index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_492_12056
|
Nitric oxide associated-1 (NOA1) is an evolutionarily conserved guanosine triphosphate (GTP) binding protein that localizes predominantly to mitochondria in mammalian cells. On the basis of bioinformatic analysis, we predicted its possible involvement in ribosomal biogenesis, although this had not been supported by any experimental evidence. Here we determine NOA1 function through generation of knockout mice and in vitro assays. NOA1-deficient mice exhibit midgestation lethality associated with a severe developmental defect of the embryo and trophoblast. Primary embryonic fibroblasts isolated from NOA1 knockout embryos show deficient mitochondrial protein synthesis and a global defect of oxidative phosphorylation (OXPHOS). Additionally, Noa1⁻/⁻ cells are impaired in staurosporine-induced apoptosis. The analysis of mitochondrial ribosomal subunits from Noa1⁻/⁻ cells by sucrose gradient centrifugation and Western blotting showed anomalous sedimentation, consistent with a defect in mitochondrial ribosome assembly. Furthermore, in vitro experiments revealed that intrinsic NOA1 GTPase activity was stimulated by bacterial ribosomal constituents. Taken together, our data show that NOA1 is required for mitochondrial protein synthesis, likely due to its yet unidentified role in mitoribosomal biogenesis. Thus, NOA1 is required for such basal mitochondrial functions as adenosine triphosphate (ATP) synthesis and apoptosis.
|
10.1091/mbc.E10-07-0643
|
pubmed_1030_15638
|
The current standard model of language production involves a sensorimotor dorsal stream connecting areas in the temporo-parietal junction with those in the inferior frontal gyrus and lateral premotor cortex. These regions have been linked to various aspects of word production such as phonological processing or articulatory programming, primarily through neuropsychological and functional imaging group studies. Most if not all the theoretical descriptions of this model imply that the same network should be identifiable across individual speakers. We tested this hypothesis by quantifying the variability of activation observed across individuals within each dorsal stream anatomical region. This estimate was based on electrical activity recorded directly from the cerebral cortex with millisecond accuracy in awake epileptic patients clinically implanted with intracerebral depth electrodes for pre-surgical diagnosis. Each region's activity was quantified using two different metrics-intra-cerebral evoked related potentials and high gamma activity-at the level of the group, the individual and the recording contact. The two metrics show simultaneous activation of parietal and frontal regions during a picture naming task, in line with models that posit interactive processing during word retrieval. They also reveal different levels of between-patient variability across brain regions, except in core auditory and motor regions. The independence and non-uniformity of cortical activity estimated through the two metrics push the current model towards sub-second and sub-region explorations focused on individualized language speech production. Several hypotheses are considered for this within-region heterogeneity.
|
10.1111/ejn.15807
|
pubmed_123_22923
|
Psychoanalysis is the search for and revelation, through interpretation and construction, of unknown, unconscious implications. But the question is raised: are the meanings being uncovered or are we providing them? This basic realist-idealist contraposition is at the heart of current discussions about the hermeneutic trend in psychoanalysis. Ricoeur's often misrepresented contribution serves as a basis for understanding Freud's method as forming a 'hermeneutic constellation', evolving within a 'moderate', in contrast to a 'radical-idealist' hermeneutic psychoanalysis. Ahumada's recent charge of 'verbal creationism' and Laplanche's re-framing of interpretation between determinism and hermeneutics are discussed in order to specify the more moderate position taken in this paper. It is argued that although they are correct in pointing to potential excesses, both authors misrepresent the hermeneuticist trend as unnecessarily idealistic. A case example from a session illustrates the discussion.
|
pubmed_123_22923
|
pubmed_1050_17295
|
Researchers have long been presented with the challenge imposed by the role of genetic heterogeneity in drug response. For many years, Pharmacogenomics and pharmacomicrobiomics has been investigating the influence of an individual's genetic background to drug response and disposition. More recently, the human gut microbiome has proven to play a crucial role in the way patients respond to different therapeutic drugs and it has been shown that by understanding the composition of the human microbiome, we can improve the drug efficacy and effectively identify drug targets. However, our knowledge on the effect of host genetics on specific gut microbes related to variation in drug metabolizing enzymes, the drug remains limited and therefore limits the application of joint host-microbiome genome-wide association studies. In this paper, we provide a historical overview of the complex interactions between the host, human microbiome and drugs. While discussing applications, challenges and opportunities of these studies, we draw attention to the critical need for inclusion of diverse populations and the development of an innovative and combined pharmacogenomics and pharmacomicrobiomics approach, that may provide an important basis in personalized medicine.
|
10.1093/bib/bbaa292
|
pubmed_216_5750
|
Exposure to environmentally relevant levels of lead (Pb(2+)) during early life produces deficits in hippocampal synaptic plasticity in the form of long-term potentiation (LTP) and spatial learning in young adult rats [Nihei MK, Desmond NL, McGlothan JL, Kuhlmann AC, Guilarte TR (2000) N-methyl-D-aspartate receptor subunit changes are associated with lead-induced deficits of long-term potentiation and spatial learning. Neuroscience 99:233-242; Guilarte TR, Toscano CD, McGlothan JL, Weaver SA (2003) Environmental enrichment reverses cognitive and molecular deficits induced by developmental lead exposure. Ann Neurol 53:50-56]. Other evidence suggests that the performance of rats in the Morris water maze spatial learning tasks is associated with the level of granule cell neurogenesis in the dentate gyrus (DG) [Drapeau E, Mayo W, Aurousseau C, Le Moal M, Piazza P-V, Abrous DN (2003) Spatial memory performance of aged rats in the water maze predicts level of hippocampal neurogenesis. Proc Natl Acad Sci U S A 100:14385-14390]. In this study, we examined whether continuous exposure to environmentally relevant levels of Pb(2+) during early life altered granule cell neurogenesis and morphology in the rat hippocampus. Control and Pb(2+)-exposed rats received bromodeoxyuridine (BrdU) injections (100 mg/kg; i.p.) for five consecutive days starting at postnatal day 45 and were killed either 1 day or 4 weeks after the last injection. The total number of newborn cells in the DG of Pb(2+)-exposed rats was significantly decreased (13%; P<0.001) 1 day after BrdU injections relative to controls. Further, the survival of newborn cells in Pb(2+)-exposed rats was significantly decreased by 22.7% (P<0.001) relative to control animals. Co-localization of BrdU with neuronal or astrocytic markers did not reveal a significant effect of Pb(2+) exposure on cellular fate. In Pb(2+)-exposed rats, immature granule cells immunolabeled with doublecortin (DCX) displayed aberrant dendritic morphology. That is, the overall length-density of the DCX-positive apical dendrites in the outer portion of the DG molecular layer was significantly reduced up to 36% in the suprapyramidal blade only. We also found that the area of Timm's-positive staining representative of the mossy fibers terminal fields in the CA3 stratum oriens (SO) was reduced by 26% in Pb(2+)-exposed rats. These findings demonstrate that exposure to environmentally relevant levels of Pb(2+) during early life alters granule cell neurogenesis and morphology in the rat hippocampus. They provide a cellular and morphological basis for the deficits in synaptic plasticity and spatial learning documented in Pb(2+)-exposed animals.
|
10.1016/j.neuroscience.2006.12.040
|
pubmed_864_11722
|
Robust well-defined tubular structural materials based on macro- and mesoporous nitridated titania (TMMN-TiO2) were obtained by a simple solution-phase approach in ammonia solution. In this approach, the gas bubbles derived from ammonia solution play the role of templates that direct the ordered growth in the form of a tubular structure. The results demonstrated that the volume ratio of ammonia to water can be favorable for the formation of TMMN-TiO2, which are characterized by FESEM and FTIR. What is more, ammonia was used not only as the template but also as the nitrogen source. Interestingly, it was found that the TiO2 nanocrystals building blocks were assembled into an interconnected mesoporous skeleton and built in ordered tubular macroporous channels. This unique architecture provides many important features that are required for high-performance anodes, such as fast ion transport, high conductivity, and structure stability, thus enabling an electrode with outstanding lithium storage performance. For example, such an electrode delivers 112 mA h g(-1) capacity at 5100 mA g(-1) (30 C) even after 1200 cycles.
|
10.1039/c3dt50575h
|
pubmed_722_13615
|
Several recent studies suggest functional and molecular interactions between striatal adenosine A(2A) and cannabinoid CB(1) receptors. Here, we demonstrate that A(2A) receptors selectively modulate reinforcing effects of cannabinoids. We studied effects of A(2A) receptor blockade on the reinforcing effects of delta-9-tetrahydrocannabinol (THC) and the endogenous CB(1) receptor ligand anandamide under a fixed-ratio schedule of intravenous drug injection in squirrel monkeys. A low dose of the selective adenosine A(2A) receptor antagonist MSX-3 (1 mg/kg) caused downward shifts of THC and anandamide dose-response curves. In contrast, a higher dose of MSX-3 (3 mg/kg) shifted THC and anandamide dose-response curves to the left. MSX-3 did not modify cocaine or food pellet self-administration. Also, MSX-3 neither promoted reinstatement of extinguished drug-seeking behavior nor altered reinstatement of drug-seeking behavior by non-contingent priming injections of THC. Finally, using in vivo microdialysis in freely-moving rats, a behaviorally active dose of MSX-3 significantly counteracted THC-induced, but not cocaine-induced, increases in extracellular dopamine levels in the nucleus accumbens shell. The significant and selective results obtained with the lower dose of MSX-3 suggest that adenosine A(2A) antagonists acting preferentially at presynaptic A(2A) receptors might selectively reduce reinforcing effects of cannabinoids that lead to their abuse. However, the appearance of potentiating rather than suppressing effects on cannabinoid reinforcement at the higher dose of MSX-3 would likely preclude the use of such a compound as a medication for cannabis abuse. Adenosine A(2A) antagonists with more selectivity for presynaptic versus postsynaptic receptors could be potential medications for treatment of cannabis abuse.
|
10.1111/j.1369-1600.2010.00258.x
|
pubmed_1115_3517
|
BACKGROUND AND PURPOSE
integrated care pathways are often implemented to guide acute stroke therapy and improve organisation of care, but there is not sufficient evidence to support their routine use. We sought to evaluate the effects of introducing an integrated care pathway for acute stroke.
METHODS
we performed a before-and-after study. The 'before' (control) group comprised 154 consecutive stroke patients admitted to the acute stroke unit over a 9-month period. The 'after' (intervention) group comprised 197 consecutive patients admitted to the same unit over a 9-month period in the year after the introduction of the integrated care pathway. Effectiveness was assessed with a variety of measures: quality of documentation; process of care; occurrence of complications; death and discharge destination. Results were adjusted for case mix using a validated model.
RESULTS
the baseline characteristics of the two groups were similar, although there were more total anterior circulation strokes (29% versus 18%, P = 0.005) and fewer partial anterior circulation strokes (30% versus 42% P = 0.04) in the intervention group. In the intervention group, we found that urinary tract infections were significantly less frequent (OR 0.37, CI 0.15-10.91) and the quality of several aspects of care (e.g. CT scanning < 48 hours) and documentation were significantly better. However, there were no significant differences in deaths, discharge destination, or length of stay between the two groups.
CONCLUSION
this before-and-after study has provided further evidence that introducing an integrated care pathway for acute stroke may improve the quality of documentation and process of care, and reduce the risk of certain post-stroke complications.
|
10.1093/ageing/afh104
|
pubmed_341_20257
|
BACKGROUND
Chronic total occlusions (CTOs) are present in more than one third of older patients with myocardial ischemia, but controversy remains about the best therapeutic approach.
AIMS
To compare long-term survival after CTO revascularization (percutaneous coronary intervention [PCI] or coronary artery bypass graft [CABG]) versus medical treatment (MT) alone in patients aged 75 and older.
METHODS AND RESULTS
A total of 1,252 consecutive patients with at least one CTO were identified from 2010 to 2014 in our center. Patients were stratified by age (<75 years vs. ≥75 years) in the present analysis. All-cause and cardiac mortality were assessed at a median follow-up of 3.5 years. In the older subgroup (26%), patients were more likely to be treated with MT alone (71% vs. 43% of younger patients; p < 0.001). Patients undergoing revascularization were younger and had higher left ventricular ejection fraction (LVEF) and lower age, creatinine, ejection fraction (ACEF) score (age/LVEF +1 if creatinine >2.0 mg/dL), compared to the MT group (p < 0.05). As compared to MT, revascularization predicted lower rates of cardiac mortality and all-cause mortality in older patients, both in the subgroups treated with CABG (hazard ratio [HR] 0.35, 95% confidence interval [CI] 0.17-0.71; HR 0.39, 95%CI 0.18-0.81) and PCI (HR 0.57, 95%CI 0.33-0.98; HR 0.59, 95%CI 0.28-1.2). No differences in mortality were observed according to type of revascularization procedure.
CONCLUSIONS
Among patients aged at least 75 years with a CTO, revascularization (PCI or CABG) rather than MT alone may portend a better outcome in terms of all-cause and cardiac mortality.
|
10.1002/ccd.28163
|
pubmed_432_10026
|
Although anemia is a frequently observed complication of phlebotomies for laboratory tests in neonates, this problem has received little attention in adult populations. We analyzed the phlebotomy records of 100 hospitalized patients and found that 50 patients who spent all of their hospitalization in general wards had blood samples drawn an average of 1.1 times a day. A mean volume of 12.4 ml a day was drawn, and the total volume drawn during their entire hospitalization was 175.0 ml. In contrast, 50 patients who spent part or all of their hospitalization in an intensive care unit were phlebotomized a mean of 3.4 times a day, for a mean volume of 41.5 ml of blood drawn a day and a total volume of 762.2 ml. Patients in the intensive care unit who had arterial lines had more blood drawn (944.0 ml), more often (4.0 times a day), than patients in the intensive care unit who did not have such lines (300.9 ml; 1.9 times a day). Of 36 patients who received transfusions, 17 (47 percent) had large losses from phlebotomy (greater than 180 ml of red cells) that contributed to their transfusion requirements. We propose the use of sample tubes of the size used in pediatrics, batching of requests for laboratory tests, and review of the cumulative volume of blood removed from individual patients as approaches to reducing blood loss from phlebotomy.
|
10.1056/NEJM198605083141906
|
pubmed_463_24792
|
PURPOSE
A transportation technique for cell sheets is necessary to standardize regenerative medicine. The aim of this article is to develop and evaluate a new transportation technique for cell sheets.
MATERIAL AND METHODS
We developed a transportation container with three basic functions: the maintenance of interior temperature, air pressure, and sterility. The interior temperature and air pressure were monitored by a recorder. Human oral mucosal epithelial cells obtained from two healthy volunteers were cultured on temperature-responsive culture dishes. The epithelial cell sheets were transported via an airplane between the Osaka University and Tohoku University using the developed cell transportation container. Histological and immunohistochemical analyses and flow cytometric analyses for cell viability and cell purity were performed for the cell sheets before and 12 h after transportation to assess the influence of transportation on the cell sheets. Sterility tests and screening for endotoxin and mycoplasma in the cell sheets were performed before and after transportation.
RESULTS
During transportation via an airplane, the temperature inside the container was maintained above 32°C, and the changes in air pressure remained within 10 hPa. The cell sheets were well stratified and successfully harvested before and after transportation. The expression patterns of keratin 3/76, p63, and MUC16 were equivalent before and after transportation. However, the expression of ZO-1 in the cell sheet after transportation was slightly weaker than that before transportation. The cell viability was 72.0% before transportation and 77.3% after transportation. The epithelial purity was 94.6% before transportation and 87.9% after transportation. Sterility tests and screening for endotoxin and mycoplasma were negative for all cell sheets.
CONCLUSION
The newly developed transportation technique for air travel is essential technology for regenerative medicine and promotes the standardization and spread of regenerative therapies.
|
10.1089/ten.TEC.2013.0266
|
pubmed_106_2895
|
The dynamics of the spread of HIV infection in Russia and the CIS countries is presented. The relationship between the spread of HIV infection and an increase in the number of injection drug users is substantiated. The factors inhibiting the spread of the epidemic of HIV/AIDS in Russia and the CIS countries are analyzed with due regard to the world experience. Attention is paid to the development of the epidemic situation in HIV infection due to, similarly to Russia and to more than 100 countries of the world, drug addiction. The effectiveness of the activity of the Russian health service organs in controlling this epidemic is emphasized. The prospects of prophylactic measures for controlling HIV infection in Russia and the CIS countries are determined.
|
pubmed_106_2895
|
pubmed_638_2038
|
RNA-protein interactions are fundamental to gene expression. Thus, the molecular basis for the sequence dependence of protein-RNA recognition has been extensively studied experimentally. However, there have been very few computational studies of this problem, and no sustained attempt has been made towards using computational methods to predict or alter the sequence-specificity of these proteins. In the present study, we provide a distance-dependent statistical potential function derived from our previous work on protein-DNA interactions. This potential function discriminates native structures from decoys, successfully predicts the native sequences recognized by sequence-specific RNA-binding proteins, and recapitulates experimentally determined relative changes in binding energy due to mutations of individual amino acids at protein-RNA interfaces. Thus, this work demonstrates that statistical models allow the quantitative analysis of protein-RNA recognition based on their structure and can be applied to modeling protein-RNA interfaces for prediction and design purposes.
|
10.1111/j.1742-4658.2007.06155.x
|
pubmed_517_12327
|
Australian courts and tribunals allow claimants with pleural plaques to "piggy back" compensation claims for mental health problems. This article contends that Australia is open to an era of diagnosis fraud by psychologists similar to that which has been experienced in the United States with radiologists. The courts will continue to reflect Australia's "compensation culture" unless legislation squarely addresses the compensability of pleural plaques and clarifies when, if at all, the courts should allow mental health claims for asymptomatic "marker" conditions such as pleural plaques.
|
pubmed_517_12327
|
pubmed_257_8924
|
The intravenous infusion market is currently experiencing rapid growth. As a result, many new and varied therapies are being conducted in the hospital, outpatient, and home settings. One therapy that has been found to be safe and cost-effective to administer is I.V. IgG. This article will describe the contents of I.V. IgG as well as indications for use, product testing, dosage, effects, and adverse reactions.
|
pubmed_257_8924
|
pubmed_485_14289
|
Selection for rapid growth in the quail resulted in a changed growth pattern of the embryo and the extra-embryonic membranes (the yolk sac and allantois). The early part of the incubation period was characterized by a reduced embryo weight and a more rapid early development of the extra-embryonic membranes. These changes were followed by an increased growth rate of the embryo. The increased growth rate was apparently linked to the more rapid early development of the extra-embryonic membranes. Thus, the growth rate was most likely restricted by the capacity to absorb and utilize yolk. It also appears that at least part of the increase in growth rate was made possible by the change in the early embryonic growth pattern.
|
pubmed_485_14289
|
pubmed_621_11153
|
This review describes the current literature on the interaction between insulin-like growth factors, endocrine hormones, and branched-chain amino acids on muscle physiology in healthy young individuals and during select pathologic conditions. Emphasis is placed on the mechanism by which physical and hormonal signals are transduced at the cellular level to either grow or atrophy skeletal muscle. The key role of the mammalian target of rapamycin and its ability to respond to hypertrophic and atrophic signals informs our understanding how a combination of physical, nutritional, and pharmacologic therapies may be used in tandem to prevent or ameliorate reductions in muscle mass.
|
10.1016/j.ecl.2012.04.012
|
pubmed_503_341
|
Neelaredoxin, a small non-heme blue iron protein from the sulfate-reducing bacterium Desulfovibrio gigas [Chen, L., Sharma, P., LeGall, J., Mariano, A.M., Teixeira M. and Xavier, A.V. (1994) Eur. J. Biochem. 226, 613-618] is shown to be encoded by a polycistronic unit which contains two additional open reading frames (ORF-1 and ORF-2) coding for chemotaxis-like proteins. ORF-1 has domains highly homologous with those structurally and functionally important in methyl-accepting chemotaxis proteins, including two putative transmembrane helices, potential methylation sites and the interaction domain with CheW proteins. Interestingly, ORF-2 encodes a protein having homologies with CheW proteins. Neelaredoxin is also shown to have significant superoxide dismutase activity (1200 U. mg-1), making it a novel type of iron superoxide dismutase. Analysis of genomic data shows that neelaredoxin-like putative polypeptides are present in strict anaerobic archaea, suggesting that this is a primordial superoxide dismutase. The three proteins encoded in this operon may be involved in the oxygen-sensing mechanisms of this anaerobic bacterium, indicating a possible transcriptional mechanism to sense and respond to potential stress agents.
|
10.1046/j.1432-1327.1999.00025.x
|
pubmed_222_15077
|
The products of the alpha genes of herpes simplex virus 1, the infected cells proteins (ICP) 0, 4, 22, and 27 perform regulatory functions, are nucleotidylylated, and share the signaling or recognition sequence (RR(A/T)(P/S)R) that correctly predicted the nucleotidylylation of viral proteins encoded by UL21, UL31, UL49, and UL47 genes expressed later in infection. Extracts from uninfected HeLa cells or casein kinase II purified from sea star nucleotidylylated the ICP22 moiety of a glutathione S-transferase-ICP22 (GST22P) fusion protein with [alpha-32P]ATP or [2-3H]ATP. We report that: (i) Purified HeLa cell casein kinase II specifically labeled a glutathione S-transferase fusion protein containing the amino-terminal 151 amino acids of ICP22 with [2-3H]ATP. (ii) Nucleotidylylation of GST-ICP22 by purified enzyme exhibited positive cooperativity (Hill coefficient of 2 and a K' of 3.7 microM) and a Km = 37.7 microM for ATP. (iii) Nucleotidylylation was inhibited by heparin, casein, or ATPalphaS but not by ATPgammaS. (iv) Mutation of the signaling sequence from RRAPRR to LKAPEK abolished nucleotidylylation. We conclude that nucleotidylylation of proteins by casein kinase II requires the presence of the signaling or recognition sequence, involves the cleavage of the phosphodiester bond between the alpha and beta phosphate, and need not be preceded by phosphorylation.
|
10.1074/jbc.272.40.25394
|
pubmed_900_16445
|
BACKGROUND
Certain hospitals play a central role in ensuring Medicaid-insured patients' access to care. Their quality of care is critical to evaluate.
OBJECTIVE
To determine whether hospitals for which Medicaid patients represent a high percentage of total discharges provide a different quality of care than other hospitals.
RESEARCH DESIGN
Cross-sectional analysis.
SUBJECTS
Acute care hospitals participating in the first Hospital Compare public report (released November 2004) and the 2004 American Hospital Association hospital survey.
MEASURES
Hospitals serving 1 standard deviation above the national mean percentage of Medicaid patients were designated high Medicaid hospitals. Performance was assessed using percent compliance with 10 processes of care for 3 conditions: myocardial infarction, congestive heart failure, and community-acquired pneumonia.
RESULTS
Among the 2874 nonteaching hospitals, high Medicaid hospitals had lower adherence (P < 0.01) than other nonteaching hospitals on all 10 indicators. Of particular clinical importance, high Medicaid nonteaching hospitals less frequently prescribed beta-blockers (83% vs. 90%%, P < 0.0001) and aspirin at discharge in myocardial infarction (85% vs. 91%%, P < 0.0001), and administered antibiotics on time in CAP (68% vs. 75%, P < 0.0001). Among teaching institutions, there were few differences between high Medicaid and other hospitals.
CONCLUSIONS
Among hospitals publicly reporting on the Hospital Compare Web site, nonteaching hospitals treating a high percentage of Medicaid patients had lower adherence to quality indicators than other nonteaching hospitals on 10 indicators. Further research is needed to determine what factors contribute to differences in reported quality.
|
10.1097/MLR.0b013e318041f723
|
pubmed_769_24374
|
BACKGROUD
Malnutrition has been confirmed to play an important role in colorectal cancer (CRC) progression via the gut microenvironment. However, the characteristics of the gut microbiota or its potential biological mechanism in CRC remain inconclusive.
METHODS
In this work, Patient-Generated Subjective Global Assessment (PG-SGA) tool and 16sRNA sequencing were prepared to detect the variation in gut microbiota and the association between nutrition status and gut microbiota. RDA/CCA analysis was used to evaluate the relationship between faecal microbiota from malnourished CRC and clinical nutrition indicators. To investigate the mechanism of the gut microbiota in CRC, faecal samples from malnourished CRC patients were transplanted into C57BL/6J and DSS/AOM mouse models. Moreover, FACS and IHC were prepared to detect the infiltration of B cells and macrophages. qPCR and Elisa assays were performed to explore the expression of cytokines.
RESULT
We found dramatic variation in the faecal microbiota among patients with different nutritional statuses, discovering that specific microbiota species, namely, Atopobium vaginae, Selenomonas sputigena and Faecalibacterium prausnitzii, may be considered diagnostic biomarkers in malnutrition and indicate poor prognosis. High expression level of A. vaginae in CRC tissues revealed the poorer overall survival compared with low expression level (Mean survival: 23.0 months vs 29.0 months). Faecal from malnourished colorectal cancer were found to be protumorigenic. More importantly, our evidence suggests that after faecal microbiota transplantation, B cells and macrophages are recruited to activate specific tumour immunity in CRC. Depletion of B cells significantly suppressed faecal microbiota-induced M2b polarization as well as the protumorigenic activity of tumour-associated macrophages in vivo.
CONCLUSION
Faecal microbiota in CRC under malnutrition conditions exhibits specific characteristics that accelerate CRC progression and regulate B cells and macrophages. The use of specific faecal microbial species could be a feasible approach for identifying the malnutrition status of patients and demonstrating the poor prognosis of CRC.
|
10.1016/j.clnu.2022.01.001
|
pubmed_815_1409
|
Passively released or actively secreted elastase from neutrophils has been linked to the pathologic processes of a variety of inflammatory diseases, including idiopathic pulmonary fibrosis, rheumatoid arthritis, adult respiratory distress syndrome, and cystic fibrosis. The serine proteinase has a broad substrate specificity and may attack a number of host proteins outside of the neutrophil, including lung elastin and fibronectin. Such a proteolysis may change the normal surrounding tissue and the protein pattern of an inflammatory focus. Additionally, it acts as a potent secretagogue in minute amounts. The reason that neutrophil elastase is present in considerable concentrations outside of the neutrophil during chronic inflammation and that the major endogenous serine proteinase inhibitor for neutrophil elastase, alpha 1-proteinase inhibitor, is easily inactivated by proteolytic and oxidative attack is unclear. Released neutrophil elastase may also be involved in regulating chronic inflammation. In a feedback mechanism, neutrophil elastase inhibits neutrophil stimulation and concomitant elastase release by cleavage of immunoglobulins, complement components, and complement receptor type 1 on neutrophils. Besides a number of harmful effects of neutrophil elastase in inflammation, the latter mechanism, although considerably impairing phagocytosis, may be beneficial particularly in the light of persistent bacterial pathogens in the human lung affected by cystic fibrosis.
|
10.1164/ajrccm/150.6_Pt_2.S114
|
pubmed_163_19109
|
Ferroptosis is an emerging cancer suppression strategy. However, how to select cancer patients for treating with ferroptosis inducers remains challenging. Here, we develop photochemical activation of membrane lipid peroxidation (PALP), which uses targeted lasers to induce localized polyunsaturated fatty acyl (PUFA)-lipid peroxidation for reporting ferroptosis sensitivity in cells and tissues. PALP captured by BODIPY-C11 can be suppressed by lipophilic antioxidants and iron chelation, and is dependent on PUFA-lipid levels. Moreover, we develop PALPv2, for studying lipid peroxidation on selected membranes along the z axis in live cells using two-photon microscopes. Using PALPv1, we detect PUFA-lipids in multiple tissues, and validate a PUFA-phospholipid reduction during muscle aging as previously reported. Patterns of PALPv1 signals across multiple cancer cell types in vitro and in vivo are concordant with their ferroptosis susceptibility and PUFA-phospholipid levels. We envision that PALP will enable rapid stratification of ferroptosis sensitivity in cancer patients and facilitate PUFA-lipid research.
|
10.1016/j.chembiol.2021.11.001
|
pubmed_189_18806
|
1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can activate nucleotide-binding oligomerization domain, leucine rich repeat and pyrin domain containing 3 (NLRP3) inflammasome in Parkinson's disease (PD) mice, while 1-methyl-4-phenyl- 1, 2, 3, 6-tetrahydropyridinium ion (MPP+), the toxic metabolite of MPTP was not enough to achieve it in vitro. We hypothesized that the accumulation of Alpha-synuclein (α-syn) caused by MPP+ can be a priming signal of MPP+ mediated NLRP3 activation, and its mechanism was explored. This study demonstrated the α-syn can mediate NLRP3 priming in BV2 cells. It can also act on ERK-p67phox-nicotinamide adenine dinucleotide phosphate oxidase 2 (Nox2) axis and induce mitochondrial damage. The co-treatment of α-syn/MPP+ can cause aberrant mitochondrial homeostasis to diminish the concentration of the coenzyme nicotinamide adenine dinucleotide (NAD+), mediate accumulation of ac-α-tubulin, and induce mitochondrial perinuclear aggregation, navigating the co-localization of NLRP3 and apoptosis-associated speck-like protein containing a CARD domain (ASC). This study suggested that α-syn/MPP+ mediated NLRP3 inflammasome activation through microtubule-driven mitochondrial perinuclear transport.
|
10.1016/j.bbrc.2022.01.047
|
pubmed_269_15741
|
Lung cancer is the most common cause of cancer mortality worldwide, and non-small cell lung cancer (NSCLC) represents 80% of lung cancer subtypes. Patients with localized non-small cell lung cancer may be considered for upfront surgical treatment. However, the overall 5-year survival rate is 59%. To improve survival, adjuvant chemotherapy (ACT) was largely explored and showed an overall benefit of survival at 5 years < 7%. The evaluation of recurrence risk and subsequent need for ACT is only based on tumor stage (TNM classification); however, more than 25% of patients with stage IA/B tumors will relapse. Recently, adjuvant targeted therapy has been approved for EGFR-mutated resected NSCLC and trials are evaluating other targeted therapies and immunotherapies in adjuvant settings. Costs, treatment duration, emergence of resistant clones and side effects stress the need for a better selection of patients. The identification and validation of prognostic and theranostic markers to better stratify patients who could benefit from adjuvant therapies are needed. In this review, we report current validated clinical, pathological and molecular prognosis biomarkers that influence outcome in resected NSCLC, and we also describe molecular biomarkers under evaluation that could be available in daily practice to drive ACT in resected NSCLC.
|
10.3390/cancers14061400
|
pubmed_1086_17250
|
PURPOSE
To evaluate the incidence and risk factors of optic nerve atrophy after vitrectomy for diabetic retinopathy.
SUBJECTS AND METHODS
Clinical charts of 48 eyes of 40 patients who underwent vitrectomy for diabetic retinopathy were retrospectively reviewed. The relationship between postoperative optic nerve atrophy and patients' physical condition was statistically analyzed.
RESULT
Postoperative optic nerve atrophy, distinct from glaucomatous optic nerve atrophy, occurred in 5 eyes (10.4%). Its incidence was correlated with higher plasma creatinine concentration (p=0.001), proliferative diabetic retinopathy (p= 0.046), and retinal white vessel formation (p= 0.007). Maintenance of the best postoperative visual acuity was difficult in the patients with optic nerve atrophy.
CONCLUSION
Patients with proliferative diabetic retinopathy accompanied by renal dysfunction were at high risk of optic nerve atrophy after vitrectomy.
|
pubmed_1086_17250
|
pubmed_224_858
|
Corticothalamic projections from postcruciate area 4, located on the rostral part of the posterior sigmoid gyrus, were traced with the autoradiographic technique in the dog. Injections of tritiated amino acids were made into the lateral and medial parts of area 4 in regions corresponding to the forelimb and hindlimb areas of the primary motor cortex, respectively. In cases with injections placed in the lateral part of area 4, dense accumulations of label were present in the lateral part of the ventral anterior nucleus (VA), the central part of the ventral lateral nucleus (VL), the ventral half of the ventral posterior inferior nucleus (VPI), the caudal part of the central lateral nucleus (CL), and the centrum medianum (CM). Lighter label was also present in the lateral part of the cytoarchitectonically distinct VL region bordering the ventrobasal complex (VB), as well as in the ventrolateral part of the mediodorsal nucleus (MD), and in the lateral posterior nucleus (LP). In one case in which the injection site involved an adjacent part of area 3a, label was also seen ventrally in the medial division of the posterior nuclear group (POm). However, no detectable differences in VL, MD, or intralaminar labeling patterns were noted between this case and the four other cases with injections confined to the lateral part of area 4. In two cases with injections restricted to the medial part of area 4, dense label was present in the lateralmost part of VL, the ventral part of VPI, the caudal part of CL, and CM. Lighter label was also present in the VL region bordering the dorsolateral edge of VB and in LP. An additional case in which the injection also involved the rostral border of area 3a showed a similar pattern of thalamic labeling. Projections from both the lateral and medial parts of area 4 were also noted in the subthalamic nucleus, zona incerta, and nucleus of Darkschewitsch. These results suggest that corticothalamic projections from postcruciate area 4 to VL are organized topographically such that projections from the lateral part of area 4 project centrally within VL while those from the medial part of area 4 project more laterally. Both parts of area 4 also project topographically to a cytoarchitectonically distinct region of VL located immediately adjacent to VB. In contrast, the projections to the intralaminar nuclei do not appear to be topographically organized. The data from cases involving spread of the injection into area 3a suggest that projection patterns from area 3a to ventral, intralaminar, and medial thalamic nuclei are similar to those from area 4. However, it appears that at least the lateral part of area 3a also projects to POm.
|
10.1002/cne.902140103
|
pubmed_1065_2958
|
Based on textual researches, it has been confirmed that Fupenzi first appeared in Han Dynasty. Both Fupenzi and Penglei had the same origin, but split up during Jin Dynasty into two different breeds. Through ages Fupenzi has been taken as the fruits of the plant Rubus of Rosaceae species. Among them, R. idaeus, R. corchorifolius and R. coreanus have long been in use. R. chingii is the new breed of modern Fupenzi.
|
pubmed_1065_2958
|
pubmed_216_13610
|
OBJECTIVE
New-onset atrial fibrillation (AF) is the most frequent arrhythmic complication after coronary artery bypass grafting (CABG). Elderly patients who undergo this operation may have a different risk profile from the general population. The aim of this study was to identify risk factors for post-CABG AF in the elderly population.
METHODS
Between September 2001 and December 2005, 426 elderly patients (age >/= 65 years) underwent CABG at our center. Ninety-one developed post-CABG AF (AF group), and the other 335 (no-AF group) did not develop this complication. Multivariate analysis (odds ratio, +/- 95 % CI, P value) was used to identify independent clinical predictors of post-CABG AF.
RESULTS
The incidence of post-CABG AF in elderly patients during the study period was 21.4 %. Multivariate analysis identified age (OR 1.07, P < 0.009), age >/= 75 years (OR 1.77, P < 0.042), preoperative renal insufficiency (OR 5.09, P < 0.035), EuroSCORE (OR 1.18, P < 0.038), and cross-clamping time (OR 1.02, P < 0.012) as predictors of AF occurrence. The AF group had a significantly longer mean intensive care unit (ICU) stay (3.8 +/- 4.7 vs. 2.5 +/- 1.3 days for AF vs. no-AF; P = 0.0001), and a significantly higher proportion of patients with prolonged (>/= 6 days) ICU stays (8.8 % vs. 3.2 %, respectively; P = 0.033). Hospital mortality was 3.2 % in the no-AF group and 2.2 % in the AF group ( P = 0.74).
CONCLUSION
This study of elderly patients reveals some novel predictors of post-CABG AF, most notably preoperative renal insufficiency and EuroSCORE. It is important to identify risk factors for post-CABG AF in all patient groups as this knowledge might lead to better prevention of this problem and its potential consequences.
|
10.1055/s-2006-924711
|
pubmed_50_20018
|
Spontaneous pattern formation is an energetically favorable process and is shown in nature in molecular-scale assembly, biological association, and soft material organizations. The opposite regime, the artificial process, which is widely applied to the fabrication of semiconducting devices, such as lithographic techniques, requires enormous amounts of energy. Here, we propose a concept of tuning the properties of semiconducting MoS2 and WSe2 devices using the spontaneous pattern formation of adjacent molecular films. The film used was a 10 nm thick ultrathin film of a molecular electron dopant, which exhibited spontaneous pattern formation and dynamically transformed the morphology of tiny holes, a network, a maze, and dots on substrates, including SiO2, MoS2, and WSe2. These patterns were exhibited only when the film came in contact with water and was tuned with temperature and time. The specific lengths of the patterns were less than 200 nm, which is sufficiently smaller than the exfoliated ∼10 μm semiconducting MoS2 and WSe2 flakes. The properties of the field-effect devices of MoS2 and WSe2 were found to be modified according to the pattern formation process of the ultrathin molecular film on the device. This concept applies the spontaneous patterning phenomena shown in nature to the fabrication and optimization of electronic devices by using molecular films and their responses to the external environment.
|
10.1021/acsnano.8b04914
|
pubmed_437_23404
|
Chlamydiae are widespread Gram-negative pathogens of humans and animals. Salicylidene acylhydrazides, developed as inhibitors of type III secretion system (T3SS) in Yersinia spp., have an inhibitory effect on chlamydial infection. However, these inhibitors also have the capacity to chelate iron, and it is possible that their antichlamydial effects are caused by iron starvation. Therefore, we have explored the modification of salicylidene acylhydrazides with the goal to uncouple the antichlamydial effect from iron starvation. We discovered that benzylidene acylhydrazides, which cannot chelate iron, inhibit chlamydial growth. Biochemical and genetic analyses suggest that the derivative compounds inhibit chlamydiae through a T3SS-independent mechanism. Four single nucleotide polymorphisms were identified in a Chlamydia muridarum variant resistant to benzylidene acylhydrazides, but it may be necessary to segregate the mutations to differentiate their roles in the resistance phenotype. Benzylidene acylhydrazides are well tolerated by host cells and probiotic vaginal Lactobacillus species and are therefore of potential therapeutic value.
|
10.1128/JB.01677-14
|
pubmed_957_2884
|
The effects of land use on pollutant loads in sediments have been well documented; however, its influence on spatial variations in sediment toxicity remains largely unknown. In the present study, the toxicological effects of 17 sediments collected from Guangzhou waterways were evaluated using two benthic invertebrates (Chironomus dilutus and Hyalella azteca), along with quantification of heavy metals and arsenic in the sediments. The impacts of land-use configuration on sediment toxicity and occurrence of heavy metals and arsenic were analyzed. The sediments presented moderate lethality (<40 %) in the two test species and significantly altered their enzymatic activity, including the activities of oxidative stress biomarkers and acetylcholine esterase. Metals (Ag, Cd, Cr, Cu, Hg, Ni, Pb, and Zn) and arsenic were detected in all the sediments, with total concentrations ranging from 238 to 1019 mg/kg of dry weight. Both the toxicity and chemical results displayed spatially dependent patterns but were related to different land use types. Toxicity was most influenced by agricultural and aquacultural activities, while metal and arsenic pollution was most influenced by urban land areas. The present findings are expected to provide essential knowledge for developing strategies that reduce the chemical pollution and ecotoxicological risk in sediments.
|
10.1016/j.jhazmat.2022.129634
|
pubmed_702_23361
|
Increasing reported complications associated with permanent soft tissue fillers have led the national medical societies and governmental institutes in Europe to send out warnings regarding their use. Regulation and legislation for the introduction of new products and the use of existing products are necessary to guarantee patient safety.
|
10.1007/s00266-009-9369-1
|
pubmed_31_7926
|
INTRODUCTION
Anchorage can be reinforced in many ways. Due to the variety of anchorage concepts, only a few general conclusions can be drawn. Therefore, more research is needed to investigate specific concepts with specific indications. The objective of this trial was to compare the anchorage capacities of miniscrews and molar blocks.
METHODS
This randomized controlled trial was conducted on 2 parallel arms. The trial was conducted at the Public Dental Service Orthodontic Clinic in Gävle, Sweden. Participants were adolescents who needed orthodontic treatment with a fixed appliance, extraction of the maxillary first premolars, and anchorage reinforcement. In group A, miniscrews were used as direct anchorage during space closure. In group B, molar blocks were used as anchorage reinforcement during leveling and alignment and space closure. The primary outcome was loss of anchorage assessed as maxillary first molar movement. Random allocation was maintained with a simple randomization stratified by sex. The observer was blinded to the allocations during the measurements.
RESULTS
Forty participants each were randomized to groups A and B. Results were analyzed on an intention-to-treat basis, meaning that all participants, successful or not, were included in the analysis. Group A showed a mean anchorage loss of 1.2 mm during leveling and alignment. During space closure with miniscrews, no significant anchorage loss was found. Group B showed mean anchorage losses of 1.4 mm during leveling and alignment and 2.4 mm during space closure. No serious harms were detected. The first molar rotation, torque, and tipping showed different characteristics during the treatment phases.
CONCLUSIONS
Miniscrews can be recommended for anchorage reinforcement. Depending on the need for anchorage reinforcement, miniscrews can be inserted at the beginning of treatment or when space closure starts. Molar blocks cannot be recommended for anchorage reinforcement.
REGISTRATION
This trial was registered at www.clinicaltrials.gov (NCT02644811).
PROTOCOL
The protocol was published after trial commencement.
FUNDING
This trial received funding from the Center for Research and Development, Uppsala University/Region Gävleborg; Thuréus Foundation for the Promotion of Dental Science; and the Swedish Dental Associations Scientific Funds.
|
10.1016/j.ajodo.2018.07.011
|
pubmed_238_680
|
Background
Eosinophilic esophagitis (EoE) patients present with dysphagia and often suffer from esophageal food impaction (EFI). EFI can lead to life-threatening perforation, and requires emergent endoscopic intervention. The aim of this study is to evaluate the risk factors for EFI in EoE patients.
Methods
This is a retrospective study performed at a tertiary health-care system. Medical records and endoscopy images of EoE cases were reviewed. Clinical characteristics and outcomes including EFIs were documented. We used Zip-code median household income as a surrogate for patients' socioeconomic status.
Results
A total of 291 EoE cases were included, mean age was 42 years. Most patients (65%) had classic EoE endoscopic findings including linear furrows and/or concentric rings; however, a significant proportion (47%) had findings suggestive of gastroesophageal reflux disease (GERD), such as the presence of erosive-esophagitis, a hiatal hernia or Schatzki's ring. Forty-eight patients (16%) developed one or more esophageal food impaction (EFI). The risk of EFI was less likely in the absence of furrows and/or rings; odds ratio (OR) = 0.28, 95% CI (0.11, 0.72) [P = 0.008]. Females had less EFI risk; OR = 0.42, 95% CI (0.19, 0.95) [P = 0.04]. The type of medical insurance and socioeconomic status was not associated with EFI risk.
Conclusion
EFI risk is higher in EoE patients with esophageal furrows and/or rings and in men. Aggressive treatment might be required in this population. GERD and EoE can coexist in many patients. Further studies are required to examine the role of the socioeconomic status in EoE complications.
|
10.2147/CEG.S364994
|
pubmed_636_4307
|
BACKGROUND
Risk scoring system for thoracic surgery patients have not been widely used, as of recently. We tried to forge a risk scoring system that predicts the risk of postoperative complications in patients undergoing major thoracic surgery. We used a prolonged ICU stay as a representative of postoperative complications and tested various possible risk factors for its relation.
METHODS
Data from all patients who underwent major lung and esophageal cancer surgeries, between 2005 and 2007 in our hospital, were collected retrospectively (n = 858). Multiple logistic regression analysis was performed with various possible risk factors to build the risk scoring system for prolonged ICU stay (> 3 days).
RESULTS
A total of 9% of patients exhibited more than 3 days of ICU stay. Age, operation name, preoperative lung injury, no epidural analgesia, and predicted post operative forced expiratory volume in 1 second (ppoFEV1) were the risk factors for prolonged ICU stay, by multivariable analysis (P < 0.05). Risk score, p was derived from the formula: logit(p/[1-p]) = -5.39 + 0.06 × age + 1.12 × operation name(2) + 1.52 × operation name(3) + 1.32 × operation name(4) + 1.56 × operation name(5) + 1.30 × preoperative lung injury + 0.72 × no epidural analgesia - 0.02 × ppoFEV1 [Age in years, operation name(2): pneumonectomy, operation name(3): esophageal cancer operation, operation name(4): completion pneumonectomy, operation name(5): extended operation, preoperative lung injury(+), epidural analgesia(-), ppoFEV1 in %].
CONCLUSIONS
Age, operation name, preoperative lung injury, epidural analgesia, and ppoFEV1 can predict postoperative morbidity in thoracic surgery patients.
|
10.4097/kjae.2012.63.6.527
|
pubmed_369_3049
|
OBJECTIVES
To establish and validate prediction equations by using body weight to predict legs, trunk, and whole-body fat-free mass (FFM) in men with chronic complete spinal cord injury (SCI).
DESIGN
Cross-sectional design.
SETTING
Research setting in a large medical center.
PARTICIPANTS
Individuals with SCI (N=63) divided into prediction (n=42) and cross-validation (n=21) groups.
INTERVENTION
Not applicable.
MAIN OUTCOME MEASURE
Whole-body FFM and regional FFM were determined by using dual-energy x-ray absorptiometry. Body weight was measured by using a wheelchair weighing scale after subtracting the weight of the chair.
RESULTS
Body weight predicted legs FFM (legs FFM=.09×body weight+6.1; R(2)=.25, standard error of the estimate [SEE]=3.1kg, P<.01), trunk FFM (trunk FFM=.21×body weight+8.6; R(2)=.56, SEE=3.6kg, P<.0001), and whole-body FFM (whole-body FFM=.288×body weight+26.3; R(2)=.53, SEE=5.3kg, P<.0001). The whole-body FFM(predicted) (FFM predicted from the derived equations) shared 86% of the variance in whole-body FFM(measured) (FFM measured using dual-energy x-ray absorptiometry scan) (R(2)=.86, SEE=1.8kg, P<.0001), 69% of trunk FFM(measured), and 66% of legs FFM(measured). The trunk FFM(predicted) shared 69% of the variance in trunk FFM(measured) (R(2)=.69, SEE=2.7kg, P<.0001), and legs FFM(predicted) shared 67% of the variance in legs FFM(measured) (R(2)=.67, SEE=2.8kg, P<.0001). Values of FFM did not differ between the prediction and validation groups.
CONCLUSIONS
Body weight can be used to predict whole-body FFM and regional FFM. The predicted whole-body FFM improved the prediction of trunk FFM and legs FFM.
|
10.1016/j.apmr.2012.02.027
|
pubmed_297_9390
|
Five chromone glycosides were isolated from the water-soluble portions of 70% EtOH extract of the roots of Saposhnikovia divaricata, including two new chromone glycosides 1 and 2. The structures of the chromone glycosides were identified as (3'S)-3'-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosylhamaudol (1), (2'S)-4'-O-β-d-apiofuranosyl-(1 → 6)-β-d-glucopyranosylvisamminol (2), 3'-O-glucopyranosylhamaudol (3), 4'-O-β-d-glucopyranosylvisamminol (4), and 4'-O-β-d-glucopyranosyl-5-O-methylvisamminol (5) on the basis of extensive spectroscopic methods, and the absolute configurations of the new compounds were elucidated by the electronic circular dichroism (ECD) calculation and acid hydrolysis. The cytotoxic activities of the glycosides 1 - 5 against three human cancer cell lines (PC-3, SK-OV-3, and H460) were evaluated. The result showed that compounds 1 - 5 had weak cytotoxic activities against the human cancer cell lines with IC50 values in the range of 48.54 ± 0.80 - 94.25 ± 1.45 μm.
|
10.1002/cbdv.201800253
|
pubmed_979_1261
|
BACKGROUND
This study was conducted to explore the psychologic morbidity of women recalled for diagnostic assessment during population-based mammographic screening.
METHODS
This study prospectively attempted to measure physical, social, and emotional well-being by the administration of a questionnaire before screening, at the time of recall; and 1 month later to women recalled and matched women with those not recalled.
RESULTS
Of the 224 women who were recalled for further diagnostic assessment and their matches, complete follow-up was obtained on 182 pairs (81.3%). In contrast to those women not recalled, recalled women exhibited increased levels of concern at the time of recall. These levels had not decreased to the initial level after 1 month, even though breast carcinoma was not diagnosed. Similar negative short term effects also were evident in the areas of physical well-being, social functioning, and anxiety and insomnia levels, although these were not sustained.
CONCLUSIONS
Women with normal results after mass mammographic breast screening experienced no increase in psychologic distress and a decrease in their concern regarding breast carcinoma. However, those women who were recalled to follow-up after abnormal findings experienced an increase in their level of concern regarding breast carcinoma and this concern was sustained, as determined by repeat questionnaire, 1 month after a negative result had been determined.
|
10.1002/(sici)1097-0142(19990301)85:5<1114::aid-cncr15>3.0.co;2-y
|
pubmed_560_3255
|
Cardiac involvement in Duchenne muscular dystrophy is asymptomatic until function is severely affected. Little is known about its evolution, and few animal models are available to study potential treatments. We therefore examined cardiac function and pathology in mdx/utrn(-/-) dystrophin/utrophin-deficient mice. Decreased left ventricular fractional shortening and ejection fraction, as well as increased end-diastolic volume, left ventricle dilation, and thinning of the ventricular wall and septum develop by 15weeks. Fibrosis is also detected in the outer region of both ventricle walls and the septum and ultrastructure analysis revealed abnormalities in mitochondrial organization, size, and shape. The functional changes observed are comparable to the evolution of dilated cardiomyopathy in Duchenne muscular dystrophy, indicating that mdx/utrn(-/-) dystrophin/utrophin-deficient mice are a possible phenotypic model for cardiomyopathy in Duchenne muscular dystrophy.
|
10.1016/j.nmd.2011.07.003
|
pubmed_298_24083
|
There are multiple definitions of stress. For this review, as a reference point, we will use the concept of acute emotional/psychosocial stress ("stress"). The presence of acute stress has been reported to have a significant effect on seizure control, with several studies showing patients with seizure disorders being able to predict with reasonable accuracy seizure occurrence within the following hours or days. However, neuroimaging investigations of the pathophysiological mechanisms underlying stress reactivity (e.g., hypothalamic-pituitary-adrenal (HPA) axis activation) in humans, in general, and in patients with seizure disorders, in particular, are scarce. The reasons for this are multiple and likely include difficulty with designing appropriate probes that test various aspects of stress response, obtaining approval for studies that induce stress in patients who are prone to having stress-induced seizures, difficulties with assessing the physiological response to stress inside the scanner (e.g., heart rate, respiratory rate, oxygenation, cortisol levels, and galvanic skin responses), participant identification, and choice of epilepsy syndrome for investigation. With the recent explosion of neuroimaging literature focusing on correlating stress of various types and levels with cortical activations in healthy and diseased populations, it is incumbent upon us to examine the available neuroimaging data in patients with seizure disorders in order to identify the existing gaps and the needs/directions for future investigations. This approach is consistent with the goals of several of the 2014 Benchmarks for Epilepsy Research for the National Institute of Neurological Disorders and Stroke and the American Epilepsy Society.
|
pubmed_298_24083
|
pubmed_861_8818
|
Nitrate (NO3-) and ammonium (NH4+) are the main inorganic nitrogen (N) sources absorbed by oilseed rape, a plant that exhibits genotypic differences in N efficiency. In our previous study, the biomass, N accumulation, and root architecture of two oilseed rape cultivars, Xiangyou 15 (high N efficiency, denoted "15") and 814 (low N efficiency, denoted "814"), were inhibited under NH4+ nutrition, though both cultivars grew normally under NO3- nutrition. To gain insight into the underlying molecular mechanisms, transcriptomic changes were investigated in the roots of 15 and 814 plants subjected to nitrogen-free (control, CK), NO3- (NT), and NH4+ (AT) treatments at the seedling stage. A total of 14,355 differentially expressed genes (DEGs) were identified. Among the enriched Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway categories of these DEGs, carbohydrate metabolism, lipid metabolism, protein metabolism, and cell wall biogenesis were inhibited by AT treatment. Interestingly, DEGs such as N transporters, genes involved in N assimilation and CESA genes related to cellulose synthase were also mostly downregulated in the AT treatment group. This downregulation of genes related to crucial metabolic pathways resulted in inhibition of oilseed rape growth after AT treatment.
|
10.3390/genes10050391
|
pubmed_291_24681
|
Neuro-electrophysiological studies on meditative breathing revealed its association with either a relaxed or an attentive state. The present study aimed to investigate whether the Shaolin Dan Tian Breathing (DTB) technique, which consists of the Passive and Active subtypes and can be considered as a relaxation exercise and Qigong, would induce both relaxed and attentive states. Twenty-two adults and 22 age-, gender- and education-matched controls received training on the Shaolin DTB (experimental group) and the progressive muscle relaxation respectively for one month. Eyes-closed resting EEG data before and immediately after each type of breathing were obtained individually at baseline and after one-month training. At baseline, the EEG changes after the Shaolin DTB between both groups were comparable. After one-month training, participants in the experimental, but not the control, group showed enhanced temporal alpha asymmetry (an index of relaxation and positive mood) after performing the Passive DTB for five minutes, and enhanced intra- and inter-hemispheric theta coherence (an index of attention and alertness) after performing the Active DTB. The present findings suggested a positive effect of the Shaolin DTB technique on enhancing human neural activity and connectivity, which may possibly enhance mood state and cognitive functions.
|
10.1155/2011/180704
|
pubmed_636_10344
|
INTRODUCTION.: The aim of this experimental study was to reduce the exothermic reaction during curing of the resins to cold. The significant exotherm generated by the reaction of polymerization of the resin curing involves many clinical complications including the high risk of necrosis against tooth. MATERIAL AND METHODS.: They were used four different types of self curing resins all based on methyl methacrylate, Jet Kit, Major Dentin, Dura Lay, Temporary Cold. The reaction of polymerization of the resins was done in Teflon pans and was monitored by a thermocouple which recorded the highest level reached by each temperature resin with and without additive. The polymerization reaction took place for each resin in the presence of an essential oil, the terpinolene, which acted as a "chain transfer" and different temperatures were recorded. RESULTS.: Resins Dura Lay and Jet kit showed a reduction of very high temperature in the presence of terpinolene, with a statistically significant difference compared to the same reaction without terpinolene Major resin dentin in the presence of the additive has reduced by 8.4°C peak temperature. Resin Temporary Cold has showed benefits with respect to peak temperature, but the reaction was much more 'consistent presence of the additive. DISCUSSION.: The system through which the chain transfer acts to lower the temperature of the reaction is that of chain transfer. Namely that interfere with the reaction of the polymer chains, by transferring these acrylic radicals are no longer active, ie, no longer able to bind to other monomer units, thus avoiding the excessive growth of macromolecules which are those that determine the temperature rise. This leads to the formation of more polymer chains with lower molecular weight.
|
pubmed_636_10344
|
pubmed_378_13761
|
In vertebrates, the paraxial mesoderm already exhibits a complex Hox gene pattern by the time that segmentation occurs and somites are formed. The anterior boundaries of the Hox genes are always maintained at the same somite number, suggesting coordination between somite formation and Hox expression. To study this interaction, we used morpholinos to knockdown either the somitogenesis gene X-Delta-2 or the complete Hox paralogous group 1 (PG1) in Xenopus laevis. When X-Delta-2 is knocked down, Hox genes from different paralogous groups are downregulated from the beginning of their expression at gastrula stages. This effect is not via the canonical Notch pathway, as it is independent of the Notch effector Su(H). We also reveal for the first time a clear role for Hox genes in somitogenesis, as loss of PG1 gene function results in the perturbation of somite formation and downregulation of the X-Delta-2 expression in the PSM. This effect on X-Delta-2 expression is also observed during neurula stages, before the somites are formed. These results show that somitogenesis and patterning of the anteroposterior axis are closely linked via a feedback loop involving Hox genes and X-Delta-2, suggesting the existence of a coordination mechanism between somite formation and anteroposterior patterning. Such a mechanism is likely to be functional during gastrulation, before the formation of the first pair of somites, as suggested by the early X-Delta-2 regulation of the Hox genes.
|
10.1016/j.mod.2006.03.001
|
pubmed_1118_18955
|
Cofactors are essential effectors of the transcription control machinery. How this functionally diverse group of factors is used in the genome remains elusive. A recent study by Neumayr, Haberle et al. sheds light on this question, showing that enhancers depend on defined combinations of cofactors for their activation.
|
10.1016/j.tibs.2022.07.008
|
pubmed_23_11579
|
Levosimendan, a pyridazinone-dinitrile derivative, is a calcium sensitiser with additional action on adenosine triphosphate (ATP)-sensitive potassium channels. It is used intravenously (IV) for the treatment of decompensated cardiac failure. At therapeutic doses, levosimendan exhibits enhanced contractility with no increase in oxygen demands. It also produces antistunning effects without increasing myocardial intracellular calcium concentrations or prolonging myocardial relaxation. Levosimendan also causes coronary and systemic vasodilation. In patients with decompensated congestive heart failure (CHF), IV levosimendan significantly reduced the incidence of worsening CHF or death. IV levosimendan significantly increased cardiac output or cardiac index and decreased filling pressure in the acute treatment of stable or decompensated CHF in large, double-blind, randomised trials and after cardiac surgery in smaller trials. Levosimendan is well tolerated, with the most common adverse events (headache, hypotension, nausea) being secondary to vasodilation. It has not been shown to be arrhythmogenic. Levosimendan has shown no clinically important pharmacokinetic interactions with captopril, felodipine, beta-blockers, digoxin, warfarin, isosorbide-5-mononitrate, carvedilol, alcohol (ethanol) or itraconazole.
|
10.2165/00003495-200161050-00006
|
pubmed_659_11250
|
Background
To assess (I) the left atrial (LA) size, function and (II) the impact of excess weight on the LA and left ventricular (LV) performance in Turner syndrome (TS) patients.
Methods
Twenty-five TS patients without congenital heart disease (CHD) and 19 healthy, age-matched controls underwent three-dimensional echocardiography (3DE) for LA volume measurements and two-dimensional speckle tracking echocardiography (2DSTE) for LA strain measurements. LV performance was measured through LV Tei-index, indexed isovolumetric contraction (ICT/√RR interval), indexed relaxation (IVRT/√RR interval) and indexed filling time (FT/√RR interval).
Results
Compared to healthy controls, normal-weight TS patients (n=16) displayed significantly increased heart rate (92.88±16.66 vs. 76.53±15.65 bpm; P=0.005), reduced indexed LV filling time (11.67±2.55 vs. 15.16±5.07; P=0.018), reduced 3D maximum LA volume at LV end systole/BSA (16.74±5.00 vs. 19.89±4.32 mL/m2; P=0.05), reduced 3D LA total emptying volume/BSA [10.04 (5.05/18.46) vs. 13.11 (7.69/18.46) mL/m2; P=0.001] and reduced 3D LA active emptying volume/BSA [2.61 (0.1/3.82) vs. 3.44 (1.64/6.37) mL/m2; P=0.006]. Compared to normal-weight TS patients, overweight/obese TS patients (n=9) showed impaired LV Tei-index [0.38 (0.26/0.55) vs. 0.27 (0.07/0.41); P=0.009], prolonged indexed IVRT (2.04±0.72 vs. 1.30±0.64; P=0.015), prolonged indexed ICT [1.96 (1.57/2.73) vs. 1.29 (0.35/2.69); P=0.009] and increased 3D LA active emptying volume/BSA (3.38±1.21 vs. 2.29±1.07 mL/m2; P=0.032).
Conclusions
Normal-weight TS patients with increased heart rate and reduced LV filling time display subtle LV diastolic dysfunction in the form of reduced LA reservoir and pump function. Manifested systolic and diastolic LV dysfunction among overweight TS patients is partially compensated through an increase in LA active pump function.
|
10.21037/qims-21-515
|
pubmed_359_19578
|
OBJECTIVE
Low serum pepsinogen I (PG I) values are common in subjects with advanced corpus atrophy with or without parietal cell antibodies (PCA). Elevated values are usual during Helicobacter pylori infection.
MATERIAL AND METHODS
PG I levels were determined in two randomly selected cross-sectional adult population samples using the Gastroset PGI test kits. The sera (408 in 1973 and 504 in 1994), tested earlier for H. pylori infection and now for PCA, represented subjects living in Vammala, Finland.
RESULTS
In the PCA-negative population, the mean (+/-SD) PG I level was significantly higher in men than in women among both H. pylori-negative (88.13+/-34.16 microg/l versus 72.43+/-29.31 microg/l; p<0.0001) and H. pylori-positive (110.50+/-50.59 microg/l, versus 97.74+/-44.82 microg/l, p<0.0001) subjects; the difference between all H. pylori-positive and -negative subjects was also significant (p<0.001). In the 10-year age groups, age had no impact on the mean PG I levels in H. pylori-negative subjects (p=0.860). In the PCA-positive population, the 10 H. pylori-positive subjects had higher mean PG I levels (112.96+/-53.62 microg/l) than the 13 H. pylori-negative subjects (32.57+/-27.59 microg/l; p=0.002); the latter mean was also significantly lower than that of the PCA- and H. pylori-negative subjects (80.08+/-32.69 microg/l; p<0.0001).
CONCLUSIONS
Men had higher normal PG I values than women, but there was no significant variation by age. H. pylori infection was associated with elevated PG I levels and a small decrease with increasing age. Non-infected PCA-positive subjects showed the lowest mean PG I level.
|
10.1080/00365510510013848
|
pubmed_49_3715
|
Using the method described, a defect prosthesis can be fastened with the help of operatively prepared retention sites and transnasal anchorage after total upper jaw resection. The technical process of manufacture is outlined and the result demonstrated in photographs.
|
pubmed_49_3715
|
pubmed_1073_20253
|
Limited data exist evaluating outcomes in patients with serious Streptococcus anginosus group infections, particularly bacteraemia. A retrospective, single-centre cohort study was conducted to characterize potential risk factors along with clinical and microbiological outcomes in patients with S. anginosus group bacteraemia (SAGB). Adult inpatients with SAGB identified using the Verigene Gram-positive blood culture assay between March 2013 and April 2014 were included. Patients aged ≤ 18 or >89 years, those with SAGB identified at an outside facility and those who were incarcerated were excluded. Differences between groups were explored using a Wilcoxon rank-sum test, χ2 test, Student's t-test or Fisher's exact test as appropriate and a two-tailed P value of ≤ 0.05 was considered statistically significant. The 34 patients who met the inclusion criteria were 57 ± 14 (mean ± SD) years old and had a median Charlson co-morbidity index of 4 [interquartile range (IQR) 1-6] and 10 (29%) were immunosuppressed at baseline. Almost half (47%) had received antibiotics in the previous 90 days. Twelve (35%) patients had gastrointestinal malignancies and the commonest source of bacteraemia was the gastrointestinal tract (53%). The primary species responsible for SAGB was S. anginosus (68%), and overall susceptibility to penicillin was 91%. Patients were most often treated with a β-lactam/β-lactamase inhibitor combination (36%) for a duration of 8 (IQR 4-13) days. Length of stay (LOS) and infection-related LOS were 10 (IQR 5-17) and 9 (IQR 4-12) days, respectively. Twenty [59%] patients achieved a clinical cure, while 29 (85%) achieved a microbiological cure. Four (12%) patients died and one patient was readmitted within 30 days. In the largest cohort of patients with SAGB to date, gastrointestinal malignancies may have been an important risk factor for SAGB, while rapid identification via a microarray assay likely contributed to improved disease recognition and timely pharmacological and non-pharmacological therapy.
|
10.1099/jmm.0.000176
|
pubmed_1000_13348
|
Recurrent and frightening dreams are commonly experienced by patients who suffer from post-traumatic stress disorder after a motor vehicle accident. Such nocturnal episodes, if left untreated, can result in the experience of severe distress with physical, emotional, and psychophysiological concomitant. The present single-case study investigated the effects of the standard autogenic exercises and autogenic abreaction in reducing the frequency and severity of post-traumatic nightmares in a survivor of a car crash. The patient was also instructed in two additional organ-specific formulas in order to improve her sleep. The results of the study showed that the interventions were successful in effectively treating the patient's distressing nightmares. Follow-up data suggested that the treatment effects persisted after the termination of therapy. Suggestions for future investigations are discussed.
|
10.1023/a:1023440731202
|
pubmed_397_10150
|
Reductive 13C-methylation of proteins has been used as an isotope labeling strategy to study protein structure, function, and dynamics by nuclear magnetic resonance (NMR) spectroscopy. However, assigning the resulting 13C-dimethylamine peaks in a 1H-13C NMR spectrum has proved to be difficult, but it is important to expand the scope of the method. The assignment strategy presented here utilizes mass spectrometry (MS) for sequence identification and varying 13C/12C isotope ratios to correlate with NMR data. The site-specific reactivity of the lysines and N-terminal amine of a protein is exploited to produce a sample with varying 13C/12C ratios at each dimethylamine. MS and NMR are used to quantitate and correlate these ratios in order to assign peaks in the 1H-13C NMR spectrum. Hen egg white lysozyme was used as a model protein to demonstrate this assignment strategy.
|
10.1021/ja056977r
|
pubmed_415_12074
|
Prediction of mutagenicity by computer is now routinely used in research and by regulatory authorities. Broadly, two different approaches are in wide use. The first is based on statistical analysis of data to find patterns associated with mutagenic activity. The resultant models are generally termed quantitative structure-activity relationships (QSAR). The second is based on capturing human knowledge about the causes of mutagenicity and applying it in ways that mimic human reasoning. These systems are generally called knowledge-based system. Other methods for finding patterns in data, such as the application of neural networks, are in use but less widely so.
|
10.1007/978-1-61779-421-6_1
|
pubmed_202_8835
|
The authors measured the binding of indium-111-labeled recombinant tissue-type plasminogen activator (rt-PA) within the recanalized femoropopliteal segment after percutaneous transluminal angioplasty (PTA) and enclosed thrombolysis. In patients with long occlusions (n = 3), 91 micrograms of rt-PA was bound 1 hour after the procedure, and the half-time of the final washout curve averaged 114 hours. After PTA in patients with multiple stenoses (n = 6), 45 micrograms of rt-PA was bound, and the half-time averaged 32 hours. These values were significantly smaller than those in patients with occlusions (P < .01). In patients with a single stenosis (n = 4), 19 micrograms of rt-PA was bound, and the half-time averaged 5 hours. These values were significantly smaller than those in patients with multiple stenoses (P < .01). The progressive accumulation of rt-PA at the sites of PTA therapy is most likely related to increasing presence of fibrin with increasing lesion severity. Fibrin accumulation may be partly responsible for early failures after PTA in extensive lesions. Removal of this fibrin with enclosed thrombolysis might improve patency.
|
10.1016/s1051-0443(92)72908-x
|
pubmed_589_7029
|
BACKGROUND
Demyelination and remyelination are common pathological processes in many neurological disorders, including multiple sclerosis (MS). Clinical evidence suggests extensive involvement of the thalamocortical (TC) system in patients suffering from MS.
METHODS
Using murine brain slices of the primary auditory cortex, we investigated the functional consequences of cuprizone-induced de- and remyelination on neuronal activity and auditory TC synaptic transmission in vitro.
RESULTS
Our results revealed an impact of myelin loss and restoration on intrinsic cellular firing patterns, synaptic transmission, and neuronal plasticity in layer 3 and 4 neurons of the auditory TC network. While there was a complex hyper- and depolarizing shift of the resting membrane potential, spontaneous and induced action potential firing was reduced during demyelination and early remyelination. In addition, excitatory postsynaptic potential amplitudes were decreased and induction of LTP was reduced during demyelination.
CONCLUSIONS
These data indicate that demyelination-induced impairment of neurons and network activity within the TC system may underlie clinical symptoms observed in demyelinating diseases, corroborating human findings that disease progression is significantly correlated with microstructural tissue damage of the TC system. Further investigation into focal inflammation-induced demyelination models ex vivo and in vivo are needed to understand the functional implication of local and remote lesion formation on TC network activity in MS.
|
10.1186/s12974-016-0629-0
|
pubmed_323_19710
|
The ground-state tautomerization of the G·C Watson-Crick base pair by the double proton transfer (DPT) was comprehensively studied in vacuo and in the continuum with a low dielectric constant (ϵ = 4), corresponding to a hydrophobic interface of protein-nucleic acid interactions, using DFT and MP2 levels of quantum-mechanical (QM) theory and quantum theory "Atoms in molecules" (QTAIM). Based on the sweeps of the electron-topological, geometric, polar, and energetic parameters, which describe the course of the G·C ↔ G*·C* tautomerization (mutagenic tautomers of the G and C bases are marked with an asterisk) through the DPT along the intrinsic reaction coordinate (IRC), it was proved that it is, strictly speaking, a concerted asynchronous process both at the DFT and MP2 levels of theory, in which protons move with a small time gap in vacuum, while this time delay noticeably increases in the continuum with ϵ = 4. It was demonstrated using the conductor-like polarizable continuum model (CPCM) that the continuum with ϵ = 4 does not qualitatively affect the course of the tautomerization reaction. The DPT in the G·C Watson-Crick base pair occurs without any intermediates both in vacuum and in the continuum with ϵ = 4 at the DFT/MP2 levels of theory. The nine key points along the IRC of the G·C base pair tautomerization, which could be considered as electron-topological "fingerprints" of a concerted asynchronous process of the tautomerization via the DPT, have been identified and fully characterized. These key points have been used to define the reactant, transition state, and product regions of the DPT reaction in the G·C base pair. Analysis of the energetic characteristics of the H-bonds allows us to arrive at a definite conclusion that the middle N1H⋯N3/N3H⋯N1 and the lower N2H⋯O2/N2H⋯O2 parallel H-bonds in the G·C/G*·C* base pairs, respectively, are anticooperative, that is, the strengthening of the middle H-bond is accompanied by the weakening of the lower H-bond. At that point, the upper N4H⋯O6 and O6H⋯N4 H-bonds in the G·C and G*·C* base pairs, respectively, remain constant at the changes of the middle and the lower H-bonds at the beginning and at the ending of the G·C ↔ G*·C* tautomerization. Aiming to answer the question posed in the title of the article, we established that the G*·C* Löwdin's base pair satisfies all the requirements necessary to cause point mutations in DNA except its lifetime, which is much less than the period of time required for the replication machinery to forcibly dissociate a base pair into the monomers (several ns) during DNA replication. So, from the physicochemical point of view, the G*·C* Löwdin's base pair cannot be considered as a source of point mutations arising during DNA replication.
|
10.1080/07391102.2013.822829
|
pubmed_494_11179
|
The identification of human T-cell antigens of Mycobacterium leprae could improve treatment and help to disrupt the transmission of leprosy by directing diagnosis and vaccine programs. This study screened a panel of M. leprae recombinant proteins for T-cell recall responses, measured by gamma interferon (IFN-gamma) production, among leprosy patients. After initial studies using peripheral blood mononuclear cells from leprosy patients, we transitioned our studies to simple whole-blood assays (WBA), which are more applicable in field or clinical settings. T-cell responses generated in WBA using blood from individuals in Goiânia, Brazil, demonstrated that several M. leprae antigens (ML0276, ML0840, ML1623, ML2044, and 46f) elicited >0.5 IU/ml IFN-gamma, and these proteins were classified as immunogenic and leprosy specific. Several of these individual antigens were recognized by cells from >60% of Brazilian paucibacillary (PB) leprosy patients, and ML0276, ML0840, ML1623, and 46f complemented each other such that 82% of PB patients had strong (>1.25 IU/ml IFN-gamma) responses to at least one of these proteins. These proteins were also recognized by cells from a significant proportion of the household contacts of multibacillary leprosy patients, but in contrast, few responses were observed in active tuberculosis patients or healthy control groups from areas of endemicity. Our results indicate several potential candidate antigens which may be useful for either leprosy diagnosis or vaccination and demonstrate the utility of leprosy WBA that can be applied broadly in clinical or field settings.
|
10.1128/CVI.00234-08
|
pubmed_852_1381
|
The present study was designed to determine the radioprotective effects of Malaysian Gelam honey on gene expression and enzyme activity of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) of human diploid fibroblasts (HDFs) subjected to gamma-irradiation. Six groups of HDFs were studied: untreated control, irradiated HDFs, Gelam honey-treated HDFs and HDF treated with Gelam honey pre-, during- and post-irradiation. HDFs were treated with 6 mg/mL of sterilized Gelam honey (w/v) for 24 h and exposed to 1 Gray (Gy) of gamma rays at the dose rate of 0.25 Gy/min. Gamma-irradiation was shown to down-regulate SOD1, SOD2, CAT and GPx1 gene expressions (p < 0.05). Conversely, HDFs treated with Gelam honey alone showed up-regulation of all genes studied. Similarly, SOD, CAT and GPx enzyme activities in HDFs decreased with gamma-irradiation and increased when cells were treated with Gelam honey (p < 0.05). Furthermore, of the three different stages of study treatment, pre-treatment with Gelam honey caused up-regulation of SOD1, SOD2 and CAT genes expression and increased the activity of SOD and CAT. As a conclusion, Gelam honey modulates the expression of antioxidant enzymes at gene and protein levels in irradiated HDFs indicating its potential as a radioprotectant agent.
|
10.3390/molecules18022200
|
pubmed_140_7865
|
PURPOSE
The purpose of this paper is to contribute new knowledge about how first line managers (FLMs) in elderly care perceive their situation, with a focus on differences in management approaches at the intersection of the central and local parts of the organization.
DESIGN/METHODOLOGY/APPROACH
The present study has a qualitative approach and is part of a larger project on FLMs in elderly care. The results presented here are based on a secondary analysis of 15 of the total of 28 interviews carried out in the project.
FINDINGS
The main results are twofold: the majority of FLMs perceived differences in management approaches between local and central management; the differences caused some struggle because FLMs perceived that the management system did not support the differences. The two main aspects that caused the FLMs to struggle were differences in the foci of the management levels and difficulties in influencing the conditions of management.
ORIGINALITY/VALUE
The results contribute to the debate on what aspects are important to sustainable management of elderly care. It is common knowledge that FLMs have a complex position, intermediate to the central, upper level management and their subordinates at the local level - levels with different foci and interests. The study contributes new knowledge about what these differences consist of and the dilemmas they cause and offers suggestions as to what can be done to reduce both energy waste and the risk of low job satisfaction.
|
10.1108/LHS-09-2018-0046
|
pubmed_743_21348
|
Tubulin alpha 1c (TUBA1C) as a member of α-tubulin was identified to take part in the occurrence and development of hepatocellular carcinoma and pancreatic cancer. Using the bioinformatics, we noticed that TUBA1C level was also increased in breast cancer was also demonstrated. Here, we explored TUBA1 role in modulation of breast cancer cell aerobic glycolysis, growth and migration and explored whether yes association protein (YAP) was involved. Fifty-five matched breast cancer tissues and the para-carcinoma normal tissues were included in this study and used to verify TUBA1C expression using quantitative reverse transcription-PCR and western blotting. ATP level, lactate secretion and glucose consumption were used to assess aerobic glycolysis. Cell growth, invasion, migration and tumorigenesis were detected using cell count kit-8, transwell, wound healing and animal assays. TUBA1 was upregulated in breast cancer, which associated with advanced primary tumor, lymph node, metastasis stage and tumor size. Silencing of TUBA1C with sh-TUBA1C infection led to significant inhibitions in ATP level, lactate secretion, glucose consumption, cell growth, migration, invasion and tumorigenesis, as well as declined YAP expression, while TUBA1C overexpression induced a opposite result. And, the above tendencies induced by TUBA1C downregulation were reversed by YAP overexpression. This study revealed that TUBA1C was overexpressed in breast cancer and promoted aerobic glycolysis and cell growth through upregulation of YAP expression.
|
10.1097/CAD.0000000000001250
|
pubmed_456_7999
|
Functional abdominal pain (FAP) and functional dyspepsia (FD) are common in adolescents and associated with low quality of life. Exposure-based cognitive-behavioral therapy (CBT) is efficient for adult and adolescent irritable bowel syndrome (IBS), but has never been evaluated for adolescent FAP/FD. The aim of this study was to evaluate the feasibility and potential efficacy of a novel disorder-specific Internet-delivered CBT (Internet-CBT) for adolescents with FAP or FD, using an uncontrolled open pilot including 31 adolescents. The Internet-CBT consisted of 10 weekly online modules, which focused mainly on exposure to abdominal symptoms. Parents received modules to help them reduce unhelpful parental behaviors. Participants reported the treatment to be credible, and an overall satisfaction with the treatment. Data attrition rate was low (7%) and adherence to treatment was acceptable. We saw a significant and large effect on the primary outcome, pain intensity, at posttreatment (d = 1.20, p < .001) that was further improved after 6 months (d = 1.69, p < .001). Participants also made significant and large improvements on gastrointestinal symptoms (d = 0.84, p < .001) and quality of life (d = 0.84, p < .001) that were sustained or further improved at follow-up 6 months after treatment. This study demonstrated that exposure-based Internet-CBT, tailored for adolescents with FAP or FD, is a feasible treatment that potentially improves pain intensity, gastrointestinal symptoms, and quality of life.
|
10.1016/j.beth.2018.05.002
|
pubmed_181_3294
|
RCN adviser in nursing practice Rosemary Wilkinson, who oversees issues relating to emergency care, retires from the college next month.
|
10.7748/en.11.5.3.s10
|
pubmed_339_11996
|
Using analogies from nature, we investigated the possibility that tyrosinase-catalyzed reactions of 3,4-dihydroxyphenethylamine (dopamine) could confer water-resistant adhesive properties to semidilute solutions of the polysaccharide chitosan. Rheological measurements showed that the tyrosinase-catalyzed, and subsequent uncatalyzed, reactions lead to substantial increases in the viscosity of the chitosan solutions. Samples from these high-viscosity modified-chitosans were spread onto dry glass slides, the slides were lapped and clipped together either in air or after being submerged in water, and the bound slides were held under water for several hours. Adhesive shear strengths of over 400 kPa were observed for these modified chitosan samples, while control chitosan solutions conferred no adhesive strength (i.e., the glass slides separated in the absence of measurable forces). High viscosities and water-resistant adhesive strengths were also observed when semidilute chitosan solutions were treated with the known cross-linking agent, glutaraldehyde. Further studies indicate a relationship between the increased viscosities and water-resistant adhesion. These results demonstrate that the renewable biopolymer chitosan can be converted into a water-resistant adhesive.
|
10.1021/bm0003009
|
pubmed_9_6720
|
32P-Postlabeling analysis and enzyme-linked immunosorbent assay (ELISA) have been used to detect DNA adducts in peripheral blood lymphocytes from primary aluminum production plant workers who were exposed occupationally to a mixture of polycyclic aromatic hydrocarbons (PAHs). Preliminary results reported here are from a comparative study being performed in two aluminum plants. The levels of aromatic DNA adducts have been determined by the 32P-postlabeling assay in samples collected on two occasions, 1 year apart. PAH-DNA adduct levels have also been determined by competitive ELISA in the second set of DNA samples. The results show the necessity of follow-up biomonitoring studies to detect possible alterations in biological effect induced by changing exposures. The comparison of the results obtained by 32P-postlabeling and ELISA may lead to a better understanding of the power and weaknesses of the two methods applied in these studies.
|
10.1289/ehp.9399307
|
pubmed_944_15792
|
We present our recent development of a high temperature high pressure cell for neutron scattering. Combining a water cooled Nb1Zr pressure cell body with an internal heating furnace, the sample environment can reach temperatures of up to 1500 K at a pressure of up to 200 MPa at the sample position, with an available sample volume of about 700 mm(3). The cell material Nb1Zr is specifically chosen due to its reasonable mechanical strength at elevated temperatures and fairly small neutron absorption and incoherent scattering cross sections. With this design, an acceptable signal-to-noise ratio of about 10:1 can be achieved. This opens new possibilities for quasielastic neutron scattering studies on different types of neutron spectrometers under high temperature high pressure conditions, which is particularly interesting for geological research on, e.g., water dynamics in silicate melts.
|
10.1063/1.3623796
|
pubmed_1073_14548
|
AIM
The aim was to screen the selected Indian plants for their antibacterial efficacy against four cariogenic bacteria Lactobacillus acidophilus (LA)(Microbial Type Culture Collection [MTCC]-*447), Lactobacillus casei (LC) (MTCC-1423), Streptococcus mutans (SMU) (MTCC-890) and Staphylococcus aureus (MTCC-96). To identify and characterize active principle present in these plants for the treatment of dental caries.
MATERIALS AND METHODS
The dried plant leaves materials are extracted by cold extraction using hexane, ethyl acetate, methanol, and distilled water. The solvents were evaporated, and the dried masses were suspended in dimethyl sulfoxide and used for anticariogenic activity by agar well diffusion method. Minimum inhibitory concentration (MIC) was evaluated by two-fold serial broth dilution method. Preliminary phytochemical analysis of effective extract was carried out by thin-layer chromatography (TLC) and bioautography.
RESULTS
Ethyl acetate and hexane extract of Eucalyptus globules was found most effective against L. acidophilus with MIC value 31 μg/ml and 62 μg/ml, respectively. Ethyl acetate extracts of Acacia nilotica and methanolic extract of E. globules also exhibited antibacterial activity against SMU and L. casei with MIC value of 50 μg/ml. Qualitative analysis of E. globules revealed the presence of alkaloids, terpenoids, phenolic compounds, and cardiac glycosides. The active principle responsible for the anticariogenic activity from E. globules were separated by TLC and subjected to bioautography using SMU, LA and LC.
CONCLUSION
Anticariogenic activity and preliminary phytochemical analysis revealed that E. globule have potential to treat dental caries.
|
10.5455/jice.20140228010459
|
pubmed_1038_2473
|
The effect of external ATP on both the membrane potential and the transmembrane current of the thyroid cell line FRTL-5 has been investigated in the patch-clamp whole-cell recording configuration. In the resting situation the membrane potential is around -70 mV and the membrane acts like a K(+)-sensitive electrode. Application of ATP at concentrations higher than 1 microM elicited an increase in Cl- conductance, responsible for a membrane depolarization which could be blocked by preincubation with the P2-antagonist quinidine. Chelation of intracellular Ca2+ also blocked the ATP induced changes in membrane potential and Cl- current. Intracellular perfusion with inositol trisphosphate (IP3) (50 microM) also stimulated a Cl- current which mimicked the response induced by ATP. ATP is able to initiate a response in the absence of extracellular Ca2+, but also opens a Ca(2+)-influx pathway, as demonstrated by a secondary response upon Ca2+ readmission in the external medium, in the continued presence of ATP. ADP and ATP gamma S were able to mimic the ATP response, whereas AMP and adenosine were unable to elicit a Cl- current. The P2X receptor agonist alpha,beta-methyleneATP was without effect as was the P2Y receptor agonist 2-methylthio ATP. We conclude that ATP is able to elicit a large IP3-mediated Ca(2+)-dependent Cl- current and membrane depolarization via a novel P2-type purinergic receptor.
|
10.1007/BF00236437
|
pubmed_548_16929
|
Reliable assessment of the BRAF mutation status is becoming increasingly important in the clinical management of colorectal carcinomas (CRC). The aim of this study was to investigate the use of a recently developed mutation-specific antibody (VE1; SpringBio, Pleasanton, CA) to detect the BRAF V600E protein in paraffin tissue. We analyzed by immunohistochemistry (IHC) 117 cases that had been evaluated for BRAF mutation using a MALDI-TOF mass spectrometry-based assay. Immunohistochemical staining was evaluated without the knowledge of the genetic data and was considered positive when there was distinct homogenous cytoplasmic staining in the tumor cells. The analyzed cases included 4 polyps, 63 primary CRC, and 50 metastatic CRC. Forty-five of the 46 (97.8%) cases that were positive by IHC had a BRAF V600E mutation by genetic analysis; the 1 discordant case was notably of signet ring cell type. Similarly, 66 of the 67 (98.5%) cases that were negative by IHC were also negative by genetic analysis. Four cases that showed weak cytoplasmic staining and/or nuclear staining in the tumor cells were considered to be IHC equivocal; by genetic analysis, 2 of the 4 were positive and 2 were negative. The overall sensitivity and specificity of IHC for the detection of a BRAF V600E mutant tumor was 93.7% and 95.6%, respectively. Our results support the use of VE1 IHC for identification of colorectal neoplasms harboring the BRAF V600E mutation. Difficulties in immunohistochemical interpretation may arise in a small number of cases and in those cases molecular testing is required.
|
10.1097/PAI.0000000000000116
|
pubmed_24_20090
|
The hyperthermophilic archaeon Sulfolobus solfataricus grows optimally above 80 degrees C and utilizes an unusual, promiscuous, non-phosphorylative Entner-Doudoroff pathway to metabolize both glucose and galactose. The first enzyme in this pathway, glucose dehydrogenase, catalyzes the oxidation of glucose to gluconate, but has been shown to have activity with a broad range of sugar substrates, including glucose, galactose, xylose, and L-arabinose, with a requirement for the glucose stereo configuration at the C2 and C3 positions. Here we report the crystal structure of the apo form of glucose dehydrogenase to a resolution of 1.8 A and a complex with its required cofactor, NADP+, to a resolution of 2.3 A. A T41A mutation was engineered to enable the trapping of substrate in the crystal. Complexes of the enzyme with D-glucose and D-xylose are presented to resolutions of 1.6 and 1.5 A, respectively, that provide evidence of selectivity for the beta-anomeric, pyranose form of the substrate, and indicate that this is the productive substrate form. The nature of the promiscuity of glucose dehydrogenase is also elucidated, and a physiological role for this enzyme in xylose metabolism is suggested. Finally, the structure suggests that the mechanism of sugar oxidation by this enzyme may be similar to that described for human sorbitol dehydrogenase.
|
10.1074/jbc.M601334200
|
pubmed_965_7101
|
The secondary structure of purified protamine, a non-specific DNA binding protein, was studied in solution at pH 4, 7 and 8 by FTIR. This permitted analysis of the folded form of the protein (acidic pH) as well as the folded conformers (neutral and basic pH). Hg(2+) was utilized to probe the accessibility of the free thiol groups (cysteine residues). The SH groups form when disulfides, which play the major role in stabilizing the conformation of this protein, are broken. It was possible to observe different conformational states in protamine as a function of pH and the presence of Hg(2+) via spectral changes primarily in the amide region. The results lead to the conclusion that protamine is not completely folded under conditions similar to those found in vivo (37 degrees , neutral pH, phosphate buffer and high protein concentration).
|
10.1016/0039-9140(92)80227-5
|
pubmed_321_3644
|
INTRODUCTION
Recent papers indicate that one-side mastectomy can produce deleterious effects on the posture and musculoskeletal system. This study was conducted to better understand the underlying mechanisms involved in trunk motion in external prosthesis users.
OBJECTIVE
The aim was to evaluate the changes in surface electromyographic (SEMG) activity of the erector spinae muscles (ES) in postmastectomy women with and without breast prostheses during functional body movement tests.
METHODS
In 51 one-side postmastectomy women the SEMG muscle activity of bilateral ES was measured during symmetrical and asymmetrical dynamic activities in a counterbalanced manner with different weights of the breast prosthesis. Range-of-motion measurements were taken for forward bending, backward bending, lateral bending, and rotation.
RESULTS
The mean level of the ES activity in the lumbar region was not affected by the weight of the external breast prosthesis during most of the functional body tests (P > 0.05). The activity of ES during functional body tests with and without different external breast prostheses did not differ between the two sides of the trunk (mastectomy and nonmastectomy) for most of the movement tests (P > 0.05).
CONCLUSION
The lumbar ES activity during functional tests is not associated with the weight of the external breast prosthesis in postmastectomy women.
|
10.1155/2017/9867694
|
pubmed_124_10607
|
The article reports on 11 cases of opercular aplasia in patients aged 5 to 44 years. Aplasia occurred to a greater extent in the frontal operculum than in the temporal operculum, and was always associated with space-requiring arachnoidal cysts. Symphyses and obstruction of the flow of the basal CSF spaces were also seen. In 91% of the cases, the aplasia was localized on the left side, 91% of the patients were males. The patients tend to decompensate after a cerebrocranial trauma, and in many cases surgery reveals a subdural haematoma which fills the aplastic region, due to detachment of the exposed cerebral veins effecting basal drainage. In the remaining cases, surgery was performed because of general signs of cerebral compression, exacerbation of an existing disease associated with attacks, or because of the space-occupying character of the concomitant arachnoidal cysts. In patients with opercular aplasia without space-occupying arachnoidal cysts, surgery is not performed for the time being; instead, regular neurological and CT control is effected.
|
10.1055/s-0028-1090311
|
pubmed_177_3185
|
BACKGROUND
We tested whether GW0742, a peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) agonist, improves endothelial dysfunction induced by plasma from patients with systemic lupus erythematosus (SLE) involving the inhibition of endoplasmic reticulum (ER) stress.
METHODS
A total of 12 non-pregnant women with lupus and 5 non-pregnant healthy women (controls) participated in the study. Cytokines and double-stranded DNA autoantibodies (anti-dsDNA) were tested in plasma samples. Endothelial cells, isolated from human umbilical cord veins (HUVECs), were used to measure nitric oxide (NO), intracellular reactive oxygen species (ROS) production, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, and ER stress markers.
RESULTS
Interferon-γ, interleukin-6, and interleukin-12 levels were significantly increased in plasma from patients with SLE with active nephritis (AN), as compared to both patients with SLE with inactive nephritis (IN) and the control group. The NO production stimulated by both the calcium ionophore A23187 and insulin was significantly reduced in HUVECs incubated with plasma from patients with AN-SLE as compared with the control group. Plasma from patients with IN-SLE did not modify A23187-stimulated NO production. Increased ROS production and NADPH oxidase activity were found in HUVECs incubated with plasma from patients with AN-SLE, which were suppressed by the ER stress inhibitor 4-PBA and the NADPH oxidase inhibitors, apocynin and VAS2870. GW0742 incubation restored the impaired NO production, the increased ROS levels, and the increased ER stress markers induced by plasma from patients with AN-SLE. These protective effects were abolished by the PPARβ/δ antagonist GSK0660 and by silencing PPARβ/δ.
CONCLUSIONS
PPARβ/δ activation may be an important target to control endothelial dysfunction in patients with SLE.
|
10.1186/s13075-017-1478-7
|
pubmed_166_20446
|
Ocular infection with herpes simplex virus 1 (HSV-1) sets off an inflammatory reaction in the cornea which leads to both virus clearance and chronic lesions that are orchestrated by CD4 T cells. Approaches that enhance the function of regulatory T cells (Treg) and dampen effector T cells can be effective to limit stromal keratitis (SK) lesion severity. In this report, we explore the novel approach of inhibiting DNA methyltransferase activity using 5-azacytidine (Aza; a cytosine analog) to limit HSV-1-induced ocular lesions. We show that therapy begun after infection when virus was no longer actively replicating resulted in a pronounced reduction in lesion severity, with markedly diminished numbers of T cells and nonlymphoid inflammatory cells, along with reduced cytokine mediators. The remaining inflammatory reactions had a change in the ratio of CD4 Foxp3+ Treg to effector Th1 CD4 T cells in ocular lesions and lymphoid tissues, with Treg becoming predominant over the effectors. In addition, compared to those from control mice, Treg from Aza-treated mice showed more suppressor activity in vitro and expressed higher levels of activation molecules. Additionally, cells induced in vitro in the presence of Aza showed epigenetic differences in the Treg-specific demethylated region (TSDR) of Foxp3 and were more stable when exposed to inflammatory cytokines. Our results show that therapy with Aza is an effective means of controlling a virus-induced inflammatory reaction and may act mainly by the effects on Treg.IMPORTANCE HSV-1 infection has been shown to initiate an inflammatory reaction in the cornea that leads to tissue damage and loss of vision. The inflammatory reaction is orchestrated by gamma interferon (IFN-γ)-secreting Th1 cells, and regulatory T cells play a protective role. Hence, novel therapeutics that can rebalance the ratio of regulatory T cells to effectors are a relevant issue. This study opens up a new avenue in treating HSV-induced SK lesions by increasing the stability and function of regulatory T cells using the DNA methyltransferase inhibitor 5-azacytidine (Aza). Aza increased the function of regulatory T cells, leading to enhanced suppressive activity and diminished lesions. Hence, therapy with Aza, which acts mainly by its effects on Treg, can be an effective means to control virus-induced inflammatory lesions.
|
10.1128/JVI.02367-16
|
pubmed_804_2089
|
OBJECTIVE
Not-for-profit hospitals are required to meet federal reporting requirements detailing their community benefit activities, which support their tax-exempt status. Children's hospitals have long provided community injury prevention (IP) programming and thus can inform public health outreach work in other areas. This work describes IP programming as a community service offered by children's hospitals in the U.S.
METHODS
The IP specialist at 232 US-based member institutions of the Children's Hospital Association were invited to complete an assessment of their hospital's IP outreach programming.
RESULTS
47.7 percent of hospitals request financial data from IP programming for tax reporting purposes. Almost all offer injury prevention (IP) services; the majority are in the community (60.3%) and 34.5% are hospital-based. Most IP units are independent (60.3%) and 71.8% are responsible for their own budgets.
CONCLUSIONS
By integrating dissemination and implementation sciences and community health needs assessments, these findings can help advance community services provided by hospitals to impact public health.
|
10.3934/publichealth.2014.4.199
|
pubmed_273_160
|
BACKGROUND
Since 1970s, a Chinese study group at Harbin Medical University First Hospital discovered the anticancer effect of arsenic trioxide (As2O3), it has become evident that apoptotic effects of As2O3 are not restricted to APL cells but also can be observed in other malignant cells in vitro, including non-APL acute myeloid leukemia cells, myeloma cells, and chronic myeloid leukemia cells, as well as various solid-tumor cells, such as esophageal, prostate, and ovarian carcinomas and neuroblastoma cells.
OBJECTIVE
To investigated if As2O3 could induce cell death and apoptosis of Hep-2 cells, a laryngeal squamous cell carcinoma (LSCC) cell line.
METHODS
Trypan blue exclusion assay, LDH release assay and cytometric method were used for the measurements of cell death and apoptosis. We measured intracellular GSH, ROS and mitochondrial membrane potential to explore the mechanisms of cell death and apoptosis induced by As2O3 in Hep-2 cells.
RESULTS
Trypan-blue-positive cells and the release of LDH into medium induced by As2O3 increased in a dose- and time-dependent manner. The rates of apoptosis increased induced by As2O3 in a dose- and time-dependent manner. In order to elucidate the mechanisms of cell death and apoptosis induced by As2O3 in Hep-2 cells through GSH, we found that As2O3 induced the decrease of intracellular GSH, increase of ROS and loss of mitochondrial membrane potential. And pretreatment of BSO, an inhibitor of GSH biosynthesis, depleted partly intracellular GSH and increased trypan-blue-positive cells, the release of LDH, apoptosis, ROS and loss of mitochondrial membrane potential. However, pretreatment of GSH had resistance to the changes to some extent as described above.
CONCLUSION
As2O3-induced apoptosis of Hep-2 cell line through modulating intracellular GSH level.
|
10.1016/j.anl.2009.04.016
|
pubmed_769_25897
|
BACKGROUND
In response to the COVID-19 pandemic, the French government took many measures, the most notable of which was a national lockdown on 17 March 2020. Its effects have been widely studied, but to our knowledge, no study has sought to determine how adolescents have adapted to cope with this situation. The present study set out to explore teenagers' stress levels, coping strategies, and substance use during this period.
METHODS
This paper is a cross-sectional study that rides on an existing prevention program interviewed 348 French middle school students (209 girls and 139 boys) in grade 8 (M age = 13.45; SDage = 0.54) using an online questionnaire between March 17 and May 11, 2020 (COVID-19 lockdown). The study examined the teenagers' perceived stress, coping strategies they had used, including recent use of tobacco, alcohol and cannabis, during COVID-19 lockdown.
RESULTS
Teenagers reported lower perceived stress during lockdown than usually, with a significant decrease for girls. Those who perceived the least social support reported the highest levels of stress. The strategies of planning, behavioral disengagement, self-distraction, positive reframing, acceptance, and religion were used more than usual, while active coping and self-blame were used less. Acceptance was the most often used strategy and a source of decreased stress during lockdown. A significant decrease in recent tobacco, alcohol and cannabis use was also observed.
CONCLUSION
Changes in the use of coping strategies, withdrawal from the stressful school environment, and greater exposure to parents than to peers caused adolescents to be less stressed and to decrease their substance use during the lockdown.
|
10.3389/fpsyt.2021.790704
|
pubmed_906_14598
|
Femoral fractures resulting from birth injuries are rare. The authors undertook a study to assess their incidence and outcome. Seven patients from a total of 55,296 live births suffered 8 femoral fractures (incidence 0.13 per 1,000 live births). Twin pregnancies, breech presentations, prematurity, and disuse osteoporosis were associated with the occurrence of a fracture. The typical injury pattern was a spiral fracture of the proximal half of the femur, which was held in an extended position. A variety of treatment modalities were used, including gallows traction, spica cast, and Pavlik harness. All patients in this study, regardless of treatment, had a satisfactory clinical outcome, with no evidence of limb length discrepancy or angular deformity on follow-up.
|
pubmed_906_14598
|
pubmed_1007_8698
|
BACKGROUND/PURPOSE
Conflicting information exists regarding the effects of maternal substance abuse on gastroschisis. The objectives of this study are to determine if maternal smoking is associated with an increased risk of gastroschisis and whether substance abuse is associated with the severity of gastroschisis.
METHODS
The Canadian Pediatric Surgery Network (CAPSNET) database was evaluated for associations between maternal substance abuse and the severity of the gastroschisis. We also compared smoking rates from this group to overall Canadian maternal smoking rates.
RESULTS
One hundred fourteen cases of gastroschisis acquired over 18 months were evaluated. After adjusting for covariates, illicit drug use was associated with bowel necrosis (OR, 9.4; 95% CI,1.3-70) and marijuana use with matting of the intestines (OR, 4.0; 95% CI, 1.0-16). Functional outcomes assessment revealed that slower initiation of enteral feeds was associated with maternal smoking (OR, 3.8; 95% CI, 1.4-10). The overall maternal smoking rate in this cohort (30.7%) was significantly higher than the known Canadian rate (13.4%). This may be accounted for by the considerably higher smoking rate of mothers 20 to 24 years of age in our cohort (48.9%).
CONCLUSIONS
Substance abuse and smoking are associated with a greater severity of gastroschisis in terms of both the degree of intestinal injury and functional outcomes. High smoking rates among young mothers may be putting children with gastroschisis at risk for poor outcomes.
|
10.1016/j.jpedsurg.2007.12.032
|
pubmed_485_10996
|
The epithelium lining the caudal surface of the mouse epiglottis occupies the transitional zone between the keratinized stratified squamous epithelium, continuing from the oral cavity, and the ciliated columnar epithelium, extending into the laryngeal cavity. The epithelium showed gradations ranging from stratified squamous through stratified cuboidal to ciliated stratified low-columnar type. It is suggested that the epithelium is identical with the 'intermediate epithelium' in the mouse nasopharynx.
|
10.1159/000146459
|
pubmed_713_883
|
Despite promising outcomes for >50 years, nonsurgical orthodontic airway plates (OAP) are only infrequently offered for babies with Robin sequence in a few parts of the world. This article demonstrates possibility of providing functional improvement using an OAP to help these babies overcome their functional and structural difficulties on their own. Two consecutively treated cases are presented exemplifying that OAP treatment that had originated from Europe is reproducible and effective in an institution in the United States.
|
10.1177/10556656211007689
|
pubmed_505_14285
|
Heme oxygenase-1 (HO-1) is a member of the heat shock protein family (HSP-32). It responds to thermal stress in cultured glial cells. To our knowledge. nothing is known about the expression and response of the HO-1 in cerebral ischemia. Therefore, we show here the induction of HO-1 in the brain of mice after global cerebral ischemia. HO-1-like immunoreactivity was detected at 12, 24, and 48 hours after ischemia recirculation. The HO-1-like immunoreactive cells were observed in astrocytes in the hippocampal dentate gyrus and CA1. The peak level of HO-1-like immunoreactivity was found 48 hours after the recirculation. HO-1-like immunoreactivity was observed in GFAP-positive astrocytes by use of a double immunostaining method. These results provide direct evidence for the induction and localization of HO-1 immunoreactivity in vivo in a mouse cerebral ischemia. We suggest that HO-1, produced in astrocytes after ischemia-recirculation, may directly affect neurons to protect from cell death.
|
10.1007/978-3-7091-0651-8_23
|
pubmed_491_20114
|
BACKGROUND AND AIM
Harmful alcohol consumption has long been recognized as being the major determinant of male premature mortality in the European countries of the former USSR. Our focus here is on Belarus and Russia, two Slavic countries which continue to suffer enormously from the burden of the harmful consumption of alcohol. However, after a long period of deterioration, mortality trends in these countries have been improving over the past decade. We aim to investigate to what extent the recent declines in adult mortality in Belarus and Russia are attributable to the anti-alcohol measures introduced in these two countries in the 2000s.
DATA AND METHODS
We rely on the detailed cause-specific mortality series for the period 1980-2013. Our analysis focuses on the male population, and considers only a limited number of causes of death which we label as being alcohol-related: accidental poisoning by alcohol, liver cirrhosis, ischemic heart diseases, stroke, transportation accidents, and other external causes. For each of these causes we computed age-standardized death rates. The life table decomposition method was used to determine the age groups and the causes of death responsible for changes in life expectancy over time.
CONCLUSION
Our results do not lead us to conclude that the schedule of anti-alcohol measures corresponds to the schedule of mortality changes. The continuous reduction in adult male mortality seen in Belarus and Russia cannot be fully explained by the anti-alcohol policies implemented in these countries, although these policies likely contributed to the large mortality reductions observed in Belarus and Russia in 2005-2006 and in Belarus in 2012. Thus, the effects of these policies appear to have been modest. We argue that the anti-alcohol measures implemented in Belarus and Russia simply coincided with fluctuations in alcohol-related mortality which originated in the past. If these trends had not been underway already, these huge mortality effects would not have occurred.
|
10.1371/journal.pone.0138021
|
pubmed_565_24399
|
BACKGROUND
To describe the presenting clinical features of coeliac disease in a single paediatric centre, and to determine if the presenting features vary with age.
METHODS
A review was conducted of children who had been referred with clinical suspicion of coeliac disease to the paediatric gastroenterology department of a tertiary paediatric hospital in Sydney, Australia. Coeliac disease was defined using standard histological criteria. Medical records were reviewed retrospectively.
RESULTS
Clinical data were available for 74 cases of proven coeliac disease. Only 9% of patients were less than 2 years of age at diagnosis. Pre-school children (age < 5 years) presented with different symptoms to school children (age > or = 5 years). The most common presenting features in younger children were diarrhoea, irritability and weight loss. However, in older children, abdominal pain was the most common presenting feature.
CONCLUSION
We found a significant difference in the clinical features of coeliac disease in pre-school compared to school age children.
|
10.1186/1471-2431-5-11
|
pubmed_813_21765
|
AIM
To evaluate the diagnostic value of telomerase expression in intracranial tumours.
METHODS
98 surgical specimens from different neoplasms were analysed by the telomeric repeat amplification protocol (TRAP) and the presence of telomerase compared with the histological diagnosis and the proliferation index.
RESULTS
A high degree of positivity for telomerase activity was found in glioblastomas and atypical/anaplastic meningiomas. Telomerase activity was poorly detected in anaplastic astrocytomas.
CONCLUSIONS
The TRAP assay seems to be a valuable index for identifying meningeal tumours with aggressive behaviour.
|
10.1136/jcp.52.3.234
|
pubmed_751_15347
|
Intracerebroventricular (i.c.v.) arginine-vasopressin (AVP) injections in rats evoke an unusual motor response termed 'barrel rotation' (BR). This report documents several aspects of BR after i.c.v. AVP in conscious, adult male Sprague-Dawley rats: single i.c.v. AVP injections (100-1000 ng/5 microliters) evoke BR in about 50% of naive rats with no relationship to dose and 20% mortality; no directional preference exists for BR, and sensitivity to BR does not vary over a weight range of 301-475 g; continuous i.c.v. AVP infusions at doses of 50-2500 ng/h evoked BR in 13 and 50% of rats tested at the extreme ranges; latency to BR was always within 3-6 min in infusion experiments; a protocol where rats received a single i.c.v. AVP injection (1 microgram) on day 1 followed on day 3 by 0.5 micrograms, increased the proportion of rats with BR from 51% to 83% (P less than 0.05), indicating a sensitization phenomenon; latency to BR after single i.c.v. injections did not fit the assumption of single underlying normal distribution; a novel method to analyze these data, hazard plotting, revealed two phases to the BR latency under ambient illumination. The following paper presents evidence of visual/vestibular involvement and the efficacy of anti-seizure drugs. Collectively, the data are compatible with the hypothesis that brain vasopressin pathways are involved in some abnormalities of motor output.
|
10.1016/0006-8993(86)90718-3
|
pubmed_712_11307
|
Strains of Streptococcus pyogenes isolated from pediatric patients with acute infections which were resistant to one or more of the antibiotics, tetracycline (TC), chloramphenicol (CP), macrolide antibiotics (erythromycin, kitasamycin, oleandomycin, josamycin), lincomycin (LCM) and clindamycin (CLM), were used for transduction of drug resistance. These drug-resistant strains were treated with mitomycin C to induce phages and transduction of drug resistance was attempted by means of phages so induced. It was found that transduction of resistance to the above antibiotics was possible. The transductants obtained on TC-containing selective agar plate were resistant to TC alone while those produced on CP- or erythromycin (EM)-containing selective agar plate were resistant to CP, macrolide antibiotics (Mac), LCM and CLM. From this finding, it was inferred that transduction of resistance to TC, CP, Mac, LCM and CLM via phages occurred in two different patterns, i.e., transfer of resistance to TC alone and that of resistance to CP, Mac, LCM and CLM. All of the transductants obtained were found to belong to group A. In T-typing, they were of the same T-12 type as the donor and recipient strains in a majority of cases though some were not typable.
|
10.7164/antibiotics.28.681
|
pubmed_876_4542
|
The heritability of the before and after meal self-ratings of palatability and their relationship to food intake was investigated with 86 identical and 78 fraternal same-sex and 51 fraternal mixed gender adult twin pairs who were paid to maintain 7-day food intake diaries. From the diary reports, the total and meal intakes of food energy and the amounts of the macronutrients ingested were estimated. Participants rated the meals for palatability on a 7-point (Bad - Good) scale both before and after eating. Linear structural modeling was applied to investigate the nature and degree of genetic and environmental influences and revealed significant genetic influences on subjective palatability both before and after the meals. In addition, the relationship between palatability and intake was influenced by the genes. Significant dominance genetic effects were found for the change in meal size between low-moderate and high palatability meals, indicating that palatability and it's relationship with intake are to some extent heritable. This suggests that the level of subjective experience and the individuals responses to them are influenced by the genes and become part of the total package of genetically determined physiological, socio/cultural, and psychological processes that regulate energy balance.
|
10.1016/s0271-5317(01)00323-2
|
pubmed_947_21308
|
Compelling evidence supports a causal role for lipoprotein(a) (Lp(a)) in cardiovascular disease. No pharmacotherapies directly targeting Lp(a) are currently available for clinical use. Here we report the discovery and development of olpasiran, a first-in-class, synthetic, double-stranded, N-acetylgalactosamine-conjugated small interfering RNA (siRNA) designed to directly inhibit LPA messenger RNA translation in hepatocytes and potently reduce plasma Lp(a) concentration. Olpasiran reduced Lp(a) concentrations in transgenic mice and cynomolgus monkeys in a dose-responsive manner, achieving up to over 80% reduction from baseline for 5-8 weeks after administration of a single dose. In a phase 1 dose-escalation trial of olpasiran (ClinicalTrials.gov: NCT03626662 ), the primary outcome was safety and tolerability, and the secondary outcomes were the change in Lp(a) concentrations and olpasiran pharmacokinetic parameters. Participants tolerated single doses of olpasiran well and experienced a 71-97% reduction in Lp(a) concentration with effects persisting for several months after administration of doses of 9 mg or higher. Serum concentrations of olpasiran increased approximately dose proportionally. Collectively, these results validate the approach of using hepatocyte-targeted siRNA to potently lower Lp(a) in individuals with elevated plasma Lp(a) concentration.
|
10.1038/s41591-021-01634-w
|
pubmed_391_13225
|
In vivo and in vitro properties of two strains of canine parainfluenza virus (CPIV) were investigated. One strain, designated CPIV(+), induced syncytial giant cell formation and cytolysis in vitro, whereas the second strain, CPIV(-), caused only a mild strand-forming cytopathic effect with few, small syncytial giant cells. Vero cells infected with CPIV(+) or CPIV(-) were 100% positive for CPIV antigen as determined by immunofluorescent staining; however, 100% of CPIV(+) and less than 10% of CPIV(-) infected cells were hemadsorption positive. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis analysis revealed no differences in electrophoretic mobility of viral polypeptides between both strains; however, in CPIV(-), reduced or absent synthesis of the putative HN and F1 proteins was observed. Isopycnic separation of CPIV(+) progeny virions showed a high proportion of viral particles with a buoyant density of 1.18 g/cm3. In contrast, CPIV(-) progeny virions had a heterogeneous density profile ranging from 1.08 to 1.18 g/cm3. Intracerebral infection of six ferrets with CPIV(+) resulted in moderate lymphocytic and histiocytic choroiditis, meningitis, and ependymitis, whereas CPIV(-) infection caused only mild to moderate inflammation. Immunohistologically, CPIV antigen was prominent in ependymal lining cells of the ventricles in CPIV(+)-infected ferrets and was reduced or lacking in CPIV(-)-infected ferrets (n = 6). Sham-injected ferrets (n = 6) did not have histologic lesions and no viral antigen was identified. The present findings suggest that certain changes in the activities of CPIV glycoproteins may lead to alterations of CPIV virulence in vivo.
|
10.1177/030098589102800409
|
pubmed_415_9080
|
Ebola hemorrhagic fever is an acute and often deadly disease caused by Ebola virus (EBOV). The possible intentional use of this virus against human populations has led to design of vaccines that could be incorporated into a national stockpile for biological threat reduction. We have evaluated the immunogenicity and efficacy of an EBOV vaccine candidate in which the viral surface glycoprotein is biomanufactured as a fusion to a monoclonal antibody that recognizes an epitope in glycoprotein, resulting in the production of Ebola immune complexes (EICs). Although antigen-antibody immune complexes are known to be efficiently processed and presented to immune effector cells, we found that codelivery of the EIC with Toll-like receptor agonists elicited a more robust antibody response in mice than did EIC alone. Among the compounds tested, polyinosinic:polycytidylic acid (PIC, a Toll-like receptor 3 agonist) was highly effective as an adjuvant agent. After vaccinating mice with EIC plus PIC, 80% of the animals were protected against a lethal challenge with live EBOV (30,000 LD(50) of mouse adapted virus). Surviving animals showed a mixed Th1/Th2 response to the antigen, suggesting this may be important for protection. Survival after vaccination with EIC plus PIC was statistically equivalent to that achieved with an alternative viral vector vaccine candidate reported in the literature. Because nonreplicating subunit vaccines offer the possibility of formulation for cost-effective, long-term storage in biothreat reduction repositories, EIC is an attractive option for public health defense measures.
|
10.1073/pnas.1117715108
|
pubmed_421_3219
|
BACKGROUND
Native valves infective endocarditis due to Escherichia coli is still a rare disease and a particular virulence of some E.coli isolate may be suspected.
CASE PRESENTATION
A 79-year-old woman presented during the post-operative period of an orthopedic surgery a urinary tract infection following obstructive ureteral lithiasis. E. coli was isolated from a pure culture of urine and blood sampled simultaneously. After evidence of sustained E.coli septicemia, further investigations revealed acute cholecystitis with the same micro-organism in biliary drainage and a native valve mitral endocarditis. E.coli was identified as O2:K7:H6, phylogenetic group B2, ST141, and presented several putative and proven virulence genes. The present isolate can be classified as both extra-intestinal pathogenic E.coli (ExPECJJ) and uropathogenic E. coli (UPECHM).
CONCLUSIONS
The relationship between the virulent factors present in ExPEC strains and some serotypes of E. coli that could facilitate the adherence to cardiac valves warrants further investigation.
|
10.1186/s12879-021-06066-y
|
pubmed_781_12915
|
Epstein-Barr virus (EBV) is an oncogenic gammaherpes virus which is linked to pathogenesis of several human lymphatic malignancies. The EBV essential latent antigen EBNA3C is critical for efficient conversion of primary human B-lymphocytes to lymphoblastic cell lines and for continued LCL growth. EBNA3C, an EBV latent antigen with oncogenic potential can bind and regulate the functions of a wide range of cellular transcription factors. In our current reverse genetics study, we deleted the full length EBNA3C, and independently the RBP-Jκ and Nm23-H1 binding sites within EBNA3C using BACmid recombinant engineering methodology. Our experiments demonstrated that deletion of the EBV EBNA3C open reading frame (ORF) and more specifically the residues 621-675 which binds Nm23H1 and SUMO-1 showed a significant reduction in the ability of the cells to proliferate. Furthermore, they exhibited lower infectivity of human peripheral blood mononuclear cells (PBMCs). We also showed that recombinant EBV with deletions of the EBNA3C ORF, as well as a recombinant with residues 621-675 within EBNA3C ORF deleted had diminished abilities to activate CD40. Our study also revealed that the full length (1-992) and 621-675 aa deletions of EBNA3C when compared to wild type EBV infected PBMCs had differential expression patterns for the phosphorylation of MAP kinases specifically p38, JNK and ERK. Regulation of β-catenin also differed among wild type and EBNA3C deleted mutants. These temporal differences in signaling activities of these recombinant viruses in PBMCs is likely important in defining their functional importance in EBV-mediated B-cell transformation.
|
10.18632/oncotarget.5002
|
pubmed_721_1395
|
In order to determine the feasibility of family record cards in general practice a research secretary created cards for 1825 households from a practice of 10 600 patients. The capital cost was pound108 and the time taken by the secretary was 1638 hours, which is equivalent to a wage of pound1330 for a maximum grade secretary, assuming a 70% rebate paid by the family practitioner committee. Approximately six and a half hours of receptionist/secretarial time are needed each week to maintain the system. The doctors spent a mean of three minutes checking and completing the initial update of each card.Before the cards were introduced, most information about families was held in the doctors' heads, and little was written in the records even though the doctors considered family information relevant in 33% of consultations. After the introduction of family record cards the doctors had access to reasonably complete information about the family at 98% of consultations and the cards were used at 95% of consultations. The doctors believed the information was useful for establishing rapport, identifying patients' concerns, obtaining relevant history, forming diagnostic hypotheses and managing the present complaint. Trainees and locums found the cards more useful than principals.
|
pubmed_721_1395
|
pubmed_205_6094
|
This review describes and discusses firstly the main characteristics and problems of psychosomatic research. One of the main problems is the validity of laboratory stressors in real-life situations. Secondly, it outlines the main philosophy and current concepts of psychosomatic medicine. The basic idea of a new integrative psychosomatic model is given. Thirdly, it presents some new methods that can be of use in psychosomatic research as well as research findings of special interest to cardiology. Especially the relationship between depression and coronary heart disease is discussed. The conclusion is that new methods and technical possibilities have great potential in enhancing psychosomatic research.
|
10.3109/07853890008995936
|
pubmed_277_16964
|
OBJECTIVE
To assess which are the most important perceived influential factors on health among the Spanish adult population. This may provide sufficient information to promote primary health care campaigns directed specifically to those that acknowledge that lifestyles are important in spite of not living healthy lifestyles themselves.
DESIGN
Observational cross-sectional study.
SETTING
Spain (Canary Islands not included).
PARTICIPANTS
A representative sample of 1000 Spanish participants over 15 years old selected by a multistage procedure.
INTERVENTION
Survey to evaluate the population choosing one of nine known health-related factors (smoking, food, alcohol intake, stress, physical activity, environment, body weight, support from family, genetics) as being one of the two most important factors influencing health through a validated questionnaire.
MEASUREMENTS AND RESULTS
The chi-square test for linear trend was used to assess the influence of factors coded on an ordinal scale. The Pearson chi-square test was applied for categorical factors. Smoking was considered the most influential health-related factor by most participants (47.8%). Males, those from lower socioeconomic and educational levels; people living in the south of Spain, and rural regions; those married and individuals who had 3 or more children below 15 years, perceived smoking more often as one of the most important determinants of health.
CONCLUSIONS
These data suggest that a large percentage of the Spanish adult population recognizes that life-styles are important determinants of health.
|
pubmed_277_16964
|
pubmed_362_4939
|
Transgender and gender non-conforming (TGNC) individuals face numerous barriers to healthcare, which contribute to many health disparities. TGNC persons may choose gender-affirming therapies with surgery and/or hormone replacement therapy (HRT) to manage gender incongruence. Despite the expanding use of HRT, the long-term outcomes on bone health and metabolism, are still relatively unknown in the TGNC population. In 2019, the International Society of Clinical Densitometry (ISCD) released an official position statement on the appropriate use of dual energy x-ray absorptiometry (DXA) to measure bone density in the TGNC population. In this study, we reviewed which "sex" is currently utilized among providers when performing DXA scans to calculate T- and Z-scores for TGNC persons and how this compares to the positions published by the ISCD. A retrospective analysis was performed utilizing HERON queries and subsequent chart review. HERON is a type of Informatics for Integrating Biology and the Bedside software that was utilized to find sets of patients of interest from electronic medical record data while preserving patient privacy through a query interface tool. Project specific sets including patient demographics, medications, gonadectomy, and DXA scan information was created in HERON to make this highly detailed data of specific patients available to the investigators on the platform, as reviewed and retrieved by the Institutional Review Board. The qualitative DXA data obtained from chart review was determined as "correct" or "incorrect" based on positions provided from the ISCD. 10 DXA scans that met inclusion criteria were obtained between 9 TGNC patients. In total, 18 T-scores and Z-scores of the 10 DXAs were reviewed and scored. Based on ISCD positions, 67% of the T-score and Z-scores were calculated incorrectly; using the erroneous "sex" based standard to compare scores. Like DXA scans, many current healthcare standards and protocols are based on a patient's sex or gender, which may cause confusion amongst healthcare personnel who have not received proper training regarding the TGNC population. In this study, 67% of T-scores and Z-scores were calculated incorrectly based on ISCD recommendations. An additional prospective research design is required to determine the consequences of incorrectly calculated DXA scans for TGNC patients. Furthermore, future research is needed to determine HRT's effects on bone mineral density in the TGNC population in the United States.
|
10.1016/j.jocd.2022.02.004
|
pubmed_486_24390
|
In this preliminary study, we examined peer victimization in adolescents with Down syndrome (DS) and how it relates to language and communication skills. We modified the Childrens' Social Experience Questionnaire (Crick and Grotpeter in Dev Psychopathol 8:367-380, 1996) to better suit adolescents with DS by simplifying vocabulary and syntax, using two step interview response format. Internal reliability was adequate, and all peer victimization measures were significantly elevated compared to a typically developing sample. Further, peer victimization (especially relational victimization) correlated with speech intelligibility, pragmatic judgment, conversational behavior, and receptive vocabulary. These preliminary data suggest that having DS may put adolescents at risk for peer victimization, but having relatively good language/communication skills may be a protective factor. Further research is warranted on this topic.
|
10.1007/s10803-019-04238-z
|
pubmed_806_5916
|
Reactions between niobium ethoxide and 8-hydroxy-2-methylquinoline or 5-chloro-8-hydroxyquinoline have been explored. Two new tetranuclear heteroleptic niobium complexes containing oxo, ethoxo, and quinolinate chelate rings have been synthesized and characterized by (1)H, (13)C and (93)Nb NMR, UV-Vis, and FT-IR spectroscopies, and single-crystal X-ray diffraction. The molecular structures of the niobium complexes, [Nb4(μ-O)4(μ-OEt)2(ONC10H8)2(OEt)8] (I) and [Nb4(μ-O)4(μ-OEt)2(ONC9H5Cl)2(OEt)8] (II), are composed of a pair of edge-sharing bioctahedral moieties in which connected via two almost linear oxo-bridges, with a large difference in the NbO distances. Single-crystal structures showed both complexes are centrosymmetric and contain two distinct Nb centers, and results confirmed by observation of two niobium signals in the (93)Nb NMR spectra of complexes.
|
pubmed_806_5916
|
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.