index
stringlengths 10
17
| text
stringlengths 101
18k
| doi
stringlengths 2
72
|
|---|---|---|
pubmed_73_605 | Focal adhesion kinase (FAK) is a critical mediator of matrix- and growth factor-induced signaling during development. Myocyte-restricted FAK deletion in mid-gestation mice results in impaired ventricular septation and cardiac compaction. However, whether FAK regulates early cardiogenic steps remains unknown. To explore a role for FAK in multi-chambered heart formation, we utilized anti-sense morpholinos to deplete FAK in Xenopus laevis. Xenopus FAK morphants exhibited impaired cardiogenesis, pronounced pericardial edema, and lethality by tadpole stages. Spatial-temporal assessment of cardiac marker gene expression revealed that FAK was not necessary for midline migration, differentiation, fusion of cardiac precursors, or linear heart tube formation. However, myocyte proliferation was significantly reduced in FAK morphant heart tubes and these tubes failed to undergo proper looping morphogenesis. Collectively our data imply that FAK plays an essential role in chamber outgrowth and looping morphogenesis likely stimulated by fibroblast growth factors (and possibly other) cardiotrophic factors. | 10.1002/dvg.20650 |
pubmed_884_6569 | Forty patients with simple atrial septal defect had left ventriculograms using cineangiography and/or Elema or Sircam still films. All had open heart surgery and careful scrutiny of the mitral valve by experienced surgeons. Prolapse of the posterior cusp was diagnosed from angiography in 28 patients but was confirmed at operation in only 5. Another 5 had a different mitral valve abnormality and the remaining 18 had no clinical signs to suggest mitral valve dysfunction after operation. It is concluded that though true ballooning or prolapse of the mitral cusps may coexist with simple atrial septal defect, its presence is overdiagnosed from the appearances of left ventriculography on anteroposterior, lateral, and right anterior oblique views. Left ventriculography was equally unreliable in the exact recognition of other anatomical abnormalities of the mitral valve in secundum defect, but accurate when the mitral valve was pronounced to be structurally normal. | 10.1136/hrt.40.1.58 |
pubmed_134_21938 | OBJECTIVE AND METHODS
To examine the involvement of neurotrophic factor receptors in the testis with acute experimental testicular torsion, the expression of tyrosine kinase receptors (trk) A and B, and p75 nerve growth factor receptor (NGFR) were studied in the rat testis with ischemia/reperfusion (I/R) injury, using Western blotting and immunohistochemistry. Apoptosis was detected using the terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) method.
RESULTS
There was a significant increase in TUNEL-positive reaction in spermatogonia in the seminiferous tubules in rat testes after testicular torsion. Western blot analysis showed that trk A expression reached a significant peak at 12 h after reperfusion (p < 0.01), as compared to sham-operated controls, whereas trk B was not increased in the testis after I/R. Constitutive expression of p75 NGFR was at or below the level detectable by Western blot analysis, and it remained unchanged in the testis after I/R. Immunohistochemistry demonstrated that after I/R trk A expression was increased in spermatocytes and spermatids in the seminiferous tubules, in contrast to the basal location of the TUNEL-positive reaction. Immunoreactivity of trk B was seen mainly in the interstitial cells in the sham-operated testis, and its localization was not changed after I/R.
CONCLUSION
It is postulated that trk A and B, but not p75 NGFR, are involved differently in the survival of testicular cells during acute experimental testicular torsion. In particular, increased trk A seems to be related to germ cell survival following I/R. | 10.1159/000082715 |
pubmed_1094_1553 | The five-layer Aurivillius phase Bi6TixFeyMnzO18 system is a rare example of a single-phase room temperature multiferroic material. To optimise its properties and exploit it for future memory storage applications, it is necessary to understand the origin of the room temperature magnetisation. In this work we use high resolution scanning transmission electron microscopy, EDX and EELS to discover how closely-packed Ti/Mn/Fe cations of similar atomic number are arranged, both within the perfect structure and within defect regions. Direct evidence for partitioning of the magnetic cations (Mn and Fe) to the central three of the five perovskite (PK) layers is presented, which reveals a marked preference for Mn to partition to the central layer. We infer this is most probably due to elastic strain energy considerations. The observed increase (>8%) in magnetic cation content at the central PK layers engenders up to a 90% increase in potential ferromagnetic spin alignments in the central layer and this could be significant in terms of creating pathways to the long-range room temperature magnetic order observed in this distinct and intriguing material system. | 10.1038/s41598-017-01902-1 |
pubmed_299_17685 | Inflammatory caspases (caspases 1, 4, 5 and 11) are activated in response to microbial infection and danger signals. When activated, they cleave mouse and human gasdermin D (GSDMD) after Asp276 and Asp275, respectively, to generate an N-terminal cleavage product (GSDMD-NT) that triggers inflammatory death (pyroptosis) and release of inflammatory cytokines such as interleukin-1β. Cleavage removes the C-terminal fragment (GSDMD-CT), which is thought to fold back on GSDMD-NT to inhibit its activation. However, how GSDMD-NT causes cell death is unknown. Here we show that GSDMD-NT oligomerizes in membranes to form pores that are visible by electron microscopy. GSDMD-NT binds to phosphatidylinositol phosphates and phosphatidylserine (restricted to the cell membrane inner leaflet) and cardiolipin (present in the inner and outer leaflets of bacterial membranes). Mutation of four evolutionarily conserved basic residues blocks GSDMD-NT oligomerization, membrane binding, pore formation and pyroptosis. Because of its lipid-binding preferences, GSDMD-NT kills from within the cell, but does not harm neighbouring mammalian cells when it is released during pyroptosis. GSDMD-NT also kills cell-free bacteria in vitro and may have a direct bactericidal effect within the cytosol of host cells, but the importance of direct bacterial killing in controlling in vivo infection remains to be determined. | 10.1038/nature18629 |
pubmed_245_3722 | A tetrahydropyranyl acetal bearing a proximal phenyl diazoketone substituent underwent Rh(ii)-catalysed C-H insertion via an 'anomalous' C-O bond-forming, rather than C-C bond-forming, transformation, giving spirocyclic orthoesters. Density functional theory calculations with M06 show that the formation of these anomalous products involves hydride transfer to the rhodium carbene, giving an intermediate zwitterion which undergoes C-O bond formation in preference to C-C bond formation. | 10.1039/c7ob02123b |
pubmed_476_16012 | For the first time we have defined naïve, central memory, effector memory and differentiated effector porcine CD8 T cells and analyzed their distribution in lymphoid and respiratory tissues after influenza infection or immunization, using peptide-MHC tetramers of three influenza nucleoprotein (NP) epitopes. The hierarchy of response to the three epitopes changes during the response in different tissues. Most NP-specific CD8 T cells in broncho-alveolar lavage (BAL) and lung are tissue resident memory cells (TRM) that express CD69 and downregulate CD45RA and CCR7. NP-specific cells isolated from BAL express genes characteristic of TRM, but gene expression differs at 7, 21 and 63 days post infection. In all tissues the frequency of NP-specific CD8 cells declines over 63 days almost to background levels but is best maintained in BAL. The kinetic of influenza specific memory CD8 T cell in this natural host species differs from that in small animal models. | 10.1038/s41385-021-00478-4 |
pubmed_11_14 | The previously published method allowing the separation of non-ferric (iron-free) and ferric (iron-saturated) forms of human serum transferrin via capillary electrophoresis has been further developed. Using a surface response methodology and a three-factorial Doehlert design we have established a new optimized running buffer composition: 50mM Tris-HCl, pH 8.5, 22.5% (v/v) methanol, 17.5mM SDS. As a result, two previously unobserved monoferric forms of protein have been separated and identified, moreover, the loss of ferric ions from transferrin during electrophoretic separation has been considerably reduced by methanol, and the method selectivity has been yet increased resulting in a total separation of proteins exerting only subtle or none difference in mass-to-charge ratio. The new method has allowed us to monitor the gradual iron saturation of transferrin by mixing the iron-free form of protein with the buffers with different concentrations of ferric ions. It revealed continuously changing contribution of monoferric forms, characterized by different affinities of two existing iron binding sites on N- and C-lobes of protein, respectively. Afterwards, the similar experiment has been conducted on-line, i.e. inside the capillary, comparing the effectiveness of two possible modes of the reactant zones mixing: diffusion mediated and electrophoretically mediated ones. Finally, the total time of separation has been decreased down to 4min, taking the advantage from a short-end injection strategy and maintaining excellent selectivity. | pubmed_11_14 |
pubmed_672_6828 | The effect of depletion of energy stores of rat hearts on their resistance to a total of 25 min ischemia was investigated by using a 31P-NMR method. Three experimental groups were compared: (1) pyruvate-perfused hearts depleted of adenine nucleotides (35% of normal) by 2-deoxyglucose (DG) treatment and containing deoxyglucose-6-phosphate (c. 40 mumol/g dry wt); (2) hearts partially depleted of glycogen stores (40 to 50% of initial) by long-term (2h) perfusion with pyruvate; (3) glucose perfused (11 nM) hearts with normal ATP and glycogen contents. By the end of ischemia the intracellular pH was decreased by 0.33, 0.90 and 1.40 units, respectively. Time to peak of ischemic contracture increased in this series from 3 to 18 and 24 min, respectively. At the peak of ischemic contracture ATP content was c. 30 to 40% (6 to 8 mumol/g dry wt) of normal value in all three groups. Reperfusion of hearts resulted in development of significant reperfusion contracture in glucose-perfused hearts and minor contracture in other series. Recovery of high energy phosphates and cardiac work index in DG-treated, glycogen-depleted and glucose-perfused hearts were: for phosphocreatine (PCr), 72, 102 and 83%; for ATP, 29, 47 and 56% and for cardiac work, 66, 78 and 24%, respectively. Recovery of cardiac work did not correlate linearly with tissue ATP. These data demonstrate that post-ischemic recovery of the contractile function of isovolumic heart may be dissociated from pre-ischemic myocardial ATP and glycogen contents. This dissociation can be explained by the two major factors: (1) the contribution of ischemic acidosis and catabolites accumulation to the cell damage and (2) by ATP compartmentation. | 10.1016/0022-2828(88)90595-0 |
pubmed_948_19592 | The inhibitory effect of a pharmacological dose of dopamine and the specific dopamine D-1 receptor agonist fenoldopam on basal and pulsatile TSH secretion was investigated in normal women. The TSH response to fenoldopam and subsequent releasing hormone administration was also studied. Six women received placebo or dopamine infusion (4.0 micrograms/kg min) for 17 h. After 9 h, blood samples were collected every 10 min between 0800 and 1600 h for measurement of TSH. Eight women received 8-h (0900-1700 h) infusions of either fenoldopam (0.5 micrograms/kg min) or placebo. After 7 h of infusion 10 micrograms TRH, 5 micrograms GnRH and 25 micrograms CRF was given i.v. Blood samples were collected every 10 min. Dopamine infusion as well as fenoldopam infusion significantly reduced both mean basal TSH secretion and TSH pulse frequency compared with corresponding control infusions (P less than 0.05). However, while the effect on TSH pulsatility was comparable (P greater than 0.05), the percentage decrease in basal TSH levels after 16 h of dopamine infusion was 51 +/- 16% (mean +/- SD) and after 7 h of fenoldopam infusion 19 +/- 12% (P less than 0.05). Neither of the drugs affected TSH pulse amplitude and fenoldopam did not influence TRH-stimulated TSH release (P greater than 0.05). The results suggest that dopamine D-1 receptors are involved in modulation of TSH pulsatility probably at the hypothalamic level. It is argued that dopaminergic inhibition of basal TSH secretion and TSH pulsatility is predominantly regulated through dopamine D-2 receptors at the pituitary level, and through D-1 receptors at the hypothalamic level, respectively. | 10.1111/j.1365-2265.1990.tb00882.x |
pubmed_671_8811 | Ferritin was purified from acute monocytic leukemia cells, and its biochemical and immunological properties were investigated. The iron content of acute monocytic leukemia cell ferritin was extremely low, and this ferritin migrated slightly faster than normal adult liver ferritin on immunoelectrophoresis and polyacrylamide gel disc electrophoresis. Isoelectric focusing in polyacrylamide gel showed predominantly acidic isoferritins. This was considered to characterize the nature of isoferritin from normal monocytes or to be the result of neoplastic change of monocytes. Immunologic studies failed to recognized any antigenic differences between isoferritin from acute monocytic leukemia cells and that from normal adult liver. Therefore, selective quantitation of acute monocytic leukemia cell isoferritin, if any in leukemic sera, by means of immunoassay was considered difficult. | 10.1002/1097-0142(19800715)46:2<289::aid-cncr2820460212>3.0.co;2-p |
pubmed_50_21115 | BACKGROUND
Surgical decision-making can be challenging when treating patients with osseous metastases. Numerous factors, including expected duration of survival, must be considered to ensure optimal operative stabilization of the affected bone. However, life expectancy of patients with metastatic carcinoma is often difficult to estimate. The goal of our study was to assess the associations of various clinical and demographic factors with survival time after intramedullary nail fixation of impending or completed pathologic femur fractures.
METHODS
One hundred thirty-eight consecutive patients treated with intramedullary nail fixation for impending or completed pathologic femur fractures between 2005 and 2017 were included in this study. Factors related to patient survival were assessed with Cox multivariate survival analysis. For all analyses, p < 0.05 was considered significant.
RESULTS
The median overall postoperative survival time was 8.4 months. Lower hemoglobin concentration (p = 0.001), lower albumin concentration (p = 0.002), and having a group 2 primary cancer (p = 0.001) were associated with shorter survival on multivariate analysis. When considering the subgroup of 88 prophylactically stabilized patients, lower hemoglobin concentration (p = 0.005), lower albumin concentration (p = 0.015), and having a group 2 primary cancer (p = 0.037) were predictive of shorter survival.
CONCLUSION
Several factors are associated with shorter survival after intramedullary nail fixation of pathologic femur fractures. These factors should be considered by orthopedic surgeons when educating patients and determining appropriate treatment. | 10.1016/j.suronc.2018.05.028 |
pubmed_1013_10883 | Complex regional pain syndrome (CRPS) is a painful condition commonly accompanied by movement disturbances and often affects the upper limbs. The basal ganglia motor loop is central to movement, however, non-motor basal ganglia loops are involved in pain, sensory integration, visual processing, cognition, and emotion. Systematic evaluation of each basal ganglia functional loop and its relation to motor and non-motor disturbances in CRPS has not been investigated. We recruited 15 upper limb CRPS and 45 matched healthy control subjects. Using functional magnetic resonance imaging, infraslow oscillations (ISO) and resting-state functional connectivity in motor and non-motor basal ganglia loops were investigated using putamen and caudate seeds. Compared to controls, CRPS subjects displayed increased ISO power in the putamen contralateral to the CRPS affected limb, specifically, in contralateral putamen areas representing the supplementary motor area hand, motor hand, and motor tongue. Furthermore, compared to controls, CRPS subjects displayed increased resting connectivity between these putaminal areas as well as from the caudate body to cortical areas such as the primary motor cortex, supplementary and cingulate motor areas, parietal association areas, and the orbitofrontal cortex. These findings demonstrate changes in basal ganglia loop function in CRPS subjects and may underpin motor disturbances of CRPS. | 10.1002/jnr.25057 |
pubmed_123_22081 | Some patients with diarrhoea predominant irritable bowel syndrome have increased rectal sensitivity. It is uncertain, however, whether the diarrhoea is a consequence of the rectal sensitivity or if it is sensitising the rectum in some way. The aim of this study was to assess whether inducing diarrhoea in normal healthy volunteers can sensitise the rectum and therefore be a potential or partial cause of the sensitive rectum seen in some patients with diarrhoea predominant irritable bowel syndrome. The anorectal responses to balloon distension were measured in 20 healthy volunteers (aged 20-43 years, 10 female) eight hours after laxative induced diarrhoea or under control conditions. Ingestion of an isoosmotic laxative increased stool output from 1.1 (0.7-2.3) (median (range)) to 8 (5-19) bowel movements per day with no significant differences between men and women. In women rectal sensitivity was significantly increased after diarrhoea compared with control conditions (vol to induce discomfort (ml): 116 (96, 136) v 153 (137, 168), mean (95% CI); p < 0.001). This was associated with a reduction in the volume to induce internal anal sphincter relaxation (16 (12, 20) v 28 (21, 36); p < 0.005), and volume to induce sustained internal anal sphincter relaxation (70 (56, 84) v 90 (67, 113); p < 0.03), but no significant change in rectal compliance (ml/cm H2O at 100 ml) 4.8 (3.5, 6.1) v 4.1 (3.0, 5.1) or distension induced motility (motility index) 994 (341, 1647) v 735 (46, 1424). Conversely, in men diarrhoea had no significant effect on anorectal physiology and their control values were not significantly different from those of the women. In conclusion, the results of this study taken with the finding that irritable bowel syndrome is more common in women, suggests that the male or female sex hormonal environment may be an important factor in allowing the gut to be sensitised to noxious stimuli. | 10.1136/gut.37.2.270 |
pubmed_115_21154 | BACKGROUND
The nondispersive isotope-selective infrared spectroscopy (NDIRS) is a valid method for the measurement of the 13CO2:12CO2 ratio in breath samples. Methodical influences have to be considered to obtain valid results.
AIM
To evaluate the effect of oxygen supply to patients on the measurement of 13C:12C ratio in breath samples by NDIRS.
METHODS
Breath samples of 26 healthy volunteers were taken before, immediately after, and 5 minutes after inhalation of 100% oxygen via a continuous positive air pressure (CPAP) mask. Analysis of breath samples was performed by NDIRS.
RESULTS
Delta per thousand before oxygen inhalation was -25.8 +/- 0.2. Immediately after 5 minutes of 100% oxygen inhalation, delta per thousand increased to -14.8 +/- 0.5 (delta over baseline [DOB] 11.0 +/- 0.4) and after additional 5 minutes of room air inhalation, delta per thousand normalized to -25.6 +/- 0.2 (DOB 0.2 +/- 0.1).
CONCLUSIONS
Oxygen supply to patients and, therefore, changes in gas composition in breath samples clearly influence 13CO2 measurement by NDIRS. This has to be taken into account in the clinical setting. Thus, oxygen supply during measurement of exhaled 13CO2 by NDIRS has to be avoided or maintained at a strictly constant level. | 10.1111/j.1523-5378.2005.00357.x |
pubmed_301_11804 | The normal mode frequencies and corresponding vibrational assignments of silylgermane are examined theoretically using the GAUSSIAN 98 set of quantum chemistry codes. All normal modes were successfully assigned to one of seven types of motion predicted by a group theoretical analysis (Si-H stretch, Ge-H stretch, Si-Ge stretch, H-Si-H bend, H-Ge-H bend, SiH(3) wag/GeH(3) wag and Si-Ge torsion) utilizing the C(3v) symmetry of the molecule. Predicted infrared and Raman intensities are presented. Molecular orbitals are presented and bonding is examined in terms of the molecular orbitals. | 10.1016/s1386-1425(03)00119-7 |
pubmed_1141_1376 | An HIV-1 p24 capture enzyme linked immunosorbent assay (ELISA) was developed and used in a study of B-cell epitopes in rabbits immunised with different gag p24 antigens. Rabbits were immunised with virion HIV-1/Lai, baculovirus recombinant p24, Escherichia coli recombinant p24-15 and a mixture of synthetic peptides representing sequences of HIV-1 gag p24 protein, respectively. Five out of nine rabbits developed antibodies that could be used for an antigen capture ELISA. No significant differences in IgG titers to the whole gag protein were seen when comparing rabbits immunised with four different antigens. Three major common linear epitope regions were mapped in the rabbits immunised with virion HIV-1/Lai and baculovirus recombinant p24. The rabbit immunised with HIV-1 gag peptides had the broadest linear epitope reactive responses whereas animals immunised with E. coli recombinant antigen had the most restricted linear epitope response. The capture ELISA method thus developed using the different rabbit anti-p24 IgG preparations was shown to capture isolates from HIV-1 subtypes or clades A to G. Only rabbits immunised with virion HIV-1/Lai and baculovirus recombinant p24 developed IgG that was capable of efficiently capturing HIV-1 p24 in ELISA, indicating the importance of preparing antibodies able to recognise native or discontinuous and linear antigen configurations. | 10.1016/s0022-1759(00)00141-1 |
pubmed_785_19192 | The purpose of this project was to examine the clinical judgment and reasoning skills of nursing students in high-fidelity simulation. Two levels of students (N = 104), novices and those who are slightly more advanced, participated in individual videotaped simulations. Afterward, interviews were conducted to explore what the student was thinking and feeling during simulation. Five themes emerged from the interviews: thinking like a nurse, assessment, looking for answers, communication, and magical or reflective thinking. There was a clear distinction in the reasoning skills of the novice students compared with students with more clinical experience. Tanner's model of clinical judgment in nursing is used to understand the findings of the study. | 10.3928/01484834-20140821-14 |
pubmed_574_11975 | The objective of our clinic-based case-control study was to identify risk factors for branch retinal vein occlusion. Between 1986 and 1990 data were obtained at five clinical centers from 270 patients with branch retinal vein occlusion and 1,142 controls. Data were collected from interviews, clinical examinations, and laboratory analyses of blood specimens. An increased risk of branch retinal vein occlusion was found in persons with a history of systemic hypertension, a history of cardiovascular disease, an increased body mass index at 20 years of age, a history of glaucoma, and higher serum levels of alpha 2-globulin. Risk of branch retinal vein occlusion decreased with higher levels of alcohol consumption and high-density lipoprotein cholesterol. The data suggest a cardiovascular risk profile for patients with branch retinal vein occlusion and indicate that 50% of patients with branch retinal vein occlusion may be attributable to hypertension. Our findings support current public health recommendations to diagnose and treat hypertension, reduce weight, increase physical activity, and maximize serum high-density lipoprotein levels. | pubmed_574_11975 |
pubmed_748_12546 | Dermal contact with some organic disinfection by-products (DBPs) such as trihalomethanes in chlorinated drinking water has been established to be an important exposure route. We evaluated dermal absorption of two haloketones (1,1-dichloropropanone and 1,1,1-trichloropropanone) and chloroform while bathing, by collecting and analyzing time profiles of expired breath samples of six human subjects during and following a 30-min bath. The DBP concentrations in breath increased towards a maximum concentration during bathing. The maximum haloketone breath concentration during dermal exposure ranged from 0.1 to 0.9 microg / m(3), which was approximately two orders of magnitude lower than the maximum chloroform breath concentration during exposure. Based on a one-compartment model, the in vivo permeability of chloroform, 1,1-dichloropropanone, and 1,1,1-trichloropropanone were approximated to be 0.015, 7.5 x 10(- 4), and 4.5 x 10(- 4) cm / h, respectively. Thus, haloketones are much less permeable across human skin under normal bathing conditions than is chloroform. These findings will be useful for future assessment of total human exposure and consequent health risk of these DBPs. | 10.1038/sj.jea.7500404 |
pubmed_1055_17270 | OBJECTIVES
Despite advances in the management of systemic vasculitis (SV), direct consequences of the disease, leading to impairments in physical and mental function can cause disability. The objective of this study was to assess work limitations in SV.
METHODS
SV patients were recruited from a tertiary care clinic. Work disabled (WD) was defined as not working, early retirement, or reduced hours at work. Participants who were working at the time of enrolment completed the Work Limitations Questionnaire (WLQ). Other work-related measures were self-reported by questionnaire. Disease outcome measures (Vasculitis Damage Index (VDI), Health Assessment Questionnaire-Disability Index (HAQ) and pain visual analogue score (VAS)) were obtained at time of WLQ.
RESULTS
103 participants were enrolled with mean age 58 (SD17), 60% females, 48% with anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), 26% with large vessel vasculitis (LVV) and 26% with other types of SV. 22 (21%) were WD secondary to SV, 29 (28%) were working and 52 (51%) subjects were not working for reasons other than SV. SV-related WD subjects were more likely to have a lower level of education (p=0.003) than non-WD subjects. The VDI was higher in SV-related WD vs. non-WD subjects: 1.9 (SD 2.7) vs. 2.9 (SD 1.4); p=0.015. 38 subjects were working in some capacity and completed the WLQ; their productivity loss was 8.2% and this was highly correlated with HAQ and pain VAS (rho=0.585 and rho=0.458, respectively).
CONCLUSIONS
SV-related work disability occurred in 21% and was associated with lower levels of education, higher disease severity and worse functional outcomes. | pubmed_1055_17270 |
pubmed_632_10449 | AIM
Although liver biopsy has long been considered the gold standard for staging fibrosis, because of the disadvantages and risks of biopsy, several noninvasive processes such as serum biomarkers have been introduced for the assessment of liver fibrosis. The aim of this study was to assess the diagnostic value of serum procollagen C-proteinase enhancer 1 (PCPE-1) as a noninvasive fibrosis marker in treatment-naive chronic hepatitis B patients.
PATIENTS AND METHODS
This study included 126 patients with biopsy-proven hepatitis B and 50 healthy controls. Fibrosis stage was determined using the Ishak scoring system. The PCPE-1 level was measured using the enzyme-linked immunosorbent assay assay, and the aspartate aminotransferase to platelet ratio index and the FIB-4 index were calculated using the formulas described in Appendix 1 (Supplemental digital content 1, http://links.lww.com/EJGH/A277).
RESULTS
Serum PCPE-1 levels of chronic hepatitis B patients were found to be significantly lower than those of the healthy control group (4.49±2.74 vs. 42.9±59.6 pg/ml, respectively, P<0.001). There was a statistically significant negative correlation between serum PCPE-1 level and fibrosis stage (P=0.011; r=-0.226). A statistically significant negative correlation was found between serum PCPE-1 level and necroinflammatory activity (P=0.030; r=-0.194). PCPE-1 levels of patients with liver fibrosis scores of F1-2 were statistically significantly lower than those of the healthy control group (P<0.001) (area under the receiver operating characteristic: 0.955). The area under the receiver operating characteristic of the PCPE-1 level was 0.615 for the prediction of fibrosis (F0 vs. F1-6) (P=0.039).
CONCLUSION
Serum PCPE-1 might be used as a noninvasive marker of liver fibrosis. Further animal and human studies are needed to assess the utility of this marker. | 10.1097/MEG.0000000000001123 |
pubmed_1041_9397 | In 2007 the Italian COM.E.T.A. (COMorbidities Evaluation and Treatment in Acromegaly) study group started to assess the application in a clinical setting of the Versailles criteria for management of acromegaly complications by a first questionnaire focusing on cardiovascular co-morbidities. A further questionnaire on sleep apnea syndrome (SAS) was delivered by the COM.E.T.A. study group to 107 endocrine centers in Italy. The results of our survey suggest that SAS is a well-known comorbidity even if its estimated prevalence is lower than in the literature. Polysomnography is the preferred tool for diagnosis. Control of SAS is considered relevant both for quality of life and co-morbidities. Continuous positive airway pressure is the cornerstone of therapy, but patients' acceptance may be critical. Control of GH/IGF-I secretion is important to improve SAS. Management of SAS requires cooperation between specialists. | 10.1007/BF03346696 |
pubmed_656_3911 | The aim of this study was to test in vitro the ability of a mixture of citrus extract, maltodextrin, sodium chloride, lactic acid and citric acid (AuraShield L) to inhibit the virulence of infectious bronchitis, Newcastle disease, avian influenza, porcine reproductive and respiratory syndrome (PRRS) and bovine coronavirus viruses. Secondly, in vivo, we have investigated its efficacy against infectious bronchitis using a broiler infection model. In vitro, these antimicrobials had expressed antiviral activity against all five viruses through all phases of the infection process of the host cells. In vivo, the antimicrobial mixture reduced the virus load in the tracheal and lung tissue and significantly reduced the clinical signs of infection and the mortality rate in the experimental group E2 receiving AuraShield L. All these effects were accompanied by a significant reduction in the levels of pro-inflammatory cytokines and an increase in IgA levels and short chain fatty acids (SCFAs) in both trachea and lungs. Our study demonstrated that mixtures of natural antimicrobials, such AuraShield L, can prevent in vitro viral infection of cell cultures. Secondly, in vivo, the efficiency of vaccination was improved by preventing secondary viral infections through a mechanism involving significant increases in SCFA production and increased IgA levels. As a consequence the clinical signs of secondary infections were significantly reduced resulting in recovered production performance and lower mortality rates in the experimental group E2. | 10.1038/s41598-020-73916-1 |
pubmed_704_5557 | Fidelity monitoring is an essential component of evidence-based replication in teen pregnancy prevention. Fidelity toolkits ensure that core curriculum is adhered to, by providing a detailed checklist of expected activities. When systematically reviewed, fidelity toolkits offer critical information on challenges and barriers that can inform and improve future programming. The purpose of this project was to implement an educational program to improve sexual health in teens, using a fidelity toolkit to promote and evaluate program fidelity. Participants, from a suburban Ohio county, included faculty, junior-level baccalaureate nursing students, and females, 15-19 years of age. Plan-do-study-act methodology was used to carry out this quality improvement initiative. Twenty-three nursing students, divided among 3 clinical sections, and their 3 faculty members completed the fidelity toolkits. Part I fidelity ranged from 82.73% to 100% (M = 97.8%), Part II fidelity ranged from 75% to 95.83% (M = 92.76%), Part III fidelity ranged from 81.5% to 95.83% (M = 91.8%), and Part IV fidelity ranged from 57% to 100% (M = 98.2%). Overall, fidelity of the program averaged 96.4%. Several themes were identified as a result of the qualitative analysis of narrative toolkit responses, in the categories of participant factors, site factors, and presenter factors. Toolkit use led to a high level of program fidelity. | 10.1891/2380-9418.10.2.149 |
pubmed_406_8917 | In this study the reinnervation of scar tissue was investigated histochemically to demonstrate catecholamine fluorescence and nonspecific cholinesterase activity. The scarring was produced by healing and contraction of a defect in the dorsal skin of the rat. The first regenerating nerves showing nonspecific cholinesterase activity were observed in the scar four weeks postoperatively. Throughout the investigation period, that is up to twenty weeks after the operation, only free regenerated nerves were found in the scar; no encapsulated nerve endings were observed. No fluorescent adrenergic nerves were found in the dense collagenous part of the scar tissue. Regenerated fluorescent nerves were, however, observed in the loose regenerated connective tissue under the scar. Most of these nerves followed the course of blood vessels. In the present work a vigorous contraction of the scar tissue was noted and a poor innervation of the scar tissue with free nerves was observed. The role of these regenerated nerve endings in sensory discrimination, and the importance of different transmitters acting in the sensory system are discussed. | 10.3109/02844317809012992 |
pubmed_1021_3479 | To explore whether pathophysiological plasma levels of atrial natriuretic peptide (ANP) actually involve sodium excretion in spontaneously hypertensive rats (SHR), we examined the in vivo and ex vivo effects of ANP and an endopeptidase inhibitor, thiorphan, on urinary sodium excretion and the elimination rate of ANP. We found the following: 1) The basal plasma ANP level was higher in 16-week-old SHR than in Wistar-Kyoto (WKY) rats (109 +/- 10 [SEM] versus 63 +/- 4 pg/ml, p less than 0.001). Thiorphan (30 mg/kg i.v.) significantly increased plasma ANP by 60% in both SHR and WKY rats. However, increases in urinary sodium excretion (+290% versus +130%, p less than 0.05) and cyclic GMP (+160% versus +60%, p less than 0.05) were greater in SHR than in WKY rats. Urinary excretion of ANP was markedly increased by thiorphan, and its increase was greater in SHR than in WKY rats. 2) The thiorphan-induced natriuresis was substantially attenuated by antiserum for ANP but not by a bradykinin receptor antagonist. 3) Isolated SHR kidneys excreted 50% less sodium than WKY rat kidneys at perfusion pressures of 100 and 160 mm Hg (p less than 0.05). Urinary sodium excretion was increased at the perfusate ANP level of 100 pg/ml, a concentration similar to the SHR plasma ANP (+70% at 160 mm Hg). 4) After bolus administration of ANP to the isolated kidney, the ANP concentration of the recirculating perfusate decreased rapidly in a log-linear fashion.(ABSTRACT TRUNCATED AT 250 WORDS) | 10.1161/01.hyp.17.6.1025 |
pubmed_870_12237 | beta2-Microglobulin has been synthesized in vitro by using a rabbit reticulocyte lysate system and mRNA from the mouse tumor cell line EL4. The molecule is synthesized as a precursor with an NH2-terminal extension of 19 amino acids: Ser-X-Ser-Val-X-Leu-Val-Phe-Leu-Val-Leu-Val-Ser-Leu-X-Gly-Leu-Tyr-X. The processing and segregation of this peripheral membrane protein are directly comparable to those of secretory proteins and integral membrane proteins: addition of dog pancreas microsomal membranes during translation caused conversion to the processed chain, but addition of membranes after synthesis did not; only the processed chain sedimented with the membrane vesicles and was protected from proteolysis by the vesicles; and processing of nascent beta 2-microglobulin was blocked by competitive inhibitors that prevent processing and segregation of secretory and integral membrane proteins. These results suggest that the signal sequences of secretory proteins, integral membrane proteins, and peripheral membrane proteins have a common function and a common receptor on the cytoplasmic face of dog pancreas microsomal membranes. This system also provides a means for studying in vitro the expression and function of the major histocompatibility antigens that are associated with beta 2-microglobulin on cell surfaces. | 10.1073/pnas.76.8.3651 |
pubmed_524_25869 | OBJECTIVE
To identify the causal relation between growth velocity and injury in elite-level youth football players, and to assess the mediating effects of motor performance in this causal pathway.
DESIGN
Prospective cohort study.
METHODS
We measured the body height of 378 male elite-level football players of the U13 to U15 age categories three to four months before and at the start of the competitive season. At the start of the season, players also performed a motor performance test battery, including motor coordination (Körperkoordinationstest für Kinder), muscular performance (standing broad jump, counter movement jump), flexibility (sit and reach), and endurance measures (YoYo intermittent recovery test). Injuries were continuously registered by the academies' medical staff during the first two months of the season. Based on the causal directed acyclic graph (DAG) that identified our assumptions about causal relations between growth velocity (standardized to cm/y), injuries, and motor performance, the causal effect of growth velocity on injury was obtained by conditioning on maturity offset. We determined the natural indirect effects of growth velocity on injury mediated through motor performance.
RESULTS
In total, 105 players sustained an injury. Odds ratios (OR) showed a 15% increase in injury risk per centimetre/year of growth velocity (1.15, 95%CI: 1.05-1.26). There was no causal effect of growth on injury through the motor performance mediated pathways (all ORs were close to 1.0 with narrow 95%CIs).
CONCLUSIONS
Growth velocity is causally related to injury risk in elite-level youth football players, but motor performance does not mediate this relation. | 10.1016/j.jsams.2021.03.004 |
pubmed_379_17366 | OBJECTIVES
The goal of this study was to determine the feasibility, safety, sensitivity and specificity of transesophageal dobutamine stress echocardiography for the detection of coronary artery disease.
BACKGROUND
Dobutamine stress echocardiography has been shown to be an extremely sensitive and specific noninvasive technique for the detection of myocardial ischemia. However, inadequate transthoracic images preclude the use of dobutamine stress echocardiography in a small but significant group of patients. Transesophageal echocardiography provides better resolution than that obtained with routine transthoracic imaging.
METHODS
Patients scheduled for routine cardiac catheterization underwent transesophageal dobutamine stress echocardiography. All patients underwent coronary arteriography within 48 h of the study, and lesion severity was determined by quantitative coronary angiography. Significant coronary obstruction was defined as stenosis > 50%.
RESULTS
Fifty-one male patients were enrolled in the study; six were excluded for technical reasons. There were no adverse outcomes or complications. Of 27 patients with significant coronary artery disease, 22 had positive study results (sensitivity 82%). Of 13 patients without significant obstructive coronary disease, 1 had a false positive study result (specificity 93%). In patients with a minimal lumen diameter < 1.25 mm, sensitivity was > 80%, and in patients with a minimal lumen diameter > 1.5 mm, sensitivity was < 70%, suggesting that lesions with a minimal lumen diameter < 1.25 mm are more likely to be physiologically significant.
CONCLUSIONS
Transesophageal dobutamine stress echocardiography is a feasible, safe and accurate technique for the detection of myocardial ischemia. There are inherent limitations to this technique in that transesophageal echocardiography must be performed. Transesophageal dobutamine stress echocardiography may allow extension of dobutamine stress testing to patients with inadequate transthoracic echocardiographic imaging and may provide an opportunity for further research applications. | 10.1016/0735-1097(94)00464-2 |
pubmed_757_12697 | Ulcerative colitis (UC) is a relapsing and remitting inflammatory bowel disease (IBD), but current conventional drugs lack efficacy. Astragalus polysaccharide (APS) is an active ingredient of Astragalus membranaceus and has been shown to ameliorate experimental colitis. In the present study, we aimed to investigate how APS affects the ferroptosis of intestinal epithelial cells in dextran sulfate sodium (DSS)-induced experimental colitis in mice. Our data showed that APS administration attenuated total weight loss, colon length shortening, disease activity index (DAI) scores, histological damage, and the expression of inflammatory cytokines in the colon of DSS-challenged mice. Moreover, we observed that treatment with APS obviously inhibited ferroptosis in both DSS-challenged mice and RSL3-stimulated Caco-2 cells, as indicated by the decrease in the expression of ferroptosis-associated genes (PTGS2, FTH, and FTL) and the levels of surrogate ferroptosis markers (MDA, GSH, and iron load). Mechanistically, the inhibitory effects of APS on ferroptosis in DSS-challenged mice and RSL3-stimulated Caco-2 cells were associated with the NRF2/HO-1 pathway. Collectively, our findings identify a new role of APS in preventing ferroptosis in a murine model of experimental colitis and human Caco-2 cells via inhibiting NRF2/HO-1 pathway. | 10.1016/j.ejphar.2021.174518 |
pubmed_1109_12265 | AIMS
This study was designed as a thorough QT (TQT) study to evaluate the effects of fluticasone furoate (FF)/vilanterol (VI) in healthy subjects. Supportive data from a TQT study conducted with FF are also presented.
METHODS
This was a randomized, placebo- and positive-controlled, double-dummy, double-blind, four-way crossover study, in which healthy subjects (n = 85) were randomized to 7 days of once-daily treatment of FF/VI (200/25 or 800/100 μg) or placebo or single-dose oral moxifloxacin (single-blind, 400 mg). In the supportive TQT study, subjects (n = 40) were randomized to single-dose inhaled FF (4000 μg), oral moxifloxacin (400 mg) or placebo.
RESULTS
There was a lack of effect of FF/VI (200/25 μg) on QTcF (Fridericia's correction); all time-matched mean differences from baseline relative to placebo (0-24 h) were <5 ms, with upper 90% confidence intervals (CI) of <10 ms. At 800/100 μg, FF/VI had no significant clinical effect on QTcF except at 30 min postdose when the 90% CI was >10 ms [mean (90% CI), 9.6 ms (7.2, 12.0)]. No effect on QTci (individually corrected) was observed at either strength of FF/VI, with mean time-matched treatment differences <5 ms at all time points [upper 90% CIs <10 ms (0-24 h)]. Assay sensitivity was confirmed; moxifloxacin prolonged QTcF and QTci, with time-matched mean differences from baseline relative to placebo of >10 ms (1-8 h postdose).
CONCLUSIONS
Repeat once-daily dosing of FF/VI (200/25 μg), which is the highest therapeutic strength used in phase III studies, is not associated with QTc prolongation in healthy subjects. Supratherapeutic strength FF/VI (800/100 μg) demonstrated a small transient effect on QTcF but not on QTci. | 10.1111/bcp.12243 |
pubmed_157_21853 | The stability of UiO-67 has been questioned for some time. We have used solid-state NMR to investigate the temporal stability of this MOF. Proper activation is necessary to achieve optimal surface area. However, even with proper activation, the long-term (30+ days) fate of UiO-67 is hydrolysis of the linker-metal bonds and, ultimately, pore collapse. | 10.1039/c5cc09919f |
pubmed_840_1022 | Retinal pigment epithelium (RPE) and transforming growth factor-beta (TGF-beta) have been shown to be involved in various retinal diseases. We have studied the role of inflammatory cytokines on the expression and secretion of TGF-beta in human RPE cells (HRPE). Confluent cultures of HRPE derived from donor eyes were used. RT-PCR analyses showed that TNF-alpha and IL-1beta increased the mRNA levels of both TGF-beta1 and TGF-beta2. IFN-gamma enhanced constitutively expressed, as well as, TNF-alpha-and IL-1beta-induced TGF-beta1 mRNA levels but decreased TGF-beta2 mRNA. The effects of these cytokines on TGF-beta1 and TGF-beta2 secretion correlated with the mRNA levels. TGF-beta1 was always produced as the latent form while 21-31% of TGF-beta2 was in the active form. IFN-gamma reduced the production of active form of TGF-beta2 to 4-9%. TGF-beta3 secretion was not detectable under any of the conditions. The Real-Time PCR analysis of TGF-beta mRNAs confirmed the observed results. The TGF-beta1 and TGF-beta2 secretion was induced by TGF-beta2 and TGF-beta1, respectively. Under these conditions, the contrasting effects of IFN-gamma on TGF-beta1 and TGF-beta2 secretion were also observed. JAK inhibitor selectively inhibited IFN-gamma induced TGF-beta1 secretion and mRNA levels while reversing the inhibitory effects of IFN-gamma on TGF-beta2. Analyses of transcription factor activity strongly indicated the role of STAT-1 but not NFkappaB, C-Myc, C-Jun, SP-1, MEF-2. Our data demonstrate that IFN-gamma differentially regulates constitutively expressed, as well as, cytokine-induced TGF-beta1 and TGF-beta2 mRNA levels and secretion of TGF-betas by HRPE. | 10.1002/jcp.20839 |
pubmed_845_23878 | Coccidioidomycosis ("Valley fever") is caused by Coccidioides immitis and C. posadasii. These fungi are thermally dimorphic, cycling between mycelia and arthroconidia in the environment and converting into spherules and endospores within a host. Coccidioides can cause a broad spectrum of disease that can be difficult to treat. There has been a steady increase in disease, with an estimated 350,000 new infections per year in the United States. With the increase in disease and difficulty in treatment, there is an unmet need to increase research in basic biology and identify new treatments, diagnostics, and vaccine candidates. Here, we describe protocols required in any Coccidioides laboratory, such as growing, harvesting, and storing the different stages of this dimorphic fungal pathogen. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Growth and harvest of liquid mycelia cultures for extractions Alternate Protocol 1: Large-volume growth and harvest of liquid mycelia cultures Basic Protocol 2: Mycelial growth on solid medium Alternate Protocol 2: Maintaining mycelial growth on solid medium Basic Protocol 3: Harvesting and quantification of arthroconidia Alternate Protocol 3: Long-term storage of arthroconidia Basic Protocol 4: Parasitic spherule growth and harvest Alternate Protocol 4: Obtaining endospores from spherules Basic Protocol 5: Intranasal infection of murine models. | 10.1002/cpmc.113 |
pubmed_55_5823 | The recognition of facial emotions is impaired following subthalamic nucleus (STN) deep brain stimulation (DBS) in Parkinson's disease (PD). These changes have been linked to a disturbance in the STN's limbic territory, which is thought to be involved in emotional processing. This was confirmed by a recent PET study where these emotional modifications were correlated with changes in glucose metabolism in different brain regions, including the amygdala and the orbitofrontal regions that are well known for their involvement in emotional processing. Nevertheless, the question as to whether these emotional changes induced by STN DBS in PD are modality-specific has yet to be answered. The objective of this study was therefore to examine the effects of STN DBS in PD on the recognition of emotional prosody. An original emotional prosody paradigm was administered to twenty-one post-operative PD patients, twenty-one pre-operative PD patients and twenty-one matched controls. Results showed that both the pre- and post-operative groups differed from the healthy controls. There was also a significant difference between the pre and post groups. More specifically, an analysis of their continuous judgments revealed that the performance of the post-operative group compared with that of the other two groups was characterized by a systematic emotional bias whereby they perceived emotions more strongly. These results suggest that the impaired recognition of emotions may not be specific to the visual modality but may also be present when emotions are expressed through the human voice, implying the involvement of the STN in the brain network underlying the recognition of emotional prosody. | 10.1016/j.neuropsychologia.2009.12.003 |
pubmed_832_3781 | Two-dimensional (2D) MoS2core-shell nanoparticles were synthesized using an eco-friendly surface functionalization-agent with L-glutathione and cystamine (L-GSH-MoS2-CYS) using ultrasonic frequency of 20-25 kHz. The novel modified electrode was evaluated for the electrochemical detection of doxorubicin (DOX), through cyclic and differential pulse voltammetric techniques. The electro-catalytic oxidation currents of DOX exhibited a linear relationship in the concentration ranges 0.1-78.3 and 98.3-1218 μM, with a detection limit of 31 nM. A sensitivity of 0.017μA μM-1 cm-2 was acquired at 0.48 V. The fabricated L-GSH-MoS2-CYS modified electrode showed excellent precision, selectivity, repeatability, and reproducibility during the determination of DOX levels in blood serum samples. Thus, the fabricated L-GSH-MoS2-CYS/GCE modified electrode has potential for clinical applications for optimization of chemotherapeutic drugs owing to its selectivity, ease of preparation, and long-term stability. Graphical abstract. | 10.1007/s00604-020-04642-8 |
pubmed_634_17171 | OBJECTIVES
Off-pump coronary artery bypass (OPCAB) may benefit select high-risk patients. We sought to analyze the long-term outcomes of OPCAB versus on-pump coronary artery bypass (ONCAB) in patients with moderate renal failure.
METHODS
A retrospective cohort analysis of primary isolated CAB surgery performed in Ontario, Canada, from October 2008 to March 2016 in the CorHealth Ontario Cardiac Registry identified 50,115 cases. Of these, 7782 (15.5%) had estimated glomerular filtration rate (eGFR) of 30 to 59 mL/min/1.73 m2. OPCAB was compared to ONCAB after propensity score matching.
RESULTS
Following propensity score matching, 1578 patient pairs were formed. Total number of bypass grafts was higher in ONCAB (3.31 ± 1.01 vs 3.12 ± 1.14; P < .01) and more arterial grafts were used in OPCAB (1.55 ± 0.71 vs 1.14 ± 0.58; P < .01). OPCAB was associated with lower rate of in-hospital stroke (0.7% vs 2.2%; P < .01), renal failure requiring dialysis (1.2% vs 2.9%; P < .01), and blood transfusion (52.4% vs 69.3%; P < .01). There was no difference in perioperative mortality (2.4% vs 3.0%; P = .36) between OPCAB and ONCAB, respectively. At 8-year follow-up, survival probability was not different when comparing OPCAB versus ONCAB: 62% versus 65%, respectively (hazard ratio, 0.98; 95% confidence interval, 0.84-1.13; P = .38). Cumulative incidence of permanent dialysis did not differ at 8-year follow-up: 7% versus 7%, respectively (hazard ratio, 1.01; 95% confidence interval, 0.72-1.43; P = .74.
CONCLUSIONS
OPCAB is associated with improved in-hospital renal outcomes, but is not associated with changes in short- or long-term mortality, or with the long-term cumulative incidence of end-stage renal failure requiring permanent dialysis in patients with moderate renal failure. | 10.1016/j.jtcvs.2019.03.142 |
pubmed_661_21611 | Two stocks of mice, hybrid (C3H X 101)F1 and inbred SEC/R1, were compared for 3-methyladenine-DNA N-glycosylase activity which is involved in removal of 3-methyladenine, 7-methylguanine and some other N-methylpurines in DNA, in cell-free extracts of different tissues. Based on activity measured both per unit weight of tissue and per mass DNA, there is a significant organ-specific and stock-specific difference in N-glycosylase activity over a range of 0.5-8.7 fmoles of 3-methyladenine released per h at 37 degrees C per micrograms DNA of tissue extract. On a per cell basis, the repair activity for 3-methyladenine is the highest in stomach in both stocks. The tissue can be arranged in order of decreasing activity of glycolytic removal as stomach greater than kidney greater than lung greater than liver greater than spleen greater than brain greater than ovary for SEC/R1 mice and stomach greater than kidney greater than ovary greater than spleen, lung and brain greater than liver for the hybrid mice. For all tissues except ovary, SEC/R1 mice have 1.5-4-fold higher specific N-glycosylase activity than (C3H X 101)F1 mice. In contrast, the ovary of SEC/R1 stock has about half as much enzyme activity as that of the hybrid stock. | 10.1016/0165-7992(88)90082-6 |
pubmed_1010_802 | Purpose: The aim of this study was to identify and rank discriminant radiomics features extracted from MR multi-modal images to construct an adaptive model for characterization of Dominant Intra-prostatic Lesions (DILs) from normal prostatic gland tissues (NT). Methods and Materials: Two cohorts were retrospectively studied: Group A consisted of 98 patients and Group B 19 patients. Two image modalities were acquired using a 3.0T MR scanner: Axial T2 Weighted (T2W) and axial diffusion weighted (DW) imaging. A linear regression method was used to construct apparent diffusion coefficient (ADC) maps from DW images. DILs and the NT in the mirrored location were drawn on each modality. One hundred and sixty-eight radiomics features were extracted from DILs and NT. A Partial-Least-Squares-Correlation (PLSC) with one-way ANOVA along with bootstrapping ratio techniques were recruited to identify and rank the most discriminant latent variables. An artificial neural network (ANN) was constructed based on the optimal latent variable feature to classify the DILs and NTs. Nineteen patients were randomly chosen to test the contour variability effect on the radiomics analysis and the performance of the ANN. Finally, the trained ANN and a two dimension (2D) convolutional sampling method were combined and used to estimate DIL-NT probability map for two test cases. Results: Among 168 radiomics-based latent variables, only the first four variables of each modality in the PLSC space were found to be significantly different between the DILs and NTs. Area Under Receiver Operating Characteristic (AUROC), Positive Predictive and Negative Predictive values (PPV and NPV) for the conventional method were 94%, 0.95, and 0.92, respectively. When the feature vector was randomly permuted 10,000 times, a very strong permutation-invariant efficiency (p < 0.0001) was achieved. The radiomic-based latent variables of the NTs and DILs showed no statistically significant differences (Fstatistic < Fc = 4.11 with Confidence Level of 95% for all 8 variables) against contour variability. Dice coefficients between DIL-NT probability map and physician contours for the two test cases were 0.82 and 0.71, respectively. Conclusion: This study demonstrates the high performance of combining radiomics information extracted from multimodal MR information such as T2WI and ADC maps, and adaptive models to detect DILs in patients with PCa. | 10.3389/fonc.2019.01313 |
pubmed_103_3556 | Telomerase is expressed in more than 85% of cancer cells. Tumor cells with metastatic potential may have a high telomerase activity, allowing cells to escape from the inhibition of cell proliferation due to shortened telomeres. Human telomerase primarily consists of two main components: hTERT, a catalytic subunit, and hTR, an RNA template whose sequence is complimentary to the telomeric 5'-dTTAGGG-3' repeat. In humans, telomerase activity is typically restricted to renewing tissues, such as germ cells and stem cells, and is generally absent in normal cells. While hTR is constitutively expressed in most tissue types, hTERT expression levels are low enough that telomere length cannot be maintained, which sets a proliferative lifespan on normal cells. However, in the majority of cancers, telomerase maintains stable telomere length, thereby conferring cell immortality. Levels of hTERT mRNA are directly related to telomerase activity, thereby making it a more suitable therapeutic target than hTR. Recent data suggests that stabilization of telomeric G-quadruplexes may act to indirectly inhibit telomerase action by blocking hTR binding. Telomeric DNA has the propensity to spontaneously form intramolecular G-quadruplexes, four-stranded DNA secondary structures that are stabilized by the stacking of guanine residues in a planar arrangement. The functional roles of telomeric G-quadruplexes are not completely understood, but recent evidence suggests that they can stall the replication fork during DNA synthesis and inhibit telomere replication by preventing telomerase and related proteins from binding to the telomere. Long-term treatment with G-quadruplex stabilizers induces a gradual reduction in the length of the G-rich 3' end of the telomere without a reduction of the total telomere length, suggesting that telomerase activity is inhibited. However, inhibition of telomerase, either directly or indirectly, has shown only moderate success in cancer patients. Another promising approach of targeting the telomere is the use of guanine-rich oligonucleotides (GROs) homologous to the 3' telomere overhang sequence (T-oligos). T-oligos, particularly a specific 11-base oligonucleotide (5'-dGTTAGGGTTAG-3') called T11, have been shown to induce DNA damage responses (DDRs) such as senescence, apoptosis, and cell cycle arrest in numerous cancer cell types with minimal or no cytostatic effects in normal, non-transformed cells. As a result, T-oligos and other GROs are being investigated as prospective anticancer therapeutics. Interestingly, the DDRs induced by T-oligos in cancer cells are similar to the effects seen after progressive telomere degradation in normal cells. The loss of telomeres is an important tumor suppressor mechanism that is commonly absent in transformed malignant cells, and hence, T-oligos have garnered significant interest as a novel strategy to combat cancer. However, little is known about their mechanism of action. In this review, we discuss the current understanding of how T-oligos exert their antiproliferative effects in cancer cells and their role in inhibition of telomerase. We also discuss the current understanding of telomerase in cancer and various therapeutic targets related to the telomeres and telomerase. | 10.3390/antiox6010015 |
pubmed_808_21467 | A moisturizing cream mixed with a steroid ointment is frequently prescribed to patients suffering from atopic dermatitis. However, there is a concern that the mixing operation causes destabilization. The present study was performed to investigate the stability of such preparations closely using magnetic resonance imaging (MRI). As sample preparations, five commercial moisturizing creams that are popular in Japan were mixed with an ointment base, a white petrolatum, at a volume ratio of 1 : 1. The mixed preparations were stored at 60°C to accelerate the destabilization processes. Subsequently, the phase separations induced by the storage test were monitored using MRI. Using advanced MR technologies including spin-spin relaxation time (T2) mapping and MR spectroscopy, we successfully characterized the phase-separation behavior of the test samples. For most samples, phase separations developed by the bleeding of liquid oil components. From a sample consisting of an oil-in-water-type cream, Urepearl Cream 10%, a distinct phase-separation mode was observed, which was initiated by the aqueous component separating from the bottom part of the sample. The resultant phase separation was the most distinct among the test samples. To investigate the phase separation quantitatively and objectively, we conducted a histogram analysis on the acquired T2 maps. The water-in-oil type creams were found to be much more stable after mixing with ointment base than those of oil-in-water type creams. This finding strongly supported the validity of the mixing operation traditionally conducted in pharmacies. | 10.1248/cpb.c16-00986 |
pubmed_177_13980 | This paper analyzes spatially ecosystem exposure to home and personal care (HPC) chemicals, accounting for market data and environmental processes in hydrological water networks, including multi-media fate and transport. We present a global modeling framework built on ScenAT (spatial scenarios of emission), SimpleTreat (sludge treatment plants), and Pangea (spatial multi-scale multimedia fate and transport of chemicals), that we apply across Asia to four chemicals selected to cover a variety of applications, volumes of production and emission, and physico-chemical and environmental fate properties: the anionic surfactant linear alkylbenzene sulphonate (LAS), the antimicrobial triclosan (TCS), the personal care preservative methyl paraben (MeP), and the emollient decamethylcyclopentasiloxane (D5). We present maps of predicted environmental concentrations (PECs) and compare them with monitored values. LAS emission levels and PECs are two to three orders of magnitude greater than for other substances, yet the literature about monitored levels of LAS in Asia is very limited. We observe a good agreement for TCS in freshwater (Pearson r=0.82, for 253 monitored values covering 12 streams), a moderate agreement in general, and a significant model underestimation for MeP in sediments. While most differences could be explained by uncertainty in both chemical/hydrological parameters (DT50water, DT50sediments, Koc, foc, TSS) and monitoring sites (e.g. spatial/temporal design), the underestimation of MeP concentrations in sediments may involve potential natural sources. We illustrate the relevance of local evaluations for short-lived substances in fresh water (LAS, MeP), and their inadequacy for substances with longer half-lives (TCS, D5). This framework constitutes a milestone towards higher tier exposure modeling approaches for identifying areas of higher chemical concentration, and linking large-scale fate modeling with (sub) catchment-scale ecological scenarios; a major limitation in model accuracy comes from the discrepancy between streams routed on a gridded, 0.5°×0.5° global hydrological network and actual locations of streams and monitoring sites. | 10.1016/j.scitotenv.2017.11.315 |
pubmed_1100_10143 | The interaction between afferent inputs from carotid body chemoreceptors (CCRs) and from slowly adapting pulmonary stretch receptors (PSRs) on the discharge patterns of medullary inspiratory (I) and expiratory (E) neurons was characterized in thiopental sodium-anesthetized, paralyzed, ventilated dogs. A cycle-triggered ventilator was used to produce control and test pulmonary afferent input patterns. The CCRs were stimulated by phase-synchronized bolus injections of CO2-saturated saline into the common carotid arteries. Only those neurons whose discharge time course was altered by both inflation and CCR activation were studied. The dorsal respiratory group (DRG) I inflation-insensitive neurons were also included. Cycle-triggered histograms of unit activity were obtained for the neuronal responses to inflation, CO2 bolus, and their combination, as well as for the spontaneous control condition. Linearity of the interaction was tested by comparing the sum of the net individual responses to the net response of the combined afferent inputs. The results suggest that a linear (additive) interaction between CCR and PSR inputs exists for the DRG I inflation-sensitive neurons, the ventral respiratory group (VRG) I decrementing, and caudal VRG E augmenting neurons, while a nonadditive interaction exists for caudal VRG E decrementing bulbospinal neurons. The implications of these findings are discussed. | 10.1152/ajpregu.1994.266.6.R1951 |
pubmed_196_2573 | BACKGROUND AND AIMS
Protein and organelle turnover by autophagy is a key component to maintain cellular homeostasis. Loss of the autophagy protein ATG16L1 is associated with reduced bacterial killing and aberrant interleukin-1β production, perpetuating inflammation and carcinogenesis. Here we hypothesized that the functional p.T300A gene variant in ATG16L1 is associated with an increased risk for hepatocellular carcinoma (HCC) in cirrhosis.
METHODS
A case-control study was performed using a prospective derivation cohort (107 patients with HCC and 101 controls) and an independent validation cohort (124 patients with HCC and 108 controls) of patients with cirrhosis of any aetiology. ATG16L1 p.T300A (rs2241880) and PNPLA3 p.I148M (rs738409) variants were determined by real-time PCR.
RESULTS
The G allele of the ATG16L1 p.T300A variant was more frequent in patients with HCC compared to controls without HCC in the derivation cohort (0.62 vs. 0.51, P = .022) and in the validation cohort (0.59 vs. 0.50, P = .045). In combined analysis, the odds ratios (OR) were 1.76 (95% CI: 1.07-2.88) for G allele positivity and 2.43 (95% CI: 1.37-4.31) for p.T300A G allele homozygosity. This association was independent from the presence of a PNPLA3 variant, which was also associated with HCC (OR 2.10; 95% CI: 1.20-3.66), and it remained significant after adjustment for male sex, age and aetiology in multivariate analysis.
CONCLUSION
The common germ-line ATG16L1 gene variant is a risk factor for HCC in patients with cirrhosis. Personalized strategies employing the genetic risk conferred by ATG16L1 and PNPLA3 may be used for risk-based surveillance in cirrhosis. | 10.1111/liv.14239 |
pubmed_19_18189 | Dichotic Listening (DL) is a valuable tool to study emotional brain lateralization. Regarding the perception of sadness and anger through affective prosody, the main finding has been a left ear advantage (LEA) for the sad but contradictory data for the anger prosody. Regarding an induced mood in the laboratory, its consequences upon DL were a diminished right ear advantage (REA) for the induction of sadness and an increased REA for the induction of anger. The global results fit with the approach-withdrawal motivational model of emotional processing, pointing to sadness as a right hemisphere emotion but anger processed bilaterally or even in the left hemisphere, depending on the subject's preferred mode of expression. On the other hand, the study of DL in clinically depressed patients found an abnormally larger REA in verbal DL tasks which was predictive of therapeutic pharmacological response. However, the mobilization of the available left hemisphere resources in these responders (reflected in a higher REA) would indicate a remission of the episode but would not assure the absence of new relapses. | 10.1016/j.bandc.2011.03.003 |
pubmed_954_19000 | Percutaneous cholangioplasty is a commonly performed procedure for both benign and malignant diseases. The most common route for accessing the biliary tree is transhepatic, following ultrasound or fluoroscopic-guided percutaneous puncture. There are situations when alternative routes can be utilized to access the common bile duct (CBD). We accessed the CBD via T-tube placed surgically in a 57-year-old man who had obstructive jaundice of obscure etiology which was likely inflammatory. | 10.4103/0971-3026.150133 |
pubmed_278_19917 | There has been an increased interest in high-level image-to-image translation to achieve semantic matching. Through a powerful translation model, we can efficiently synthesize high-quality images with diverse appearances while retaining semantic matching. In this paper, we address an imbalanced learning problem using a cross-species image-to-image translation. We aim to perform the data augmentation through the image translation to boost the recognition performance of imbalanced learning. It requires a strong ability of the model to perform a biomorphic transformation on a semantic level. To tackle this problem, we propose a novel, simple, and effective structure of Multi-Branch Discriminator (termed as MBD) based on Generative Adversarial Networks (GANs). We demonstrate the effectiveness of the proposed MBD through theoretical analysis as well as empirical evaluation. We provide theoretical proof of why the proposed MBD is an effective and optimal case to achieve remarkable performance. Comprehensive experiments on various cross-species image translation tasks illustrate that our MBD can dramatically promote the performance of popular GANs with state-of-the-art results in terms of both objective and subjective assessments. Extensive downstream image recognition evaluations at a few-shot setting have also been conducted to demonstrate that the proposed method can effectively boost the performance of imbalanced learning. | 10.1016/j.neunet.2021.04.013 |
pubmed_1067_18399 | BACKGROUND & AIMS
Gastroesophageal reflux disease (GERD) is prevalent worldwide. Until recently patients and physicians have had a choice between long-term medical therapy, usually in the form of proton pump inhibitors (PPIs), or surgical fundoplication. During the past several years, endoscopic antireflux therapies have been approved for GERD patients to potentially obviate the risks of surgery and avoid long-term medication use. The objective of this review was to critically evaluate existing literature on endoscopic antireflux therapies with regards to efficacy and safety.
METHODS
A review of human studies by using Pub Med was performed.
RESULTS
Injectable LES implants, endoscopically placed gastric plications, and radio frequency energy application to the LES comprise the 3 modes of antireflux therapies. These techniques received approval by the Food and Drug Administration on the basis of symptomatic evidence supplied by numerous uncontrolled trials. As a group, these techniques have demonstrated efficacy less than medical and surgical options, and yet they carry a rare but significant risk of serious complications and even death.
CONCLUSIONS
The field is still evolving at this stage, and there is a need for more randomized sham and placebo-controlled trials to better define the subjective and objective outcomes of these endoscopic procedures. At this time endoscopic antireflux procedures should be used with caution after discussing risks and benefits with the patient. | 10.1016/s1542-3565(05)00406-4 |
pubmed_932_23708 | Quantitative high-throughput mass spectrometry has become an established tool to measure relative gene expression proteome-wide. The output of such an experiment usually consists of a list of expression ratios (fold changes) for several thousand proteins between two conditions. However, we observed that individual peptide fold changes may show a significantly different behavior than other peptides from the same protein and that these differences cannot be explained by imprecise measurements. Such outlier peptides can be the consequence of several technical (misidentifications, misquantifications) or biological (post-translational modifications, differential regulation of isoforms) reasons. We developed a method to detect outlier peptides in mass spectrometry data which is able to delineate imprecise measurements from real outlier peptides with high accuracy when the true difference is as small as 1.4 fold. We applied our method to experimental data and investigated the different technical and biological effects that result in outlier peptides. Our method will assist future research to reduce technical bias and can help to identify genes with differentially regulated protein isoforms in high throughput mass spectrometry data. | 10.1016/j.jprot.2012.03.032 |
pubmed_877_3493 | Bovine leukemia virus (BLV) causes enzootic bovine leukosis and is closely related to the human T cell leukemia virus. Since BLV infection mostly occurs via cell-to-cell transmission, BLV infectivity is generally measured by culturing BLV-infected cells with reporter cells that form syncytia upon BLV infection. However, this method is time-consuming and requires skill. To visualize the infectivity of BLV, we developed a new assay called the luminescence syncytium induction assay (LuSIA) that is based on a new reporter cell line designated CC81-BLU3G. CC81-BLU3G is stably transfected with pBLU3-EGFP, which contains the BLV long terminal repeat U3 region linked to the enhanced-green fluorescence protein (EGFP) gene. CC81-BLU3G expresses the EGFP in response to BLV Tax expression specifically, and forms fluorescing syncytia when transfected with an infectious BLV plasmid or when cultured with BLV-infected cells. Compared to the conventional assay, LuSIA was more specific and detected cattle samples with low proviral loads. The fluorescing syncytia was easily detected by eye and automated scanning and LuSIA counts correlated strongly with the proviral load of infected cattle (R2 = 0.8942). | 10.1007/s00705-018-3744-7 |
pubmed_798_5947 | In deciduous trees, the delta(13)C values of leaves are known to diverge during growth from those of woody organs. The main purpose of this study is to determine whether the divergence in delta(13)C between leaves and current-year twigs of Fagus sylvatica (L.) is influenced by changes (i) in the relative contents of organic matter fractions and (ii) in the delta(13)C of respired CO(2). The delta(13)C values of bulk matter, extractive-free matter, lignin, holocellulose, starch, soluble sugars, water-soluble fraction and respired CO(2), as well as their relative contents in bulk matter were determined. The delta(13)C values of biochemical fractions and respired CO(2) showed very similar temporal variations for both leaves and twigs. Variations in bulk matter delta(13)C during growth were, therefore, poorly explained by changes in biochemical composition or in respiratory fractionation and were attributed to the transition from (13)C-enriched reserves (mainly starch) to (13)C-depleted new photoassimilates. The divergence between leaves and twigs was related to higher values of soluble sugar delta(13)C in twigs. However, the difference between lignin and holocellulose delta(13)C varied during growth. This phenomenon was attributed to the delay between holocellulose and lignin deposition. These results may have implications for analysis of organic matter delta(13)C in trees and forest ecosystems. | 10.1093/treephys/tpp013 |
pubmed_321_19012 | To identify active compounds in the roots of Euphorbia pekinensis for treatment of diabetic complications, an active column fraction from a 70% EtOH extract of E. pekinensis root was purified by preparative reversed-phase high-performance liquid chromatography, leading to the isolation of a new ellagic acid derivative, 3,3'-di-O-methylellagic acid 4-O-(6"-O-galloyl)-β-D-galactopyranoside (1: ), along with three known compounds, geraniin (2: ), 3,3'-di-O-methylellagic acid 4-O-β-D-xylopyranoside (3: ), and ellagic acid 3,3'-dimethyl ether (4: ). The structure of the new compound was established by extensive spectroscopic studies and chemical evidence. The inhibitory effects of isolated compounds 1: -4: on advanced glycation end-products (AGEs) formation were examined. All compounds exhibited considerable inhibition of AGEs formation and IC50 values of 0.41 - 12.33 µM, compared with those of the positive controls aminoguanidine (IC50 = 1122.34 µM) and quercetin (IC50 = 27.80 µM). In addition, the effects of 2: and 4: on the dilation of hyaloid-retinal vessels induced by high glucose (HG) in larval zebrafish were investigated; both compounds significantly reduced the HG-induced dilation of hyaloid-retinal vessels relative to the HG-treated control group. | 10.1055/s-0043-120447 |
pubmed_553_4021 | Previous studies have found that subjects report a raised critical flicker frequency (CFF) threshold after smoking a cigarette and a lowered CFF after drinking a moderate dose of alcohol. The present aim was to examine the joint effects of these two drugs on CFF. Although the changes in CFF were in the expected direction for each drug separately, the combined effects were variable, depending in part on the type of test being used. In a lengthy signal detection task (Experiment I), combining the drugs resulted in antagonism, but with short probe tests (Experiments II and III), the smokers showed little effect for alcohol alone, but decreased thresholds if they were allowed to smoke at the same time. Experiment IV examined the effects of both drugs on long and short threshold tests within the same session, essentially confirming the previous findings. Additional pre-drug threshold differences were found between smokers who were required to refrain from smoking overnight before testing and those who were nondeprived. | 10.1016/0306-4603(82)90052-1 |
pubmed_607_8427 | To establish the optimal conditions for recanalization of obstructed arteries without damage to vessel walls, an Nd-YAG laser coupled to a 0.2-mm-diameter optical fiber was used on obstructed human cadaver coronary and peripheral arteries and on popliteal arteries in amputated limbs. Vaporization of atheromatous plaques was consistently obtained with energy of 360-600 J and a diluted blood perfusate (3 g/100 ml hemoglobin) at a rate of 30 ml/min. The arterial wall was protected from thermal injury by inserting the optical fiber into an inflated balloon catheter and by cooling the system with the perfusate. Since recanalization of occluded arteries was consistently obtained without damage to the arterial wall or debris and thin and flexible optical fibers were easy to guide in the arteries, percutaneous transluminal Nd-YAG laser angioplasty was used in obstructed femoral and popliteal arteries in 12 patients. The first trials in man with Nd-YAG laser showed the method to be feasible, effective, and at low risk, although further studies are required to improve penetration of the obstruction and increase the diameter tunnel. | 10.1007/BF02577962 |
pubmed_721_8290 | Clazamycin, a novel pyrrolizidine antitumor antibiotic, exists in aqueous solution as a mixture of two epimers, clazamycins A and B [1A, 1B], the ratio of which is pH dependent. Several lines of evidence are presented, including the results of trapping experiments and a study demonstrating base promoted interconversion of the two forms, that implicate an azacyclooctenone species [3] as an intermediate in the interconversion process. This result supports a previous observation, that the C6a carbinolamidine hydroxyl of clazamycin is unreactive towards nucleophiles and may be significant in helping to elucidate the mechanism of action of this antibiotic. | 10.1021/np50051a004 |
pubmed_794_15586 | The impact of finite cycles on the phantom modulus in an otherwise perfect network is computed exactly. It is shown that pending cycles reduce the phantom modulus of the network by kT/V independent of junction functionality. The correction for nonpending cycles is larger than estimated previously within this particular approximation of the surrounding network structure. It is discussed that loop formation inevitably leads to streched chain conformations, if the loops are built step by step as part of the network structure. All network loops tend to contract simultaneously to optimize conformations, which leads to an increasing stretch of chains in larger loops that can be observed in computer simulations. Possible other corrections to the phantom modulus that were left aside in previous work are discussed briefly. | 10.1021/acsmacrolett.8b00020 |
pubmed_573_24294 | Permutation entropy (PE) has been recently suggested as a novel measure to characterize the complexity of nonlinear time series. In this paper, we propose a simple method to address some of PE's limitations, mainly its inability to differentiate between distinct patterns of a certain motif and the sensitivity of patterns close to the noise floor. The method relies on the fact that patterns may be too disparate in amplitudes and variances and proceeds by assigning weights for each extracted vector when computing the relative frequencies associated with every motif. Simulations were conducted over synthetic and real data for a weighting scheme inspired by the variance of each pattern. Results show better robustness and stability in the presence of higher levels of noise, in addition to a distinctive ability to extract complexity information from data with spiky features or having abrupt changes in magnitude. | 10.1103/PhysRevE.87.022911 |
pubmed_636_8741 | Advanced adult soft-tissue sarcomas (STSs) are rare tumors with a dismal prognosis and limited systemic treatment options. STSs may originate from mesenchymal stem cells (MSCs); the latter have mainly been isolated from adult bone marrow as plastic-adherent cells with differentiation capacity into mesenchymal tissues. Recently, a panel of antibodies has been established that allows for the prospective isolation of primary MSCs with high selectivity. Similar to cancer stem cells in other malignancies, sarcoma stem cells may bear immunophenotypic similarity with the corresponding precursor, that is, MSCs. We therefore set out to establish the expression pattern of MSC markers in sarcoma cell lines and primary tumor samples by flow cytometry. In addition, fibroblasts from different sources were examined. The results document a significant amount of MSC markers shared by sarcoma cells. The expression pattern includes uniformly expressed markers, as well as MSC markers that only stained subpopulations of sarcoma cells. Expression of W5C5, W8B2 (tissue nonspecific alkaline phosphatase [TNAP]), CD344 (frizzled-4), and CD271 marked subpopulations displaying increased proliferation potential. Moreover, CD271+ cells displayed in vitro doxorubicin resistance and an increased capacity to form spheres under serum-free conditions. Interestingly, another set of antigens, including the bona fide progenitor cell markers CD117 and CD133, were not expressed. Comparative expression patterns of novel MSC markers in sarcoma cells, as well as fibroblasts and MSCs, are presented. Our data suggest a hierarchical cytoarchitecture of the most common adult type sarcomas and introduce W5C5, TNAP, CD344, and CD271 as potential sarcoma progenitor cell markers. | 10.5966/sctm.2012-0055 |
pubmed_870_5145 | The differentiation of the ectoderm in Ambystoma mexicanum (Harrison stage 26--27) was examined under in vivo and in vitro conditions by scanning electron microscopy under different experimental conditions. About one out of three flank epidermal cells was found to be ciliated in the undistrubed or control embryos. The shape of ciliated cells in the explants from the animal region was only slightly affected. In no case was it possible to find two adjacent ciliated cells, implying that these cells prevent the appearance of cilia in the cells in direct contact. Transformation to ciliated cells is suppressed by hypertonicity but favoured in a hypotonic medium. The differentiation of epidermis is also dependent upon the synthesis of RNA and some kind of sulphated glucosaminoglycan, corroborated by the inhibitory effect of actinomycin and selenate. The differences between the test series and the controls are discussed with regard to factors controlling embryonic epidermal differentiation. | pubmed_870_5145 |
pubmed_19_24339 | The coexistence of infected abdominal aortic aneurysms and spondylitis is rare but challenging. The etiology of the infection is frequently unknown. The aim of this study was to review the outcome of surgical repair of this complex disease. From 2004 to 2006, six patients were identified who underwent surgical repair of concomitant infected abdominal aortic aneurysm and spondylitis. Diagnosis, treatment and intermediate-term results are presented. The clinical manifestation included the signs of ongoing systemic infection, neurological deficit and abdominal or back pain. Computed tomography revealed abdominal aortic aneurysms associated with polysegmental spondylitis. Patients underwent radical debridement and aortic replacement with cryopreserved aortic allografts or silver-coated prostheses followed by antibiotic treatment. Only one patient received a simultaneous anterior vertebral stabilization. Greater omentum was placed in the abscess cavity. Intensive care unit and hospital stay averaged 3.0 and 28.0 days, respectively. Organisms were identified in all but one patient. Over a follow-up period of 4.4 years, four patients are alive and showing freedom from infection, and two patients had died unrelated at seven and eight months. In conclusion, surgical repair of infected aortic aneurysms with resection of infected tissues and implantation of a homograft or a silver-coated prosthesis achieved favorable results in this sick patient group. Simultaneous vertebral stabilization is rarely necessary. | 10.1258/vasc.2010.oa0255 |
pubmed_319_5367 | AIMS
The aims were to isolate a raw starch-degrading α-amylase gene baqA from Bacillus aquimaris MKSC 6.2, and to characterize the gene product through in silico study and its expression in Escherichia coli.
METHODS AND RESULTS
A 1539 complete open reading frame of a starch-degrading α-amylase gene baqA from B. aquimaris MKSC 6·2 has been determined by employing PCR and inverse PCR techniques. Bioinformatics analysis revealed that B. aquimaris MKSC 6.2 α-amylase (BaqA) has no starch-binding domain, and together with a few putative α-amylases from bacilli may establish a novel GH13 subfamily most closely related to GH13_1. Two consecutive tryptophans (Trp201 and Trp202, BaqA numbering) were identified as a sequence fingerprint of this novel GH13 subfamily. Escherichia coli cells produced the recombinant BaqA protein as inclusion bodies. The refolded recombinant BaqA protein degraded raw cassava and corn starches, but exhibited no activity with soluble starch.
CONCLUSIONS
A novel raw starch-degrading B. aquimaris MKSC 6.2 α-amylase BaqA is proposed to be a member of new GH13 subfamily.
SIGNIFICANCE AND IMPACT OF THE STUDY
This study has contributed to the overall knowledge and understanding of amylolytic enzymes that are able to bind and digest raw starch directly. | 10.1111/jam.12025 |
pubmed_857_16674 | Yeast strains were constructed in which a single telomere could be eliminated from the end of a dispensable chromosome. In wild-type cells, elimination of a telomere caused a RAD9-mediated cell cycle arrest, indicating that telomeres help cells to distinguish intact chromosomes from damaged DNA. However, many cells recovered from the arrest without repairing the damaged chromosome, replicating and segregating it for as many as ten cell divisions prior to its eventual loss. Telomere elimination caused a dramatic increase in loss of the chromosome in all strains examined, demonstrating that yeast telomeres are also essential for maintaining chromosome stability. Thus, in spite of checkpoint and DNA damage repair systems, many chromosomes that lose a telomere are themselves destined for loss. | 10.1016/0092-8674(93)90493-a |
pubmed_866_2597 | Electrochemical performance of nanostructured carbon electrodes was evaluated using cyclic voltammetry and a simple simulation model. The electrodes were prepared from soluble precursors by anodic electrodeposition of two sizes of graphene quantum dot assemblies (hexabenzocoronene (HBC) and carbon quantum dot (CQD)) onto a conductive support. Experimental and simulated voltammograms enabled the extraction of the following electrode parameters: conductivity of the electrodes (a combination of ionic and electronic contributions), density of available electrode states at different potentials, and tunneling rate constant (Marcus-Gerischer model) for interfacial charge transfer to ferrocene/ferrocenium (Fc/Fc+) couple. The parameters indicate that HBC and CQD have significant density of electronic states at potentials more positive than -0.5 V versus Ag/Ag+. Enabled by these large densities, the electron transfer rates at the Fc/Fc+ thermodynamic potential are several orders of magnitude slower than those commonly observed on other carbon electrodes. This study is expected to accelerate the discovery of improved synthetic carbon electrodes by providing fast screening methodology of their electrochemical behavior. | 10.1021/acsami.9b14161 |
pubmed_419_8777 | Combined heart-kidney transplantation (HKT) is a growing therapeutic strategy in patients with advanced heart failure (HF) and concomitant chronic kidney disease (CKD). Although patients with advanced HF and need for chronic haemodialysis have a clear indication for combined HKT, challenges to current practice lie in identifying those patients with severely depressed kidney function, which will not recover kidney function after restoration of appropriate haemodynamic conditions following heart transplantation (HT) alone. Because of the paucity of available organs, maximisation of kidney graft utility whilst minimising the operative risks associated with combined transplantation is mandatory. The benefits of HKT go beyond the mere restoration of kidney function. Data from registry analysis show that HKT improves overall survival in patients with CKD, as compared to heart transplant only, and it is associated with reduced incidence of heart allograft rejection, likely through the promotion of host immune tolerance mechanisms. In patients not requiring chronic dialysis, kidney-after-heart strategy may be explored, instead of combined HKT, in particular when the aetiology of CKD is unclear. This indeed allows for monitoring and gaging of indications for combined transplantation in the postoperative period. This approach however should be matched with priority listing for kidney transplantation given the high waitlist mortality in heart transplant recipients with associated CKD. The use of kidney machine perfusion may represent an additional tool to optimise the outcome of HKT, allowing more time to stabilise the patient after HT surgery. | 10.1097/MOT.0000000000000989 |
pubmed_881_4444 | OBJECTIVE
To examine the postpartum bleeding experience of a cohort of breast-feeding women and to compare it with the conventional definition of lochia.
METHODS
Four hundred seventy-seven experienced breast-feeding women in Manila, the Philippines, were followed prospectively from delivery and recorded vaginal bleeding in a menstrual diary. The median duration of lochia was calculated using survival analysis. In addition, all bleeding separate from lochia within the first 8 weeks postpartum was noted.
RESULTS
The median duration of lochia was 27 days and did not vary by age, parity, sex or weight of the infant, breast-feeding frequency, or level of supplementation. More than one-fourth of the women experienced a bleeding episode separated from the original lochial flow by at least 4 bleeding-free days and beginning no later than postpartum day 56. Ten breast-feeding women may have had their first menstrual bleed before day 56.
CONCLUSIONS
Lochia lasted substantially longer than the conventional assumption of 2 weeks. It was common for postpartum bleeding to stop and start again or to be characterized by intermittent spotting or bleeding. Return of menses is rare among fully breast-feeding women in the first 8 weeks postpartum. | 10.1016/S0029-7844(96)00482-6 |
pubmed_967_73 | Electroconvulsive shock (ECS) decreases fascia dentata responses to entorhinal stimulation by 50% in unanesthetized rats. Synaptic potentials and population spikes return to pre-ECS level during 1 h and 3 h, respectively. This recovery rate is compared with the dynamics of ECS-induced anterograde amnesia. | 10.1007/BF01949767 |
pubmed_973_8118 | Thumb hypoplasia is characterized by diminished thumb size, metacarpal adduction, metacarpophalangeal joint instability, thenar muscle hypoplasia or aplasia, extrinsic tendon dysplasia, and in the most severe cases, carpometacarpal joint instability or thumb aplasia. Severe thumb hypoplasia and aplasia are best treated by thumb ablation and pollicization of the index finger. Less severe thumb hypoplasia can be reconstructed by a combination of soft tissue release, first web space local flap coverage, metacarpophalangeal joint collateral ligament and capsule reconstruction, extrinsic tendon tenolysis, and muscle or tendon transfers. | 10.1016/j.jhsa.2009.12.020 |
pubmed_900_7131 | INTRODUCTION
Vascular response at edges of drug-eluting stents is still not well established, particularly in diabetic patients who are prone to aggressive atherosclerosis progression. Recently, Biolimus and Zotarolimus have demonstrated potent antiproliferative effects.
OBJECTIVE
To compare the vascular responses at edges of sirolimus analogous-eluting stents in patients with and without diabetes, using intravascular ultrasound (IVUS).
METHODS
306 edges were analyzed in 153 patients treated with drug-eluting stents and divided in: diabetics (122 edges) and nondiabetics (166 edges). IVUS was performed postintervention and at 6-month follow-up and included 5 mm distal and proximal to the stented segment. Vessel, lumen, and plaque volumes were calculated. Volume variation (follow-up minus basal) was also calculated. Edge restenosis was defined as obstruction >50%.
RESULTS
Baseline characteristics were similar between groups. In both groups the entire lesion length was covered (stent length/lesion length ratio was 1.5 for both groups). There were no differences in edge volumes and restenosis rate between the groups. Among diabetics, there was no significant volume variation. However, in nondiabetic patients there was significant increase in vessel volume in proximal (from 67.1 +/- 22 mm(3) to 72.2 +/- 25 mm(3): P = 0.02) and distal (from 54.4 +/- 22 mm(3) to 59.8 +/- 22 mm(3): P = 0.001) edges.
CONCLUSION
Nondiabetic patients showed a significant positive vascular remodeling in proximal and distal edges of sirolimus analogous-eluting stent. This vascular mechanism was not observed in diabetic patients. Although different vascular responses were observed, restenosis rates were equivalent between the 2 groups at 6-month follow-up. | 10.1002/ccd.21139 |
pubmed_1080_7530 | That the soul of a human person is infused at conception is a metaphysical claim. But given its traditional articulation, it has the empirical consequence that the zygote must have a substantial continuity with the adult person, a continuity which is already determined at conception. This empirical consequence is contradicted by the fact that the zygote may become a hydatidiform mole, or several persons. The metaphysical claim is falsified by the facts. | 10.1093/jmp/14.6.647 |
pubmed_68_1922 | In order to describe the status of long-term survivors of brain stem glioma, neuropsychological and behavioral measures were obtained a median of 2.5 (range 1.5-5.6) years after diagnosis from 16 survivors of 51 consecutively diagnosed children with brain stem glioma between 1983 and 1991. Among 11 children with dorsally exophytic tumors, 7 were treated with surgery alone (SRG) and 4 received conventionally fractionated local cranial radiation therapy (CFRT; 54-56 Gy) to the brain stem following surgery, 3 of these because of recurrent disease. Five others with diffusely infiltrative brain stem tumors received hyperfractionated radiation therapy (HFRT; 70.2 Gy) to the brain stem; 4 following biopsy or limited resection and 1 without prior surgery. IQs of children in the CFRT (mean 89, SD 24.4) and HFRT (mean 85, SD 12.7) groups were not significantly different. Children in the SRG group had significantly higher IQs (mean 100, SD 11.0) and fewer neurologic deficits than those who had received CFRT or HFRT. However, after statistically controlling for severity of neurologic deficits, treatment had no effect on IQ. The severity of residual neurologic deficits accounted for 42% of the variance in IQ scores; children with fewer neurologic problems scored higher. Additional studies are required to evaluate the potential neuropsychological benefits of equivalent total doses of HFRT compared to CFRT. | 10.1159/000120795 |
pubmed_27_17679 | To compare the histological features of non-drug-induced and drug-induced coma blister, we performed histopathological and immunopathological studies of four biopsy specimens from three patients with non-drug-induced coma. These results were compared with the previously well-documented histology of drug-induced coma. The findings of the present study of non-drug-induced coma included (a) a variable degree of epidermal cell degeneration, including vacuolation of basal cells, intraepidermal blister formation with pale cytoplasm, and extensive coagulation necrosis with pale nuclei; (b) alteration of the outer root sheath of telogen follicles, ranging from focal necrosis to total coagulation necrosis, and degeneration of sebaceous gland with disappearance of the germinative cell layer; (c) secretory eccrine cells with pyknotic nuclei, vacuolation of the cytoplasm, and intercellular edema, resulting in poorly defined cytoplasm, although the nuclei of the outer basal layer were partially preserved; (d) from slight edema of the vessel wall of the venules to fibrinoid, thrombosis and/or fibrinoid necrotic degeneration of arterioles and venules; and (e) deposits of immunoglobulins or complement as detected by direct immunofluorescent technique in all the three cases. One significant difference between non-drug-induced and drug-induced coma blister was the presence of fibrinoid thrombi in the lumina of non-drug-induced coma blisters. Since one of the three cases of non-drug-induced coma studied in the present report did not show thrombi in the lumina, this feature may not always be available for the differential diagnosis of these two conditions. However, fibrinoid thrombi may be a good marker for the differentiation of these two conditions, when the depth and duration of non-drug-induced coma are severe enough to induce these lesions. | 10.1097/00000372-199608000-00003 |
pubmed_453_17269 | The use of classification and regression tree (CART) methodology is explored for the diagnosis of patients complaining of anterior chest pain. The results are compared with those previously obtained using correspondence analysis and independent Bayes classification. The technique is shown to be of potential value for identifying important indicators and cutpoints for continuous variables, although the overall classification performance was rather disappointing. Suggestions are made for extensions to the methodology to make it more suitable for clinical practice. | 10.1002/(sici)1097-0258(19970415)16:7<717::aid-sim504>3.0.co;2-e |
pubmed_482_8558 | The current COVID-19 pandemic has a tremendous impact on daily life world-wide. Despite the ability to dampen the spread of SARS-CoV-2, the causative agent of the diseases, through restrictive interventions, it is believed that only effective vaccines will provide sufficient control over the disease and revert societal live back to normal. At present, a double-digit number of efforts are devoted to the development of a vaccine against COVID-19. Here, we provide an overview of these (pre)clinical efforts and provide background information on the technologies behind these vaccines. In addition, we discuss potential hurdles that need to be addressed prior to mass scale clinical translation of successful vaccine candidates. | 10.1002/anie.202008319 |
pubmed_648_12473 | This study aimed to investigate the effects of hypoxia on Cu-induced antioxidant defense, Cu transport, and mitophagy in the liver of the large yellow croaker. Fish were exposed to hypoxia (3.0 mg L-1), Cu (120 μg L-1), and hypoxia (3.0 mg L-1) plus Cu (120 μg L-1) for 48 h. Hypoxia exposure increased antioxidant abilities to maintain cellular redox balance. Although Cu exposure alone improved antioxidant defense, Cu transport, and mitophagy, these stress responses could not completely neutralize Cu toxicity, as reflected by the elevated reactive oxygen species (ROS) and lipid peroxidation (LPO) and hepatic vacuoles. When compared with Cu stress alone, hypoxia increased Cu toxicity by inhibiting antioxidant defense, Cu transport, and mitophagy, leading to the increment of mortality, ROS, and LPO, and the deterioration of histological structure. The adverse effects of hypoxia on Cu-induced metal transport and mitophagy might be involved in metal-responsive element-binding transcription factor-1 (MTF-1) and Forkhead box O-3 (FoxO3) signaling pathways, respectively. Overall, hypoxia reduced antioxidant response, Cu transport, and mitophagy in fish exposed to Cu, which contributes to understanding the molecular mechanisms underlying negative effects of hypoxia on Cu toxicity in fish. | 10.1007/s10695-020-00765-0 |
pubmed_980_12784 | Multifunctional nanocomposites that exhibit well-defined physical properties and encode spatiotemporally controlled responses are emerging as components for advanced responsive systems, for example, in soft robotics or drug delivery. Here an example of such a system, based on simple magnetic hydrogels composed of iron oxide magnetic nanoflowers and Pluronic F127 that generates heat upon alternating magnetic field irradiation is described. Rules for heat-induction in bulk hydrogels and the heat-dependence on particle concentration, gel volume, and gel exposed surface area are established, and the dependence on external environmental conditions in "closed" as compared to "open" (cell culture) system, with controllable heat jumps, of ∆T 0-12°C, achieved within ≤10 min and maintained described. Furthermore the use of extrusion-based 3D printing for manipulating the spatial distribution of heat in well-defined printed features with spatial resolution <150 µm, sufficiently fine to be of relevance to tissue engineering, is presented. Finally, localized heat induction in printed magnetic hydrogels is demonstrated through spatiotemporally-controlled release of molecules (in this case the dye methylene blue). The study establishes hitherto unobserved control over combined spatial and temporal induction of heat, the applications of which in developing responsive scaffold remodeling and cargo release for applications in regenerative medicine are discussed. | 10.1002/smll.202004452 |
pubmed_201_11064 | Options for gender affirming therapy in trans men include social transitioning, mental coaching, hormonal therapy and gender affirming surgery. Research has concluded that gender affirming therapy is safe and feasible and generally leads to high satisfaction rates. However, research regarding the cost-effectiveness is scarce. Areas covered: A literature research was conducted on PubMed, Google scholar and Scopus, searching for relevant articles on the subject of the effects of gender affirming hormone therapy, gender affirming surgery and fertility in trans persons. Out of the 77 full text articles, 29 on the topic of quality of life and sexual desire following the initiation of gender affirming hormonal therapy and gender affirming surgery were selected for this review. Expert commentary: Multiple studies have shown the positive effect of gender affirming hormonal therapy and gender affirming surgery on quality of life of trans persons and several studies describe an increase in their psychological wellbeing. In addition, satisfaction rates after gender affirming surgery are high and surgery is rarely regretted. However, as only one study has addressed cost-effectiveness of gender affirming treatment in trans men, further research is necessary. | 10.1080/14737167.2017.1388164 |
pubmed_533_413 | The chronic behavior of mature lymphoid malignancies, with relapses occurring years apart in many patients, has until recently been unexplained. Patterns of relapse also differ vastly between disease entities, with some being highly curable by chemotherapy whereas others are destined to reemerge after treatment. Lately, the use of next-generation sequencing techniques has revealed essential information on the clonal evolution of lymphoid malignancies. Also, experimental xenograft transplantation point to the possible existence of an ancestral (stem) cell. Such a malignant lymphoid stem cell population could potentially evade current therapies and be the cause of chronicity and death in lymphoma patients; however, the evidence is divergent across disease entities and between studies. In this review we present an overview of genetic studies, case reports, and experimental evidence of the source of mature lymphoid malignancy and discuss the perspectives. | 10.1182/bloodadvances.2017008854 |
pubmed_930_5727 | Count-based scintigraphic left ventricular end-diastolic (LVED) volume measurement was optimized using a reproducible method for determining left ventricular counts and an independently measured average apparent tissue attenuation coefficient (0.16 cm-1). Tissue depth was calculated by triangulation. Results were compared to single-plane contrast ventriculographic volumes by an area-length method, performed within one hour, in 18 patients. The overall correlation of measurements of LVED volume by the 2 methods was 0.96 with standard error of the scintigraphic estimate of 15.8 ml. For 6 patients with angiographically normal wall motion, the correlation of volume measurements was 0.99 with standard error of the estimate of 5.1 ml. The mean absolute difference in LVED volume by the 2 methods was 3.8 ml in the group with normal wall motion compared to 19.2 ml in the 12 patients with angiographically abnormal wall motion. Area-length LVED volume calculation assumes that the left ventricle conforms to a standard shape. Discrepancies in volume estimates with abnormal ventricular wall motion suggest that the area-length method is less accurate. Optimized count-based LVED left ventricular volume measurement is accurate and might be preferable to single-plane contrast angiographic volume measurement of abnormal ventricles. | pubmed_930_5727 |
pubmed_188_22154 | Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease caused by the degeneration of upper and lower motor neurons. Defects in axonal transport have been observed pre-symptomatically in the SOD1G93A mouse model of ALS, and have been proposed to play a role in motor neuron degeneration as well as in other pathologies of the nervous system, such as Alzheimer's disease and hereditary neuropathies. In this study, we screen a library of small-molecule kinase inhibitors towards the identification of pharmacological enhancers of the axonal retrograde transport of signalling endosomes, which might be used to normalise the rate of this process in diseased neurons. Inhibitors of p38 mitogen-activated protein kinases (p38 MAPK) were identified in this screen and were found to correct deficits in axonal retrograde transport of signalling endosomes in cultured primary SOD1G93A motor neurons. In vitro knockdown experiments revealed that the alpha isoform of p38 MAPK (p38 MAPKα) was the sole isoform responsible for SOD1G93A-induced transport deficits. Furthermore, we found that acute treatment with p38 MAPKα inhibitors restored the physiological rate of axonal retrograde transport in vivo in early symptomatic SOD1G93A mice. Our findings demonstrate the pathogenic effect of p38 MAPKα on axonal retrograde transport and identify a potential therapeutic strategy for ALS. | 10.1038/s41419-018-0624-8 |
pubmed_488_12115 | The study of the distribution law of human peripheral blood cultures for the sensitivity to thiophosphamide was performed. In the first experiment the blood from one person was used, in the second one the blood was used from different persons. "The percent of aberrant cells" and "the number of chromosome breaks per 100 cells" were scored. The distribution law of the cultures in all the experiments was found to be normal. Analysis of the variances on the percent of aberrant cells showed that the distribution law of the cultures received from one donor corresponded to the binomial one, and that of the cultures received from different donors--to the Poisson's one. | pubmed_488_12115 |
pubmed_165_16514 | The profile of daily release of somatolactin (SL) and effects of hypothalamic factors on SL secretion from the organ-cultured pituitary of rainbow trout were examined. The daily release of SL was relatively high (340-380 ng/pituitary/day) for the first 2 days and then decreased. After Day 5, the SL release was maintained at a low level (30-50 ng/pituitary/day) until the end of the experiment at Day 7. The secretory patterns of SL differed from those of growth hormone (GH) and prolactin (PRL); GH secretion was consistently high (15-20 microg/pituitary/day), whereas PRL secretion was low (10 ng/pituitary/day) during the experiment. SL release was not stimulated by calcium ionophore on Days 2 and 6, suggesting that SL release was maximal. Dopamine and epinephrine, added separately to the medium, inhibited SL release. In contrast, serotonin, corticotropin-releasing factor, and gonadotropin-releasing hormone stimulated the dopamine-inhibited SL release. Thus, SL secretion is concluded to be under hypothalamic control and regulated by mechanisms different from those affecting PRL and GH secretion. | 10.1006/gcen.1996.6799 |
pubmed_1135_21901 | Cow's milk protein allergy in exclusively breastfed infants, the main cause of food intolerance during the first 6 months of life, is triggered by the mother's diet. β-Lactoglobulin (BLG) present in cow's milk is one of the most potent allergens for newborns. Since no prophylactic treatment is available, finding ligands capable of binding BLG and reducing its allergenicity is currently the focus of research. In this work, an innovative methodology encompassing microfluidics based on fully automated chip-nanoelectrospray ionization (nanoESI), coupled with high-resolution mass spectrometry (MS) on a quadrupole time-of-flight (QTOF MS) instrument was developed. This platform was employed for the assessment of the noncovalent interactions between maltohexaose (Glc6) and β-lactoglobulin extracted from human milk upon deliberate intake of cow's milk. The experiments were carried out in (+) ESI mode, using ammonium acetate (pH 6.0) as the buffer and also in pure water. In both cases, the MS analysis revealed the formation of BLG-Glc6 complex, which was characterized by top-down fragmentation in tandem MS (MS/MS) using collision-induced dissociation (CID). Our findings have a significant biomedical impact, indicating that Glc6 binds BLG under conditions mimicking the in vivo environment and therefore might represent a ligand, able to reduce its allergenicity. | 10.1007/s00726-015-2030-1 |
pubmed_660_24821 | Ovarian cancer, the deadliest of gynecologic cancers, is usually not diagnosed until advanced stages. Although carboplatin has been popular for treating ovarian cancer for decades, patients eventually develop resistance to this platinum-containing drug. Expression of neurogenic locus notch homolog 3 (Notch3) is associated with chemoresistance and poor overall survival in ovarian cancer patients. Overexpression of NICD3 (the constitutively active form of Notch3) in OVCA429 ovarian cancer cells (OVCA429/NICD3) renders them resistance to carboplatin treatment compared to OVCA429/pCEG cells expressing an empty vector. We have previously shown that methylseleninic acid (MSeA) induces oxidative stress and activates ataxia-telangiectasia mutated and DNA-dependent protein kinase in cancer cells. Here we tested the hypothesis that MSeA and carboplatin exerted a synthetic lethal effect on OVCA429/NICD3 cells. Co-treatment with MSeA synergistically sensitized OVCA429/NICD3 but not OVCA429/pCEG cells to the killing by carboplatin. This synergism was associated with a cell cycle exit at the G2/M phase and the induction of NICD3 target gene HES1. Treatment of N-acetyl cysteine or inhibitors of the above two kinases did not directly impact on the synergism in OVCA429/NICD3 cells. Taken together, these results suggest that the efficacy of carboplatin in the treatment of high grade ovarian carcinoma can be enhanced by a combinational therapy with MSeA. | 10.1371/journal.pone.0101664 |
pubmed_1001_7488 | The effect of combinations of organic acids on digestive microbial population and total tract digestibility of piglets was studied. Thirty 19-21 days weaned pigs (5.4 +/- 0.23 kg, six pigs per treatment) were given a mixed feed with 10 ml water/kg (CTL) or 200 mEq/kg of formic acid (FOR), 1:1 formic:fumaric (FOFU), 1:1 formic:lactic (FOLA) or 2:1 formic:lactic (2FOLA). After 6-8 days, animals were slaughtered. In gastric contents, pH was higher (p = 0.01) with FOFU and lactobacilli tended (p = 0.08) to be lower with FOFU than CTL and FOLA, but coliform counts did not differ (p = 0.14). Acetate proportion was lower (p = 0.03), and propionate (p = 0.05) and butyrate (p = 0.01) higher, with FOFU than CTL, FOLA and 2FOLA. Intestinal coliform counts were higher (p = 0.03) with CTL than FOLA and 2FOLA, but there were no differences on lactobacilli. In intestinal contents, acetate tended (p = 0.06) to be lower with FOR than FOLA and 2FOLA, and butyrate was higher (p = 0.001) with FOR. Although not significantly, dry matter digestibility was 0.03-0.05 lower with CTL than with the other treatments. Combinations of organic acids in piglet diets modify gastric and intestinal microflora, the mixtures of formic:lactic appearing as the most interesting. | 10.1111/j.1439-0396.2005.00553.x |
pubmed_325_6456 | In recent years, rapid developments in several omics platforms and next generation sequencing technology have generated a huge amount of biological data about plants. Systems biology aims to develop and use well-organized and efficient algorithms, data structure, visualization, and communication tools for the integration of these biological data with the goal of computational modeling and simulation. It studies crop plant systems by systematically perturbing them, checking the gene, protein, and informational pathway responses; integrating these data; and finally, formulating mathematical models that describe the structure of system and its response to individual perturbations. Consequently, systems biology approaches, such as integrative and predictive ones, hold immense potential in understanding of molecular mechanism of agriculturally important complex traits linked to agricultural productivity. This has led to identification of some key genes and proteins involved in networks of pathways involved in input use efficiency, biotic and abiotic stress resistance, photosynthesis efficiency, root, stem and leaf architecture, and nutrient mobilization. The developments in the above fields have made it possible to design smart crops with superior agronomic traits through genetic manipulation of key candidate genes. | 10.1089/omi.2015.0106 |
pubmed_20_23190 | Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) is a subtype of Hodgkin lymphoma characterized by a unique clinical and histological presentation. Because of the rare nature of this disease, few large-scale studies are available. We conducted a cohort study in which patients were identified in the Netherlands Cancer Registry in the Southeast of the Netherlands between 1990 and 2010. Of these patients, we collected all clinical characteristics and re-reviewed pathologic material to confirm NLPHL diagnosis. Seventy-three histologically confirmed cases of NLPHL were analyzed with a median follow-up of 65 months (range 4-257 months). Median age at diagnosis was 43 years (range 1-87); 84.9 % of the patients were male; B symptoms were present in 5.5 %; and stage I/II disease was most common (75.4 %). Patients were primarily treated with radiotherapy (50.7 %), chemotherapy (26 %), combined modality (radiotherapy and chemotherapy) (11 %), or surgical excision with careful watch-and-wait (12.3 %). Relapses occurred in seven patients (9.6 %) after a median of 26 months (21-74 months). Six patients (8.2 %) developed histologic transformation to large cell lymphoma. Five patients (6.8 %) died during follow-up due to progression of NLPHL (n = 1), histologic transformation (n = 2) and intercurrent deaths (n = 2). The estimated 10-year overall survival was 94.0 % and the 10-year progression-free survival 75.8 %. Our study confirms the distinct characteristics of NLPHL with a relatively good long-term prognosis. It may be possible to reduce treatment intensity in early stage NLPHL without affecting long-term outcome. | 10.1007/s00277-015-2578-6 |
pubmed_868_23585 | Chediak-Higashi syndrome (CHS) is a rare autosomal recessive lysosomal disorder characterized by frequent infections, oculocutaneous albinism, bleeding diathesis, and progressive neurologic deterioration. In 85% of cases, CHS patients develop the accelerated phase characterized by pancytopenia, high fever, and lymphohistiocytic infiltration of liver, spleen, and lymph nodes. Treatment of accelerated-phase CHS is difficult and the prognosis is poor. Here, we report a case of CHS in a 2-year-old boy who presented in the accelerated phase of the disease. CHS diagnosis was made on the basis of clinical characteristics, hair analysis, and identification of pathognomonic giant azurophilic granules in peripheral blood and bone marrow. | pubmed_868_23585 |
pubmed_457_13469 | BACKGROUND AND AIMS
People with opioid use disorder (OUD) in prison face an acute risk of death after release. We estimated whether prison-based opioid substitution treatment (OST) reduces this risk.
DESIGN
Prospective observational cohort study using prison health care, national community drug misuse treatment and deaths registers.
SETTING
Recruitment at 39 adult prisons in England (32 male; seven female) accounting for 95% of OST treatment in England during study planning.
PARTICIPANTS
Adult prisoners diagnosed with OUD (recruited: September 2010-August 2013; first release: September 2010; last release: October 2014; follow-up to February 2016; n = 15 141 in the risk set).
INTERVENTION AND COMPARATOR
At release, participants were classified as OST exposed (n = 8645) or OST unexposed (n = 6496). The OST unexposed group did not receive OST, or had been withdrawn, or had a low dose.
MEASUREMENTS
Primary outcome: all-cause mortality (ACM) in the first 4 weeks.
SECONDARY OUTCOMES
drug-related poisoning (DRP) deaths in the first 4 weeks; ACM and DRP mortality after 4 weeks to 1 year; admission to community drug misuse treatment in the first 4 weeks. Unadjusted and adjusted Cox regression models (covariates: sex, age, drug injecting, problem alcohol use, use of benzodiazepines, cocaine, prison transfer and admission to community treatment), tested difference in mortality rates and community treatment uptake.
FINDINGS
During the first 4 weeks after prison release there were 24 ACM deaths: six in the OST exposed group and 18 in the OST unexposed group [mortality rate 0.93 per 100 person-years (py) versus 3.67 per 100 py; hazard ratio (HR) = 0.25; 95% confidence interval (CI) = 0.10-0.64]. There were 18 DRP deaths: OST exposed group mortality rate 0.47 per 100 py versus 3.06 per 100 py in the OST unexposed group (HR = 0.15; 95% CI = 0.04-0.53). There was no group difference in mortality risk after the first month. The OST exposed group was more likely to enter drug misuse treatment in the first month post-release (odds ratio 2.47, 95% CI = 2.31-2.65). The OST mortality protective effect on ACM and DRP mortality risk was not attenuated by demographic, overdose risk factors, prison transfer or community treatment (fully adjusted HR = 0.25; 95% CI = 0.09-0.64 and HR = 0.15; 95% CI = 0.04-0.52, respectively).
CONCLUSIONS
In an English national study, prison-based opioid substitution therapy was associated with a 75% reduction in all-cause mortality and an 85% reduction in fatal drug-related poisoning in the first month after release. | 10.1111/add.13779 |
pubmed_292_14786 | PURPOSE
To explore which variables are associated to or determinants of work-related difficulties or unemployment in persons with multiple sclerosis (MS).
METHOD
Papers published between 1993 and February 2015 were included. Quality was judged as poor, acceptable, good or excellent. Determinants were extracted from prospective and retrospective data, associated variables from cross-sectional data; variables were grouped by similarity. Evidence was judged as strong if there were at least two good studies reporting the same results; limited if there was only one good and some acceptable studies.
RESULTS
Forty-two papers were selected, for a total of 31,192 patients (75% females). Work-related difficulties were referred as unemployment, lower amount of worked hours or job cessation. Strong evidence of impact over work-related difficulties was found for a core set of variables, i.e., expanded disability status scale, MS duration, patients' age, fatigue and walking problems. Little evidence exists on the impact of contextual factors.
DISCUSSION
Most of the variables identified as associated to or determinants of work-related difficulties can be treated through rehabilitative interventions. It is important that future research addresses not only unemployment issues in MS, but also the amount and severity of problems affecting work-related tasks relying on specific assessment instruments.
IMPLICATIONS FOR REHABILITATION
Multiple sclerosis (MS) affects young persons of working age and limitation in work activities is part of MS-related disability, but they are not consistently addressed in MS research: EDSS, MS duration, patients' age, fatigue, walking problems, cognitive and neuropsychological impairments were the factors most commonly found as associated to or determinant of difficulties with work. Evidence exists that rehabilitation interventions are effective for fatigue, cognitive impairment, mobility and walking difficulties. However, research did not address the impact of rehabilitation programmes on vocational outcomes. Rehabilitation researchers should include MS-specific assessment instruments for work-related difficulties to standardised clinical protocols, so that the benefits of rehabilitation on persons' ability to work can be demonstrated directly: in this way, cost-benefit balance analyses can be added to the evaluation of treatment effectiveness. | 10.3109/09638288.2015.1070295 |
pubmed_929_20673 | Introduction Selenium (Se) is an antioxidotic element that is able to protect the pancreatic islets from oxidative stress, improve their functionality, and suspend atherosclerosis. The current paper is an attempt to demonstrate the beneficiary impact of administrating Se to patients with diabetes type 2 who are being treated with oral hypoglycemic agents, based on their glycemic and lipidemic profile. Methods The study involves 94 individuals, 72 male and 22 female patients aged 48 to 64 years old with diabetes mellitus type 2. They did not present any diabetic complications or significant comorbidities. They were following a Mediterranean diet and were monitored in order to maintain a steady body mass index (BMI). They were administered with Se 200 μg, taken once daily on an empty stomach. The laboratory testing included fasting blood glucose, hemoglobin A1c (HbA1c), total cholesterol, triglycerides, high-density lipoprotein (HDL), and low-density lipoprotein (LDL). The tests were performed before, three months after, and six months after the administration of selenium. Results The study resulted in a statistically significant reduction in the blood levels of glucose, HbA1c, cholesterol, and LDL in both three months and six months after the beginning of the treatment. HDL did not present any change during the first three months but did present a statistically significant increase in six months. Triglycerides did not present a significant reduction in both three and six months. Conclusion It appears that the administration of Se to type-2 diabetic patients can improve their glycemic and lipidemic profile, while larger definite trials are needed to provide further evidence. | 10.7759/cureus.6443 |
pubmed_824_13531 | Gingival squamous papilloma (SP) is a mucocutanous, benign proliferation rarely seen in the pediatric population. The majority of publications of affected younger patients have been confined to datasets from clinicopathologic investigations. A limited number of case reports in this age group have appeared in the literature, usually featuring primary gingival lesions. Recognition of recurrent gingival SPs in pediatric patients has been underappreciated. The purpose of this report is to present the case of a four-year-old boy with a gingival SP that recurred twice within 18 months and to increase awareness of this entity in children. | pubmed_824_13531 |
pubmed_931_9594 | The aim of this study was to examine the relationship between the developmental competence of oocytes and their total RNA and protein contents, and the level of Cyclin B1 transcription. Ovaries from prepubertal goats were collected from a slaughterhouse. Oocytes were recovered by slicing and those with two or more layers of cumulus cells and homogenous cytoplasm were matured in vitro (20-25 oocytes per drop) for 27 h. Both before and after IVM, samples of oocytes were denuded and categorised into four group treatments by diameter (<110 microm, 110-125 microm, 125-135 microm; >135 microm), separated into sub-groups of 10 oocytes per treatment-replicate and stored in liquid nitrogen until total RNA content analysis by spectophotometry, total protein content analysis by a colorimetric assay and Cyclin B1 transcription analysis by RT-PCR. For the study of developmental competence, the rest of the matured oocytes were fertilised in vitro in groups of 20-25 for 24 h. Presumptive zygotes were denuded, sorted into the four categories of diameter noted above, and placed into culture drops in groups of 18-25 for in vitro culture. Cleavage rate was evaluated at 48 hpi and embryo development at 8 d post-insemination. There were four replicates of each treatment for each assay or evaluation point of the experiment. There were no significant differences between the size categories of oocytes at collection in total RNA content, total protein content and Cyclin B1 mRNA. There were significant differences (P<0.05) in the expression of Cyclin B1 before IVM with oocytes in the >135 mm diameter category having the highest value for this variant. There were no significant differences in these characteristics between the categories of oocyte diameter after IVM except in respect of total RNA content, which was lower for the largest size of oocytes (>135 microm; mean+/-S.D.=12.3+/-1.84 ng/oocyte) than the other three size groups (19.2+/-1.38-22.1+/-4.44 ng/oocyte; P<0.05). Significant differences (P<0.05) in cleavage rate were observed between the different oocyte size categories (<110 microm, 3.0%; 110-125 microm, 32%; 125-135 microm, 50%; >135 microm, 73%). Only oocytes >125 microm diameter developed to the blastocyst stage (125-135 microm, 7%; >135 microm, 10%). This study showed that the RNA content and the Cyclin B1 RNA expression of prepubertal goat oocytes, and their development to embryos varied between the different size categories of the oocytes. | 10.1016/j.anireprosci.2006.12.018 |
pubmed_58_13132 | Cancer is a collection of genetic diseases, with large phenotypic differences and genetic heterogeneity between different types of cancers and even within the same cancer type. Recent advances in genome-wide profiling provide an opportunity to investigate global molecular changes during the development and progression of cancer. Meanwhile, numerous statistical and machine learning algorithms have been designed for the processing and interpretation of high-throughput molecular data. Molecular subtyping studies have allowed the allocation of cancer into homogeneous groups that are considered to harbor similar molecular and clinical characteristics. Furthermore, this has helped researchers to identify both actionable targets for drug design as well as biomarkers for response prediction. In this review, we introduce five frequently applied techniques for generating molecular data, which are microarray, RNA sequencing, quantitative polymerase chain reaction, NanoString and tissue microarray. Commonly used molecular data for cancer subtyping and clinical applications are discussed. Next, we summarize a workflow for molecular subtyping of cancer, including data preprocessing, cluster analysis, supervised classification and subtype characterizations. Finally, we identify and describe four major challenges in the molecular subtyping of cancer that may preclude clinical implementation. We suggest that standardized methods should be established to help identify intrinsic subgroup signatures and build robust classifiers that pave the way toward stratified treatment of cancer patients. | 10.1093/bib/bby026 |
pubmed_977_20550 | Since the start of the current COVID-19 pandemic, for the first time a significant fraction of the world's population cover their respiratory system for an extended period with mostly medical facemasks and textile masks. This new situation raises questions about the extent of mask related debris (fibers and particles) being released and inhaled and possible adverse effects on human health. This study aimed to quantify the debris release from a textile-based facemask in comparison to a surgical mask and a reference cotton textile using both liquid and air extraction. Under liquid extractions, cotton-based textiles released up to 29'452 ± 1'996 fibers g-1 textile while synthetic textiles released up to 1'030 ± 115 fibers g-1 textile. However, when the masks were subjected to air-based extraction scenarios, only a fraction (0.1-1.1%) of this fiber amount was released. Several metals including copper (up to 40.8 ± 0.9 µg g-1) and iron (up to 7.0 ± 0.3 µg g-1) were detected in acid dissolved textiles. Additionally the acute in vitro toxicity of size-fractionated liquid extracts (below and above 0.4 µm) were assessed on human alveolar basal epithelial cells. The current study shows no acute cytotoxicity response for all the analyzed facemasks. | 10.1016/j.envint.2022.107364 |
pubmed_709_2164 | Experiments were designed to test the hypothesis that insulin-induced hyperpolarization of rat skeletal muscle is mediated by stimulation of a ouabain-inhibitable electrogenic pump. Parallel experiments were carried out on rat caudofemoralis with isoproterenol, known to hyperpolarize rat skeletal muscle by stimulation of such a pump. Ouabain (10(-5) M) completely inhibited isoproterenol-induced hyperpolarization within 15 min but had no effect on half-maximal insulin-induced hyperpolarization. Ouabain (10(-6) M) inhibited isoproterenol effect by 60% during a period of 5-15 min. Ouabain (10(-4) M) had no effect on insulin-induced hyperpolarization within 10 min but depolarized during the next 10 min. In a separate series of studies in rat extensor digitorum longus muscle, 10(-5) M ouabain increased intracellular Na+ within 14 min. It is concluded that in rat caudofemoralis muscle, insulin-induced hyperpolarization is not mediated by a ouabain-inhibitable electrogenic pump. | 10.1152/ajpcell.1981.241.3.C145 |
pubmed_948_9821 | Antistasin is a 119 amino acid heparin-binding protein from the leech Haementaria officinalis which has anticoagulant and antimetastatic properties. A series of peptides representing the basic amino acid-rich domains of the amino- and carboxyl-terminal regions of the inhibitor were synthesized by solid-phase peptide chemistry and their ability to bind sulfated glycolipids was investigated. The findings show that [A103,106,108] antistasin 93-119 has high affinity for sulfatide and inhibits the specific interaction of whole antistasin with [Gal(3-SO4)beta 1-1Cer]. We conclude that the 93-119 region is a critical domain that mediates the interaction of antistasin with sulfated glycolipids. | 10.1016/s0006-291x(05)81409-3 |
pubmed_158_680 | We investigated the antiproliferative effects of two planar 4,9-diazapyrenium hydrogenasulphates against human malignant MiaPaCa 2 (pancreatic carcinoma), Hep 2 (laryngeal carcinoma) and human normal fibroblasts (WI 38) cell lines. The tested compounds were very potent in inhibiting the growth of the treated cell lines. Treatment with molar concentrations of the substances (10(-4)-10(-7) M) caused growth inhibition by more than 50%. The morphological changes of treated cells were also observed. Cells became smaller, with condensed chromatin and fragmented nuclei, the characteristics of dying cells. The identification of DNA-fragmentation and the appearance of chromatin aggregation leads us to assume the tested substances induced apoptosis of the investigated tumor cell lines. | pubmed_158_680 |
pubmed_105_15455 | Circadian nutritional behaviors, defined by the daily eating/fasting cycle, have been linked with breast cancer. This study aimed to further disentangle the association of nighttime fasting duration and time of breakfast with breast cancer risk. We analyzed data from 1,181 breast cancer cases and 1,326 population controls from the Spanish multicase-control study (MCC-Spain), 2008-2013. We collected circadian nutritional behaviors at mid-age via a telephonic interview. We applied logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CIs) for the association of nighttime fasting duration and time of breakfast with breast cancer risk in all women and stratified by menopausal status. Models were adjusted for age, center, education, family history of breast cancer, age at menarche, number of children, breastfeeding, age at first child, body mass index (BMI), contraceptive use, and hormonal replacement therapy (HRT). A later time of breakfast was associated with a non-significant increased risk of breast cancer (OR = 1.05, 95% CI: 0.95-1.16, per hour increase). This association was stronger among premenopausal women, among whom each hour later, the time of breakfast was associated with an 18% increase in breast cancer risk (OR = 1.18, 95% CI: 1.01-1.40). The association was not observed in postmenopausal women. We did not observe an association between nighttime fasting duration and breast cancer risk after adjusting for the time of breakfast. In this study, late breakfast was associated with increased breast cancer risk, especially among premenopausal women, compared with early breakfast. Aside from nutritional quality, circadian nutritional behaviors should be further studied in relation to cancer. | 10.3389/fnut.2022.941477 |
pubmed_211_16404 | BACKGROUND
Complement activation plays a pivotal role in hyperacute xenograft rejection. In humans, activation of complement is regulated by a number of cell surface regulatory proteins. Membrane cofactor protein (CD46) is one such regulator that protects cells by acting as a cofactor for the factor I-mediated cleavage of C3b and C4b. Transgenic animals expressing human CD46 may provide organs that are resistant to complement attack. However, attempts to generate mice expressing human CD46 using cDNA-based constructs have been largely unsuccessful.
METHODS
Transgenic mice expressing a glycosylphosphatidyl inositol (GPI)-linked form of CD46 were generated by microinjection of a hybrid CD46/CD55 cDNA under the control of the human intercellular adhesion molecule-2 promoter. Expression of CD46-GPI on the vascular endothelium was determined by immunohistochemistry. The ability of CD46-GPI to protect mouse tissues from human complement attack was determined using an ex vivo isolated perfused heart model.
RESULTS
Three founder animals expressing CD46-GPI were identified. Histological analysis showed strong and uniform expression of CD46-GPI on the vascular endothelium of all organs examined. Ex vivo perfusion of transgenic mouse hearts with human plasma showed a reduction in C3c deposition and a slightly prolonged function compared with controls.
CONCLUSIONS
High-level expression of CD46-GPI was achieved in transgenic mice by using a modified cDNA-based construct. The CD46-GPI was functional, providing some protection from complement-mediated damage in the ex vivo model, and may be useful in xenotransplantation if expressed in combination with CD55 and CD59. | 10.1097/00007890-199812150-00001 |
Subsets and Splits
No community queries yet
The top public SQL queries from the community will appear here once available.