determined by detergent lysis with RNase A treatment. In vitro, fluorescently labeled saliva exosomes could communicate with human keratinocytes, transferring their genetic information to human oral keratinocytes to alter gene expression at a new location.
CONCLUSION
Our findings are consistent with the hypothesis that exosomes shuttle RNA between cells and that the RNAs present in the exosomes may be a possible resource for disease diagnostics.
|
10.1371/journal.pone.0008577
|
pubmed_780_14345
|
OBJECTIVE
The aim of this study was to evaluate the contribution of in utero infection to the vertical transmission of human immunodeficiency virus type 1 during the second trimester.
STUDY DESIGN
We examined fetal tissues from 21 second-trimester prostaglandin-induced abortions among human immunodeficiency virus type 1-infected women and compared the fetal vertical transmission rates with those among children born to human immunodeficiency virus-seropositive women. The presence of human immunodeficiency virus type 1 nucleic acid sequences was investigated with two different highly sensitive polymerase chain reaction techniques in tissue samples from the fetal thymus, lung, and brain.
RESULTS
No human immunodeficiency virus type 1 deoxyribonucleic acid was detected in any of the samples.
CONCLUSION
The absence of human immunodeficiency virus type 1 in all fetuses in our study is compatible with a low rate of maternal-fetal transmission during the second trimester of pregnancy.
|
10.1067/mob.2000.106591
|
pubmed_76_6016
|
BACKGROUND
Changes in tumor necrosis factor-alpha (TNF-alpha), interleukin-1 alpha (IL-1 alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), and granulocyte macrophage-colony-stimulating factor (GM-CSF) were investigated before and after operation in patients with hepatocellular carcinoma (HCC), metastatic liver carcinoma, and gastrointestinal carcinoma.
RESULTS
Serum levels of TNF-alpha, IL-1 alpha, and IL-1 beta were high in patients with liver carcinoma (HCC and metastatic liver carcinoma) before operation in comparison with those of normal controls (P less than 0.01). In patients with gastrointestinal carcinoma, serum levels of cytokines, except those of TNF-alpha, were the same as in patients with liver carcinoma. The level of TNF-alpha in patients with gastrointestinal carcinoma was low compared with that in patients with liver carcinoma. Within 1 day after operation, the peak level of TNF-alpha was observed at 15 hours, IL-1 alpha at 18 hours, IL-1 beta at 21 hours, and IL-6 at 24 hours after operation. Subsequently, these cytokine levels peaked again: TNF-alpha at 48 hours, IL-1 alpha at 72 hours, IL-1 beta at 120 hours, and IL-6 at 168 hours after operation. GM-CSF levels increased gradually after operation. Moreover, in HCC, serum levels of TNF-alpha were high in patients with recurrence compared with those without recurrence (P less than 0.01). The difference in IL-1 alpha and IL-1 beta levels between patients with recurrence and those without recurrence can be regarded as significant (P less than 0.01).
CONCLUSION
These results suggest that TNF-alpha, IL-1, IL-6, and GM-CSF may play an important role in the pathogenesis of cancers; TNF-alpha may be especially important as a tumor marker in HCC and metastatic liver carcinoma.
|
10.1002/1097-0142(19920801)70:3<709::aid-cncr2820700328>3.0.co;2-o
|
pubmed_974_13500
|
UNLABELLED
NucleusJ is a simple and user-friendly ImageJ plugin dedicated to the characterization of nuclear morphology and chromatin organization in 3D. Starting from image stacks, the nuclear boundary is delimited by combining the Otsu segmentation method with optimization of nuclear sphericity. Chromatin domains are segmented by partitioning the nucleus using a 3D watershed algorithm and by thresholding a contrast measure over the resulting regions. As output, NucleusJ quantifies 15 parameters including shape and size of nuclei as well as intra-nuclear objects and their position within the nucleus. A step-by-step documentation is available for self-training, together with data sets of nuclei with different nuclear organization.
AVAILABILITY AND IMPLEMENTATION
Dataset of nuclei is available at https://www.gred-clermont.fr/media/WorkDirectory.zip. NucleusJ is available at http://imagejdocu.tudor.lu/doku.php?id=plugin:stacks:nuclear_analysis_plugin:start.
SUPPLEMENTARY INFORMATION
Supplementary data are available at Bioinformatics online.
|
10.1093/bioinformatics/btu774
|
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