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pubmed_1071_14799
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BACKGROUND
There is an increasing interest in the role of regulatory factor X1 (RFX1) and RNA-binding proteins (RBPs) during neural development. However, there are few reports about their interaction.
METHODS
We extracted RNA and performed reverse transcription polymerase chain reaction (RT-PCR) to identify RFX1 expression in imprinting control region (ICR) mouse tissues, analyzed RFX1 domains and motif consensus by comparing public databases on the Internet, tested the motif consensus with affinity-capture and western blotting experiments with mouse brain tissue, and predicted the binding sites of RFX1 in promoter regions of mouse RBPs genes.
RESULTS
The expression of RFX1 was higher in embryonic brain compared to embryonic kidney, heart, and liver, and its expression level was relatively stable and higher in mouse embryonic brain than neonatal brain. RFX1 had several domains, including domain A as an activation domain, DBD as a DNA binding domain, domain B and C which played an important role in dimerization, and domain D as dimerization domain. RFX1 had three different profiles motif consensus RFX1M00281, RFX1M00280, and RFX1 (EF-C) M00626. There were 79 RFX1 binding sites at the promoters of 65 of 323 RBPs genes.
CONCLUSION
RFX1 as regulatory factor will have putative important regulating role in the expression of RBPs genes during embryonic development of mouse brain.
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013167/AIM.006
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pubmed_714_21655
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This paper covers five questions: (1) What is cost-effectiveness analysis;quest; (2) How can cost-effectiveness analysis help policymakers allocate scarce resources;quest; (3) What are misconceptions about the cost effectiveness of health care interventions;quest; (4) What is an attractive cost-effectiveness ratio;quest; (5) What is the relevance of cost effectiveness to clinicians? The cost side of the equation includes more than simply the cost of the intervention, but rather the cost of all of the downstream clinical events that occur with either therapeutic alternative. Cost-effectiveness analyses are used to help decisionmakers rank programs competing for scarce resources in order to achieve the following objective: to maximize the net health benefits derived from a fixed budget for a target population. A simple example is shown. Measured cost-effectiveness ratios for selected cardiovascular interventions are displayed. The systematic use of information on effectiveness and cost effectiveness should help those involved in setting policies to have a more rational basis for funding of new programs and discontinuation of funding for old programs. In Canadian health care it is important that we use this information to make room for innovations that are effective and efficient, and to remove funding from programs that are either known to be ineffective and costly or inefficient use of resources. More energy should be put toward generating the information necessary to make these kinds of decisions.
|
10.1007/BF00132409
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pubmed_270_10016
|
We investigated the immunomodulatory activity of allogenic whole tumor cell vaccine in oral cancer patients in vitro by two-color flow cytometry. Vaccine treatment significantly increased the expression of CD69 and HLA-DR in CD3+ T-cell subsets. The frequency of Interferon-gamma and Interleukin (IL)-2 expressing CD4+/CD8+ T-cell subsets was significantly higher with a concomitant reduction in IL-4 and IL-10 expressing T-cells in the vaccine treated group as compared with the untreated controls. Vaccine treatment significantly increased T-cell receptor (TCR), Vbeta3, Vbeta5 and Vbeta8 usage. The results indicate that the allogenic whole tumor cell vaccine is able to trigger T-cell mediated immunity in patients with intraoral squamous cell carcinoma.
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10.1080/08923970600927348
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pubmed_979_4339
|
In this study, it is reported that human Chorionic Gonadotropin (hCG), being one of the most important hormones of pregnancy, has a growth-stimulating effect on the asexual stages of Plasmodium falciparum in vitro. On the one hand, it is shown that the effect of the hormone is dose-related: The highest growth-rates of Plasmodium falciparum in vitro are achieved, when doses of 8.32 i.u./ml (= 50 i.u. hCG/6 ml) and 16.67 I.U./ml (= 100 i.u. hCG/6 ml) are added to the culture medium. These doses correspond to the physiological peak amounts of hCG between the 9th and 16th week of pregnancy, when parasitaemia also reaches its highest rate. On the other hand, it is shown, that any growth-stimulating effect disappears after inactivation of the hormone by heating at 120 degrees C for 20 minutes. These data support the hypothesis, that hCG does not only possess immunosuppressive properties acting on the response of T-lymphocytes, but also increases the growth of Plasmodium falciparum in vitro. The combination of both effects may explain why malaria still remains one of the most serious complications of pregnancy.
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10.1016/s0934-8840(99)80128-5
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pubmed_518_15951
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Familial atrioventricular heart block affected by the autonomic nervous system has rarely been documented. We describe a 35-year-old man who had first-degree atrioventricular heart block with a PR interval of 0.46 s. He had a family history of 2 members with complete heart block and 1 with documented atrial standstill. The man's P-R interval was shortened by exercise and phenylephrine administration. In the electrophysiolgic study, a "split His" with an H-H' of 220 ms was recognized. Such a case of familial atrioventricular heart block with abnormal His-Purkinje conduction affected by the autonomic nervous system is very rare and worthy of description.
|
10.1054/jelc.2001.27840
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pubmed_468_5916
|
Systemic lupus erythematosus is a multifactorial autoimmune disease with an as yet unknown etiopathogenesis. It is widely thought that self-immunization in systemic lupus is driven by defective clearance of dead and dying cells. In lupus patients, large numbers of apoptotic cells accumulate in various tissues including germinal centers. In the present review, we discuss the danger signals released by apoptotic cells, their triggering of inflammatory responses, and the breakdown of B-cell tolerance. We also review the pathogenic role of apoptotic cell clearance in systemic lupus erythematosus.
|
10.1186/ar3206
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pubmed_1061_4289
|
Great progress has been made in unravelling the evolutionary history of Asian colobines, largely through the use of dated molecular phylogenies based on multiple markers. The Presbytis langurs are a case in point, with more allopatric species being identified, recognition of Presbytis thomasi from Sumatra rather than P. potenziani from the Mentawai Islands as being the most basal species of the group, and the discovery that P. rubicunda from Borneo is nested among the Sumatran species and only made it to Borneo in the last 1.3 million years. Based on variation in mitochondrial d-loop, it has recently been argued that Malaysia's P. femoralis femoralis is actually P. neglectus neglectus. Unfortunately, despite being available, sequences from the type locality, Singapore, were excluded from the analysis, and none of the newly generated sequences was deposited in GenBank. I manually reconstructed these sequences, which allowed me to present a molecular phylogeny that includes 8 additional sequences from West Malaysia and Singapore. P. neglectus from Malaysia and P. femoralis from Singapore form one monophyletic clade, with minimal divergence. I conclude that recognition of P. neglectus is erroneous and the name is a junior synonym of P. femoralis. Colobine taxonomy and systematics have advanced, and continue to advance, mostly by considering evidence from a wide range of individuals, species and data sets (molecular, behavioural and morphological) rather than focusing on single molecular markers from 1 or 2 species from one small geographic area. For an orderly taxonomic debate where evidence can be evaluated and reinterpreted it is essential that newly generated sequences are deposited in public repositories.
|
10.1159/000502093
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pubmed_680_11030
|
OBJECTIVE
Neonatal encephalopathy remains a major cause of infant mortality and neurodevelopmental impairment. Infection may exacerbate brain injury and mitigate the effect of therapeutic hypothermia (TH). Additionally, infants with sepsis treated with TH may be at increased risk of adverse effects. This study aimed to review the clinical characteristics and outcomes for infants with sepsis treated with TH.
DESIGN AND SETTING
Retrospective cohort study of infants treated with TH within Australia and New Zealand.
PATIENTS
1522 infants treated with TH, including 38 with culture-positive sepsis from 2014 to 2018.
INTERVENTION
Anonymised retrospective review of data from Australian and New Zealand Neonatal Network. Infants with culture-positive sepsis within 48 hours were compared with those without sepsis.
MAIN OUTCOME MEASURES
Key outcomes include in-hospital mortality, intensive care support requirements and length of stay.
RESULTS
Overall the rate of mortality was similar between the groups (13% vs 13%). Infants with sepsis received a higher rate of mechanical ventilation (89% vs 70%, p=0.01), high-frequency oscillatory ventilation (32% vs 13%, p=0.003) and inhaled nitric oxide for persistent pulmonary hypertension (38% vs 16%, p<0.001). Additionally, the sepsis group had a longer length of stay (20 vs 11 days, p<0.001).
CONCLUSION
Infants with sepsis treated with TH required significantly more respiratory support and had a longer length of stay. Although this may suggest a more severe illness the rate of mortality was similar. Further research is warranted to review the neurodevelopmental outcomes for these infants.
|
10.1136/bmjpo-2022-001420
|
pubmed_82_11751
|
Histone RNA 3' processing in vitro produces one or more 5' cleavage products corresponding to the mature histone mRNA 3' end, and a group of 3' cleavage products whose 5' ends are mostly located several nucleotides downstream of the mRNA 3' end. The formation of these 3' products is coupled to the formation of 5' products and dependent on the U7 snRNP and a heat-labile processing factor. These short 3' products therefore are a true and general feature of the processing reaction. Identical 3' products are also formed from a model RNA containing all spacer nucleotides downstream of the mature mRNA 3' end, but no sequences from the mature mRNA. Again, this reaction is dependent on both the U7 snRNP and a heat-labile factor. Unlike the processing with a full-length histone pre-mRNA, this reaction produces only 3' but no 5' fragments. In addition, product formation is inhibited by addition of cap structures at the model RNA 5' end, indicating that product formation occurs by 5'-3' exonucleolytic degradation. This degradation of a model 3' product by a 5'-3' exonuclease suggests a mechanism for the release of the U7 snRNP after processing by shortening the cut-off histone spacer sequences base paired to U7 RNA.
|
10.1017/s1355838298971771
|
pubmed_181_17780
|
Parachute mitral valve and Pacman heart (incomplete muscular ventricular septal defect) are rare congenital deformities usually reported in infants and children. Very few adult patients with these anomalies are reported but the association of the two has not been described. This report describes a 56-year-old male with exertional dyspnea who was detected to have moderately severe mitral regurgitation and mitral stenosis. Typical parachute deformity of the mitral valve with a reduced opening and common attachment of all the chordae to a single posteromedial papillary muscle was evident. The chordae were elongated, lax, and redundant, which is atypical for this anomaly. Incidentally, detected aneurysm of the basal muscular interventricular septum (Pacman deformity or incomplete triangular septal defect) was also present.
|
10.1016/j.ihj.2015.09.012
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pubmed_12_16380
|
A natural tumor suppressor of human fetal liver origin with low molecular weight (LMW-NTS) was studied. The methanol extract of human fetal liver supernatant (FLS-MeOH), a crude preparation of LMW-NTS, showed preferential suppression on the growth of leukemic cell lines HL-60, L833, WEHI-3, and L1210, but less effect on the growth of normal bone marrow granulocyte-macrophage colony-forming units (CFU-GM) in vitro. Preliminary experiments showed that FLS-MeOH also exhibited preferential suppression on the growth of leukemic colony-forming units (L-CFU) from six patients suffering from acute myeloid leukemia (AML). In combination with a long-term in vitro liquid culture system, FLS-MeOH could be adopted as an effective purging agent in the autologous bone marrow transplantation treatment of myeloid leukemia.
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pubmed_12_16380
|
pubmed_198_17378
|
A case of a severe but brief period of shivering following a retrobulbar block (RBB) is presented. The shivering occurred within two minutes after completion of the RBB and subsided gradually within five minutes, without specific treatment. The patient remained conscious during the episode of shivering. The shivering was so abrupt and severe as to be misjudged as a seizure, but its onset appeared to be slower than a seizure. The mechanism of shivering appeared to be the central spread of local anaesthetic solution into the brain stem, along the optic nerve. Shivering may be a warning sign of brain stem anaesthesia and demands special care to anticipate life-threatening complications.
|
10.1007/BF03010633
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pubmed_189_7644
|
Microbial cocultivation has been applied as a strategy to induce the biosynthesis of specialized metabolites. However, most previous studies have focused on competitive interactions between test strains. During our LC-MS-based chemical screening of randomized cocultures of Basidiomycetous fungi, we discovered that the coculture of Phellinus orientoasiaticus (Hymenochaetaceae) and Xylodon flaviporus (Schizoporaceae) induces multiple metabolites, although they did not show any competitive morphology. Targeted isolation yielded three new sesquiterpenes (1-3) along with five known analogues (4-8). The structures of the isolates were determined by MS and NMR experiments as well as electronic circular dichroism analysis. LC-MS analysis suggested that cyclohumulanoids of illudane-, sterpurane-, and tremulane-type scaffolds (1-7) were produced by P. orientoasiaticus, whereas a drimane-type sesquiterpene (8) was produced by X. flaviporus. None of the isolates exhibited antifungal activity or cytotoxicity, and compounds 1-7 exhibited NO production of LPS-treated RAW276.4 cells in a range of 15.9% to 38.0% at 100 μM.
|
10.1021/acs.jnatprod.1c01022
|
pubmed_913_8639
|
One hundred and forty-seven patients requiring a hypnotic, took soft gelatine capsules containing 10 mg temazepam (Euhypnos) 10-30 mg at night, for up to twelve weeks. One hundred and thirty-three patients (90-5%) completed twelve weeks on drug. Hypnotic performance was rated Good or Very Good in 90% of their assessments and 93-2% of the assessments recorded no hangover effect. Adverse reactions were occasional headaches and nausea. There were no drug-related accidents. One hundred and forty-two patients (96-6%) said there was no adverse effect on their work. Seven patients who did not complete twelve weeks resumed normal sleep patterns and had no further need for hypnotics.
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10.1177/030006057700500501
|
pubmed_321_6472
|
OBJECTIVES
Current guidelines suggest limiting the use of vasopressors following traumatic injury; however, wide variations in practice exist. Although excessive vasoconstriction may be harmful, these agents may help reduce administration of potentially harmful resuscitation fluids. This systematic review aims to compare early vasopressor use to standard resuscitation in adults with trauma-induced shock.
DESIGN
Systematic review.
DATA SOURCES
We searched MEDLINE, EMBASE, ClinicalTrials.gov and the Central Register of Controlled Trials from inception until October 2016, as well as the proceedings of 10 relevant international conferences from 2005 to 2016.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
Randomised controlled trials and controlled observational studies that compared the early vasopressor use with standard resuscitation in adults with acute traumatic injury.
RESULTS
Of 8001 citations, we retrieved 18 full-text articles and included 6 studies (1 randomised controlled trial and 5 observational studies), including 2 published exclusively in abstract form. Across observational studies, vasopressor use was associated with increased short-term mortality, with unadjusted risk ratios ranging from 2.31 to 7.39. However, the risk of bias was considered high in these observational studies because patients who received vasopressors were systematically sicker than patients treated without vasopressors. One clinical trial (n=78) was too imprecise to yield meaningful results. Two clinical trials are currently ongoing. No study measured long-term quality of life or cognitive function.
CONCLUSIONS
Existing data on the effects of vasopressors following traumatic injury are of very low quality according to the Grading of Recommendations, Assessment, Development and Evaluation methodology. With emerging evidence of harm associated with aggressive fluid resuscitation and, in selected subgroups of patients, with permissive hypotension, the alternatives to vasopressor therapy are limited. Observational data showing that vasopressors are part of usual care would provide a strong justification for high-quality clinical trials of early vasopressor use during trauma resuscitation.
TRIAL REGISTRATION NUMBER
CRD42016033437.
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10.1136/bmjopen-2017-017559
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pubmed_405_8280
|
The CRISPR-Cas9 system consists of a site-specific, targetable DNA nuclease that holds great potential in gene editing and genome-wide screening applications. To apply the CRISPR-Cas9 system to these assays successfully, the rate at which Cas9 induces DNA breaks at undesired loci must be understood. We characterized the rate of Cas9 off-target activity in typical Cas9 experiments in two human and one mouse cell lines. We analyzed the Cas9 cutting activity of 12 gRNAs in both their targeted sites and ∼90 predicted off-target sites per gRNA. In a Cas9-based knockout experiment, gRNAs induced detectable Cas9 cutting activity in all on-target sites and in only a few off-target sites genome-wide in human 293FT, human-induced pluripotent stem (hiPS) cells, and mouse embryonic stem (ES) cells. Both the cutting rates and DNA repair patterns were highly correlated between the two human cell lines in both on-target and off-target sites. In clonal Cas9 cutting analysis in mouse ES cells, biallelic Cas9 cutting was observed with low off-target activity. Our results show that off-target activity of Cas9 is low and predictable by the degree of sequence identity between the gRNA and a potential off-target site. Off-target Cas9 activity can be minimized by selecting gRNAs with few off-target sites of near complementarity.
|
10.1002/dvg.22835
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pubmed_881_11098
|
PURPOSE
This study radiographically evaluated the stability of mandibular height during a 2-year follow-up after augmentation with prefabricated hydroxylapatite/fibrin glue (HA/FG) implants.
PATIENTS AND METHODS
Standardized, lateral oblique cephalometric radiographs were made of 22 patients 6, 12, and 24 months postoperatively and analyzed with a newly developed, computerized image analysis technique.
RESULTS
The average height of the HA/FG implants after augmentation was 9.45 mm. Average loss of total height of the augmented mandibles was 2.31 mm after 6 months, 2.90 mm after 12 months, and 3.93 mm after 24 months. Reduction of HA/FG implant height alone was 0.62 mm after 6 months, 1.24 mm after 12 months, and 2.03 mm after 24 months. Reduction occurred mainly during the first 6-month evaluation period and was probably primarily caused by adaptation of the implant to the surface of the mandible. An inferior compression of the implant or resorption of the alveolar crest and underlying basilar bone are possible reasons for loss of total mandibular height.
CONCLUSION
The results indicate that prefabricated HA/FG implants used for augmentation of edentulous mandibles show little reduction in height, but are not completely stable during a 2-year evaluation period.
|
10.1016/s0278-2391(97)90229-9
|
pubmed_1055_9874
|
Here we demonstrate how the Fermi surface topology and quantum many-body interactions can be manipulated via epitaxial strain in the spin-triplet superconductor Sr_{2}RuO_{4} and its isoelectronic counterpart Ba_{2}RuO_{4} using oxide molecular beam epitaxy, in situ angle-resolved photoemission spectroscopy, and transport measurements. Near the topological transition of the γ Fermi surface sheet, we observe clear signatures of critical fluctuations, while the quasiparticle mass enhancement is found to increase rapidly and monotonically with increasing Ru-O bond distance. Our work demonstrates the possibilities for using epitaxial strain as a disorder-free means of manipulating emergent properties, many-body interactions, and potentially the superconductivity in correlated materials.
|
10.1103/PhysRevLett.116.197003
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pubmed_308_6760
|
The cyclooxygenase (COX) enzyme system is the major pathway catalyzing the conversion of arachidonic acid into prostaglandins (PGs). PGs are lipid mediators implicated in a variety of physiological and pathophysiological processes in the kidney, including renal hemodynamics, body water and sodium balance, and the inflammatory injury characteristic in multiple renal diseases. Since the beginning of 1990s, it has been confirmed that COX exists in 2 isoforms, referred to as COX-1 and COX-2. Even though the 2 enzymes are similar in size and structure, COX-1 and COX-2 are regulated by different systems and have different functional roles. This review summarizes the current data on renal expression of the 2 COX isoforms and highlights mainly the role of COX-2 and PGE2 in several physiological and pathophysiological processes in the kidney.
|
10.1016/j.krcp.2015.10.004
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pubmed_126_2330
|
Data from the national representative epidemiologic survey (PAK-KID-study) assessed by the German versions of Achenbach'S Child Behavior Checklist and Youth Self-Report of N = 1757 parents and their children aged 11 to 18 years are compared by using the corresponding Cross-Informant-Scales. On all problem scales adolescents report more problems than parents. For some scales the differences between girls and their parents are higher than between boys and their parents (social withdrawal, somatic complaints, anxious/depressed, attention problems, internalizing and total score). Averaged Pearson correlations of the eight subscales are in a moderate rage (r < 0.50). For all problem scales an agreement of 30% in the area of high problems (> PR95) is found. If one informant scores above PR95 the Relative Risk of the other one scoring in this range too is significantly higher than one for nearly all scales.
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pubmed_126_2330
|
pubmed_621_19018
|
Syphilis is one of the unrecognized etiologies of liver dysfunction. The incidence of syphilitic hepatitis is currently unknown. We conducted a retrospective study of causative agents of liver dysfunction at the time of diagnosis of early syphilis. Our study shows that 39 % (44/112) of early syphilis patients have liver enzyme abnormalities at the time of diagnosis and that 2.7 % (3/112) of patients are diagnosed with syphilitic hepatitis. Clinicians should include syphilitic hepatitis in the differential diagnosis for those patients with sexually transmitted diseases presenting with liver enzyme abnormalities.
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10.1007/s10156-012-0440-5
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pubmed_462_17990
|
The genes encoding the individual A and B polypeptides of the type I enterotoxin LTp-I and type II enterotoxins LT-IIa and LT-IIb were cloned and tested for complementation in Escherichia coli. Each gene encoding an A polypeptide was cloned into pACYC184, and each gene encoding a B polypeptide was cloned into the compatible plasmid Bluescript KS+. In addition, operon fusions representing all combinations of A and B genes were constructed in Bluescript KS+. Extracts from strains of E. coli expressing each combination of A and B genes, either from compatible plasmids or from operon fusions, were tested for immunoreactive holotoxin by radioimmunoassays and for toxicity by Y1 adrenal cell assays. Biologically active holotoxin was detected in each case, but the toxicity of extracts containing the hybrid toxins was usually less than that of extracts containing the wild-type holotoxins. The ganglioside-binding activity of each holotoxin was tested, and in each case, the B polypeptide determined the ganglioside-binding specificity. The A and B polypeptides of the type II heat-labile enterotoxins were also shown to form holotoxin in vitro without exposure to denaturing conditions, in contrast to the polypeptides of the type I enterotoxins that failed to form holotoxin in vitro under comparable conditions. These findings suggest that type I and type II enterotoxins have conserved structural features that permit their A and B polypeptides to form hybrid holotoxins, although the B polypeptides of the type I and type II enterotoxins have very little amino acid sequence homology.
|
10.1128/iai.60.4.1653-1661.1992
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pubmed_516_15037
|
BACKGROUND
Pilonidal sinus is a common disease that mostly affects young people. Despite numerous treatment modalities, the best technique has not yet been determined and there are many recurrences, causing economic losses and serious discomfort for the patients.
METHODS
The authors used V-Y rotation flaps for coverage of the defects after excision and debridement of chronic pilonidal sinuses in eight patients. The results were evaluated and compared with previously reported studies regarding the grade of disease at presentation, duration of surgery, blood loss, hospitalization period and active mobilization periods, complications, and loss of sensitivity.
RESULTS
No major complications occurred; hospitalization and immobilization periods were acceptably convenient. Recurrence was not seen, and sensitivity of the gluteal region did not diminish. The outcome was also satisfactory regarding aesthetics, and all the patients were satisfied with the result.
CONCLUSION
The authors believe that the V-Y rotation advancement flap is a good alternative method for the treatment of pilonidal sinus.
|
10.1097/01.prs.0000219170.74059.94
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pubmed_977_20074
|
We examined the moderating influence of home location and school type across time on cardiometabolic risk and active school commuting over 5 years in a sample of children from southern Brazil. We recruited a sample of children (n = 154; baseline age = 9.6 ± 1.5 years old; 56.8% female) who were followed for 5 years from 2011/2012 to 2016/2017. We collected home location, school type, and school commute data using self-report methods and collected cardiometabolic risk measures to calculate a cardiometabolic composite risk score (cMetSyn). General and generalized linear mixed effects models were employed to examine the moderating influence of home location and school type across time on cardiometabolic risk and active school commuting. We found a significant three-way home location × school type × time interaction on cMetSyn scores (b = 0.62, 95% confidence interval [CI]: 0.13-1.12, p = 0.014), indicating that children who were living within rural areas and enrolled in state schools during 2016/2017 had higher cardiometabolic risk compared with children enrolled in municipal schools and living in urban areas at the end of the study. Additionally, we found that children living in rural areas had an 86% lower rate of active school commuting compared with students living in urban areas (rate ratio = 0.14, 95% CI: 0.07-0.32, p < 0.001). The results suggest that Brazilian children enrolled in state schools and living in rural areas had higher cardiometabolic risk scores at the end of the study and that southern Brazilian children residing in rural areas had a much lower rate of actively commuting to school.
|
10.1089/chi.2021.0299
|
pubmed_1140_480
|
OBJECTIVE
The purpose of this study was to evaluate the imaging features of desmoplastic fibroma of the bone, with an emphasis on MRI signal characteristics.
CONCLUSION
Significant T2 shortening of a nonsclerotic fibroosseous lesion should place desmoplastic fibroma high among the diagnostic considerations.
|
10.2214/ajr.184.6.01841762
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pubmed_889_23684
|
Purpose: Abdominal muscles are key in maintaining body stability and balance and an improvement in the functioning of these muscles could influence the rehabilitation process in lower limb pathologies such as Achilles Tendinopathy (AT). The aim was to explore whether calf eccentric exercise (EE) with vibration training was more effective at causing adaptation to the rectus anterior (RA) thickness and inter-rectus distance (IRD) than calf EE with cryotherapy. Methods: The investigation was a single-blinded, randomized, controlled clinical trial (NCT03515148). Sixty-one individuals diagnosed with mid-portion AT were recruited and divided in two groups: group A (n = 30) followed an EE with vibration program and group B (n = 31) an EE program with cryotherapy, for 12-weeks. RA muscle thickness and IRD were measured in maximal isometric contraction and at rest as an indication of superficial abdominal muscle activation. Results: IRD measures showed a significant (P < 0.05) decrease at baseline, 4 and at 12-weeks in both groups, but no significant differences were observed between the intervention groups. RA thickness was significantly increased (P < 0.05) in measures at baseline, 4 and 12-weeks showed a significant increase in maximal isometric contraction and at rest in favor of the EE vibration program group. Conclusions: The present study showed a RA thickness increase in both groups in favor of the EE vibration program with respect to cryotherapy added to EE in short and mid term in maximal isometric contraction and at rest in subjects with chronic mid-portion AT. IRD was decreased in both groups without between-groups differences.
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10.7150/ijms.28656
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pubmed_400_22210
|
Disaster plans need practical approaches to ensure that all staff function well. This article describes how a disaster plan was customized within a department. Decision trees have been created for each staff position (manager, supervisor, resource nurse, staff nurse) as well as for key processes (triage and supplies). Simplicity is the key because it decreases confusion before and during the disaster. These templates and processes can be easily understood and applied in any ED or setting.
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pubmed_400_22210
|
pubmed_918_6293
|
AIMS
Butyric acid (BUT), a short chain fatty acid produced daily by the gut microbiota, has proven beneficial in models of cardiovascular diseases. With advancements in cancer survival, an increasing number of patients are at risk of anticancer drug cardiotoxicity. Here we assess whether the novel BUT derivative phenylalanine-butyramide (FBA) protects from doxorubicin (DOXO) cardiotoxicity, by decreasing oxidative stress and improving mitochondrial function.
METHODS AND RESULTS
In C57BL6 mice, DOXO produced left ventricular dilatation assessed by echocardiography. FBA prevented left ventricular dilatation, fibrosis and cardiomyocyte apoptosis when co-administered with DOXO. DOXO increased atrial natriuretic peptide, brain natriuretic peptide, connective tissue growth factor, and matrix metalloproteinase-2 mRNAs, which were not elevated on co-treatment with FBA. DOXO, but not FBA + DOXO mice, also showed higher nitrotyrosine levels, and increased inducible nitric oxide synthase expression. Accordingly, DOXO hearts showed lower levels of intracellular catalase vs. sham, while pre-treatment with FBA prevented this decrease. We then assessed for reactive oxygen species (ROS) emission: DOXO induced increased activity of mitochondrial superoxide dismutase and higher production of H2 O2 , which were blunted by FBA pre-treatment. FBA also ameliorated mitochondrial state 3 and state 4 respiration rates that were compromised by DOXO. Furthermore, in DOXO animals, the mitochondrial degree of coupling was significantly increased vs. sham, while FBA was able to prevent such increase, contributing to limit ROS production, Finally, FBA reduced DOXO damage in human cellular models, and increased the tumour-killing action of DOXO.
CONCLUSIONS
Phenylalanine-butyramide protects against experimental doxorubicin cardiotoxicity. Such protection is accompanied by reduction in oxidative stress and amelioration of mitochondrial function.
|
10.1002/ejhf.1439
|
pubmed_98_2117
|
This study aims to quantify the stresses of sonographers using two different ultrasound devices, one of conventional and one of ergonomic design. A total of 20 obstetricians and gynecologists participated in this study, and two types of tasks (scanning and positioning) were evaluated while using the two different devices. To quantify workload, four dependent variables (muscle activity, estimated grip force, subjective comfort rating, and task time) were measured. The muscular activity required while using the conventional device was 14.4% MVC (Maximum voluntary contraction) for the scanning task, which was significantly higher than that of the ergonomic device. The subjective comfort rating for the conventional design was lower than that of the ergonomic design. For the positioning task, the ergonomic device (33.2% MVC) resulted in significantly higher muscle activity in the extensor digitorum (ED) and flexor digitorum superficialis (FDS) than the conventional design (22.2% MVC), whereas the deltoid muscle showed significantly lower activity than in users of conventional design (4.5% MVC). Ergonomically-designed ultrasound devices improve ease of moving and the probe's supporters, reduce physical load and increase ease of use for sonographers. Our results may be used as guidelines for usability testing of ultrasound devices.
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10.1016/j.apergo.2021.103665
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pubmed_321_8412
|
Providers in pediatric post-acute care facilities were surveyed about knowledge of and resources for antimicrobial stewardship. All agreed that antibiotics were overused in such pediatric facilities, but 60% had not implemented stewardship strategies. Lack of treatment guidelines (47%) was identified as the most common barrier to antimicrobial stewardship.
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10.1016/j.ajic.2017.09.031
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pubmed_182_4961
|
This study uses data from the 2012 National Inpatient Sample to determine if mortality, length of stay, and discharge disposition are different between rural and urban American Indians and Alaska Natives (AI/ANs) with alcohol abuse, depression, diabetes, and post-traumatic stress disorder. Results show no difference in mortality between groups. Alcohol abuse, depression, and diabetes are less prevalent in rural AI/ANs, and rural patients have shorter lengths of stay and fewer chronic conditions, diagnoses, and procedures. Finally, urban patients are discharged to short-term hospitals or skilled nursing facilities at higher rates. Rural diabetes patients exhibit increased mortality, but there is little evidence that rurality adversely affects the AI/AN population for the conditions we studied.
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10.5820/aian.2503.2018.78
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pubmed_365_8733
|
OBJECTIVE
To design a test rig for measuring isometric quadriceps' force which is easily adjustable, dismountable, transportable, relatively lightweight and inexpensive. Also to produce a data-acquisition software program that enables real-time feedback of the force signal, automatic analysis of maximal voluntary contraction (MVC) force, and submaximal target levels to be displayed on a computer screen, as well as acquisition of other signals such as electromyographic (EMG) activity.
METHODOLOGY
A test rig was constructed using an aluminium tubing system which was fully adjustable and could be flat-packed for transportation. The data acquisition software program was written in Borland C++ and is suitable for use with an IBM-compatible PC. The interface is user friendly, and the entire testing system is relatively inexpensive compared to commercially available systems.
CONCLUSIONS
The equipment is suitable for various applications in rehabilitation research and clinical testing, and is suitable for examining different muscles. Further technical details are freely available from the authors.
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10.1191/026921598666172433
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pubmed_681_64
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We have improved the method of measuring dioxins in the blood of Yusho patients; with this improved method, it is possible to take measurements quickly and precisely, using as little as 5g of blood. The specific points of improvement of this method are the extraction of lipids from blood by accelerated solvent extractor (ASE), the miniaturization of column cleanup for the purification of dioxins, and the use of a solvent cut large volume (SCLV) injection system with high-resolution gas chromatography/high-resolution mass spectrometry (HRGC/HRMS). Using this improved method of analysis, we are currently investigating dioxins in the blood of 400 Yusho patients collected in Japan in 2002. We here describe the details of our announcement at Dioxin 2002 Symposium about the improvement of this analysis method, and discuss several other modifications.
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10.2486/indhealth.41.197
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pubmed_379_19173
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A model has been proposed to explain at least one of the possible pathways through which a xenobiotic might produce proximal tubule necrosis. The model is formulated on the idea that a compound must possess two structural features: (i) a carboxyl or amino acid moiety that would allow for selective uptake into proximal tubule cells via the strategically located antiluminal membrane-bound organic anion transport system or the luminal membrane-bound amino acid transport system(s), respectively, and (ii) a highly reactive moiety that can directly alkylate proximal tubular components, or a moiety that can be biotransformed within proximal tubular cells to such a substance. In an attempt to validate the proposed structural features as prerequisites for xenobiotic induction of proximal tubular necrosis, a novel compound, 4-maleimidohippuric acid (4-MHA), was synthesized which possesses an anionic group and a reactive moiety. Following the administration of 4-MHA directly into the renal artery of pentobarbital-anesthetized dogs, specific unilateral ultrastructural damage was noted only in the S1 and S2 cell types of the proximal tubule; the most notable renal function changes included proteinuria and glucosuria. Anionic, but non-alkylating, relatives of 4-MHA failed to alter renal function or ultrastructure. The specific proximal tubular toxicity of 4-MHA validates the proposed structural requirements for induction of proximal tubular necrosis.
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10.1016/0300-483x(94)02916-i
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pubmed_856_2746
|
OBJECTIVE
To determine the possible alterations of retinal microcirculation associated with right-sided intracardiac pressures in patients with IPAH.
METHODS
Twenty patients with IPAH and 20 age- and sex-matched healthy controls were included in the study. Hemodynamic data were obtained from the most recent right heart catheterization. Echocardiographic examination was performed within 24 h of ophthalmological examination. For the right eyes of all participants, high-resolution scans of chorioretinal microvascular networks at different depths of the retina were captured via OCT angiography.
RESULTS
The perfusion of the superficial and deep capillary plexus (SCP and DCP), and choriocapillaris (CCP) flow area were significantly lower than those in healthy control subjects (p < .05 for all). In IPAH group, PVR and mPAP were correlated significantly with the perfusion measurements at SCP and DCP (r = .461, r = .626 and r = .625, r =0.730, respectively, p < .05). sPAP and TRV were positively correlated with the perfusion measurements at SCP and DCP (r = .600, r = .662 and r = .670, r = .655 p < .05).
CONCLUSIONS
The positive correlation of retinal perfusion at SCP and DCP with right-sided echocardiographic and hemodynamic measurements unveiled that retinal microcirculation is affected by the pressure alterations in the pulmonary circulation of IPAH patients.
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10.1111/micc.12704
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pubmed_615_14865
|
Mixed populations of Saccharomyces cerevisiae yeasts and lactic acid bacteria occur in many dairy, food, and beverage fermentations, but knowledge about their interactions is incomplete. In the present study, interactions between Saccharomyces cerevisiae and Lactobacillus delbrueckii subsp. bulgaricus, two microorganisms that co-occur in kefir fermentations, were studied during anaerobic growth on lactose. By combining physiological and transcriptome analysis of the two strains in the cocultures, five mechanisms of interaction were identified. (i) Lb. delbrueckii subsp. bulgaricus hydrolyzes lactose, which cannot be metabolized by S. cerevisiae, to galactose and glucose. Subsequently, galactose, which cannot be metabolized by Lb. delbrueckii subsp. bulgaricus, is excreted and provides a carbon source for yeast. (ii) In pure cultures, Lb. delbrueckii subsp. bulgaricus grows only in the presence of increased CO2 concentrations. In anaerobic mixed cultures, the yeast provides this CO2 via alcoholic fermentation. (iii) Analysis of amino acid consumption from the defined medium indicated that S. cerevisiae supplied alanine to the bacterium. (iv) A mild but significant low-iron response in the yeast transcriptome, identified by DNA microarray analysis, was consistent with the chelation of iron by the lactate produced by Lb. delbrueckii subsp. bulgaricus. (v) Transcriptome analysis of Lb. delbrueckii subsp. bulgaricus in mixed cultures showed an overrepresentation of transcripts involved in lipid metabolism, suggesting either a competition of the two microorganisms for fatty acids or a response to the ethanol produced by S. cerevisiae. This study demonstrates that chemostat-based transcriptome analysis is a powerful tool to investigate microbial interactions in mixed populations.
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10.1128/AEM.01115-13
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pubmed_20_17751
|
OBJECTIVE
To explore the effect of the interaction between PLIN gene polymorphisms and open lifestyle intervention on weight-loss in Chinese Han adults.
METHODS
Totally 109 overweight or obese subjects were assigned by random number table to the intervention group (n=56) or control group (n=53),and subjects in the intervention group received 22-week open lifestyle intervention. Anthropometric and metabolic indicators were measured for all subjects before and after intervention,and the PLIN1,PLIN4,and PLIN6 genotypes were amplified by polymerase chain reaction and sequenced through the first-generation sequencing technologies.
RESULTS
Among all these subjects,the rare allele C was dominant at PLIN1 (0.619),the common allele G was dominant at PLIN4 (0.606),and the common allele A was dominant at PLIN6 (0.564),in which PLIN1 and PLIN4 as well as PLIN4 and PLIN6 were in strong linkage disequilibrium (D'>0.9). After intervention,the body mass index,waist circumference,and body fat percent of female subjects were significantly decreased in intervention group and were lower than in control group;in male subjects,however,only the waist circumference showed significant difference with the control group (P<0.05). Subjects carrying rare allele homozygote of PLIN6 got less weight/fat loss than those carrying common alleles in intervention group,while subjects carrying rare allele of PLIN1 had more weight/fat increase than those with common allele homozygote in control group (P<0.05). Females in intervention group carrying any one of rare allele homozygotes of PLIN1,PLIN4 and PLIN6 got less weight/fat loss than those with common alleles,and female subjects carrying the rare allele homozygote haplotype of PLIN1/PLIN4 or PLIN4/PLIN6 got less weight/fat loss than those with other haplotypes (P<0.05).
CONCLUSION
The interaction between open lifestyle intervention and PLIN gene polymorphisms can directly influence weight-loss in Chinese Han overweight and obese adults.
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10.3881/j.issn.1000-503X.2015.06.008
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pubmed_67_15808
|
BACKGROUND
The revised vancomycin guidelines recommend replacing trough-only with trough or peak/trough Bayesian and first-order equations monitoring, citing their better AUC predictions and poor AUC-trough R2. Yet, evidence suggesting good AUC-trough correlation has been overlooked, and the optimality of peak/trough samples has been doubted. The guidelines recommend Bayesian programs implement richly-sampled PopPK priors despite their scarcity. Therefore, whether complex Bayesian and sample-demanding first-order equations can bring significant advantages to the practice over simple trough-only monitoring is worth weighing.
OBJECTIVES
The primary aim is to compare the predictive performance of the AUC monitoring methods. Then, we investigate the impact of not adhering to trough sampling on the Bayesian-based predictions. Moreover, we report the nature of PopPK priors used in Bayesian programs to assess the applicability of the guideline recommendations.
METHODS
We calculated the predictive performance of the monitoring methods using a standard PopPK modeling and simulation approach. We thoroughly explored the prior PK models implemented in Bayesian programs.
RESULTS
Predictive performances of the monitoring methods were comparable at steady-state relative to the number of samples. Contrary to the recommendation, Bayesian trough monitoring did not result in better predictive performances compared to using random levels. Very few programs implemented richly-sampled priors.
CONCLUSION
All the monitoring methods can be, relatively, reliable at steady-state, if properly implemented. Although only Bayesian-based monitoring can be used pre-steady-state, its predictive performance can be modest. Trough-only monitoring is the simplest approach. Constraints regarding trough sampling times could be relaxed. The scarcity of richly-sampled Bayesian priors questions the applicability of the revised guidelines recommendation.
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10.1016/j.biopha.2022.113777
|
pubmed_314_22081
|
The Wnt gene family encodes a set of highly conserved secreted signaling proteins that have major roles in embryogenesis and tissue homeostasis. Yet the expression of this family of important mediators in psoriasis, a disease characterized by marked changes in keratinocyte growth and differentiation, is incompletely understood. We subjected 58 paired biopsies from lesional and uninvolved psoriatic skin and 64 biopsies from normal skin to global gene expression profiling. WNT5A transcripts were upregulated fivefold in lesional skin, accompanied by increased Wnt-5a protein levels. Notably, WNT5A mRNA was markedly induced by IL-1alpha, tumor necrosis factor-alpha, IFN-gamma, and transforming growth factor-alpha in cultured keratinocytes. Frizzled 2 (FZD2) and FZD5, which encode receptors for Wnt5A, were also increased in lesional psoriatic skin. In contrast, expression of WIF1 mRNA, encoding a secreted antagonist of the Wnt proteins, was downregulated >10-fold in lesional skin, along with decreased WNT inhibitory factor (WIF)-1 immunostaining. Interestingly, pathway analysis along with reduced AXIN2 expression and lack of nuclear translocation of beta-catenin indicated a suppression of canonical Wnt signaling in lesional skin. The results of our study suggest a shift away from canonical Wnt signaling toward noncanonical pathways driven by interactions between Wnt-5a and its cognate receptors in psoriasis, accompanied by impaired homeostatic inhibition of Wnt signaling by WIF-1 and dickkopf.
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10.1038/jid.2010.67
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pubmed_403_14992
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Objective: To summarize the clinical and fundus imaging features of purified protein derivative and T-spot positive tubercular serpiginous-like choroiditis (PTP-SLC) patients. Methods: This retrospective study consecutively enrolled 13 PTP-SLC patients (21 eyes) in Beijing Tongren Hospital from November 2015 to November 2017. There were 8 males and 5 females with an average age of (45.2±12.1) years. Medical history and results of systemic and ophthalmological examinations, such us fundus autofluorescence photography, optical coherence tomography (OCT), fluorescein fundus angiography (FFA) and indocyanine green angiography, were evaluated. Results: Eight patients had binocular disease with an average interval time of (8.4±7.9) years. The average visual acuity of all patients was 0.3, and 4 patients had a clear history of exposure to tuberculosis. The active lesions in the PTP-SLC patients were homogeneous and creamish-yellow with unclear boundaries. Fundus autofluorescence showed an ill-defined, diffuse hyperautofluorescent zone. OCT showed punctate hyperreflexes between the choroidal stroma, destruction of the outer retinal structure with intraretinal edema and discrete vitreal hyper-reflective spots. FFA showed hypofluorescence in the active lesion at early stage and diffuse hyperfluorescence with leakage. Indocyanine green angiography showed persistent hypofluorescence. Conclusions: PTP-SLC fundus lesions are mainly manifested as homogeneous creamish-yellow lesions with unclear boundaries and high in autofluorescence. The involvement of the choroid and the outer layer of the retina can be observed on OCT. FFA can find more retinal vascular inflammatory changes. It is difficult to distinguish PTP-SLC from serpiginous choroiditis simply based on clinical and epidemiological characteristics. The pathogenic examination of tuberculosis is still the key to differential diagnosis (Chin J Ophthalmol, 2020, 56: 914-919).
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10.3760/cma.j.cn112142-20200509-00317
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pubmed_764_4739
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The unfolding by guanidine hydrochloride (GuHCl) and the refolding on dilution of zinc and apoazurin have been monitored by far-UV circular dichroism (CD). With the native protein, the unfolding was followed by CD and optical absorption in the visible spectral region. With the zinc protein, the reversible unfolding has also been followed by tryptophan fluorescence and NMR. The zinc and Cu2+ metal ions remain associated with the protein in the unfolded state. When the unfolding of the native protein is followed by CD, the initial, reversible transition due to unfolding is followed by a slow change associated with the reduction of Cu2+ by the thiol group of the ligand Cys112. The unfolding of apoazurin displays two CD transitions, which evidence suggests represent different folding domains, the least stable one including the metal-binding site and the other one the rest of the beta-sheet structure. Both occur at a lower GuHCl concentration than the unfolding of the native protein. The CD titrations also demonstrate that zinc azurin has a lower stability than the copper protein. Unfolding of zinc azurin followed by tryptophan fluorescence occurs at a much lower GuHCl concentration than the CD changes, and NMR spectra show that there is no loss of secondary and tertiary structure at this concentration, whereas the CD-detected loss of secondary structure correlates with the NMR changes. Thus, the fluorescence change is ascribed to a small local perturbation of the structure around the single tryptophan residue. The differences in stability of the three forms of azurin are discussed in terms of the rack mechanism. A bound metal ion stabilizes the native fold, and this stabilization is larger for Cu(II) than for Zn(II), reflecting the higher affinity of the protein for Cu(II).
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10.1016/s0167-4838(97)00074-5
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pubmed_1142_18117
|
Paraeducators, who increasingly serve as implementers for students in special education, can struggle with intervention fidelity. Special educators, often responsible for providing paraeducators with support, receive limited supervision training. From organizational behavior management, the Performance Diagnostic Checklist-Human Services (PDC-HS) is a checklist to detect reasons for poor workplace performance and identify aligned support. Utilizing a multiple baseline design, this study evaluated the impact of PDC-HS indicated implementation support on the intervention fidelity of five paraeducators implementing six behavior intervention plans for students receiving special education services. The PDC-HS indicated that all paraeducators would benefit from behavior skills training and visuals of the plans, in addition to other specific supports for individual paraeducators (e.g., prompts, feedback). These implementation supports were effective in improving intervention fidelity for four paraeducators, whereas one paraeducator (across two students) did not respond to these supports. Changes in student outcomes (i.e., academic engagement, disruptive behavior) were inconsistent, suggesting that the behavior intervention plans may have needed to be revised. Usability data suggested that the PDC-HS and indicated supports were generally acceptable, but revisions may be warranted. The implications of this study for school-based implementation support research are discussed.
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10.1016/j.jsp.2021.02.005
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pubmed_552_2874
|
Two-core LPS antibodies, the rabbit J5 polyclonal antiserum and the human anti-lipid A IgM mAb HA-1A, did not improve the survival of mice challenged with E. coli O111 or P. aeruginosa 3, or with the LPS extracted from them, and did not decrease the incidence of Shwartzman reactions in rabbits challenged with O111 LPS. In contrast, O side chain-specific rabbit antisera were protective in these models. The protection afforded by O side chain-specific antisera against endotoxin lethality was associated with decreased LPS-induced serum TNF and IL-6 levels, whereas core LPS antibodies had no effect on TNF or IL-6 levels. The absence of reduction of LPS-induced cytokines levels by core LPS antibodies suggests that these antibodies are not able to prevent the interactions between LPS and target cells.
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10.1084/jem.171.3.889
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pubmed_729_4673
|
BACKGROUND
The prevalence and incidence of syphilis infection were examined in a cohort study of factory workers in Ethiopia.
METHOD
Between February 1997 and March 1999, 409 men and 348 women were enrolled and followed in the cohort study.
RESULTS
The prevalence (95% CI) of past/current syphilis (positive TPPA serology) was 28.9% (25.7% to 32.3%), and factors associated with past/current syphilis were markers of risky sexual behaviours including HIV infection. In this cohort of factory workers subject to public information/education meetings, testing for HIV antibodies, and individual counselling, the incidence (97.5% one sided CI) of new syphilis infections was 0/691 = 0 (0 to 0.5) per 100 person years.
CONCLUSION
This study has documented a reduction in risky sexual behaviours and a low syphilis incidence among factory workers participating in a cohort study on HIV infection progression in Addis Ababa.
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10.1136/sti.78.2.123
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pubmed_712_6461
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One hundred fifty human cadaver kidneys have been preserved by a combination of topical hypothermia and pulsatile perfusion with cryoprecipitated plasma in our laboratory. Post-transplant acute renal failure was reduced from 58 to 21 per cent in those kidneys protected with furosemide and methylprednisolone.
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10.1016/0002-9610(75)90232-9
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pubmed_1043_11832
|
PP10 was isolated from aqueous extracts of human term placentae by fractionating the proteins with rivanol and ammonium sulfate, by gelfiltration on Sephadex G-150 and by use of immunoadsorbents. PP10 apparently is a protein specific for the placenta; it could not be detected in extracts from other human tissues. From one human term placenta an average amount of 20 mg PP10 can be extracted. In sera from pregnant women PP10 is usually present only in trace amounts (less than 0.1 mg/100 ml). PP10 has the electrophoretic mobility of an alpha1-globulin and an isoelectric point of 5.1. The purified protein sediments with 3.8 S. PP10 was found to have a molecular weight of 48,000 as determined by ultracentrifugation and a molecular weight of 65,000 as determined by SDS-PAA gel electrophoresis. PP10 is a glycoprotein containing 6.65% carbohydrates (hexoses 4.8%, hexosamines 1.2%, fucose 0.05%, sialic acid 0.6%). The amino acid composition of PP10 has been determined, too; the most abundant amino acids in this protein are glutamic acid, aspartic acid, leucine and alanine.
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10.1007/BF02103286
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pubmed_295_20201
|
Human post-partum tissue mesenchymal stromal cells (hPPT-MSCs) are widely used in research to investigate their differentiation capabilities and therapeutic effects as potential agents in cell-based therapy. This is ascribed to the advantages offered by the use of MSCs isolated from hPPT over other MSC sources. A paradigm shift in related research is evident that focuses on the secretome of the human MSCs (hMSCs), as therapeutic effects of hMSCs are attributed more so to their secreted growth factors, cytokines and chemokines and to the extracellular vesicles (EVs), all of which are components of the hMSC secretome. Positive therapeutic effects of the hPPT-MSC secretome have been demonstrated in diseases related to skin, kidney, heart, nervous system, cartilage and bones, that have aided fast recovery by replacing damaged, non-functional tissues, via differentiating and regenerating cells. Although certain limitations such as short half -life of the secretome components and irregular secreting patterns exist in secretome therapy, these issues are successfully addressed with the use of cutting-edge technologies such as genome editing and recombinant cytokine treatment. If the current limitations can be successfully overcome, the hPPT-MSC secretome including its EVs may be developed into a cost-effective therapeutic agent amenable to be used against a wide range of diseases/disorders.
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10.4103/ijmr.IJMR_1450_18
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pubmed_146_5807
|
OBJECTIVE
The objective of this study was to evaluate women's preferences in selecting their gynecologist or obstetrician.
METHODS
This cross-sectional study was performed at the Women's Health Center "Netka", Tel Aviv over a 1-month period in 2006 and included 287 participants. Women were asked to complete an anonymous questionnaire.
RESULTS
Most women (60.3%) reported that the gender of their gynecologist or obstetrician was not an important consideration when choosing a gynecologist or an obstetrician. The major determinants in their choice of a gynecologist or an obstetrician included professionalism (98.9%), courtesy (96.6%) and board certification (92%). The rating of the two most important factors in their choice revealed the following order: professionalism (45.3%), courtesy (25.8%), board certification (10.8%), availability (10.1%), comprehension (6.5%) and communication (1.5%).
CONCLUSION
Israeli women's model of choice of their gynecologist involved physicians' professionalism and courtesy while availability and physician's gender was significantly less important.
PRACTICE IMPLICATIONS
The presented data may help health providers during patients' education and counseling along with facilitating better understanding of patients' needs.
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10.1016/j.pec.2008.02.004
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pubmed_806_13931
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The prevention and control of methicillin-resistant Staphylococcus aureus (MRSA) are important, particularly in emergency units. The active surveillance of MRSA was prospectively performed at the emergency medical center of Nagasaki University Hospital. After obtaining nasal swab specimens, a fully automated molecular test (FAMT) and a culture-screening method were utilized for MRSA detection. A total of 150 patients were enrolled in the study, and 366 nasal swab specimens were obtained. MRSA was detected by culture in 11 (7.3%) patients including one new acquisition and by the FAMT in 34 (22.7%) patients including 13 new acquisitions. The sensitivity, specificity, positive predictive value, and negative predictive value of the FAMT at the patient level were 86.7, 85.2, 39.4, and 98.3%, respectively, when compared with the culture-based results. An FAMT can effectively detect MRSA colonization, which may remain undetected with the conventional method, and it may be useful in detecting newly acquired MRSAs.
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10.7883/yoken.JJID.2014.352
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pubmed_968_3109
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Low-barrier to access programs has emerged as a way to overcome the significant hurdles associated with buprenorphine initiation. However, there has been limited research evaluating services set in low-barrier programs outside of buprenorphine. In this issue of the Journal of Addiction Medicine, Harvey and colleagues evaluate a sexually transmitted and blood-borne infection screening protocol implemented in a low-barrier access program in Boston, Massachusetts. The data supports that infection protocols can be efficiently implemented in the low-barrier setting, yielding high rates of diagnosis, and the potential for decentralized models of treatment.
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10.1097/ADM.0000000000000802
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pubmed_796_3248
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A rapid and simple quantitative dot immunoassay for a cell-adapted reference strain of cytomegalovirus (CMV) and for wild strains of CMV present in clinical urine samples was developed. The assay was performed on nitrocellulose paper dotted with several dilutions of viral pellets free of cellular debris. Viral dilutions were treated with a monoclonal antibody to the major component of the viral capsid. To amplify the reaction, a three-dimensional complex of streptavidin and biotinylated horseradish peroxidase was used as the detector system. The dot immunoassay, which does not require cell cultures, yielded results within one day. A significant correlation was found between CMV titers obtained by dot immunoassay and CMV infectious units determined by immunoalkaline phosphatase staining of CMV-late antigen positive cells.
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10.1016/0166-0934(89)90045-1
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pubmed_122_14508
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Approximately one in five men will demonstrate biochemical recurrence (BCR) following local therapy for prostate cancer (PCa). Advanced imaging modalities including positron emission tomography (PET) imaging of various radiotracers have become more commonplace to visualize foci of disease recurrence. We performed a systematic review of the literature to describe current evidence in support of 18F-fluciclovine (Axumin) PET imaging in this clinical setting. An English literature search was conducted on PubMed/Medline for original investigations on 18F-fluciclovine PET for PCa. Boolean criteria included the terms: prostate, fluciclovine, FACBC and Axumin. Published articles meeting these criteria and their respective bibliographies and diagnostic modalities were included after review, when appropriate. Our literature review identified 93 articles. Among these, 18 met our inclusion criteria. Evidence suggests 18F-fluciclovine PET imaging is safe, well-tolerated and offers acceptable sensitivity and specificity for the detection of localized intraglandular and extraprostatic PCa foci in the setting of persistence or recurrence after primary treatment. Compared to other available PET radiotracers available, evidence suggests that 18F-fluciclovine may outperform ProstaScint and 11C-choline in this clinical setting. Furthermore, 18F-fluciclovine PET may aid guiding decision-making in regards to salvage therapy planning. Further investigation is warranted to validate these early findings and to further compare this agent to other available radiotracers in this setting.
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10.21037/tau.2018.07.17
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pubmed_944_1958
|
This study focused on key aspects of organ transplantation programs in various States of Brazil. The study showed wide disparities between States, based on various performance indicators. States in the South, Southeast, and Midwest regions had the highest transplantation and productivity rates and the largest per capita transplantation teams. São Paulo proved to be a benchmark due to its high performance on several indicators.
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pubmed_944_1958
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pubmed_745_15392
|
The antidepressant properties of monoamine precursors were evaluated by the forced-swimming test for mice developed by Porsolt et al. DOPA but not 5-hydroxytryptophan (5HTP) shortened immobility at doses that did not increase locomotor activity. Although L-threo-dihydroxyphenylserine (DOPS), an artificial norepinephrine (NE) precursor, did not change immobility in intact mice, DOPS significantly reduced immobility in mice pretreated with the selective NE neurotoxin DSP4. These results suggest possible antidepressant properties of DOPA and DOPS, the latter of which may act as an antidepressant in a certain NE-depleting condition.
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10.1007/BF00174513
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pubmed_626_9897
|
Colon cancer comprises a small population of cancer stem cells (CSC) that is responsible for tumor maintenance and resistant to cancer therapies, possibly allowing for tumor recapitulation once treatment stops. We previously demonstrated that such chemoresistance is mediated by autocrine production of IL-4 through the up-regulation of antiapoptotic proteins. Several innate and adaptive immune effector cells allow for the recognition and destruction of cancer precursors before they constitute the tumor mass. However, cellular immune-based therapies have not been experimented yet in the population of CSCs. Here, we show that the bisphosphonate zoledronate sensitizes colon CSCs to Vgamma9Vdelta2 T cell cytotoxicity. Proliferation and production of cytokines (TNF-alpha and IFN-gamma) and cytotoxic and apoptotic molecules (TRAIL and granzymes) were also induced after exposure of Vgamma9Vdelta2 T cells to sensitized targets. Vgamma9Vdelta2 T cell cytotoxicity was mediated by the granule exocytosis pathway and was highly dependent on isoprenoid production by of tumor cells. Moreover, CSCs recognition and killing was mainly TCR mediated, whereas NKG2D played a role only when tumor targets expressed several NKG2D ligands. We conclude that intentional activation of Vgamma9Vdelta2 T cells by zoledronate may substantially increase antitumor activities and represent a novel strategy for colon cancer immunotherapy.
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10.4049/jimmunol.0804288
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pubmed_794_1846
|
Bone marrow fibrosis in myelodysplastic syndromes (MDS) has been associated with poor outcome. However, these studies were conducted prior to the widespread use of azacitidine in the management of MDS. Our study aimed to assess whether treatment with azacitidine ameliorates the inferior outcome in MDS with fibrosis. A retrospective study of all patients diagnosed with MDS and treated with azacitidine over 3 years in two institutions was performed. A total of 21 patients were included in this study. Approximately half of these had moderate to severe bone marrow fibrosis at the start of treatment with azacitidine. The median overall survival was 34 months in patients with non-fibrotic bone marrow compared to 14 months in patients with fibrotic marrow (p=0.0007). Median event-free survival was 26 months versus 12 months (p=0.0027) in patients with non-fibrotic and fibrotic marrow, respectively. In multivariate analysis, bone marrow fibrosis was an independent factor in overall survival. Transfusion requirement was not different between the two groups. Despite the small sample size, we observed a worse outcome in azacitidine treated patients with MDS and fibrotic marrow. We suggest a prospective larger study to confirm the above finding.
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10.1016/j.pathol.2022.02.011
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pubmed_326_11855
|
Occurrence of various forms of thyroiditis is getting higher in the last ten years. Subacute or granulomatous or thyroiditis de Quervain has, most certainly, the greatest practical and clinical importance. We present a case of subacute thyroiditis in a female patient 50 years of age in whom Q-fever was positively diagnosed. The disease had had a benign course nevertheless the cause and it passed without any consequences.
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pubmed_326_11855
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pubmed_475_25010
|
Youth represent almost half of all new HIV infections globally. Although condom use is an effective method of HIV prevention among sexually active youth in sub-Saharan Africa (SSA), they face substantial barriers in obtaining condoms in environments where adults hold attitudes condemning premarital sex. More research is needed to better understand the multitude of factors that affect SSA youths' behaviors regarding safe sex practices, including factors that may influence their ability to obtain condoms, and decisions to be tested for HIV. In this study of Uganda youth (n = 1503) from five secondary schools, logistic regression models highlight factors that influence perceptions regarding respect and confidentiality at health centers, condom acquisition, and HIV testing. Family support appears to be an especially important factor that affects youth perceptions about how they will be treated when seeking condoms and HIV testing. Condom acquisition and HIV-testing behaviors are also associated with peer influence, self-esteem, and demographic characteristics, such as age.
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10.1080/09540121.2014.894612
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pubmed_215_18139
|
Structure analysis of [(C(2)H(5))(n)(C(6)H(5))(4-n)P](2)[TeBr(6)(Se(2)Br(2))(2)] is presented for n = 1 and 0 [hereafter (I) and (II)]. Crystal (I) has been synthesized from elemental selenium, tellurium tetrabromide, ethyltriphenylphosphonium bromide and bromine. It has a standard monoclinic structure, space group P2(1)/c, and has been solved and refined to R = 0.0357 for 4803 observed X-ray reflections by traditional techniques. Crystal (II), which has been prepared from elemental selenium, tellurium tetrabromide, tetraphenylphosphonium bromide and bromine, is an incommensurately one-dimensionally modulated structure with planar monoclinic superspace group. (II) has been refined to R = 0.0501 for 4247 observed reflections. The modulation of the atoms that belong to the anion switches between two different basic positions, which are described by the crenel function algorithm. The modulation of the phenyl groups is much weaker and it could be refined within the rigid-body approximation. The TeBr(6) octahedron is nearly regular in both structures. The two Br atoms of the octahedron have a bond to one of the Se atoms in an Se(2)Br(2) molecule. For (I) both bonded Br atoms are trans positioned, while for (II) they can be either trans or cis positioned. The alternations of those arrangements are caused by modulation. The point group of the anion is -1 for crystal (I) and 2/m for the average structure of crystal (II).
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10.1107/s010876810201772x
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pubmed_846_12120
|
The clinical course of olfactory neuroblastoma was not predictable by histologic criteria. Local recurrences were common (62%) and were often treated with multiple surgical procedures and radiation therapy. Metastatic neoplasm occurred in 28% of the patients. The recurrence-free interval decreased in those patients treated with radiation therapy initially, compared with those who had surgery initially. It is justifiable with respect to this study to treat disease in stages A and B with surgery and to reserve radiation therapy for recurrence. Stage C disease should be treated with combined therapy. Craniofacial resection should be promoted.
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10.1002/hed.2890050205
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pubmed_616_10781
|
In our ongoing pursuit of CXCR4 antagonists as potential anticancer agents, we recently developed a potent, selective, and plasma stable peptide, Ac-Arg-Ala-[d-Cys-Arg-Phe-Phe-Cys]-COOH (3). Nevertheless, this compound was still not potent enough (IC50 ≈ 53 nM) to enter preclinical studies. Thus, a lead-optimization campaign was here undertaken to further improve the binding affinity of 3 while preserving its selectivity and proteolytic stability. Specifically, extensive structure-activity relationships (SARs) investigations were carried out on both its aromatic and disulfide forming amino acids. One among the synthesized analogue, Ac-Arg-Ala-[d-Cys-Arg-Phe-His-Pen]-COOH (19), displayed subnanomolar affinity toward CXCR4, with a marked selectivity over CXCR3 and CXCR7. NMR and molecular modeling studies disclosed the molecular bases for the binding of 19 to CXCR4 and for its improved potency compared to the lead 3. Finally, biological assays on specific cancer cell lines showed that 19 can impair CXCL12-mediated cell migration and CXCR4 internalization more efficiently than the clinically approved CXCR4 antagonist plerixafor.
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10.1021/acs.jmedchem.7b01062
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pubmed_142_3203
|
PURPOSE
The present study established the national prevalence of substance use disorders (SUDs) among Danish psychiatric patients. Furthermore, patients with SUDs and those without SUDs were compared on a range of socio-demographic, clinical, and treatment characteristics.
METHODS
Data were obtained from several Danish population-based registers. The study population was defined as all individuals with incidents of schizophrenia, schizotypal disorder, other psychoses, bipolar disorder, depression, anxiety, obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and personality disorders since 1969. The prevalence of SUDs was examined for the following psychoactive substances: alcohol, opioids, cannabis, sedatives, cocaine, psycho-stimulants and hallucinogens.
RESULTS
A total of 463,003 patients were included in the analysis. The prevalence of any lifetime SUD was: 37 % for schizophrenia, 35 % for schizotypal disorder, 28 % for other psychoses, 32 % for bipolar disorder, 25 % for depression, 25 % for anxiety, 11 % for OCD, 17% for PTSD, and 46 % for personality disorders. Alcohol use disorder was the most dominating SUD in every psychiatric category (25 % of all included patients). Patients with SUDs were more often men, had fewer years of formal education, more often received disability pension and died due to unnatural causes.
CONCLUSIONS
The study was the most comprehensive of its kind so far to estimate the prevalence of SUDs in an unselected population-based cohort, and it revealed remarkably high prevalence among the psychiatric patients. The results should encourage continuous focus on possible comorbidity of psychiatric patients, as well as specialised and integrated treatment along with increased support of patients with comorbid disorders.
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10.1007/s00127-015-1104-4
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pubmed_582_4682
|
BACKGROUND
Plasmacytoma is a localized mass of metastatic plasma cells. These lesions rarely involve the petroclival region and carry a high risk of progression to MM and poor prognosis.
CASE DESCRIPTION
We report a 65-year-old woman who presented with a large clival plasmacytoma causing right trigeminal and abducens nerve palsies and was diagnosed with MM after transsphenoidal biopsy. She underwent neoadjuvant chemoradiotherapy followed by radical resection of the residual tumor.
CONCLUSION
We presented our treatment strategy including neoadjuvant chemoradiotherapy followed by radical resection of the lesion. The patient has experienced complete remission, and succeeding MRI revealed no evidence of local recurrence.
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10.1016/j.surneu.2007.10.020
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pubmed_484_23618
|
Because of the rapid decline of the endangered European mink (Mustela lutreola) populations in France, a national conservation program has been put into action, including research to understand the causes of decline. As part of this research, concentrations of eight anticoagulant rodenticides were examined in livers from 122 carcasses of four species of free-ranging mustelids collected between 1990 and 2002 in southwestern France. Bromadiolone residue was found in all species and 9% of the sample (one of 31 European mink, three of 47 American mink [Mustela vison], five of 33 polecats [Mustela putorius], and two of 11 European otters [Lutra lutra]). Liver concentrations ranged from 0.6 mug/g to 9.0 mug/g. Chlorophacinone residue was found in two species and 4% of the sample (in four of the American mink and in one of the otters), with liver concentrations ranging from 3.4 mug/g to 8.5 mug/g. Two polecats and one American mink had lesions and liver residues indicating bromadiolone was directly responsible for their death. However, most of our study animals survived secondary poisoning until they were caught; this study certainly underestimates the extent of fatal exposure of mustelids to rodenticides. Moreover, anticoagulant poisoning could increase their vulnerability to other causes of death. The current status of the endangered European mink population is such that any additional risk factor for mortality is important, and it is thus urgent to monitor and reduce the extensive use of bromadiolone and chlorophacinone against field rodents in France.
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10.7589/0090-3558-40.4.688
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pubmed_642_5038
|
Incidence and nematode population densities of plant-parasitic nematodes were determined in 64 samples of soil and grapevine roots collected from commercial vineyards in southern Spain between October 2003 and May 2005. In addition, a histopathological study was done of root-stock roots naturally infected by root-knot nematodes (Meloidogyne spp.). Nematodes infecting the rootstocks were identified according to conventional procedures, and the Meloidogyne spp. were furthermore identified by sequence characterized amplified region-polymerase chain reaction (SCAR-PCR) and isozyme esterase analyses. The most important plant-parasitic nematodes detected, in order of decreasing frequency of total soil infestation and root infection (percentage of samples), were Mesocriconema xenoplax (34.4%), Meloidogyne incognita (26.6%), Meloidogyne javanica (14.1%), Xiphinema index (12.5%), Xiphinema italiae (10.9%), Pratylenchus vulnus (6.3%), and Meloidogyne arenaria (1.6%). No disease symptoms were observed on aboveground plant parts of the infected grapevines, except for plants in some fields where soil was infested with the virus-vector nematodes X. index and X. italiae. Those grapevines showed a yellow mosaic pattern in leaves early in the growing season and the internode shortening characteristic of infections by Grapevine fanleaf virus. Rootstocks infected by root-knot nematodes (Meloidogyne spp.) showed distorted feeder roots and large- to moderate-sized root galls, present either singly or in clusters. Histopathology of galled roots showed a typical susceptible response to infection by root-knot nematodes: cellular alterations were induced in the cortex, endodermis, pericycle, and vascular system, including giant-cell formation and severe distortion of vascular tissues. Most Meloidogyne egg masses ocurred on the surface of the galled root tissues, a position that could facilitate dispersion of the nematode eggs and juveniles and the occurrence of secondary infections. Some of the grapevine rootstocks surveyed in this study (Paulsen 1103, Richter 110, Rupestris du Lot, and SO4) had previously been reported to be resistant to Meloidogyne spp.; however, the population densities of these nematodes found in soil and roots sampled in the present study, as well as the compatible host-parasite relationship revealed by histopathology, indicate a susceptible response to Meloidogyne spp. from southern Spain.
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10.1094/PDIS-91-9-1147
|
pubmed_750_9429
|
Diffusion of small ions in materials with confined space for translational dynamics can be quite different to isotropic (3D) diffusion, which is found in the majority of solids. Finding credible indications for 2D diffusion is not as easy as it looks at first glance, especially if only powder samples are available. Here we chose the ternary fluoride RbSn2F5 as a new model system to seek out low-dimensional anion diffusion in a nanocrystalline material. We prepared RbSn2F5via mechanochemically-assisted solid state synthesis and used both ac conductivity spectroscopy and spin-lock NMR relaxation measurements to find evidence that the fluorine ions preferably diffuse between the Rb-rich layers. In both cases the diffusion induced spin-lock NMR rates are only consistent with conductivity data if they are analyzed with the semi-empirical spectral density function for 2D jump diffusion as introduced by P. M. Richards [Solid State Commun., 1978, 25, 1019].
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10.1039/c8cp07206j
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pubmed_741_651
|
When added to the culture medium, 3H-labeled GM1 (tritiated predominantly in the terminal galactose residue) was taken up by murine NCTC 2071 and rat glioma C6 cells, both of which are GM1-deficient. Upon incubating the labeled cells in fresh medium, the cell-associated GM1 was metabolized by the cells with a half-life of 1 to 2 days. Some of the GM1 was converted to GD1a but the bulk of the label appeared in the medium as degradation products. When GM1 labeled in the sialic acid or lipid portion of the molecule was utilized, GM2 also was detected with time in the cells and only a small fraction of the radioactivity was detected in the medium. The rat glioma C6 cells appeared unable to degrade the GM2 that they accumulated; this was demonstrated directly by incubating the cells with labeled GM2. The uptake and subsequent metabolism of GM1 was observed over a wide range of GM1 concentrations (10(-8) to 10(-4) M). The GM1-treated cells initially bound more iodinated choleragen than did untreated cells; but with time, binding capacity decreased. When GM1-treated cells were transferred to fresh medium in the presence of excess choleragen, the amount of cell-associated GM1 remained relatively constant for several days; the conversion of GM1 to GD1a also was blocked. Although labeled GM3 and GD1b also were taken up by the cells, choleragen had no effect on their subsequent metabolism. Choleragenoid, the binding subunit of choleragen, also inhibited GM1 metabolism without activating adenylate cyclase. These results indicate that exogenous gangliosides taken up by cultured cells are metabolized and that choleragen, which binds with high affinity to GM1, specifically prevents the metabolism of this ganglioside.
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pubmed_741_651
|
pubmed_743_4337
|
Microbial fuel cells (MFCs) are sensitive to acidity variations in both bioelectricity generation and biochemical digestion aspects, therefore online pH monitoring is of necessity to guarantee optimal function of MFCs. Present pH meters hardly fulfill this special need. In this work, we designed a novel voltammetric pH sensor based on electrochemically reduced graphene oxide (rGO) modified screen printed electrode. By surface doping of alizarin, good linearity of pH sensing over the range of 4.0-9.0 can be realized. Fast readout can be acquired within 15 s for each test. pH monitoring for artificial wastewater with inoculum of granular activated sludge in a MFC was successfully illustrated. Specially, it was verified that the performance was improved with alizarin doping due to the enhanced rGO surface proton diffusion. This approach provides an online, calibration-free and long stable pH monitoring method for the future MFC development.
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10.1016/j.chemosphere.2021.132277
|
pubmed_844_6945
|
It has been suggested that hypoxic pulmonary vasoconstriction (HPV) may mainly proceed via loss of normoxic vasodilation, forwarded by tonic O2-dependent formation of nitric oxide and superoxide (23). Both agents may stimulate guanylate cyclase, the latter via conversion to hydrogen peroxide and formation of compound I with catalase. We probed this hypothesis in perfused rabbit lungs, employing the superoxide scavengers superoxide dismutase (SOD), 4,5-dihydroxy-1,3-benzene disulfonic acid (Tiron), and nitro blue tetrazolium (NBT) and the catalase inhibitor aminotriazole (AT). NBT turned out to be a potent dose-dependent inhibitor of HPV in a concentration range of 200 nM to 1 microM, and superimposable dose-inhibition curves were obtained when lung synthesis of nitric oxide and vasodilatory prostanoids was preblocked by NG-monomethyl-L-arginine (L-NMMA) and acetylsalicylic acid (ASA). The NBT effect was specific because no inhibition in the vasoconstrictor responses to the stable thromboxane analog U-46619 and angiotensin II was observed. In contrast, SOD and Tiron were ineffective. AT exerted nonspecific inhibition of the hypoxia- and chemical vasoconstrictor-induced pressor responses. When applied under normoxic conditions, however, NBT alone or coapplied with L-NMMA or ASA, both for blockage of parallel vasodilatory pathways, did not mimic the hypoxia-induced vasoconstrictor response. In conclusion, the present study supports an important role for superoxide in the basic mechanism of HPV, but it questions the concept that loss of tonic vasorelaxation via this pathway is the underlying event in rabbit lungs. The mechanisms relating O2 tension-dependent superoxide and hydrogen peroxide generation to the vasoconstrictor event occurring in HPV remain to be further elucidated.
|
10.1152/ajplung.1998.274.5.L721
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pubmed_507_18888
|
The purpose of this study is to use voxel-based analysis to simultaneously elucidate regional changes in gray/white matter volume, mean diffusivity (MD), and fractional anisotropy (FA) in patients with unipolar major depressive disorder. We studied 21 right-handed patients and 42 age- and gender-matched right-handed normal subjects. Local areas showing significant gray matter volume reduction in depressive patients compared with controls were observed in the right parahippocampal gyrus, hippocampus, bilateral middle frontal gyri, bilateral anterior cingulate cortices, left parietal and occipital lobes, and right superior temporal gyrus. Local areas showing an increase of MD in depressive patients were observed in the bilateral parahippocampal gyri, hippocampus, pons, cerebellum, left frontal and temporal lobes, and right frontal lobe. There was no significant difference between the two groups for FA and white matter volume in the entire brain. Although there was no local area where brain volume and MD were significantly correlated with disease severity, FA tended to correlate negatively with total days depressed in the right anterior cingulate and the left frontal white matter. These results suggest that the frontolimbic neural circuit might play an important role in the neuropathology of patients with major depressive disorder.
|
10.1016/j.pscychresns.2009.07.007
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pubmed_500_2983
|
A fraction of the low-density lipoprotein (LDL) internalized by cells via receptor-mediated endocytosis follows a short-circuit pathway, termed "retro-endocytosis," that results in the rapid exocytosis of ligand. Results from the current study suggest that retro-endocytosis of LDL in human fibroblasts is caused by resurfacing of endocytotic vesicles that contain both free and receptor-bound ligand, resulting in discharge of vesicular contents and in spontaneous dissociation of LDL from its receptor. The bulk of the released LDL particles had the same size, density, and immunogenic properties as native LDL, indicating that they were discharged intact. Some of the retro-endocytosed LDL was larger than native LDL, and some exhibited altered sedimentation properties. When fusion of endosomes with lysosomes was inhibited by chilling cells to 18 degrees C, the proportion of intracellular LDL subsequently released was unaffected, suggesting that retro-endocytosis does not require lysosomal participation. Furthermore, the shorter the internalization phase the greater was the proportion of LDL subsequently released, suggesting that LDL was discharged from compartments formed early in endocytosis. Retro-endocytosis of LDL was stimulated by agents that neutralize acid intracellular compartments, such as ionophores (monensin) and weak bases (chloroquine and methylamine). Monensin increased the proportion of intracellular LDL released, suggesting that it had a direct effect on retro-endocytosis. The effect of weak bases appeared to be secondary to their ability to promote cellular accumulation of undegraded LDL. Thus, retro-endocytosis of LDL becomes a major pathway when intracellular compartments fail to maintain a low pH or where the intracellular concentration of LDL reaches abnormal levels.
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10.1161/01.atv.5.1.45
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pubmed_926_2274
|
BACKGROUND AND PURPOSE
Determining the minimal clinically important difference (MCID) is essential for evaluating novel therapies. For acute ischemic stroke, expert surveys have yielded MCIDs that are substantially higher than the MCIDs observed in actual expert behavior in guideline writing and clinical practice, potentially because of anchoring bias.
METHODS
We administered a structured, internet-based survey to a cross-section of academic stroke neurologists in the United States. Survey responses assessed demographic and clinical experience, and expert judgment of the MCID of the absolute increase needed in the proportion of patients achieving functional independence at 3 months to consider a novel, safe neuroprotective agent as clinically worthwhile. To mitigate anchoring bias, the survey response framework used a base 1000 rather than base 100 patient framework.
RESULTS
Survey responses were received from 122 of 333 academic stroke neurologists, there were 23% women, 72.8% had ≥6 years of practice experience, and neurovascular disease accounted for more than half of practice time in >70%. Responder-nonresponder and continuum of resistance tests indicated that responders were representative of the full expert population. Among respondents, the median MCID was 1.3% (interquartile range, 0.8% to >2%).
CONCLUSIONS
Stroke expert responses to MCID surveys are affected by anchoring and centrality bias. When survey design takes these into account, the expert-derived MCID for a safe acute ischemic stroke treatment is 1.1% to 1.5%, in accord with actual physician behavior in guideline writing and clinical practice. This revised MCID value can guide clinical trial design and grant-funding and regulatory agency decisions.
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10.1161/STROKEAHA.117.017496
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pubmed_440_23654
|
Ongoing climate change and land-use change have the potential to substantially alter the distribution of large herbivores. This may result in drastic changes in ecosystems by changing plant-herbivore interactions. Here, we developed a model explaining sika deer persistence and colonization between 25 years in terms of neighborhood occupancy and habitat suitability. We used climatic, land-use, and topographic variables to calculate the habitat suitability and evaluated the contributions of the variables to past range changes of sika deer. We used this model to predict the changes in the range of sika deer over the next 100 years under four scenario groups with the combination of land-use change and climate change. Our results showed that both climate change and land-use change had affected the range of sika deer in the past 25 years. Habitat suitability increased in northern or mountainous regions, which account for 71.6% of Japan, in line with a decrease in the snow cover period. Habitat suitability decreased in suburban areas, which account for 28.4% of Japan, corresponding to land-use changes related to urbanization. In the next 100 years, the decrease in snow cover period and the increase in land abandonment were predicted to accelerate the range expansion of sika deer. Comparison of these two driving factors revealed that climate change will contribute more to range expansion, particularly from the 2070s onward. In scenarios that assumed the influence of both climate change and land-use change, the total sika deer range increased by between +4.6% and +11.9% from the baseline scenario. Climate change and land-use change will require additional efforts for future management of sika deer, particularly in the long term.
|
10.1002/ece3.2514
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pubmed_970_23388
|
To analyze the registered clinical trial protocols of traditional Chinese medicine(TCM) for the prevention and treatment of coronavirus disease 2019(COVID-19), in order to provide information for improving the quality of research design. The website of the Chinese Clinical Trial Registry(www.chictr.org.cn) and the American Clinical Trial Registry(clinicaltrials.gov) were searched to collect protocols of TCM for COVID-19. Documents were screened following the inclusion criteria, and data were extracted in regard to registration date, study objective, type of design, sponsor, patient, sample size, intervention, and evaluation index. Descriptive analysis was conducted. A total of 49 clinical trial protocols of TCM for COVID-19 were included. Primary sponsors were mainly hospitals or universities in places like Hubei, Beijing, Zhejiang and other regions. The implementation units are mainly in Hubei, Guangdong, Zhejiang, Henan and other regional hospitals. The types of study design were mainly experimental studies(40), including 30 randomized parallel controlled trials, 7 non-randomized controlled trials, 2 single arm trials and 1 consecutively recruited trial; besides, there were also 6 observational studies, 2 health service studies and 1 preventive study. The sample size reached a total of 30 562 cases, with a maximum of 20 000 for a single study and a minimum of 30. The 49 trials subjects included healthy people(3), isolation and observation cases(1), suspected cases(10),confirmed COVID-19 patients(31) and COVID-19 recovery patients(4). Of the 31 trials planned to include confirmed COVID-19 patients, 16 protocols no definite disease classification, 3 with a clear exclusion of severe subjects, 4 with common subjects, 2 with light, common or severe subjects, 1 with light and common subjects, 1 with common or severe subjects, 3 with severe subjects, and 1 with severe or critical subjects. The experimental interventions included Chinese patent medicine(Lianhua Qingwen Capsules/Granules, Huoxiang Zhengqi Dropping Pills/Oral Liquid, Babao Dan, Gubiao Jiedu Ling, Jinhao Jiere Granules, Compound Yu-xingcao Mixture, Jinye Baidu Granules, Shufeng Jiedu Capsuless, Shuanghuanglian Oral Liquid, Tanreqing Injection, Xuebijing Injection, Reduning Injection, Xiyanping Injection), Chinese medicinal decoction and taichi. The primary evaluation outcomes mainly included antipyretic time, clinical symptom relief, novel coronavirus nucleic acid turning to negative, conversion rate of severe cases and chest CT. There was a quick response of clinical research on the prevention and treatment of COVID-19 with TCM, with the current registered protocols covers the whole process of disease prevention, treatment and rehabilitation. However, issues need to be concerned, including unclear definition of patient's condition, unclear research objectives, unclear intervention process and inappropriate outcomes, etc. In addition, researchers should consider the actual difficulties and workload of doctors in epidemic response environment, and make effort to optimize the process and improve the operability of research protocols under the principle of medical ethics.
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10.19540/j.cnki.cjcmm.20200220.501
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pubmed_334_1293
|
It has been established that hyperbaric oxygen (HBO) treatment reduces brain edema, decreases infarct volume, contributes to neurological functional recovery and suppresses apoptosis in suture-induced focal cerebral ischemic animal models. In the present study, we evaluated the therapeutic effect of HBO in an endothelin-1-induced focal cerebral ischemia in rats and explored the associated mechanisms of HBO-induced brain protection. One hundred twenty male Sprague-Dawley rats (280 to 320 g) were randomly assigned to sham, focal cerebral ischemia and focal cerebral ischemia treated with HBO groups. Brain water content, neurological function, morphology and molecular biological markers were assessed. HBO (100% O2, 2.5 atmosphere absolute for 2 h) was initiated at 1 h after focal cerebral ischemia. Rats were killed at 24 h to harvest tissues for Western blot or for histology. In HBO-treated animals, an enhanced ratio of Bcl-2 and Bax and a reduced expression of hypoxia-inducible factor-1alpha (HIF-1alpha) in the hippocampus after focal cerebral ischemia were observed. These results indicate that HBO provides brain protection that is probably associated with the inhibition of HIF-1alpha and the elevation of Bcl-2.
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10.1016/j.brainres.2007.03.061
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pubmed_1011_2870
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B.M. cells of RLV-infected BALB/c mice can proliferate in methylcellulose in the absence of E.P., while normal B.M. cells cannot (12). Not only the more primitive BFU-E shows hormone-independency (18). This phenomenon is in favour of the view that the Rauscher virus induced erythroblastosis is a true neoplasia although transplantation experiments failed so far. The experiments in which transformation in vitro of B.M. cells by RLV is established (19) show that the CFU-E can serve as a target for the virus. Treatment of normal mice with CFA leads to a rapid increase in CFU-E in the bone marrow (18). Splenomegaly of RLV-infected mice is enhanced by CFA-treatment probably due to an increase in targets. Transfection with proviral DNA also can transform the CFU-E of BALB-c mice. This approach allows in vitro studies on the resistence of mouse strains to RLV in vitro. The studies are of interest for the human disease in two aspects. In vitro transformation assays are needed to study the oncogenic potential of putative human leukemia viruses. Furthermore the studies have yielded some new insight in the pathogenesis of virally induced erythroblastosis. This might serve as a model for e.g. acute myeloid leukemia in man.
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10.1007/978-3-642-87524-3_15
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pubmed_520_7546
|
Graphene oxide (GO) films with natural "quantum-confined-superfluidics" (QSF) channels for moisture actuation have emerged as a smart material for actuators and soft robots. However, programming the deformation of GO by engineering QSF nanochannels around 1 nm is extremely challenging. Herein, we report the reconfigurable, reversible, and redefinable deformation of GO under moisture actuation by tailoring QSF channels via moisture-assisted strain-induced wrinkling (MSW). The shape fixity ratio of a general GO film can reach ∼84% after the MSW process, and the shape recovery ratio is ∼83% at room temperature under moisture actuation. The flexible shaping and deformation abilites, as well as the self-healing property of GO make it possible to fabricate soft robots using GO. Besides, as a proof-of-concept, passive electronics and soft robots capable of crawling, turning, switching circuit, and automatic somersault are demonstrated. With unique shaping and deformation abilities, GO may bring great implications for future soft robotics.
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10.1021/acs.nanolett.2c02212
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pubmed_289_14644
|
Poly(o-aminophenol-co-pyrogallol) (PAP) was first synthesized via the electrochemical copolymerization of o-aminophenol and pyrogallol in the acidic solution, using a reduced graphene oxide/glassy carbon (RGO/GC) electrode as a working electrode. Reduced graphene oxide played an important role in increasing PAP amount deposited on the RGO/GC electrode compared to that on the bare GC electrode, which is due to that RGO has the large specific surface area. The results from the spectra of IR, (1)H NMR and ESR and the measurement of molecular weight demonstrated that PAP is an oligomer with the free radicals and exhibited good redox activity in a wide pH range from pH<1-9.0 and can effectively catalyze xanthine oxidation due to the presence of the free radicals and the reversible redox groups in the copolymer chain. On the basis of the direct oxidation of xanthine on PAP, the PAP/RGO/GC electrode was used as a xanthine biosensor. The biosensor showed a linear range from 1.0 to 120μM xanthine at pH 6.0 with a correction coefficient of 0.9965 and fast response to xanthine oxidation. The peak potential of xanthine oxidation shifted from 0.814 to 0.668V as pH increased from 5.0 to 7.5.
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pubmed_289_14644
|
pubmed_845_19344
|
Copper nanoparticles (Cu NPs) are increasingly used as an animal feed additive in China. In previous studies, it was determined that Cu NPs can penetrate the placental barrier, however, its toxic effects on the fetus have not yet been elucidated. Therefore, in this study, we investigated the potential fetal toxic effects of Cu NPs. Cu NPs were orally administered to pregnant Sprague-Dawley rats from gestation days (GDs) 3-18 at a dose of 60, 120, and 180 mg/kg/day. Cesarean sections were conducted on GD 19. During fetal examination, no toxicities were observed regarding general clinical signs, however, Cu NPs significantly decreased fetal body weight, body length, and liver weights. Cu ions and Cu MPs exhibited similar effects on the fetal development. Cu NPs increased the liver concentration of Cu, and decreased protein levels and Fe in fetuses. Cu NPs also increased oxidative stress and inflammation in the fetus after pregnant rats were exposed to high doses of Cu NPs. Oral exposure to Cu NPs during pregnancy increased Cu concentrations in the fetus, which not only affected fetal development, but also significantly induced oxidative stress and inflammatory responses in fetal liver. Taken together, these findings are valuable to evaluate fetal risk assessment after oral exposure of Cu NPs during pregnancy. Additional comprehensive toxicity studies are deemed necessary to clarify the underlying mechanisms involved.
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10.1016/j.ecoenv.2020.111206
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pubmed_266_3270
|
In recent years, collaboration between medical educators and art museum educators has emerged as an important trend. The museum environment can support a kind of professional reflection and conversation that is difficult to develop in a medical setting. Skills such as close looking, empathic communication, resilience, and cultural awareness may also be developed in the art museum when plans for the visit are developed with attention to their relevance to health professions. Working across disciplines requires identifying and cultivating a strong partner as well as clear communication about goals and possibilities. The following tips were developed by museum educators based on their extensive experience working with medical students, interns, residents and faculty at Harvard Medical School and the University of Texas at Austin's Dell Medical School over the past twelve years.
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10.1007/s10912-020-09655-1
|
pubmed_270_20771
|
The spatial-temporal dynamics of farm animal diseases depend both on disease specific processes and the underlying contact network between farms. Indirect transmission via free-living bacteria in the environment is an important transmission route and contributes significantly to the dynamics. The pair-wise model has been developed to include both direct transmission and indirect transmission via free stages. The model is compared with stochastic simulations of epidemics on contact networks. The network framework is applied to the investigation of the epidemiological dynamics of between-herd transmission of Salmonella spp. The main results help to explain differences in observed epidemiological patterns and to identify possible causes for different strains of Salmonella developing so much variation in their infection dynamics in UK dairy herds. Numerical results show that shorter infectious period, more persistent immune response and more rapid removal of faeces result in a lower prevalence of infection and a greater tendency for (damped) oscillation. A possible control strategy is consequently suggested. Furthermore, the effect of network structure on long-term dynamics is examined.
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10.1016/j.jtbi.2006.08.019
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pubmed_807_8832
|
BACKGROUND
We present a case of a 13-year-old girl with a congenital vascular lesion in her right ankle.
RESULTS AND CONCLUSIONS
Clinical and pathologic examinations led to the diagnosis of a verrucous hemangioma, a distinct, uncommon vascular lesion. The appearance of verrucous hemangiomas evolves with time and may represent a diagnostic challenge. We present this case report and a review of the literature.
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10.2310/7750.2009.08093
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pubmed_1142_9601
|
Nanodevices, harvesting the power of synthetic catalysts and enzymes to perform enantioselective synthesis inside cell, have never been reported. Here, we synthesized round bottom jar-like silica nanostructures (SiJARs) with a chemo-responsive metal-silicate lid. This was isolated as an intermediate structure during highly controlled solid-state nanocrystal-conversion at the arc-section of silica shell. Different catalytic noble metals (Pt, Pd, Ru) were selectively modified on the lid-section through galvanic reactions. And, lid aperture-opening was regulated by mild acidic conditions or intracellular environment which accommodated the metal nanocrystals and enzymes, and in turn created an open-mouth nanoreactor. Distinct from the free enzymes, SiJARs performed asymmetric aldol reactions with high activity and enantioselectivity (yield >99 %, ee=95 %) and also functioned as the artificial catalytic organelles inside living cells. This work bridges the enormous potential of sophisticated nanocrystal-conversion chemistry and advanced platforms for new-to-nature catalysis.
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10.1002/anie.202103165
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pubmed_1026_10678
|
BACKGROUND
The pathogenesis of teratozoospermia (<4% morphologically normal sperm cells) and the relationship between sperm morphological abnormalities and abnormal sperm nuclear DNA fragmentation, which are considered indicators of male fertility, have not been elucidated. Our research was designed to determine the prevalence of different sperm DNA fragmentation (SDF) levels in men with teratozoospermia and to establish a discriminating threshold value for SDF in assessing sperm morphology.
METHODS
Basic semen characteristics and detailed sperm morphological analysis (head, neck, midpiece, and tail defects and excess residual cytoplasm) (WHO, 2010), and the nuclear sperm DNA dispersion test were performed on semen samples obtained from 523 men with teratozoospermia (n=296) and those without teratozoospermia (n=227).
RESULTS
Subjects with abnormal sperm morphology had not only lower results for standard sperm characteristics, including detailed sperm morphological abnormalities, but also a higher proportion of sperm cells with SDF vs. men with normal sperm morphology. Moreover, significantly fewer subjects with low SDF levels (≤15%), more subjects with high SDF levels (>30%) and a higher odds ratio (OR) for having high SDF levels were found in the group of men with teratozoospermia vs. men without teratozoospermia. However, the receiving operating characteristic (ROC) curve analysis indicated that a SDF >18% was a significant negative predictive value to distinguish between men with normal sperm morphology or men with abnormal sperm morphology. The optimal area under the ROC curve (AUC) was 0.746. In the group of men with teratozoospermia, a higher incidence of men with >18% SDF and a higher OR for having >18% SDF were observed. SDF negatively correlated with sperm number, morphologically normal sperm cells, sperm motility and sperm vitality but positively correlated with the teratozoospermia index (TZI) and detailed sperm morphological abnormalities.
CONCLUSIONS
The obtained findings demonstrated that: (I) detailed sperm structural defects coexist with abnormal nuclear sperm DNA dispersion, (II) men with teratozoospermia may have a higher risk for sperm DNA damage, (III) the calculated optimal SDF value of 18% measured by the DNA sperm dispersion test is the best criterion to predict normal and abnormal sperm morphology.
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10.21037/tau.2020.01.31
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pubmed_849_14656
|
PURPOSE
To develop and test the feasibility of a new method for non-ECG-gated first-pass perfusion (FPP) cardiac MR capable of imaging multiple short-axis slices at the same systolic cardiac phase.
METHODS
A magnetization-driven pulse sequence was developed for non-ECG-gated FPP imaging without saturation-recovery preparation using continuous slice-interleaved radial sampling. The image reconstruction method, dubbed TRACE, used self-gating based on reconstruction of a real-time image-based navigator combined with reference-constrained compressed sensing. Data from ischemic animal studies (n = 5) was used in a simulation framework to evaluate temporal fidelity. Healthy subjects (n = 5) were studied using both the proposed approach and the conventional method to compare the myocardial contrast-to-noise ratio (CNR). Patients (n = 2) underwent adenosine stress studies using the proposed method.
RESULTS
Temporal fidelity of the developed method was shown to be sufficient at high heart-rates. The healthy volunteers studies demonstrated normal perfusion and no dark-rim artifacts. Compared with the conventional scheme, myocardial CNR for the proposed method was slightly higher (8.6 ± 0.6 versus 8.0 ± 0.7). Patient studies showed stress-induced perfusion defects consistent with invasive angiography.
CONCLUSION
The presented methods and results demonstrate feasibility of the proposed approach for high-resolution non-ECG-gated FPP imaging of 3 myocardial slices at the same systolic phase, and indicate its potential for achieving desirable image quality (high CNR and no dark-rim artifacts).
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10.1002/mrm.25752
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pubmed_1_25655
|
QTLs for delayed canopy wilting from five soybean populations were projected onto the consensus map to identify eight QTL clusters that had QTLs from at least two independent populations. Quantitative trait loci (QTLs) for canopy wilting were identified in five recombinant inbred line (RIL) populations, 93705 KS4895 × Jackson, 08705 KS4895 × Jackson, KS4895 × PI 424140, A5959 × PI 416937, and Benning × PI 416937 in a total of 15 site-years. For most environments, heritability of canopy wilting ranged from 0.65 to 0.85 but was somewhat lower when averaged over environments. Putative QTLs were identified with composite interval mapping and/or multiple interval mapping methods in each population and positioned on the consensus map along with their 95% confidence intervals (CIs). We initially found nine QTL clusters with overlapping CIs on Gm02, Gm05, Gm11, Gm14, Gm17, and Gm19 identified from at least two different populations, but a simulation study indicated that the QTLs on Gm14 could be false positives. A QTL on Gm08 in the 93705 KS4895 × Jackson population co-segregated with a QTL for wilting published previously in a Kefeng1 × Nannong 1138-2 population, indicating that this may be an additional QTL cluster. Excluding the QTL cluster on Gm14, results of the simulation study indicated that the eight remaining QTL clusters and the QTL on Gm08 appeared to be authentic QTLs. QTL × year interactions indicated that QTLs were stable over years except for major QTLs on Gm11 and Gm19. The stability of QTLs located on seven clusters indicates that they are possible candidates for use in marker-assisted selection.
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10.1007/s00122-015-2566-1
|
pubmed_743_17459
|
The goal of this study was to see if automatic biopsy guided by ultrasound could be used to provide a qualitative diagnosis of a liver tumor. Methods. A total of 40 patients (101 focuses) were treated with automatic liver parenchyma biopsy under ultrasound guidance, and the correlation between pathological outcomes and ultrasound images was investigated. The lesion size in the observation group was compared to that in the control group using conventional ultrasound (P > 0.05), and there was no significant difference. Under contrast-enhanced ultrasound (CEUS), there was no statistically significant difference in lesion size between the observation and control groups (P > 0.05). The difference in lesion size between the conventional ultrasonography and CEUS observation groups was statistically significant (P 0.05). Conclusion. Ultrasound-guided automated biopsy of the liver parenchyma is a simple and effective procedure with fewer problems and a high diagnostic rate, and it deserves to be promoted clinically.
|
10.1155/2021/8585887
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pubmed_1129_18377
|
Initial state-selected reaction probabilities for the H + CHD3 → H2 + CD3 reaction starting from various different ro-vibrational states of CHD3 are studied by accurate full-dimensional (12D) quantum dynamics calculation for vanishing total angular momentum (J = 0). The calculations employ the quantum transition state concept and the multi-layer multi-configurational time-dependent Hartree approach. First results focusing on fundamental excitations and the reactivity borrowing effect were communicated recently [R. Ellerbrock and U. Manthe, J. Chem. Phys. 147, 241104 (2017)]. In the present work, all vibrational states of the methane reactant are considered. It is found that energy deposited in overtones and combination bands is less efficient in promoting reactivity than expected from separable or sudden models. Furthermore, the effects of rotational excitation on the reactivity are studied in detail.
|
10.1063/1.5037797
|
pubmed_948_13718
|
The human papillomavirus detection and oncogenes amplifications were studied on DNAs from fifteen cervical cancers. We detected HPV16 and HPV18 using Southern blot hybridization and polymerase chain reaction (PCR) technique. The positive subjects of HPVs were eight cases (53%) observed by Southern blot hybridization and fourteen cases (93%) by PCR technique. The gene amplifications of oncogenes (c-myc and N-myc) were analysed by slot-blot method and were observed in c-myc but not in N-myc. The "LARGE" gene amplification (more than five fold) in c-myc was observed in one case (7%) and the "SMALL" gene amplifications (less than five fold) were observed in six cases (40%) in human cervical cancers. Although one of five cases (20%) with HPV16 was present c-myc gene amplification, all of three cases (100%) with HPV18 were found c-myc gene amplifications. In two out of three cases obtained more than three fold c-myc gene amplifications, HPV were not detectable. It is suggested that the negative correlation between gene amplification and numbers of HPV copies exist in advanced cervical cancers.
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pubmed_948_13718
|
pubmed_379_6930
|
The cholesterol metabolism of cultured smooth muscle cells (SMC) from the thoracic aorta of SMC from stroke-prone spontaneously hypertensive rats (SHRSP) and Wistar-Kyoto rats (WKY) was compared. SMC from SHRSP had a higher acylCoA:cholesterol acyltransferase (ACAT) activity and accumulated more cholesterol than those from WKY. By using SMC from SHRSP, the effects of a novel ACAT inhibitor, HL-004, on the accumulation and removal of cholesterol were investigated. HL-004 inhibited microsomal ACAT activity from rabbit liver, intestine, aorta, and cultured SMC of SHRSP with 50% inhibition (IC50) values of 2.2, 1.7, 7.9, and 20 nM, respectively. HL-004 suppressed the accumulation of the intracellular cholesteryl ester (CE), but did not affect the intracellular free cholesterol (FC) content. Removal of cholesterol from the lipid-loaded SMC was accelerated by HL-004. These effects of HL-004 on cholesterol levels showed a good parallel to ACAT inhibition. It would thus appear that the suppression of cholesterol accumulation and the removal of cholesterol in SMC by HL-004 can be attributed to its ACAT inhibition in the cell, which reduces the content of intracellular CE.
|
10.1016/0024-3205(94)00480-g
|
pubmed_196_4972
|
Neospora caninum is an apicomplexan parasite considered one of the main causes of abortion in cattle worldwide; thus, there is an urgent need to develop novel therapeutic agents to control the neosporosis. Enoyl acyl carrier protein reductase (ENR) is a key enzyme of the type II fatty acid synthesis pathway (FAS II), which is essential for apicomplexan parasite survival. The antimicrobial agent triclosan has been shown to be a very potent inhibitor of ENR. In this study, we identified an E. coli ENR-like protein in N. caninum. Multiple sequence alignment showed all the requisite features of ENR existed in this protein, so we named this protein NcENR. Swiss-Model analysis showed NcENR interacts with triclosan. We observed that ENR is localized in the apicoplast, a plastid-like organelle. Similar to the potent inhibition of triclosan on other apicomplexa parasites, this compound markedly inhibits the growth of N. caninum at low concentrations. Further research showed that triclosan attenuated the invasion ability and proliferation ability of N. caninum at low concentrations. The results from in vivo studies in the mouse showed that triclosan attenuated the virulence of N. caninum in mice mildly and reduced the parasite burden in the brain significantly. Taken together, triclosan inhibits the growth of N. caninum both in vitro and in vivo at low concentrations.
|
10.1007/s00436-019-06449-w
|
pubmed_400_6258
|
Plants release complex mixtures of volatiles important in the interaction with insects and other organisms. In the search for compounds that contribute to the perception of odour quality in the weevil Pissodes notatus, single olfactory receptor neurones on the antennae were screened for sensitivity to naturally produced plant volatiles by the use of gas chromatography linked to single cell recordings. We here present 60 olfactory neurones responding to 25 of the numerous compounds released by host and non-host plants. All the neurones show high selectivity and are classified into 12 distinct types. The two most abundant types respond to alpha-pinene, beta-pinene, and 3-carene ( n=17), and to isopinocamphone and pinocamphone ( n=17), respectively. Other neurone types respond to limonene ( n=9), beta-phellandrene ( n=3), and fenchone ( n=4). Responses to beta-caryophyllene ( n=1) and to ethanol ( n=4) are also shown. Except for two pairs, the neurone types do not show overlap of the molecular receptive range. The active compounds are present in the host, Pinus pinaster, as well as in non-hosts, supporting the idea that plant odour quality is mediated by the ratio of the compounds rather than specific odorants.
|
10.1007/s00359-003-0391-5
|
pubmed_51_14386
|
Mechanochemical methods of neat grinding and liquid-assisted grinding have been applied to the synthesis of mono- and bis(thiourea)s by using the click coupling of aromatic and aliphatic diamines with aromatic isothiocyanates. The ability to modify the reaction conditions allowed the optimization of each reaction, leading to the quantitative formation of chiral bis(thiourea)s with known uses as organocatalysts or anion sensors. Quantitative reaction yields, combined with the fact that mechanochemical reaction conditions avoid the use of bulk solvents, enabled solution-based purification methods (such as chromatography or recrystallization) to be completely avoided. Importantly, by using selected model reactions, we also show that the described mechanochemical reaction procedures can be readily scaled up to at least the one-gram scale. In that way, mechanochemical synthesis provides a facile method to fully transform valuable enantiomerically pure reagents into useful products that can immediately be applied in their designed purpose. This was demonstrated by using some of the mechanochemically prepared reagents as organocatalysts in a model Morita-Baylis-Hillman reaction and as cyanide ion sensors in organic solvents. The use of electronically and sterically hindered ortho-phenylenediamine revealed that mechanochemical reaction conditions can be readily optimized to form either the 1:1 or the 1:2 click-coupling product, demonstrating that reaction stoichiometry can be more efficiently controlled under these conditions than in solution-based syntheses. In this way, it was shown that excellent stoichiometric control by mechanochemistry, previously established for mechanochemical syntheses of cocrystals and coordination polymers, can also be achieved in the context of covalent-bond formation.
|
10.1002/chem.201200632
|
pubmed_744_35
|
Noninvasive positive pressure ventilation has been demonstrated to be of benefit in preventing endotracheal intubation and reducing mortality in specific patients in the setting of acute exacerbations of chronic obstructive pulmonary disease. The successful application of noninvasive positive pressure ventilation depends on a multitude of factors, including patient selection, choice of interface, physician experience, and patient-ventilator synchrony. The use of clinical practice guidelines has been shown to improve the process and outcomes of care. This paper presents a guideline for the use of noninvasive positive pressure ventilation in the setting of acute ventilatory failure in patients with acute exacerbations of chronic obstructive pulmonary disease.
|
10.1016/j.jcrc.2004.04.006
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pubmed_137_2793
|
A recently disclosed Erk-induced PARP1 activation mechanism mediates the expression of immediate early genes (IEGs) in response to a variety of extra- and intracellular signals implicated in memory acquisition, development and proliferation. Here, we review this mechanism, which is initiated by stimulation-induced binding of PARP1 to phosphorylated Erk translocated into the nucleus. This binding maintains long-lasting synergistic activity of these proteins, which offers a new pattern for targeted therapy.
|
10.1038/s41392-019-0042-0
|
pubmed_508_14447
|
OBJECTIVE
We investigated whether personal exposure to particulate matter </= 10 microm in diameter (PM10) contributes to impaired cardiovascular function and increased systemic inflammation and oxidative stress in diabetic patients.
METHODS
We monitored 25 patients' personal exposure to PM10 for 24 hours and then measured their heart rate, blood pressure, brachial arterial diameter, flow-mediated vasodilation (FMD), plasma cytokines, and thiobarbituric acid reactive substances (TBARS), which is an oxidative stress marker. We repeated this procedure for 7 weeks on each subject. We tested the associations using mixed-effects models.
RESULTS
PM10 was significantly positively associated with FMD and TBARS but inversely associated with end-systolic basal brachial arterial diameter (P < 0.05). Moreover, in subjects not taking vasoactive medications, PM10 was significantly positively associated with blood pressure but inversely associated with artery flow.
CONCLUSION
Elevated PM10 may contribute to oxidative stress and impaired cardiovascular function in patients with diabetes mellitus.
|
10.1097/JOM.0b013e31803220ef
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pubmed_17_11068
|
Caldesmon immunoanalogues were detected in Amoeba proteus cell homogenates by the Western blot technique. Three immunoreactive bands were recognized by polyclonal antibodies against the whole molecule of chicken gizzard caldesmon as well as by a monoclonal antibody against its C-terminal domain: one major and two minor bands corresponding to proteins with apparent molecular masses of 150, 69, and 60 kDa. The presence of caldesmon-like protein(s) in amoebae was revealed as well in single cells after their fixation, staining with the same antibodies, and recording their total fluorescence in a confocal laser scanning microscope. Proteins recognized by the antibodies bind to filamentous actin. This was established by a cosedimentation assay in cell homogenates and by colocalization of the caldesmon-related immunofluorescence with the fluorescence of filamentous actin stained with rhodamine-labelled phalloidin, demonstrated in optical sections of single cells in a confocal microscope. Caldesmon is colocalized with filamentous actin in the withdrawn cell regions where the cortical actomyosin network contracts and actin is depolymerized, in the frontal zone where actin is polymerized again and the cortical cytoskeleton is reconstructed, inside the nucleus and in the perinuclear cytoskeleton, and probably at the cell-to-substratum adhesion sites. The regulatory role of caldesmon in these functionally different regions of locomoting amoebae is discussed.
|
10.1007/s00709-003-0002-x
|
pubmed_624_1386
|
A 27-year-old black male with secondary syphilis and cholestatic jaundice is presented. The liver biopsy was believed to be most consistent with large bile duct obstruction, but both the ultrasound and endoscopic retrograde cholangiography were normal. Prior to treatment with penicillin, his serum was positive for antimitochondrial antibody. After treatment, the antibody was no longer detectable and the jaundice gradually resolved. The patient's pretreatment serum was, after further analysis, found to be positive for the antibody to the M1 antimitochondrial antigen subtype, which is identical to cardiolipin, the antigen in both the VDRL and Wasserman tests. A review of hepatic involvement in secondary syphilis is presented.
|
10.1007/BF01537283
|
pubmed_429_8371
|
In management of fluid and electrolyte problems in the emergency department several important principles are: (1) never completely trust the laboratory, (2) abnormalities should be treated at approximately the rate at which they developed, (3) correct only half the calculated deficit at a time and reevaluate the patient, (4) the highest priority in treatment is maintenance of intravascular volume and tissue perfusion. The osmolarity of fluid compartments as related to the fluid and electrolyte responses to stress and resultant fluid requirements for basic needs, current losses and deficits of fluid and electrolytes are discussed in depth. The characteristics of volume, sodium, potassium, chloride, bicarbonate, calcium and magnesium deficits and how to correct them are outlined.
|
10.1016/s0361-1124(76)80058-5
|
pubmed_1093_16660
|
Deposition of islet amyloid polypeptide (IAPP) as amyloid is a pathological hallmark of the islet in type 2 diabetes, which is toxic to β-cells. We previously showed that the enzyme neprilysin reduces islet amyloid deposition and thereby reduces β-cell apoptosis, by inhibiting fibril formation. Two other enzymes, matrix metalloproteinase (MMP)-2 and MMP-9, are extracellular gelatinases capable of degrading another amyloidogenic peptide, Aβ, the constituent of amyloid deposits in Alzheimer disease. We therefore investigated whether MMP-2 and MMP-9 play a role in reducing islet amyloid deposition. MMP-2 and MMP-9 mRNA were present in mouse islets but only MMP-9 activity was detectable. In an islet culture model where human IAPP (hIAPP) transgenic mouse islets develop amyloid but nontransgenic islets do not, a broad spectrum MMP inhibitor (GM6001) and an MMP-2/9 inhibitor increased amyloid formation and the resultant β-cell apoptosis. In contrast, a specific MMP-2 inhibitor had no effect on either amyloid deposition or β-cell apoptosis. Mass spectrometry demonstrated that MMP-9 degraded amyloidogenic hIAPP but not nonamyloidogenic mouse IAPP. Thus, MMP-9 constitutes an endogenous islet protease that limits islet amyloid deposition and its toxic effects via degradation of hIAPP. Because islet MMP-9 mRNA levels are decreased in type 2 diabetic subjects, islet MMP-9 activity may also be decreased in human type 2 diabetes, thereby contributing to increased islet amyloid deposition and β-cell loss. Approaches to increase islet MMP-9 activity could reduce or prevent amyloid deposition and its toxic effects in type 2 diabetes.
|
10.1074/jbc.M112.438457
|
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